Frequent mutations in chromatin-remodelling genes in pulmonary carcinoids
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Frequent mutations in chromatin-remodelling genes in pulmonary carcinoids

The European Genome-phenome Archive (EGA) is a service for permanent archiving and sharing of personally identifiable genetic, phenotypic, and clinical data generated for the purposes of biomedical research projects or in the context of research-focused healthcare systems. Cohort A includes glioma tumors of varied grading and pathology from male and female individuals. Tumor DNA was isolated from fresh frozen tissue. We aimed to investigate underlying molecular networks shaping the therapeutic susceptibility of ALK-driven lung adenocarcinoma cells via tumor microenvironmental cues using three-dimensional (3D) spheroid co-culture settings. We identify 3 immunologic response categories, which frequently co-exist within individual patients. We present an integrated analysis of copy number and gene expression in a discovery and validation set of 997 and 995 primary breast tumours, respectively, with long-term clinical follow-up. Here we perform gene copy number analysis (n¼54), genome/exome (n¼44) and transcriptome (n¼69) sequencing of pulmonary carcinoids and observe frequent mutations in chromatin-remodelling genes.

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10.1038/S41423-025-01369-5
ISSN:2042-0226

A phase I/II trial of WT1-specific TCR gene therapy for patients with acute myeloid leukemia and active disease post-allogeneic hematopoietic cell transplantation: skewing towards NK-like phenotype impairs T cell function and persistence

Francesco MazziottaLauren E. MartinDaniel N. EganMerav BarSinéad Kinsella24
Nature Communications
2025
2025/6/5
Vol.16 No.1 p.1-20
Relapsed and/or refractory acute myeloid leukemia (AML) post-allogeneic hematopoietic cell transplantation (HCT) is usually fatal. We previously reported that post-HCT immunotherapy with Epstein-Barr virus (EBV)-specific donor CD8+ T cells engineered to express a Wilms Tumor Antigen 1-specific T-cel...
CancerTranslational immunology
10.1038/S41467-025-60394-0
ISSN:2041-1723

Downregulation of the FTO m6A RNA demethylase promotes EMT-mediated progression of epithelial tumors and sensitivity to Wnt inhibitors

Jana JeschkeEvelyne CollignonClémence Al WardiMohammad KrayemMartin Bizet38
Nature Cancer
2021
2021/6/23
Vol.2 No.6 p.611-628
Post-transcriptional modifications of RNA constitute an emerging regulatory layer of gene expression. The demethylase fat mass- and obesity-associated protein (FTO), an eraser of N6-methyladenosine (m6A), has been shown to play a role in cancer, but its contribution to tumor progression and the unde...
CancerCell signallingEpithelial–mesenchymal transitionRNA metabolism
10.1038/S43018-021-00223-7
ISSN:2662-1347

Cancer-associated fibroblast heterogeneity in axillary lymph nodes drives metastases in breast cancer through complementary mechanisms

Floriane PelonBrigitte BourachotYann KiefferIlaria MagagnaFanny Mermet-Meillon18
Nature Communications
2020
2020/1/21
Vol.11 No.1 p.1-20
Although fibroblast heterogeneity is recognized in primary tumors, both its characterization in and its impact on metastases remain unknown. Here, combining flow cytometry, immunohistochemistry and RNA-sequencing on breast cancer samples, we identify four Cancer-Associated Fibroblast (CAF) subpopula...
Breast cancerCancerCancer microenvironmentTumour heterogeneity
10.1038/S41467-019-14134-W
ISSN:2041-1723

Federated analysis of autosomal recessive coding variants in 29,745 developmental disorder patients from diverse populations

V. Kartik ChundruZhancheng ZhangKlaudia WalterSarah J. LindsayPetr Danecek29
Nature Genetics
2024
2024/9/23
00 p.1-8
Autosomal recessive coding variants are well-known causes of rare disorders. We quantified the contribution of these variants to developmental disorders in a large, ancestrally diverse cohort comprising 29,745 trios, of whom 20.4% had genetically inferred non-European ancestries. The estimated fract...
Clinical geneticsGenomicsNeurodevelopmental disorders
10.1038/S41588-024-01910-8
ISSN:1061-4036

Mapping the breast cancer metastatic cascade onto ctDNA using genetic and epigenetic clonal tracking

George D. CresswellDaniel NicholInmaculada SpiteriHaider TariLuis Zapata12
Nature Communications
2020
2020/3/27
Vol.11 No.1 p.1-12
Circulating tumour DNA (ctDNA) allows tracking of the evolution of human cancers at high resolution, overcoming many limitations of tissue biopsies. However, exploiting ctDNA to determine how a patient’s cancer is evolving in order to aid clinical decisions remains difficult. This is because ctDNA i...
Breast cancerCancer genomicsMolecular evolutionPhylogeny
10.1038/S41467-020-15047-9
ISSN:2041-1723

Analysis of mitochondrial m1A/G RNA modification reveals links to nuclear genetic variants and associated disease processes

Aminah Tasnim AliYoussef IdaghdourAlan Hodgkinson
Communications Biology
2020
2020/3/27
Vol.3 No.1 p.1-11
RNA modifications affect the stability and function of RNA species, regulating important downstream processes. Modification levels are often dynamic, varying between tissues and individuals, although it is not always clear what modulates this or what impact it has on biological systems. Here, we qua...
EpigenomicsMitochondriaQuantitative traitRNA sequencingTranscriptomics
10.1038/S42003-020-0879-3
ISSN:2399-3642

Independent somatic evolution underlies clustered neuroendocrine tumors in the human small intestine

Elias ErikArdalan ArmanLindberg MarkusReinsbach Susanne E.Muth Andreas8
Nature Communications
2021
2021/11/4
Vol.12 No.1 p.1-8
Small intestine neuroendocrine tumor (SI-NET), the most common cancer of the small bowel, often displays a curious multifocal phenotype with several tumors clustered together in a limited intestinal segment. SI-NET also shows an unusual absence of driver mutations explaining tumor initiation and met...
Cancer genomicsGastrointestinal cancerMetastasisTumour heterogeneity
10.1038/S41467-021-26581-5
ISSN:2041-1723

Healthspan and lifespan extension by fecal microbiota transplantation into progeroid mice

Clea BárcenaRafael Valdés-MasPablo MayoralCecilia GarabayaSylvère Durand17
Nature Medicine
2019
2019/7/22
Vol.25 No.8 p.1234-1242
The gut microbiome is emerging as a key regulator of several metabolic, immune and neuroendocrine pathways1,2. Gut microbiome deregulation has been implicated in major conditions such as obesity, type 2 diabetes, cardiovascular disease, non-alcoholic fatty acid liver disease and cancer3–6, but its p...
AgeingMetagenomics
10.1038/S41591-019-0504-5
ISSN:1078-8956

A body map of somatic mutagenesis in morphologically normal human tissues

Li RuoyanDi LinLi JieFan WenyiLiu Yachen21
Nature
2021
2021/8/25
00 p.1-6
Somatic mutations that accumulate in normal tissues are associated with ageing and disease1,2. Here we performed a comprehensive genomic analysis of 1,737 morphologically normal tissue biopsies of 9 organs from 5 donors. We found that somatic mutation accumulations and clonal expansions were widespr...
Cancer genomicsGenetic variationMutationPhylogenetics
10.1038/S41586-021-03836-1
ISSN:0028-0836

Genome-wide DNA methylation analysis on C-reactive protein among Ghanaians suggests molecular links to the emerging risk of cardiovascular diseases

Felix P. ChilungaPeter HennemanAndrea VenemaKarlijn A. C. MeeksAna Requena-Méndez14
Npj Genomic Medicine
2021
2021/6/11
Vol.6 No.1 p.1-9
Molecular mechanisms at the intersection of inflammation and cardiovascular diseases (CVD) among Africans are still unknown. We performed an epigenome-wide association study to identify loci associated with serum C-reactive protein (marker of inflammation) among Ghanaians and further assessed whethe...
Molecular medicineRisk factors
10.1038/S41525-021-00213-9
ISSN:2056-7944

Deep convolutional neural networks for accurate somatic mutation detection

Sayed Mohammad Ebrahim SahraeianRuolin LiuBayo LauKarl PodestaMarghoob Mohiyuddin6
Nature Communications
2019
2019/3/4
Vol.10 No.1 p.1-10
Accurate detection of somatic mutations is still a challenge in cancer analysis. Here we present NeuSomatic, the first convolutional neural network approach for somatic mutation detection, which significantly outperforms previous methods on different sequencing platforms, sequencing strategies, and ...
Cancer genomicsGenomicsMachine learning
10.1038/S41467-019-09027-X
ISSN:2041-1723

Cis -effects on gene expression in the human prenatal brain associated with genetic risk for neuropsychiatric disorders

Lynsey S. HallOliver PainHeath E. O’BrienRichard AnneyJames T. R. Walters8
Molecular Psychiatry
2020
2020/5/4
00 p.1-7
The majority of common risk alleles identified for neuropsychiatric disorders reside in noncoding regions of the genome and are therefore likely to impact gene regulation. However, the genes that are primarily affected and the nature and developmental timing of these effects remain unclear. Given th...
GeneticsSchizophrenia
10.1038/S41380-020-0743-3
ISSN:1359-4184

Clonal architecture predicts clinical outcomes and drug sensitivity in acute myeloid leukemia

Benard Brooks A.Leak Logan B.Azizi ArmonThomas DanielGentles Andrew J.6
Nature Communications
2021
2021/12/13
Vol.12 No.1 p.1-13
The impact of clonal heterogeneity on disease behavior or drug response in acute myeloid leukemia remains poorly understood. Using a cohort of 2,829 patients, we identify features of clonality associated with clinical features and drug sensitivities. High variant allele frequency for 7 mutations (in...
Acute myeloid leukaemiaCancer genomicsData integrationRisk factors
10.1038/S41467-021-27472-5
ISSN:2041-1723

Enhanced CAR T cell expansion and prolonged persistence in pediatric patients with ALL treated with a low-affinity CD19 CAR

Sara GhorashianAnne Marijn KramerShimobi OnuohaGary WrightJack Bartram44
Nature Medicine
2019
2019/9/2
Vol.25 No.9 p.1408-1414
Chimeric antigen receptor (CAR)-modified T cells targeting CD19 demonstrate unparalleled responses in relapsed/refractory acute lymphoblastic leukemia (ALL)1–5, but toxicity, including cytokine-release syndrome (CRS) and neurotoxicity, limits broader application. Moreover, 40–60% of patients relapse...
Acute lymphocytic leukaemiaCancer immunotherapyT cellsTranslational immunologyTranslational research
10.1038/S41591-019-0549-5
ISSN:1078-8956

The transferability of lipid loci across African, Asian and European cohorts

Karoline KuchenbaeckerNikita TelkarTheresa ReikerRobin G. WaltersKuang Lin24
Nature Communications
2019
2019/9/24
Vol.10 No.1 p.1-10
Most genome-wide association studies are based on samples of European descent. We assess whether the genetic determinants of blood lipids, a major cardiovascular risk factor, are shared across populations. Genetic correlations for lipids between European-ancestry and Asian cohorts are not significan...
Cardiovascular geneticsGenome-wide association studiesHeritable quantitative traitPopulation genetics
10.1038/S41467-019-12026-7
ISSN:2041-1723

Partner independent fusion gene detection by multiplexed CRISPR-Cas9 enrichment and long read nanopore sequencing

Christina StanglSam de BlankIvo RenkensLiset WesteraTamara Verbeek14
Nature Communications
2020
2020/6/5
Vol.11 No.1 p.1-14
Fusion genes are hallmarks of various cancer types and important determinants for diagnosis, prognosis and treatment. Fusion gene partner choice and breakpoint-position promiscuity restricts diagnostic detection, even for known and recurrent configurations. Here, we develop FUDGE (FUsion Detection f...
Cancer genomicsCancer therapy
10.1038/S41467-020-16641-7
ISSN:2041-1723

Prolonged persistence of mutagenic DNA lesions in somatic cells

Michael Spencer ChapmanEmily MitchellKenichi YoshidaNicholas WilliamsMargarete A. Fabre26
Nature
2025
2025/1/15
00 p.1-10
DNA is subject to continual damage, leaving each cell with thousands of individual DNA lesions at any given moment1–3. The efficiency of DNA repair means that most known classes of lesion have a half-life of minutes to hours3,4, but the extent to which DNA damage can persist for longer durations rem...
Cancer genomicsDNA damage and repairGenomic instabilityGenomicsOncogenesis
10.1038/S41586-024-08423-8
ISSN:0028-0836

Single cell sequencing identifies clonally expanded synovial CD4+ TPH cells expressing GPR56 in rheumatoid arthritis

Argyriou AlexandraWadsworth Marc H.Lendvai AdrianChristensen Stephen M.Hensvold Aase H.11
Nature Communications
2022
2022/7/13
Vol.13 No.1 p.1-13
Rheumatoid arthritis (RA) is an autoimmune disease affecting synovial joints where different CD4+ T cell subsets may contribute to pathology. Here, we perform single cell sequencing on synovial CD4+ T cells from anti-citrullinated protein antibodies (ACPA)+ and ACPA- RA patients and identify two per...
AutoimmunityCD4-positive T cells
10.1038/S41467-022-31519-6
ISSN:2041-1723

Deciphering the genomic, epigenomic, and transcriptomic landscapes of pre-invasive lung cancer lesions

Vitor H. TeixeiraChristodoulos P. PipinikasAdam PennycuickHenry Lee-SixDeepak Chandrasekharan32
Nature Medicine
2019
2019/1/21
Vol.25 No.3 p.517-525
The molecular alterations that occur in cells before cancer is manifest are largely uncharted. Lung carcinoma in situ (CIS) lesions are the pre-invasive precursor to squamous cell carcinoma. Although microscopically identical, their future is in equipoise, with half progressing to invasive cancer an...
Cancer genomicsEpigenomicsNon-small-cell lung cancerOncogenesis
10.1038/S41591-018-0323-0
ISSN:1078-8956

Early evolutionary branching across spatial domains predisposes to clonal replacement under chemotherapy in neuroblastoma

Jenny KarlssonHiroaki YasuiAdriana MañasNatalie AnderssonKarin Hansson18
Nature Communications
2024
2024/10/18
Vol.15 No.1 p.1-19
Neuroblastoma (NB) is one of the most lethal childhood cancers due to its propensity to become treatment resistant. By spatial mapping of subclone geographies before and after chemotherapy across 89 tumor regions from 12 NBs, we find that densely packed territories of closely related subclones prese...
Cancer genomicsCNS cancerEvolutionary geneticsPaediatric cancerTumour heterogeneity
10.1038/S41467-024-53334-X
ISSN:2041-1723

A clinically applicable integrative molecular classification of meningiomas

Nassiri FarshadLiu JeffPatil VikasMamatjan YasinWang Justin Z.26
Nature
2021
2021/8/25
00 p.1-7
Meningiomas are the most common primary intracranial tumour in adults1. Patients with symptoms are generally treated with surgery as there are no effective medical therapies. The World Health Organization histopathological grade of the tumour and the extent of resection at surgery (Simpson grade) ar...
Cancer epigeneticsCancer genomicsCNS cancer
10.1038/S41586-021-03850-3
ISSN:0028-0836

Genetic immune escape landscape in primary and metastatic cancer

Francisco Martínez-JiménezPeter PriestleyCharles ShaleJonathan BaberErik Rozemuller6
Nature Genetics
2023
2023/5/10
00 p.1-12
Studies have characterized the immune escape landscape across primary tumors. However, whether late-stage metastatic tumors present differences in genetic immune escape (GIE) prevalence and dynamics remains unclear. We performed a pan-cancer characterization of GIE prevalence across six immune escap...
Genome informaticsTumour immunology
10.1038/S41588-023-01367-1
ISSN:1061-4036

Long-molecule scars of backup DNA repair in BRCA1- and BRCA2-deficient cancers

Jeremy SettonKevin HadiZi-Ning ChooKatherine S. KuchinHuasong Tian21
Nature
2023
2023/8/16
00 p.1-9
Homologous recombination (HR) deficiency is associated with DNA rearrangements and cytogenetic aberrations1. Paradoxically, the types of DNA rearrangements that are specifically associated with HR-deficient cancers only minimally affect chromosomal structure2. Here, to address this apparent contradi...
Breast cancerCancer genomicsDNA sequencingGenome evolutionHomologous recombination
10.1038/S41586-023-06461-2
ISSN:0028-0836

Multi-omics analysis identifies therapeutic vulnerabilities in triple-negative breast cancer subtypes

Lehmann Brian D.Colaprico AntonioSilva Tiago C.Chen JianjiaoAn Hanbing15
Nature Communications
2021
2021/11/1
Vol.12 No.1 p.1-18
Triple-negative breast cancer (TNBC) is a collection of biologically diverse cancers characterized by distinct transcriptional patterns, biology, and immune composition. TNBCs subtypes include two basal-like (BL1, BL2), a mesenchymal (M) and a luminal androgen receptor (LAR) subtype. Through a compr...
Breast cancerCancer genomicsData integrationTranslational research
10.1038/S41467-021-26502-6
ISSN:2041-1723

The Anglo-Saxon migration and the formation of the early English gene pool

Gretzinger JoschaSayer DuncanJusteau PierreAltena EvelinePala Maria80
Nature
2022
2022/9/21
Vol.610 No.7930 p.112-119
The history of the British Isles and Ireland is characterized by multiple periods of major cultural change, including the influential transformation after the end of Roman rule, which precipitated shifts in language, settlement patterns and material culture1. The extent to which migration from conti...
ArchaeologyCultural evolutionEvolutionary geneticsPopulation genetics
10.1038/S41586-022-05247-2
ISSN:0028-0836

Breast Cancer Consensus Subtypes: A system for subtyping breast cancer tumors based on gene expression

Horr ChristinaBuechler Steven A.
Npj Breast Cancer
2021
2021/10/12
Vol.7 No.1 p.1-13
Breast cancer is heterogeneous in prognoses and drug responses. To organize breast cancers by gene expression independent of statistical methodology, we identified the Breast Cancer Consensus Subtypes (BCCS) as the consensus groupings of six different subtyping methods. Our classification software i...
Breast cancerCancer genomicsDiagnostic markersTranscriptomics
10.1038/S41523-021-00345-2
ISSN:2374-4677

Human proximal tubular epithelial cell interleukin-1 receptor signalling triggers G2/M arrest and cellular senescence during hypoxic kidney injury

Kurt T. K. GiulianiPurba NagBenjamin C. AdamsXiangju WangSeokchan Hong18
Cell Death & Disease
2025
2025/1/31
Vol.16 No.1 p.1-12
Hypoxia and interleukin (IL)-1β are independent mediators of tubulointerstitial fibrosis, the histological hallmark of chronic kidney disease (CKD). Here, we examine how hypoxia and IL-1β act in synergy to augment maladaptive proximal tubular epithelial cell (PTEC) repair in human CKD. Ex vivo patie...
End-stage renal diseaseTranslational research
10.1038/S41419-025-07386-6
ISSN:2041-4889

Selection for somatic escape variants in SERPINA1 in the liver of patients with alpha-1 antitrypsin deficiency

Natalia BrzozowskaLily Y. D. WuVera KhodzhaevaWilliam J. GriffithsAdam Duckworth12
Nature Genetics
2025
2025/3/10
00 p.1-9
Somatic variants accumulate in non-malignant tissues with age. Functional variants, leading to clonal advantage of hepatocytes, accumulate in the liver of patients with acquired chronic liver disease (CLD). Whether somatic variants are common to CLD from differing etiologies is unknown. We analyzed ...
DNA sequencingLiver diseases
10.1038/S41588-025-02125-1
ISSN:1061-4036

Circulating tumor cell copy-number heterogeneity in ALK-rearranged non-small-cell lung cancer resistant to ALK inhibitors

Marianne OulhenPatrycja PawlikowskaTala TayounMarianna GaronziGenny Buson15
Npj Precision Oncology
2021
2021/7/16
Vol.5 No.1 p.1-11
Gatekeeper mutations are identified in only 50% of the cases at resistance to Anaplastic Lymphoma Kinase (ALK)-tyrosine kinase inhibitors (TKIs). Circulating tumor cells (CTCs) are relevant tools to identify additional resistance mechanisms and can be sequenced at the single-cell level. Here, we pro...
CancerMolecular medicine
10.1038/S41698-021-00203-1
ISSN:2397-768X

Chromothripsis-associated chromosome 21 amplification orchestrates transformation to blast-phase MPN through targetable overexpression of DYRK1A

Charlotte K. BrierleyBon Ham YipGiulia OrlandoJeremy WenSean Wen41
Nature Genetics
2025
2025/6/9
Vol.57 No.6 p.1478-1492
Chromothripsis, the chaotic shattering and repair of chromosomes, is common in cancer. Whether chromothripsis generates actionable therapeutic targets remains an open question. In a cohort of 64 patients in blast phase of a myeloproliferative neoplasm (BP-MPN), we describe recurrent amplification of...
DNA sequencingLeukaemia
10.1038/S41588-025-02190-6
ISSN:1061-4036

A novel patient-derived 3D model recapitulates mantle cell lymphoma lymph node signaling, immune profile and in vivo ibrutinib responses

Araujo-Ayala FerranDobaño-López CèliaValero Juan GarcíaNadeu FerranGava Fabien19
Leukemia
2023
2023/4/8
00 p.1-13
Mantle cell lymphoma (MCL), a rare and aggressive B-cell non-Hodgkin lymphoma, mainly develops in the lymph node (LN) and creates a protective and immunosuppressive niche that facilitates tumor survival, proliferation and chemoresistance. To capture disease heterogeneity and tumor microenvironment (...
B-cell lymphomaCancer microenvironmentCancer models
10.1038/S41375-023-01885-1
ISSN:0887-6924

Evolutionary and immune microenvironment dynamics during neoadjuvant treatment of esophageal adenocarcinoma

Melissa BarrouxJacob HousehamEszter LakatosTahel RonelAnn-Marie Baker30
Nature Cancer
2025
2025/5/14
00 p.1-18
Locally advanced esophageal adenocarcinoma remains difficult to treat and the ecological and evolutionary dynamics responsible for resistance and recurrence are incompletely understood. Here, we performed longitudinal multiomic analysis of patients with esophageal adenocarcinoma in the MEMORI trial....
Applied immunologyCancerCancer genomicsCancer microenvironmentOesophageal cancer
10.1038/S43018-025-00955-W
ISSN:2662-1347

MDM2 amplification in rod-shaped chromosomes provides clues to early stages of circularized gene amplification in liposarcoma

Saskia SydowPaul PiccinelliShamik MitraPanagiotis TsagkozisAsle Hesla14
Communications Biology
2024
2024/5/20
Vol.7 No.1 p.1-12
Well-differentiated liposarcoma (WDLS) displays amplification of genes on chromosome 12 (Chr12) in supernumerary ring or giant marker chromosomes. These structures have been suggested to develop through chromothripsis, followed by circularization and breakage-fusion-bridge (BFB) cycles. To test this...
ChromosomesGenomic instability
10.1038/S42003-024-06307-1
ISSN:2399-3642

Partially methylated domains are hypervariable in breast cancer and fuel widespread CpG island hypermethylation

Arie B. BrinkmanSerena Nik-ZainalFemke SimmerF. Germán Rodríguez-GonzálezMarcel Smid29
Nature Communications
2019
2019/4/15
Vol.10 No.1 p.1-10
Global loss of DNA methylation and CpG island (CGI) hypermethylation are key epigenomic aberrations in cancer. Global loss manifests itself in partially methylated domains (PMDs) which extend up to megabases. However, the distribution of PMDs within and between tumor types, and their effects on key ...
Cancer genomicsDNA methylation
10.1038/S41467-019-09828-0
ISSN:2041-1723

The RNA landscape of the human placenta in health and disease

Sungsam GongFrancesca GaccioliJustyna DopieralaUlla SovioEmma Cook11
Nature Communications
2021
2021/5/11
Vol.12 No.1 p.1-17
The placenta is the interface between mother and fetus and inadequate function contributes to short and long-term ill-health. The placenta is absent from most large-scale RNA-Seq datasets. We therefore analyze long and small RNAs (~101 and 20 million reads per sample respectively) from 302 human pla...
Data publication and archivingEndocrine reproductive disordersGene expression
10.1038/S41467-021-22695-Y
ISSN:2041-1723

Accelerating functional gene discovery in osteoarthritis

Natalie C. ButterfieldKatherine F. CurryJulia SteinbergHannah DewhurstDavide Komla-Ebri27
Nature Communications
2021
2021/1/20
Vol.12 No.1 p.1-18
Osteoarthritis causes debilitating pain and disability, resulting in a considerable socioeconomic burden, yet no drugs are available that prevent disease onset or progression. Here, we develop, validate and use rapid-throughput imaging techniques to identify abnormal joint phenotypes in randomly sel...
BoneCartilage
10.1038/S41467-020-20761-5
ISSN:2041-1723

Circulating tumor cell plasticity determines breast cancer therapy resistance via neuregulin 1–HER3 signaling

Roberto WürthElisa DonatoLaura L. MichelMassimo SainiLisa Becker42
Nature Cancer
2025
2025/1/3
00 p.1-19
Circulating tumor cells (CTCs) drive metastasis, the leading cause of death in individuals with breast cancer. Due to their low abundance in the circulation, robust CTC expansion protocols are urgently needed to effectively study disease progression and therapy responses. Here we present the establi...
Breast cancerCancerCancer modelsMechanisms of disease
10.1038/S43018-024-00882-2
ISSN:2662-1347

Evolutionary trajectories of IDH-mutant astrocytoma identify molecular grading markers related to cell cycling

Wies R. VallentgoedYouri HoogstrateKarin A. van GarderenLevi van HijfteErik van Dijk34
Nature Cancer
2025
2025/8/19
00 p.1-21
The evolutionary processes that drive malignant progression of IDH-mutant astrocytomas remain unclear. Here, we performed multiomics on matched initial and recurrent tumor samples from a cohort of 105 patients and overlaid the data with detailed clinical annotation. We identified overlapping feature...
CancerCancer genomicsCNS cancerTumour heterogeneity
10.1038/S43018-025-01023-Z
ISSN:2662-1347

The AML cellular state space unveils NPM1 immune evasion subtypes with distinct clinical outcomes

Henrik LilljebjörnPablo Peña-MartínezHanna ThorssonRasmus HenningssonMarianne Rissler20
Nature Communications
2025
2025/11/25
Vol.16 No.1 p.105920
Acute myeloid leukemia is a genetically and cellularly heterogeneous disease. We characterize 120 AMLs using genomic and transcriptomic analyses, including single-cell RNA sequencing. Our results reveal an extensive cellular heterogeneity that distorts the bulk transcriptomic profiles. Selective exa...
Acute myeloid leukaemiaCancer geneticsCancer genomicsTranscriptomics
10.1038/S41467-025-66546-6
ISSN:2041-1723

Pan-cancer computational histopathology reveals mutations, tumor composition and prognosis

Yu FuAlexander W. JungRamon Viñas TorneSantiago GonzalezHarald Vöhringer10
Nature Cancer
2020
2020/7/27
Vol.1 No.8 p.800-810
We use deep transfer learning to quantify histopathological patterns across 17,355 hematoxylin and eosin-stained histopathology slide images from 28 cancer types and correlate these with matched genomic, transcriptomic and survival data. This approach accurately classifies cancer types and provides ...
CancerCancer genomicsCancer imagingComputational science
10.1038/S43018-020-0085-8
ISSN:2662-1347

Whole-genome sequencing reveals an association between small genomic deletions and an increased risk of developing Parkinson’s disease

Oh Ji-HyeJo SungyangPark Kye WonLee Eun-JaeLee Seung Hyun15
Experimental & Molecular Medicine
2023
2023/3/3
00 p.1-10
Single-nucleotide variants (SNVs) associated with Parkinson’s disease (PD) have been investigated mainly through genome-wide association studies. However, other genomic alterations, including copy number variations, remain less explored. In this study, we conducted whole-genome sequencing of primary...
Genetics researchParkinson's disease
10.1038/S12276-023-00952-Y
ISSN:2092-6413

Comprehensive characterization of claudin-low breast tumors reflects the impact of the cell-of-origin on cancer evolution

Roxane M. PommierAmélien SanlavilleLaurie TononJanice KielbassaEmilie Thomas13
Nature Communications
2020
2020/7/9
Vol.11 No.1 p.1-12
Claudin-low breast cancers are aggressive tumors defined by the low expression of key components of cellular junctions, associated with mesenchymal and stemness features. Although they are generally considered as the most primitive breast malignancies, their histogenesis remains elusive. Here we sho...
BioinformaticsBreast cancerEpigenetics analysisGene expression analysisMethylation analysis
10.1038/S41467-020-17249-7
ISSN:2041-1723

Reconstituting the transcriptome and DNA methylome landscapes of human implantation

Fan ZhouRui WangPeng YuanYixin RenYunuo Mao12
Nature
2019
2019/8/21
Vol.572 No.7771 p.660-664
Implantation is a milestone event during mammalian embryogenesis. Implantation failure is a considerable cause of early pregnancy loss in humans1. Owing to the difficulty of obtaining human embryos early after implantation in vivo, it remains unclear how the gene regulatory network and epigenetic me...
Cell lineageGene expression
10.1038/S41586-019-1500-0
ISSN:0028-0836

DNA methylation signatures of monozygotic twins clinically discordant for multiple sclerosis

Nicole Y. SourenLisa A. GerdesPavlo LutsikGilles GasparoniEduardo Beltrán11
Nature Communications
2019
2019/5/7
Vol.10 No.1 p.1-12
Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system with a modest concordance rate in monozygotic twins, which strongly argues for involvement of epigenetic factors. We observe highly similar peripheral blood mononuclear cell-based methylomes in 45 MS-disc...
AutoimmunityDNA methylationEpigenomicsMultiple sclerosis
10.1038/S41467-019-09984-3
ISSN:2041-1723

Mutant ribosomal protein RPS15 drives B cell malignancy through oxidative stress and genomic instability

Catherine GutierrezMarwan KwokNeil RuthenPeyton WaddicorChristina Curran44
Nature Communications
2026
2026/3/30
0
Ribosomal protein mutations are increasingly associated with cancer risk and thought to perturb ribosome function. At the same time, they reportedly activate p53, a critical anti-cancer barrier. To determine how these mutations overcome this protective block to enable tumorigenesis, we generate an i...
Cancer modelsHaematological cancerRibosome
10.1038/S41467-026-70655-1
ISSN:2041-1723

Identification of HER2-positive breast cancer molecular subtypes with potential clinical implications in the ALTTO clinical trial

Mattia ReditiDavid VenetAndrea Joaquin GarciaMarion MaetensDelphine Vincent17
Nature Communications
2024
2024/11/29
Vol.15 No.1 p.1-17
In HER2-positive breast cancer, clinical outcome and sensitivity to HER2-targeted therapies are influenced by both tumor and microenvironment features. However, we are currently unable to depict the molecular heterogeneity of this disease with sufficient granularity. Here, by performing gene express...
Breast cancerPrognostic markersTumour heterogeneity
10.1038/S41467-024-54621-3
ISSN:2041-1723

Genetic insights into human cortical organization and development through genome-wide analyses of 2,347 neuroimaging phenotypes

Varun WarrierEva-Maria StaufferQin Qin HuangEmilie M. WigdorEric A. W. Slob21
Nature Genetics
2023
2023/8/17
00 p.1-11
Our understanding of the genetics of the human cerebral cortex is limited both in terms of the diversity and the anatomical granularity of brain structural phenotypes. Here we conducted a genome-wide association meta-analysis of 13 structural and diffusion magnetic resonance imaging-derived cortical...
AnatomyGenome-wide association studiesMagnetic resonance imaging
10.1038/S41588-023-01475-Y
ISSN:1061-4036

Organismal metabolism regulates the expansion of oncogenic PIK3CA mutant clones in normal esophagus

Albert HermsBartomeu ColomGabriel PiedrafitaArgyro KalogeropoulouUjjwal Banerjee19
Nature Genetics
2024
2024/8/21
00 p.1-14
Oncogenic PIK3CA mutations generate large clones in aging human esophagus. Here we investigate the behavior of Pik3ca mutant clones in the normal esophageal epithelium of transgenic mice. Expression of a heterozygous Pik3caH1047R mutation drives clonal expansion by tilting cell fate toward prolifera...
AgeingCancer preventionDiabetes complicationsOesophageal cancer
10.1038/S41588-024-01891-8
ISSN:1061-4036

Age-specific nasal epithelial responses to SARS-CoV-2 infection

Maximillian N. J. WoodallAna-Maria CujbaKaylee B. WorlockKatie-Marie CaseTereza Masonou39
Nature Microbiology
2024
2024/4/15
00 p.1-19
Children infected with SARS-CoV-2 rarely progress to respiratory failure. However, the risk of mortality in infected people over 85 years of age remains high. Here we investigate differences in the cellular landscape and function of paediatric (<12 years), adult (30–50 years) and older adult (>...
Mechanisms of diseaseMolecular biologySARS-CoV-2
10.1038/S41564-024-01658-1
ISSN:2058-5276

Spatially-resolved transcriptomics reveal macrophage heterogeneity and prognostic significance in diffuse large B-cell lymphoma

Min LiuGiorgio BertolazziShruti SridharRui Xue LeePatrick Jaynes29
Nature Communications
2024
2024/3/8
Vol.15 No.1 p.1-15
Macrophages are abundant immune cells in the microenvironment of diffuse large B-cell lymphoma (DLBCL). Macrophage estimation by immunohistochemistry shows varying prognostic significance across studies in DLBCL, and does not provide a comprehensive analysis of macrophage subtypes. Here, using digit...
B-cell lymphomaCancer genomicsCancer microenvironmentTumour immunology
10.1038/S41467-024-46220-Z
ISSN:2041-1723

Noninvasive prenatal diagnosis by genome-wide haplotyping of cell-free plasma DNA

Huiwen Che MSDarine Villela PhDEftychia Dimitriadou PhDCindy Melotte PhDNathalie Brison PhD13
Genetics In Medicine
2020
2020/2/6
Vol.22 No.5 p.962-973
Whereas noninvasive prenatal screening for aneuploidies is widely implemented, there is an increasing need for universal approaches for noninvasive prenatal screening for monogenic diseases. Here, we present a cost-effective, generic cell-free fetal DNA (cffDNA) haplotyping approach to scan the feta...
Biomedicine, generalHuman GeneticsLaboratory Medicine
10.1038/S41436-019-0748-Y
ISSN:1098-3600

Scalable genetic screening for regulatory circuits using compressed Perturb-seq

Douglas YaoLoic BinanJon BezneyBrooke SimontonJahanara Freedman12
Nature Biotechnology
2023
2023/10/23
00 p.1-14
Pooled CRISPR screens with single-cell RNA sequencing readout (Perturb-seq) have emerged as a key technique in functional genomics, but they are limited in scale by cost and combinatorial complexity. In this study, we modified the design of Perturb-seq by incorporating algorithms applied to random, ...
Gene expression profilingHigh-throughput screening
10.1038/S41587-023-01964-9
ISSN:1087-0156

Deciphering brain organoid heterogeneity by identifying key quality determinants

Tom BoerstlerDaniil KachkinElizaveta GerasimovaNaime ZaghaFederica Furlanetto20
Communications Biology
2025
2025/10/1
Vol.8 No.1 p.1-11
Brain organoids derived from human pluripotent stem cells (hPSCs) hold immense potential for modeling neurodevelopmental processes and disorders. However, their experimental variability and undefined organoid selection criteria for analysis hinder reproducibility. As part of the Bavarian ForInter co...
Induced pluripotent stem cellsMesenchymal stem cellsStem-cell differentiation
10.1038/S42003-025-08855-6
ISSN:2399-3642

Evidence for 28 genetic disorders discovered by combining healthcare and research data

Joanna KaplanisKaitlin E. SamochaLaurens WielZhancheng ZhangKevin J. Arvai22
Nature
2020
2020/10/14
Vol.586 No.7831 p.757-762
De novo mutations in protein-coding genes are a well-established cause of developmental disorders1. However, genes known to be associated with developmental disorders account for only a minority of the observed excess of such de novo mutations1,2. Here, to identify previously undescribed genes assoc...
Clinical geneticsGenetics researchNeurodevelopmental disordersStatistical methods
10.1038/S41586-020-2832-5
ISSN:0028-0836

Large B-cell lymphomas with CCND1 rearrangement have different immunoglobulin gene breakpoints and genomic profile than mantle cell lymphoma

Ece ÖzoğulAnna MontanerMelina PolGerard FrigolaOlga Balagué34
Blood Cancer Journal
2024
2024/9/23
Vol.14 No.1 p.1-10
Mantle cell lymphoma (MCL) is genetically characterized by the IG::CCND1 translocation mediated by an aberrant V(D)J rearrangement. CCND1 translocations and overexpression have been identified in occasional aggressive B-cell lymphomas with unusual features for MCL. The mechanism generating CCND1 rea...
B-cell lymphomaOncogenesis
10.1038/S41408-024-01146-Z
ISSN:2044-5385

A first-generation pediatric cancer dependency map

Neekesh V. DhariaGuillaume KugenerLillian M. GuentherClare F. MaloneAdam D. Durbin26
Nature Genetics
2021
2021/3/22
00 p.1-10
Exciting therapeutic targets are emerging from CRISPR-based screens of high mutational-burden adult cancers. A key question, however, is whether functional genomic approaches will yield new targets in pediatric cancers, known for remarkably few mutations, which often encode proteins considered chall...
CancerFunctional genomicsHigh-throughput screening
10.1038/S41588-021-00819-W
ISSN:1061-4036

A prognostic human brain network for diffuse midline glioma

Jai SidpraValentina LindAlexander L. CohenFrederic L. W. V. J. SchaperThomas J. Stone51
Nature
2026
2026/6/10
00 p.1-11
Diffuse midline gliomas (DMGs) are near-universally lethal tumours of the childhood central nervous system1,2. In animal models, DMGs form brain-wide integrated networks through neuron-to-glioma synapses3–6 and glioma-to-glioma gap junctional coupling3. This extensive connectivity robustly prom...
Cancer genomicsCancer imagingCancer in the nervous systemCNS cancerPaediatric cancer
10.1038/S41586-026-10631-3
ISSN:0028-0836

Long-term prognostic value of ctDNA in early breast cancer: insights from the neoadjuvant ABCSG-34 Trial

Daniel EgleDominik HlauschekSimon Peter GampenriederGabriel RinnerthalerChristian Singer21
Npj Breast Cancer
2026
2026/4/8
0
Circulating tumor DNA (ctDNA) is a promising biomarker in early breast cancer for assessing treatment response, minimal residual disease (MRD), and recurrence risk. In the ABCSG-34 phase II trial, we previously reported that persistent ctDNA during neoadjuvant therapy (NAT) was associated with highe...
BiomarkersCancerComputational biology and bioinformaticsOncology
10.1038/S41523-026-00934-Z
ISSN:2374-4677

Tebentafusp, a T cell engager, promotes macrophage reprogramming and in combination with IL-2 overcomes macrophage immunosuppression in cancer

Esra GüçAgatha TreveilEmma LeachAnna BroomfieldAntonio Camera18
Nature Communications
2025
2025/3/10
Vol.16 No.1 p.1-16
Uveal melanoma (UM) is the most common intraocular cancer in adults, with metastatic disease (mUM) occurring in approximately half of the patients. Tebentafusp, an immune-mobilizing monoclonal T cell receptor against cancer (ImmTAC), is a therapeutic shown to improve overall survival (OS) in HLA-A*0...
Cancer microenvironmentImmunotherapyInterleukinsMonocytes and macrophages
10.1038/S41467-025-57470-W
ISSN:2041-1723

Precancerous neoplastic cells can move through the pancreatic ductal system

Alvin P. Makohon-MooreKaren MatsukumaMing ZhangJohannes G. ReiterJeffrey M. Gerold17
Nature
2018
2018/9/3
Vol.561 No.7722 p.201-205
Most adult carcinomas develop from noninvasive precursor lesions, a progression that is supported by genetic analysis. However, the evolutionary and genetic relationships among co-existing lesions are unclear. Here we analysed the somatic variants of pancreatic cancers and precursor lesions sampled ...
Cancer genomicsOncogenesisTumour heterogeneity
10.1038/S41586-018-0481-8
ISSN:0028-0836

Dynamics of genome architecture and chromatin function during human B cell differentiation and neoplastic transformation

Roser Vilarrasa-BlasiPaula Soler-VilaNúria Verdaguer-DotNúria RussiñolMarco Di Stefano20
Nature Communications
2021
2021/1/28
Vol.12 No.1 p.1-18
To investigate the three-dimensional (3D) genome architecture across normal B cell differentiation and in neoplastic cells from different subtypes of chronic lymphocytic leukemia and mantle cell lymphoma patients, here we integrate in situ Hi-C and nine additional omics layers. Beyond conventional a...
B cellsChromatin structureDifferentiationGene regulationHaematological cancer
10.1038/S41467-020-20849-Y
ISSN:2041-1723

Genomic insights into population history and biological adaptation in Oceania

Jeremy ChoinJavier Mendoza-RevillaLara R. AraunaSebastian Cuadros-EspinozaOlivier Cassar22
Nature
2021
2021/4/14
Vol.592 No.7855 p.583-589
The Pacific region is of major importance for addressing questions regarding human dispersals, interactions with archaic hominins and natural selection processes1. However, the demographic and adaptive history of Oceanian populations remains largely uncharacterized. Here we report high-coverage geno...
AnthropologyEvolutionary geneticsGenetic variationPopulation genetics
10.1038/S41586-021-03236-5
ISSN:0028-0836

Glucose-dependent partitioning of arginine to the urea cycle protects β-cells from inflammation

Accalia FuJuan Carlos Alvarez-PerezDaina AvizonisTatsuya KinScott B. Ficarro22
Nature Metabolism
2020
2020/5/11
Vol.2 No.5 p.432-446
Chronic inflammation is linked to diverse disease processes, but the intrinsic mechanisms that determine cellular sensitivity to inflammation are incompletely understood. Here, we show the contribution of glucose metabolism to inflammation-induced changes in the survival of pancreatic islet β-cells....
DiabetesMetabolomics
10.1038/S42255-020-0199-4
ISSN:2522-5812

MethCORR modelling of methylomes from formalin-fixed paraffin-embedded tissue enables characterization and prognostication of colorectal cancer

Trine B. MattesenMads H. RasmussenJuan SandovalHalit OngenSigrid S. Árnadóttir14
Nature Communications
2020
2020/4/24
Vol.11 No.1 p.1-15
Transcriptional characterization and classification has potential to resolve the inter-tumor heterogeneity of colorectal cancer and improve patient management. Yet, robust transcriptional profiling is difficult using formalin-fixed, paraffin-embedded (FFPE) samples, which complicates testing in clin...
Classification and taxonomyColorectal cancerPrognostic markers
10.1038/S41467-020-16000-6
ISSN:2041-1723

Human DEF6 deficiency underlies an immunodeficiency syndrome with systemic autoimmunity and aberrant CTLA-4 homeostasis

Nina K. SerwasBirgit HoegerRico C. ArdySigrun V. StulzZhenhua Sui42
Nature Communications
2019
2019/7/15
Vol.10 No.1 p.1-15
Immune responses need to be controlled tightly to prevent autoimmune diseases, yet underlying molecular mechanisms remain partially understood. Here, we identify biallelic mutations in three patients from two unrelated families in differentially expressed in FDCP6 homolog (DEF6) as the molecular cau...
DiseasesGeneticsImmunology
10.1038/S41467-019-10812-X
ISSN:2041-1723

Genome-wide mutational signatures in low-coverage whole genome sequencing of cell-free DNA

Wan Jonathan C. M.Stephens DennisLuo LingqiWhite James R.Stewart Caitlin M.8
Nature Communications
2022
2022/8/23
Vol.13 No.1 p.1-12
Mutational signatures accumulate in somatic cells as an admixture of endogenous and exogenous processes that occur during an individual’s lifetime. Since dividing cells release cell-free DNA (cfDNA) fragments into the circulation, we hypothesize that plasma cfDNA might reflect mutational signatures....
Cancer genomicsColorectal cancerDiagnostic markersMachine learningTumour biomarkers
10.1038/S41467-022-32598-1
ISSN:2041-1723

The LMSz method - an automatable scalable approach to constructing gene-specific growth charts in rare disorders

Karen J. LowJulia ForemanRachel J. HobsonHannah KwuoElena Martinez-Cayuelas16
European Journal Of Human Genetics
2025
2025/10/13
00 p.1-9
Children with monogenic neurodevelopmental disorders often grow abnormally. Gene-specific growth charts would be useful but require large samples to construct them using the conventional LMS method. We transformed anthropometry to British 1990 reference z-scores for 328 UK and 264 international indi...
Genetic testingGrowth disorders
10.1038/S41431-025-01947-1
ISSN:1018-4813

Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation

Min Josine L.Hemani GibranHannon EilisDekkers Koen F.Castillo-Fernandez Juan156
Nature Genetics
2021
2021/9/6
Vol.53 No.9 p.1311-1321
Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. In the present study, we describe results of DNAm quantitative trait locus (mQTL) analyses on 32,851 participants, identifying genetic variants assoc...
EpigeneticsGenetics research
10.1038/S41588-021-00923-X
ISSN:1061-4036

The tumor immune microenvironment of nasopharyngeal carcinoma after gemcitabine plus cisplatin treatment

Jiawei LvYuan WeiJian-Hua YinYu-Pei ChenGuan-Qun Zhou31
Nature Medicine
2023
2023/6/6
00 p.1-13
Gemcitabine plus cisplatin (GP) chemotherapy is the standard of care for nasopharyngeal carcinoma (NPC). However, the mechanisms underpinning its clinical activity are unclear. Here, using single-cell RNA sequencing and T cell and B cell receptor sequencing of matched, treatment-naive and post-GP ch...
CancerImmunology
10.1038/S41591-023-02369-6
ISSN:1078-8956

Clinical response to nivolumab in an INI1-deficient pediatric chordoma correlates with immunogenic recognition of brachyury

Williamson Laura M.Rive Craig M.Di Francesco DanielaTitmuss EmmaChun Hye-Jung E.25
Npj Precision Oncology
2021
2021/12/20
Vol.5 No.1 p.1-12
Poorly differentiated chordoma (PDC) is a recently recognized subtype of chordoma characterized by expression of the embryonic transcription factor, brachyury, and loss of INI1. PDC primarily affects children and is associated with a poor prognosis and limited treatment options. Here we describe the...
Molecular medicinePaediatric cancerPredictive markersSarcoma
10.1038/S41698-021-00238-4
ISSN:2397-768X

The molecular landscape of glioma in patients with Neurofibromatosis 1

Fulvio D’AngeloMichele CeccarelliTalaLuciano GarofanoJing Zhang47
Nature Medicine
2018
2018/12/10
Vol.25 No.1 p.176-187
Neurofibromatosis type 1 (NF1) is a common tumor predisposition syndrome in which glioma is one of the prevalent tumors. Gliomagenesis in NF1 results in a heterogeneous spectrum of low- to high-grade neoplasms occurring during the entire lifespan of patients. The pattern of genetic and epigenetic al...
CancerCancer genomicsCNS cancer
10.1038/S41591-018-0263-8
ISSN:1078-8956

Identifying rare genetic variants in 21 highly multiplex autism families: the role of diagnosis and autistic traits

More Ravi PrabhakarWarrier VarunBrunel HelenaBuckingham ClaraSmith Paula9
Molecular Psychiatry
2023
2023/1/26
00 p.1-10
Autism is a highly heritable, heterogeneous, neurodevelopmental condition. Large-scale genetic studies, predominantly focussing on simplex families and clinical diagnoses of autism have identified hundreds of genes associated with autism. Yet, the contribution of these classes of genes to multiplex ...
Autism spectrum disordersGenetics
10.1038/S41380-022-01938-4
ISSN:1359-4184

Unraveling the genetic landscape and admixture dynamics of urban populations across Peru

Victor BordaOmar CaceresCesar SanchezCarlos PadillaDiego Veliz-Otani13
Communications Biology
2026
2026/4/2
Vol.9 No.1 p.4100
Latin American populations exhibit high genetic and phenotypic diversity shaped by complex admixture histories, yet remain underrepresented in genomic research. Here, we analyze genome-wide data from 432 urban individuals across 13 regions of Peru, including 346 newly genotyped from the Peruvian Gen...
Genetic variationGenomics
10.1038/S42003-026-09671-2
ISSN:2399-3642

Spatio-temporal analysis of prostate tumors in situ suggests pre-existence of treatment-resistant clones

Marklund MajaSchultz NiklasFriedrich StefanieBerglund EmelieTarish Firas13
Nature Communications
2022
2022/9/17
Vol.13 No.1 p.1-18
The molecular mechanisms underlying lethal castration-resistant prostate cancer remain poorly understood, with intratumoral heterogeneity a likely contributing factor. To examine the temporal aspects of resistance, we analyze tumor heterogeneity in needle biopsies collected before and after treatmen...
Cancer genomicsPrognostic markersProstate cancerTranscriptomicsTumour heterogeneity
10.1038/S41467-022-33069-3
ISSN:2041-1723

Oncogenic structural aberration landscape in gastric cancer genomes

Mihoko Saito-AdachiNatsuko HamaYasushi TotokiHiromi NakamuraYasuhito Arai11
Nature Communications
2023
2023/6/22
Vol.14 No.1 p.1-13
Structural variants (SVs) are responsible for driver events in gastric cancer (GC); however, their patterns and processes remain poorly understood. Here, we examine 170 GC whole genomes to unravel the oncogenic structural aberration landscape in GC genomes and identify six rearrangement signatures (...
Cancer genomicsGastric cancerGene amplificationStructural variation
10.1038/S41467-023-39263-1
ISSN:2041-1723

Disentangling oncogenic amplicons in esophageal adenocarcinoma

Alvin Wei Tian NgDylan Peter McClurgBen WesleyShahriar A. ZamaniEmily Black18
Nature Communications
2024
2024/5/14
Vol.15 No.1 p.1-13
Esophageal adenocarcinoma is a prominent example of cancer characterized by frequent amplifications in oncogenes. However, the mechanisms leading to amplicons that involve breakage-fusion-bridge cycles and extrachromosomal DNA are poorly understood. Here, we use 710 esophageal adenocarcinoma cases w...
Cancer genomicsCancer modelsOesophageal cancerOncogenesTumour heterogeneity
10.1038/S41467-024-47619-4
ISSN:2041-1723

Deciphering the spatial landscape and plasticity of immunosuppressive fibroblasts in breast cancer

Hugo CroizerRana MhaidlyYann KiefferGeraldine GentricLounes Djerroudi16
Nature Communications
2024
2024/4/1
Vol.15 No.1 p.1-28
Although heterogeneity of FAP+ Cancer-Associated Fibroblasts (CAF) has been described in breast cancer, their plasticity and spatial distribution remain poorly understood. Here, we analyze trajectory inference, deconvolute spatial transcriptomics at single-cell level and perform functional assays to...
Breast cancerCancer microenvironment
10.1038/S41467-024-47068-Z
ISSN:2041-1723

Imaging mass cytometry and multiplatform genomics define the phenogenomic landscape of breast cancer

H. Raza AliHartland W. JacksonVito R. T. ZanotelliEsther DanenbergJana R. Fischer7
Nature Cancer
2020
2020/2/17
Vol.1 No.2 p.163-175
Genomic alterations shape cell phenotypes and the structure of tumor ecosystems in poorly defined ways. To investigate these relationships, we used imaging mass cytometry to quantify the expression of 37 proteins with subcellular spatial resolution in 483 tumors from the METABRIC cohort. Single-cell...
Breast cancerCancerCancer genomicsCancer imaging
10.1038/S43018-020-0026-6
ISSN:2662-1347

Detecting and quantifying clonal selection in somatic stem cells

Verena KörberNiels Asger JakobsenNaser Ansari-PourRachel MooreNina Claudino23
Nature Genetics
2025
2025/7/3
00 p.1-12
As DNA variants accumulate in somatic stem cells, become selected or evolve neutrally, they may ultimately alter tissue function. When, and how, selection occurs in homeostatic tissues is incompletely understood. Here, we introduce SCIFER, a scalable method that identifies selection in an individual...
AgeingCancerPopulation geneticsSystems biology
10.1038/S41588-025-02217-Y
ISSN:1061-4036

Neoantigen-directed immune escape in lung cancer evolution

Rachel RosenthalElizabeth Larose CadieuxRoberto SalgadoMaise Al BakirDavid A. Moore28
Nature
2019
2019/3/20
Vol.567 No.7749 p.479-485
The interplay between an evolving cancer and a dynamic immune microenvironment remains unclear. Here we analyse 258 regions from 88 early-stage, untreated non-small-cell lung cancers using RNA sequencing and histopathology-assessed tumour-infiltrating lymphocyte estimates. Immune infiltration varied...
Cancer genomicsCancer microenvironmentNon-small-cell lung cancerTumour heterogeneity
10.1038/S41586-019-1032-7
ISSN:0028-0836

SEAD reference panel with 22,134 haplotypes boosts rare variant imputation and genome-wide association analysis in Asian populations

Meng-Yuan YangJia-Dong ZhongXin LiGeng TianWei-Yang Bai37
Nature Communications
2024
2024/12/30
Vol.15 No.1 p.1-14
Limited whole genome sequencing (WGS) studies in Asian populations result in a lack of representative reference panels, thus hindering the discovery of ancestry-specific variants. Here, we present the South and East Asian reference Database (SEAD) panel ( https://imputationserver.westlake.edu.cn/ ),...
Genome-wide association studiesRare variants
10.1038/S41467-024-55147-4
ISSN:2041-1723

Single-cell landscape in mammary epithelium reveals bipotent-like cells associated with breast cancer risk and outcome

Weiyan ChenSamuel J. MorabitoKai KessenbrockTariq EnverKerstin B. Meyer6
Communications Biology
2019
2019/8/9
Vol.2 No.1 p.1-13
Adult stem-cells may serve as the cell-of-origin for cancer, yet their unbiased identification in single cell RNA sequencing data is challenging due to the high dropout rate. In the case of breast, the existence of a bipotent stem-like state is also controversial. Here we apply a marker-free algorit...
Adult stem cellsCancerStatistical methods
10.1038/S42003-019-0554-8
ISSN:2399-3642

Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa

Hunna J. WatsonZeynep YilmazLaura M. ThorntonChristopher HübelJonathan R. I. Coleman14
Nature Genetics
2019
2019/7/15
Vol.51 No.8 p.1207-1214
Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness1, affecting 0.9–4% of women and 0.3% of men2–4, with twin-based heritability estimates of 50–60%5. Mortality rates are higher than those in other psychiatric disorders6, and outcomes are unacceptably ...
GeneticsMolecular biologyPsychology
10.1038/S41588-019-0439-2
ISSN:1061-4036

Cannabis impacts female fertility as evidenced by an in vitro investigation and a case-control study

Cyntia DuvalBrandon A. WyseNoga Fuchs WeizmanIryna KuznyetsovaSvetlana Madjunkova6
Nature Communications
2025
2025/9/9
Vol.16 No.1 p.1-13
Cannabis consumption and legalization is increasing globally, raising concerns about its impact on fertility. In humans, we previously demonstrated that tetrahydrocannabinol (THC) and its metabolites reach the ovarian follicle. An extensive body of literature describes THC’s impact on sperm, however...
EmbryologyMolecular medicineTranslational research
10.1038/S41467-025-63011-2
ISSN:2041-1723

Single-cell dissection of intratumoral heterogeneity and lineage diversity in metastatic gastric adenocarcinoma

Ruiping WangMinghao DangKazuto HaradaGuangchun HanFang Wang32
Nature Medicine
2021
2021/1/4
Vol.27 No.1 p.141-151
Intratumoral heterogeneity (ITH) is a fundamental property of cancer; however, the origins of ITH remain poorly understood. We performed single-cell transcriptome profiling of peritoneal carcinomatosis (PC) from 15 patients with gastric adenocarcinoma (GAC), constructed a map of 45,048 PC cells, pro...
Gastric cancerMetastasisTranscriptomicsTumour biomarkersTumour heterogeneity
10.1038/S41591-020-1125-8
ISSN:1078-8956

Cancer of unknown primary stem-like cells model multi-organ metastasis and unveil liability to MEK inhibition

Federica VerginelliAlberto PisacaneGennaro GambardellaAntonio D’AmbrosioErmes Candiello17
Nature Communications
2021
2021/5/3
Vol.12 No.1 p.1-16
Cancers of unknown primary (CUPs), featuring metastatic dissemination in the absence of a primary tumor, are a biological enigma and a fatal disease. We propose that CUPs are a distinct, yet unrecognized, pathological entity originating from stem-like cells endowed with peculiar and shared propertie...
Cancer modelsCancer of unknown primaryCancer stem cellsMetastasisTargeted therapies
10.1038/S41467-021-22643-W
ISSN:2041-1723

SMARCB1 loss activates patient-specific distal oncogenic enhancers in malignant rhabdoid tumors

Ning Qing LiuIrene PaassenLars CustersPeter ZellerHans Teunissen12
Nature Communications
2023
2023/12/1
Vol.14 No.1 p.1-14
Malignant rhabdoid tumor (MRT) is a highly malignant and often lethal childhood cancer. MRTs are genetically defined by bi-allelic inactivating mutations in SMARCB1, a member of the BRG1/BRM-associated factors (BAF) chromatin remodeling complex. Mutations in BAF complex members are common in human c...
Cancer epigeneticsEpigeneticsEpigenomics
10.1038/S41467-023-43498-3
ISSN:2041-1723

Molecular map of chronic lymphocytic leukemia and its impact on outcome

Knisbacher Binyamin A.Lin ZiaoHahn Cynthia K.Nadeu FerranDuran-Ferrer Martí39
Nature Genetics
2022
2022/8/4
00 p.1-11
Recent advances in cancer characterization have consistently revealed marked heterogeneity, impeding the completion of integrated molecular and clinical maps for each malignancy. Here, we focus on chronic lymphocytic leukemia (CLL), a B cell neoplasm with variable natural history that is conventiona...
Chronic lymphocytic leukaemiaGenetics researchGenome informaticsGenomicsOutcomes research
10.1038/S41588-022-01140-W
ISSN:1061-4036

Pathogenic variants reveal candidate genes for prostate cancer germline testing for men of African ancestry

Kazzem GheybiPamela X. Y. SohJue JiangTumisang M. N. MbekiMelanie Louw41
Nature Communications
2025
2025/10/2
Vol.16 No.1 p.1-16
Prostate cancer (PCa) germline testing, while gaining momentum, is ancestry restrictive and African exclusive. Through whole genome sequencing for 217 African ancestral cases (186 southern African, 31 Pan representative), we identify 172 potentially pathogenic variants in 78 DNA damage repair or PCa...
Cancer geneticsProstate cancer
10.1038/S41467-025-63865-6
ISSN:2041-1723

Histone acetylome-wide associations in immune cells from individuals with active Mycobacterium tuberculosis infection

del Rosario Ricardo C. H.Poschmann JeremieLim CareyCheng Catherine Y.Kumar Pavanish30
Nature Microbiology
2022
2022/1/31
Vol.7 No.2 p.312-326
Host cell chromatin changes are thought to play an important role in the pathogenesis of infectious diseases. Here we describe a histone acetylome-wide association study (HAWAS) of an infectious disease, on the basis of genome-wide H3K27 acetylation profiling of peripheral blood granulocytes and mon...
Functional genomicsTuberculosis
10.1038/S41564-021-01049-W
ISSN:2058-5276

Genomic ALK alterations in primary and relapsed neuroblastoma

Rosswog CarolinaFassunke JanaErnst AngelaSchömig-Markiefka BirgidMerkelbach-Bruse Sabine23
British Journal Of Cancer
2023
2023/2/17
00 p.1-13
Genomic alterations of the anaplastic lymphoma kinase gene (ALK) occur recurrently in neuroblastoma, a pediatric malignancy of the sympathetic nervous system. However, information on their development over time has remained sparse. ALK alterations were assessed in neuroblastomas at diagnosis and/or ...
Cancer geneticsPaediatric cancer
10.1038/S41416-023-02208-Y
ISSN:0007-0920

A 3D system to model human pancreas development and its reference single-cell transcriptome atlas identify signaling pathways required for progenitor expansion

Carla A. GonçalvesMichael LarsenSascha JungJohannes StratmannAkiko Nakamura17
Nature Communications
2021
2021/5/25
Vol.12 No.1 p.1-17
Human organogenesis remains relatively unexplored for ethical and practical reasons. Here, we report the establishment of a single-cell transcriptome atlas of the human fetal pancreas between 7 and 10 post-conceptional weeks of development. To interrogate cell–cell interactions, we describe InterCom...
OrganogenesisStem-cell differentiation
10.1038/S41467-021-23295-6
ISSN:2041-1723

Evolving epigenomics of immune cells at single-nucleus resolution in children en route to type 1 diabetes

Tomi PastinenElin GrundbergTodd BradleyJarno HonkanenWarren A. Cheung14
Nature Communications
2026
2026/2/25
Vol.17 No.1 p.31680
The appearance of diabetes-associated autoantibodies is the first detectable sign of the disease process leading to type 1 diabetes (T1D). Evidence suggests that T1D is a heterogenous disease, where the type of antibodies first formed implies subtypes. Here, we leverage longitudinal samples collecte...
AutoimmunityImmunogeneticsImmunological disordersMonocytes and macrophagesPredictive markers
10.1038/S41467-026-69923-X
ISSN:2041-1723

Exploiting evolutionary steering to induce collateral drug sensitivity in cancer

Ahmet AcarDaniel NicholJavier Fernandez-MateosGeorge D. CresswellIros Barozzi19
Nature Communications
2020
2020/4/21
Vol.11 No.1 p.1-14
Drug resistance mediated by clonal evolution is arguably the biggest problem in cancer therapy today. However, evolving resistance to one drug may come at a cost of decreased fecundity or increased sensitivity to another drug. These evolutionary trade-offs can be exploited using ‘evolutionary steeri...
Computer modellingGenome informaticsLung cancerMolecular medicineStochastic modelling
10.1038/S41467-020-15596-Z
ISSN:2041-1723

Long-term life history predicts current gut microbiome in a population-based cohort study

Si JiyeonVázquez-Castellanos Jorge F.Gregory Ann C.Decommer LindseyRymenans Leen19
Nature Aging
2022
2022/10/14
Vol.2 No.10 p.885-895
Extensive scientific and clinical microbiome studies have explored contemporary variation and dynamics of the gut microbiome in human health and disease1–3, yet the role of long-term life history effects has been underinvestigated. Here, we analyzed the current, quantitative microbiome composition i...
AgeingMachine learningMicrobiology
10.1038/S43587-022-00286-W
ISSN:2662-8465

EFA6B regulates a stop signal for collective invasion in breast cancer

Racha FayadMonserrat Vázquez RojasMariagrazia PartisaniPascal FinettiShiraz Dib14
Nature Communications
2021
2021/4/13
Vol.12 No.1 p.1-17
Cancer is initiated by somatic mutations in oncogenes or tumor suppressor genes. However, additional alterations provide selective advantages to the tumor cells to resist treatment and develop metastases. Their identification is of paramount importance. Reduced expression of EFA6B (Exchange Factor f...
Breast cancerRHO signalling
10.1038/S41467-021-22522-4
ISSN:2041-1723

Lack of caspase 8 directs neuronal progenitor-like reprogramming and small cell lung cancer progression

Ariadne AndroulidakiFanyu LiuChristina M. BebberIlmars KisisVignesh Sakthivelu33
Nature Communications
2025
2025/12/18
Vol.16 No.1 p.112800
Most neuroendocrine cancers lack caspase 8 protein expression. While this feature was thought to facilitate escape from extrinsic apoptosis, its cancer-regulatory function has remained unexplored. Here, we devise a mouse model of small cell lung cancer (SCLC) recapitulating the lack of expression of...
Cancer modelsNecroptosis
10.1038/S41467-025-67142-4
ISSN:2041-1723

Somatic mutations in lymphocytes in patients with immune-mediated aplastic anemia

Sofie LundgrenMikko A. I. KeränenMatti KankainenJani HuuhtanenGunilla Walldin19
Leukemia
2021
2021/3/30
00 p.1-15
The prevalence and functional impact of somatic mutations in nonleukemic T cells is not well characterized, although clonal T-cell expansions are common. In immune-mediated aplastic anemia (AA), cytotoxic T-cell expansions are shown to participate in disease pathogenesis. We investigated the mutatio...
AnaemiaAutoimmune diseasesGenetics research
10.1038/S41375-021-01231-3
ISSN:0887-6924

Dissecting tumor transcriptional heterogeneity from single-cell RNA-seq data by generalized binary covariance decomposition

Yusha LiuPeter CarbonettoJason WillwerscheidScott A. OakesKay F. Macleod6
Nature Genetics
2025
2025/1/2
00 p.1-11
Profiling tumors with single-cell RNA sequencing has the potential to identify recurrent patterns of transcription variation related to cancer progression, and to produce therapeutically relevant insights. However, strong intertumor heterogeneity can obscure more subtle patterns that are shared acro...
CancerComputational biology and bioinformaticsStatistics
10.1038/S41588-024-01997-Z
ISSN:1061-4036

Neuroblastoma arises in early fetal development and its evolutionary duration predicts outcome

Körber VerenaStainczyk Sabine A.Kurilov RomaHenrich Kai-OliverHero Barbara8
Nature Genetics
2023
2023/3/27
00 p.1-12
Neuroblastoma, the most frequent solid tumor in infants, shows very diverse outcomes from spontaneous regression to fatal disease. When these different tumors originate and how they evolve are not known. Here we quantify the somatic evolution of neuroblastoma by deep whole-genome sequencing, molecul...
Embryonal neoplasmsPopulation dynamicsPopulation genetics
10.1038/S41588-023-01332-Y
ISSN:1061-4036

Genetic determinants of the molecular portraits of epithelial cancers

Youli XiaCheng FanKatherine A. HoadleyJoel S. ParkerCharles M. Perou
Nature Communications
2019
2019/12/11
Vol.10 No.1 p.1-13
The ability to characterize and predict tumor phenotypes is crucial to precision medicine. In this study, we present an integrative computational approach using a genome-wide association analysis and an Elastic Net prediction method to analyze the relationship between DNA copy number alterations and...
Cancer genomics
10.1038/S41467-019-13588-2
ISSN:2041-1723

Sequential genomic analysis using a multisample/multiplatform approach to better define rhabdomyosarcoma progression and relapse

Henry de Traux de WardinJosephine K. DermawanMarie-Sophie MerlinLeonard H. WexlerDaniel Orbach15
Npj Precision Oncology
2023
2023/9/20
Vol.7 No.1 p.1-13
The genomic spectrum of rhabdomyosarcoma (RMS) progression from primary to relapse is not fully understood. In this pilot study, we explore the sensitivity of various targeted and whole-genome NGS platforms in order to assess the best genomic approach of using liquid biopsy in future prospective cli...
OncogenesisPaediatric cancerPredictive markers
10.1038/S41698-023-00445-1
ISSN:2397-768X

The integrated genomic and epigenomic landscape of brainstem glioma

Lee H. ChenChangcun PanBill H. DiplasCheng XuLandon J. Hansen28
Nature Communications
2020
2020/6/17
Vol.11 No.1 p.1-11
Brainstem gliomas are a heterogeneous group of tumors that encompass both benign tumors cured with surgical resection and highly lethal cancers with no efficacious therapies. We perform a comprehensive study incorporating epigenetic and genomic analyses on a large cohort of brainstem gliomas, includ...
Cancer genomicsCNS cancer
10.1038/S41467-020-16682-Y
ISSN:2041-1723

Transferability of genetic risk scores in African populations

Kamiza Abram B.Toure Sounkou M.Vujkovic MarijanaMachipisa TafadzwaSoremekun Opeyemi S.16
Nature Medicine
2022
2022/6/2
00 p.1-4
The poor transferability of genetic risk scores (GRSs) derived from European ancestry data in diverse populations is a cause of concern. We set out to evaluate whether GRSs derived from data of African American individuals and multiancestry data perform better in sub-Saharan Africa (SSA) compared to...
GenomicsMedical genetics
10.1038/S41591-022-01835-X
ISSN:1078-8956

Whole-genome sequencing identifies ADGRG6 enhancer mutations and FRS2 duplications as angiogenesis-related drivers in bladder cancer

Song WuTong OuNianzeng XingJiang LuShengqing Wan10
Nature Communications
2019
2019/2/12
Vol.10 No.1 p.1-12
Bladder cancer is one of the most common and highly vascularized cancers. To better understand its genomic structure and underlying etiology, we conduct whole-genome and targeted sequencing in urothelial bladder carcinomas (UBCs, the most common type of bladder cancer). Recurrent mutations in noncod...
Bladder cancerTumour angiogenesis
10.1038/S41467-019-08576-5
ISSN:2041-1723

Comprehensive molecular portrait reveals genetic diversity and distinct molecular subtypes of small intestinal neuroendocrine tumors

Céline PatteRoxane M. PommierAnthony FerrariFelicia Fei-Lei ChungMaria Ouzounova29
Nature Communications
2025
2025/3/4
Vol.16 No.1 p.1-15
Small intestinal neuroendocrine tumors (siNETs) are rare bowel tumors arising from malignant enteroendocrine cells, which normally regulate digestion throughout the intestine. Though infrequent, their incidence is rising through better diagnosis, fostering research into their origin and treatment. T...
Cancer genomicsCancer microenvironmentGastrointestinal cancerNeuroendocrine cancerTumour heterogeneity
10.1038/S41467-025-57305-8
ISSN:2041-1723

Combined ctDNA and serum PSA for dynamic monitoring of metastatic prostate cancer starting first-line treatment: a prospective national cohort study

Anuradha JayaramMemuna RashidAlison H. M. ReidFrancesco OrlandoSuparna Thakali29
Nature Cancer
2026
2026/5/15
00 p.1-13
The prognosis of newly diagnosed metastatic prostate cancer is highly variable. The primary objective of the PARADIGM prospective cohort study was to evaluate predictors of survival in blood collected at the start of each of the first six treatment cycles from 114 patients with high-volume metastati...
CancerProstate cancerTumour biomarkers
10.1038/S43018-026-01172-9
ISSN:2662-1347

Temporal evolution and inter-patient heterogeneity in primary and recurrent head and neck squamous cell carcinoma

Luisa BresadolaDavid WeberChristoph RitzelMartin LöwerValesca Bukur14
Bjc Reports
2024
2024/8/29
Vol.2 No.1 p.1-11
Head and neck squamous cell carcinomas (HNSCCs) are heterogeneous in terms of origin and aetiology. In addition, there is uncertainty about the genetic evolution from initial diagnosis to recurrence after primary treatments and further disease progression following systemic treatment. Changes in the...
Cancer ResearchOncology
10.1038/S44276-024-00091-5
ISSN:2731-9377

Identification and characterisation of pathogenic and non-pathogenic FGF14 repeat expansions

Lars MohrenFriedrich ErdlenbruchElsa LeitãoFabian KilpertG. Sebastian Hönes28
Nature Communications
2024
2024/9/3
Vol.15 No.1 p.1-20
Repeat expansions in FGF14 cause autosomal dominant late-onset cerebellar ataxia (SCA27B) with estimated pathogenic thresholds of 250 (incomplete penetrance) and 300 AAG repeats (full penetrance), but the sequence of pathogenic and non-pathogenic expansions remains unexplored. Here, we demonstrate t...
DiagnosisGenetic variationMedical geneticsNeurodegenerative diseasesNext-generation sequencing
10.1038/S41467-024-52148-1
ISSN:2041-1723

A non-canonical lymphoblast in refractory childhood T-cell leukaemia

Bram S. J. LimHolly J. WhitfieldMi K. TrinhGianna BloyeRebecca Thomas29
Nature Communications
2025
2025/11/12
Vol.16 No.1 p.93970
Refractory cancers may arise either through the acquisition of resistance mechanisms or represent distinct disease states. The origin of childhood T-cell acute lymphoblastic leukaemia (T-ALL) that does not respond to initial treatment, i.e. refractory disease, is unknown. Refractory T-ALL carries a ...
Acute lymphocytic leukaemiaCancer genomicsCancer therapy
10.1038/S41467-025-65049-8
ISSN:2041-1723

Large-scale genome-wide enrichment analyses identify new trait-associated genes and pathways across 31 human phenotypes

Xiang ZhuMatthew Stephens
Nature Communications
2018
2018/10/19
Vol.9 No.1 p.1-14
Genome-wide association studies (GWAS) aim to identify genetic factors associated with phenotypes. Standard analyses test variants for associations individually. However, variant-level associations are hard to identify and can be difficult to interpret biologically. Enrichment analyses help address ...
Genome-wide association studiesGenomicsSoftwareStatistical methods
10.1038/S41467-018-06805-X
ISSN:2041-1723

Spatial multiomics map of trophoblast development in early pregnancy

Arutyunyan AnnaRoberts KennyTroulé KevinWong Frederick C. K.Sheridan Megan A.27
Nature
2023
2023/3/29
Vol.616 No.7955 p.143-151
The relationship between the human placenta—the extraembryonic organ made by the fetus, and the decidua—the mucosal layer of the uterus, is essential to nurture and protect the fetus during pregnancy. Extravillous trophoblast cells (EVTs) derived from placental villi infiltrate the decidua, tra...
BiotechnologyDevelopment
10.1038/S41586-023-05869-0
ISSN:0028-0836

Delivery of a BET protein degrader via a CEACAM6-targeted antibody–drug conjugate inhibits tumour growth in pancreatic cancer models

Youya NakazawaMasayuki MiyanoShuntaro TsukamotoHiroyuki KogaiAkihiko Yamamoto18
Nature Communications
2024
2024/3/11
Vol.15 No.1 p.1-17
Pancreatic ductal adenocarcinoma (PDAC) has the worst prognosis of all cancers. To improve PDAC therapy, we establish screening systems based on organoid and co-culture technologies and find a payload of antibody–drug conjugate (ADC), a bromodomain and extra-terminal (BET) protein degrader named EBE...
Drug developmentPancreatic cancerTargeted therapies
10.1038/S41467-024-46167-1
ISSN:2041-1723

Targetable NOTCH1 rearrangements in reninoma

Taryn D. TregerJohn E. G. LawrenceNathaniel D. AndersonTim H. H. CoorensAleksandra Letunovska21
Nature Communications
2023
2023/9/25
Vol.14 No.1 p.1-10
Reninomas are exceedingly rare renin-secreting kidney tumours that derive from juxtaglomerular cells, specialised smooth muscle cells that reside at the vascular inlet of glomeruli. They are the central component of the juxtaglomerular apparatus which controls systemic blood pressure through the sec...
Cancer genomicsMedical genomicsRenal cancerStructural variationTranscriptomics
10.1038/S41467-023-41118-8
ISSN:2041-1723

Conserved neutrophil degranulation transcripts in HIV-TB coinfected children across East and Southern Africa

Eric KatagiryaBusisiwe MlotshwaSamuel KyobeSavannah MwesigwaGaone Retshabile28
Communications Medicine
2026
2026/3/24
0
HIV-tuberculosis (HIV-TB) coinfection poses a significant public health challenge among children in high-burden African regions. Most previous transcriptomic studies have concentrated on adults and non-African populations, primarily analyzing gene-level differential expression. This approach overloo...
TranscriptomicsTuberculosis
10.1038/S43856-025-01284-W
ISSN:2730-664X

RNF43 mutations predict response to anti-BRAF/EGFR combinatory therapies in BRAFV600E metastatic colorectal cancer

Elez ElenaRos JavierFernández JoseVillacampa GuillermoMoreno-Cárdenas Ana Belén30
Nature Medicine
2022
2022/9/12
Vol.28 No.10 p.2162-2170
Anti-BRAF/EGFR therapy was recently approved for the treatment of metastatic BRAFV600E colorectal cancer (mCRCBRAF-V600E). However, a large fraction of patients do not respond, underscoring the need to identify molecular determinants of treatment response. Using whole-exome sequencing in a discovery...
Colorectal cancerPredictive markersTumour biomarkers
10.1038/S41591-022-01976-Z
ISSN:1078-8956

Characterizing and decoding ultraconserved regions uncovers their regulatory significance in human brain development and disorders

Yun BaiXuehan ZhangXiangting WangMeiting WangTao Shen
Communications Biology
2025
2025/11/27
Vol.8 No.1 p.17130
Ultraconserved regions (UCRs) represent genomic elements with perfect sequence conservation across humans, rats, and mice. Though evolutionarily significant, most UCRs’ functions remain elusive. Here, by leveraging current reference genomes from 34 species spanning diverse taxonomic groups, we refin...
EvolutionGenome informatics
10.1038/S42003-025-09115-3
ISSN:2399-3642

Chromatin landscape and epigenetic heterogeneity of acute myeloid leukaemia

Yotaro OchiMarkus Liew-LittorinYasuhito NannyaSofia BengtzenBenedicte Piauger51
Nature
2026
2026/7/8
00 p.1-11
Acute myeloid leukaemia (AML) is an aggressive blood cancer characterized by the unregulated proliferation of immature myeloblasts. Gene mutations have been shown to have a large effect on pathogenesis, inter-tumour heterogeneity and clinical outcomes in AML1–8; however, the role of epigenetic alter...
Acute myeloid leukaemiaCancer epigeneticsClassification and taxonomyEpigenomics
10.1038/S41586-026-10703-4
ISSN:0028-0836

Genome-wide association study of population-standardised cognitive performance phenotypes in a rural South African community

Soo Cassandra C.Brandenburg Jean-TristanNebel AlmutTollman StephenBerkman Lisa7
Communications Biology
2023
2023/3/27
Vol.6 No.1 p.1-13
Cognitive function is an indicator for global physical and mental health, and cognitive impairment has been associated with poorer life outcomes and earlier mortality. A standard cognition test, adapted to a rural-dwelling African community, and the Oxford Cognition Screen-Plus were used to capture ...
Behavioural geneticsGenome-wide association studies
10.1038/S42003-023-04636-1
ISSN:2399-3642

Chromothripsis followed by circular recombination drives oncogene amplification in human cancer

Rosswog CarolinaBartenhagen ChristophWelte AnneKahlert YvonneHemstedt Nadine20
Nature Genetics
2021
2021/11/15
00 p.1-13
The mechanisms behind the evolution of complex genomic amplifications in cancer have remained largely unclear. Using whole-genome sequencing data of the pediatric tumor neuroblastoma, we here identified a type of amplification, termed ‘seismic amplification’, that is characterized by multiple rearra...
CancerDNA sequencingEmbryonal neoplasmsOncogenes
10.1038/S41588-021-00951-7
ISSN:1061-4036

Polygenic risk modeling for prediction of epithelial ovarian cancer risk

Dareng Eileen O.Tyrer Jonathan P.Barnes Daniel R.Jones Michelle R.Yang Xin258
European Journal Of Human Genetics
2022
2022/1/14
00 p.1-14
Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented comput...
Clinical geneticsGenetic markersRisk factors
10.1038/S41431-021-00987-7
ISSN:1018-4813

A biobank of pediatric patient-derived-xenograft models in cancer precision medicine trial MAPPYACTS for relapsed and refractory tumors

Maria Eugénia Marques Da CostaSakina ZaidiJean-Yves ScoazecRobin DroitWan Ching Lim36
Communications Biology
2023
2023/9/18
Vol.6 No.1 p.1-15
Pediatric patients with recurrent and refractory cancers are in most need for new treatments. This study developed patient-derived-xenograft (PDX) models within the European MAPPYACTS cancer precision medicine trial (NCT02613962). To date, 131 PDX models were established following heterotopical and/...
Cancer modelsPaediatric cancer
10.1038/S42003-023-05320-0
ISSN:2399-3642

Genomic evolution of pancreatic cancer at single-cell resolution

Haochen ZhangPalash SashittalElias-Ramzey KarnoubAkhil JakatdarShigeaki Umeda19
Nature Genetics
2026
2026/1/22
Vol.58 No.2 p.355-365
Most evolutionary studies on pancreatic cancer rely on bulk sequencing, yet clonal evolution happens at the single-cell level. We used single-nucleus DNA sequencing to study 137,491 single nuclei from 24 pancreatic neoplasms reflecting various clinical scenarios. We found higher frequencies of somat...
Genome informaticsGenomicsPancreatic cancer
10.1038/S41588-025-02468-9
ISSN:1061-4036

Whole-genome sequencing of patients with rare diseases in a national health system

Ernest TurroWilliam J. AstleKaryn MegyStefan GräfDaniel Greene53
Nature
2020
2020/6/24
Vol.583 No.7814 p.96-102
Most patients with rare diseases do not receive a molecular diagnosis and the aetiological variants and causative genes for more than half such disorders remain to be discovered1. Here we used whole-genome sequencing (WGS) in a national health system to streamline diagnosis and to discover unknown a...
Computational biology and bioinformaticsDisease geneticsGenetics research
10.1038/S41586-020-2434-2
ISSN:0028-0836

Polygenic prediction of preeclampsia and gestational hypertension

Michael C. HonigbergBuu TruongRaiyan R. KhanBrenda XiaoLaxmi Bhatta32
Nature Medicine
2023
2023/5/29
00 p.1-10
Preeclampsia and gestational hypertension are common pregnancy complications associated with adverse maternal and child outcomes. Current tools for prediction, prevention and treatment are limited. Here we tested the association of maternal DNA sequence variants with preeclampsia in 20,064 cases and...
Genetic association studyGenetics researchReproductive disorders
10.1038/S41591-023-02374-9
ISSN:1078-8956

Chromosomal microarray analysis of 410 Han Chinese patients with autism spectrum disorder or unexplained intellectual disability and developmental delay

Liu YiLv YuqiangZarrei MehdiDong RuiYang Xiaomeng14
Npj Genomic Medicine
2022
2022/1/12
Vol.7 No.1 p.1-10
Copy number variants (CNVs) are recognized as a crucial genetic cause of neurodevelopmental disorders (NDDs). Chromosomal microarray analysis (CMA), the first-tier diagnostic test for individuals with NDDs, has been utilized to detect CNVs in clinical practice, but most reports are still from popula...
Molecular medicineNeurodevelopmental disorders
10.1038/S41525-021-00271-Z
ISSN:2056-7944

Longitudinal gut microbiota tracking reveals the dynamics of horizontal gene transfer

Haoran PengSergio Andreu-SanchezAngel J. Ruiz-MorenoAsier Fernández-PatoJiafei Wu9
Nature Communications
2025
2025/11/22
0
Horizontal gene transfer (HGT) is a major driver of bacterial evolution, but its role in shaping the human gut microbiome over time remains poorly understood. Here, we present a longitudinal metagenomic analysis of 676 fecal samples from 338 individuals in the Lifelines-DEEP study collected ~4 years...
Bacterial geneticsMicrobiome
10.1038/S41467-025-66612-Z
ISSN:2041-1723

MGMT genomic rearrangements contribute to chemotherapy resistance in gliomas

Barbara OldriniNuria Vaquero-SigueroQuanhua MuPaula KroonYing Zhang19
Nature Communications
2020
2020/8/4
Vol.11 No.1 p.1-10
Temozolomide (TMZ) is an oral alkylating agent used for the treatment of glioblastoma and is now becoming a chemotherapeutic option in patients diagnosed with high-risk low-grade gliomas. The O-6-methylguanine-DNA methyltransferase (MGMT) is responsible for the direct repair of the main TMZ-induced ...
Cancer genomicsCancer therapyCNS cancer
10.1038/S41467-020-17717-0
ISSN:2041-1723

Identification of genetic subtypes in follicular lymphoma

Victoria SheltonRajesh DetrojaTing LiuKeren IsaevAnjali Silva33
Blood Cancer Journal
2024
2024/8/7
Vol.14 No.1 p.1-13
Follicular lymphoma (FL) exhibits considerable variability in biological features and clinical trajectories across patients. To dissect the diversity of FL, we utilized a Bernoulli mixture model to identify genetic subtypes in 713 pre-treatment tumor tissue samples. Our analysis revealed the existen...
B-cell lymphomaCancer genomicsTranslational research
10.1038/S41408-024-01111-W
ISSN:2044-5385

Accounting for heterogeneity due to environmental sources in meta-analysis of genome-wide association studies

Siru WangOyesola O. OjewunmiAbram KamizaMichele RamsayAndrew P. Morris8
Communications Biology
2024
2024/11/14
Vol.7 No.1 p.1-12
Meta-analysis of genome-wide association studies (GWAS) across diverse populations offers power gains to identify loci associated with complex traits and diseases. Often heterogeneity in effect sizes across populations will be correlated with genetic ancestry and environmental exposures (e.g. lifest...
Genome-wide association studiesGenomics
10.1038/S42003-024-07236-9
ISSN:2399-3642

Structural variation in the gut microbiome associates with host health

David ZeeviTal KoremAnastasia GodnevaNoam BarAlexander Kurilshikov11
Nature
2019
2019/3/27
Vol.568 No.7750 p.43-48
Differences in the presence of even a few genes between otherwise identical bacterial strains may result in critical phenotypic differences. Here we systematically identify microbial genomic structural variants (SVs) and find them to be prevalent in the human gut microbiome across phyla and to repli...
Bacterial geneticsGenome informaticsMicrobial ecologyMicrobiomeRisk factors
10.1038/S41586-019-1065-Y
ISSN:0028-0836

Alternative lengthening of telomeres in childhood neuroblastoma from genome to proteome

Sabine A. HartliebLina SieverlingMichal Nadler-HollyMatthias ZiehmUmut H. Toprak30
Nature Communications
2021
2021/2/24
Vol.12 No.1 p.1-18
Telomere maintenance by telomerase activation or alternative lengthening of telomeres (ALT) is a major determinant of poor outcome in neuroblastoma. Here, we screen for ALT in primary and relapsed neuroblastomas (n = 760) and characterize its features using multi-omics profiling. ALT-positive tumors...
Cancer genomicsEmbryonal neoplasmsPaediatric cancer
10.1038/S41467-021-21247-8
ISSN:2041-1723

Multi-organ landscape of therapy-resistant melanoma

Liu SixueDharanipragada PrashanthiLomeli Shirley H.Wang YanZhang Xiao14
Nature Medicine
2023
2023/4/27
00 p.1-12
Metastasis and failure of present-day therapies represent the most common causes of mortality in patients with cutaneous melanoma. To identify the underlying genetic and transcriptomic landscapes, in this study we analyzed multi-organ metastases and tumor-adjacent tissues from 11 rapid autopsies aft...
Cancer genomicsMelanomaMetastasisOncogenesisTranslational research
10.1038/S41591-023-02304-9
ISSN:1078-8956

Long runs of homozygosity are associated with Alzheimer’s disease

Sonia Moreno-GrauMaria Victoria FernándezItziar de RojasPablo Garcia-GonzálezIsabel Hernández43
Translational Psychiatry
2021
2021/2/24
Vol.11 No.1 p.1-12
Long runs of homozygosity (ROH) are contiguous stretches of homozygous genotypes, which are a footprint of inbreeding and recessive inheritance. The presence of recessive loci is suggested for Alzheimer’s disease (AD); however, their search has been poorly assessed to date. To investigate homozygosi...
GenomicsPsychiatric disorders
10.1038/S41398-020-01145-1
ISSN:2158-3188

Gut metagenome associations with extensive digital health data in a volunteer-based Estonian microbiome cohort

Aasmets OliverKrigul Kertu LiisLüll KreeteMetspalu AndresOrg Elin
Nature Communications
2022
2022/2/15
Vol.13 No.1 p.1-11
Microbiome research is starting to move beyond the exploratory phase towards interventional trials and therefore well-characterized cohorts will be instrumental for generating hypotheses and providing new knowledge. As part of the Estonian Biobank, we established the Estonian Microbiome Cohort which...
Diagnostic markersDiseasesDrug regulationMetagenomicsPublic health
10.1038/S41467-022-28464-9
ISSN:2041-1723

Obesity risk in young adults from the Jerusalem Perinatal Study (JPS): the contribution of polygenic risk and early life exposure

Hagit HochnerRachely ButtermanIdo MargaliotYechiel FriedlanderMichal Linial
International Journal Of Obesity
2024
2024/3/12
00 p.1-10
The effects of early life exposures on offspring life-course health are well established. This study assessed whether adding early socio-demographic and perinatal variables to a model based on polygenic risk score (PRS) improves prediction of obesity risk. We used the Jerusalem Perinatal study (JPS)...
GeneticsRisk factors
10.1038/S41366-024-01505-7
ISSN:0307-0565

Whole-genome sequencing of a sporadic primary immunodeficiency cohort

James E. D. ThaventhiranHana Lango AllenOliver S. BurrenWilliam RaeDaniel Greene50
Nature
2020
2020/5/6
Vol.583 No.7814 p.90-95
Primary immunodeficiency (PID) is characterized by recurrent and often life-threatening infections, autoimmunity and cancer, and it poses major diagnostic and therapeutic challenges. Although the most severe forms of PID are identified in early childhood, most patients present in adulthood, typicall...
GenomicsImmunology
10.1038/S41586-020-2265-1
ISSN:0028-0836

Cross-ancestry genome-wide association studies of brain imaging phenotypes

Jilian FuQuan ZhangJianhua WangMeiyun WangBing Zhang44
Nature Genetics
2024
2024/5/29
Vol.56 No.6 p.1110-1120
Genome-wide association studies of brain imaging phenotypes are mainly performed in European populations, but other populations are severely under-represented. Here, we conducted Chinese-alone and cross-ancestry genome-wide association studies of 3,414 brain imaging phenotypes in 7,058 Chinese Han a...
Genome-wide association studiesNeuroscience
10.1038/S41588-024-01766-Y
ISSN:1061-4036

Epigenetic landscape of pancreatic neuroendocrine tumours reveals distinct cells of origin and means of tumour progression

Annunziata Di DomenicoChristodoulos P. PipinikasRenaud S. MaireKonstantin BräutigamCedric Simillion10
Communications Biology
2020
2020/12/7
Vol.3 No.1 p.1-11
Recent data suggest that Pancreatic Neuroendocrine Tumours (PanNETs) originate from α- or β-cells of the islets of Langerhans. The majority of PanNETs are non-functional and do not express cell-type specific hormones. In the current study we examine whether tumour DNA methylation (DNAme) profiling c...
Cancer epigeneticsDNA methylationNeuroendocrine cancer
10.1038/S42003-020-01479-Y
ISSN:2399-3642

Multiomic analysis of homologous recombination-deficient end-stage high-grade serous ovarian cancer

Burdett Nikki L.Willis Madelynne O.Alsop KathrynHunt Allison L.Pandey Ahwan37
Nature Genetics
2023
2023/2/27
Vol.55 No.3 p.437-450
High-grade serous ovarian cancer (HGSC) is frequently characterized by homologous recombination (HR) DNA repair deficiency and, while most such tumors are sensitive to initial treatment, acquired resistance is common. We undertook a multiomics approach to interrogate molecular diversity in end-stage...
GenomicsOvarian cancer
10.1038/S41588-023-01320-2
ISSN:1061-4036

Genetic predisposition to hypertension is associated with preeclampsia in European and Central Asian women

Valgerdur SteinthorsdottirRalph McGinnisNicholas O. WilliamsLilja StefansdottirGudmar Thorleifsson75
Nature Communications
2020
2020/11/25
Vol.11 No.1 p.1-14
Preeclampsia is a serious complication of pregnancy, affecting both maternal and fetal health. In genome-wide association meta-analysis of European and Central Asian mothers, we identify sequence variants that associate with preeclampsia in the maternal genome at ZNF831/20q13 and FTO/16q12. These ar...
Genome-wide association studiesHypertensionReproductive disorders
10.1038/S41467-020-19733-6
ISSN:2041-1723

Comparison of the diagnostic yield of aCGH and genome-wide sequencing across different neurodevelopmental disorders

Francisco Martinez-GraneroFiona Blanco-KellyCarolina Sanchez-JimenoAlmudena Avila-FernandezAna Arteche15
Npj Genomic Medicine
2021
2021/3/25
Vol.6 No.1 p.1-12
Most consensus recommendations for the genetic diagnosis of neurodevelopmental disorders (NDDs) do not include the use of next generation sequencing (NGS) and are still based on chromosomal microarrays, such as comparative genomic hybridization array (aCGH). This study compares the diagnostic yield ...
Molecular medicineNeurodevelopmental disorders
10.1038/S41525-021-00188-7
ISSN:2056-7944

Correction of a Factor VIII genomic inversion with designer-recombinases

Lansing FelixMukhametzyanova LiliyaRojo-Romanos TeresaIwasawa KentaroKimura Masaki17
Nature Communications
2022
2022/1/20
Vol.13 No.1 p.1-15
Despite advances in nuclease-based genome editing technologies, correcting human disease-causing genomic inversions remains a challenge. Here, we describe the potential use of a recombinase-based system to correct the 140 kb inversion of the F8 gene frequently found in patients diagnosed with severe...
Molecular evolutionTargeted gene repair
10.1038/S41467-022-28080-7
ISSN:2041-1723

Targeting lysyl oxidase (LOX) overcomes chemotherapy resistance in triple negative breast cancer

Ozge SaatciAysegul KaymakUmar RazaPelin G. ErsanOzge Akbulut23
Nature Communications
2020
2020/5/15
Vol.11 No.1 p.1-17
Chemoresistance is a major obstacle in triple negative breast cancer (TNBC), the most aggressive breast cancer subtype. Here we identify hypoxia-induced ECM re-modeler, lysyl oxidase (LOX) as a key inducer of chemoresistance by developing chemoresistant TNBC tumors in vivo and characterizing their t...
CancerCell biology
10.1038/S41467-020-16199-4
ISSN:2041-1723

Insight into genetic predisposition to chronic lymphocytic leukemia from integrative epigenomics

Helen E. SpeedyRenée BeekmanVicente ChapaprietaGiulia OrlandoPhilip J. Law18
Nature Communications
2019
2019/8/9
Vol.10 No.1 p.1-9
Genome-wide association studies have provided evidence for inherited genetic predisposition to chronic lymphocytic leukemia (CLL). To gain insight into the mechanisms underlying CLL risk we analyze chromatin accessibility, active regulatory elements marked by H3K27ac, and DNA methylation at 42 risk ...
Cancer epigeneticsChronic lymphocytic leukaemiaGenome-wide association studies
10.1038/S41467-019-11582-2
ISSN:2041-1723

Proteogenomics of different urothelial bladder cancer stages reveals distinct molecular features for papillary cancer and carcinoma in situ

Zhenmei YaoNing XuGuoguo ShangHaixing WangHui Tao19
Nature Communications
2023
2023/9/13
Vol.14 No.1 p.1-25
The progression of urothelial bladder cancer (UC) is a complicated multi-step process. We perform a comprehensive multi-omics analysis of 448 samples from 190 UC patients, covering the whole spectrum of disease stages and grades. Proteogenomic integration analysis indicates the mutations of HRAS reg...
BladderBladder cancerTumour biomarkers
10.1038/S41467-023-41139-3
ISSN:2041-1723

Unmapped exome reads implicate a role for Anelloviridae in childhood HIV-1 long-term non-progression

Savannah MwesigwaLesedi WilliamsGaone RetshabileEric KatagiryaGerald Mboowa26
Npj Genomic Medicine
2021
2021/3/19
Vol.6 No.1 p.1-9
Human immunodeficiency virus (HIV) infection remains a significant public health burden globally. The role of viral co-infection in the rate of progression of HIV infection has been suggested but not empirically tested, particularly among children. We extracted and classified 42 viral species from w...
Risk factorsViral genetics
10.1038/S41525-021-00185-W
ISSN:2056-7944

Tracing human genetic histories and natural selection with precise local ancestry inference

Jon Lerga-JasoBiljana NovkovićDeepu UnnikrishnanVaruna BamunusingheMarcelinus R. Hatorangan16
Nature Communications
2025
2025/5/16
Vol.16 No.1 p.1-13
Local ancestry inference is crucial for unraveling demographic histories, discovering selection signals, and including admixed individuals in genomic studies for improved equity and portability. To date, the precision and resolution of local ancestry inference were limited by technical and dataset i...
EvolutionGenomicsPopulation genetics
10.1038/S41467-025-59936-3
ISSN:2041-1723

Prostate cancer genetic risk and associated aggressive disease in men of African ancestry

Pamela X. Y. SohNaledi MmekwaDesiree C. PetersenKazzem GheybiSmit van Zyl12
Nature Communications
2023
2023/12/5
Vol.14 No.1 p.1-14
African ancestry is a significant risk factor for prostate cancer and advanced disease. Yet, genetic studies have largely been conducted outside the context of Sub-Saharan Africa, identifying 278 common risk variants contributing to a multiethnic polygenic risk score, with rare variants focused on a...
Cancer geneticsGenetics researchProstateProstate cancer
10.1038/S41467-023-43726-W
ISSN:2041-1723

Autoreactive T cells target peripheral nerves in Guillain–Barré syndrome

L. SúkeníkováA. MalloneB. SchreinerP. RipellinoJ. Nilsson9
Nature
2024
2024/1/17
00 p.1-9
Guillain–Barré syndrome (GBS) is a rare heterogenous disorder of the peripheral nervous system, which is usually triggered by a preceding infection, and causes a potentially life-threatening progressive muscle weakness1. Although GBS is considered an autoimmune disease, the mechanisms that...
Autoimmune diseasesAutoimmunityNeuroimmunologyT-cell receptorT cells
10.1038/S41586-023-06916-6
ISSN:0028-0836

IκBε deficiency accelerates disease development in chronic lymphocytic leukemia

Jessica BordiniChiara LenziMichela FrenquelliAlessia MorabitoAthanasios Pseftogas27
Leukemia
2024
2024/4/4
00 p.1-12
The NFKBIE gene, which encodes the NF-κB inhibitor IκBε, is mutated in 3–7% of patients with chronic lymphocytic leukemia (CLL). The most recurrent alteration is a 4-bp frameshift deletion associated with NF-κB activation in leukemic B cells and poor clinical outcome. To study the functional consequ...
Chronic lymphocytic leukaemiaTranslational research
10.1038/S41375-024-02236-4
ISSN:0887-6924

Deficient H2A.Z deposition is associated with genesis of uterine leiomyoma

Berta Davide G.Kuisma HeliVälimäki NikoRäisänen MarittaJäntti Maija27
Nature
2021
2021/8/4
00 p.1-6
One in four women suffers from uterine leiomyomas (ULs)—benign tumours of the uterine wall, also known as uterine fibroids—at some point in premenopausal life. ULs can cause excessive bleeding, pain and infertility1, and are a common cause of hysterectomy2. They emerge through at least three distinc...
Cancer epigeneticsCancer genomicsDisease geneticsInfertility
10.1038/S41586-021-03747-1
ISSN:0028-0836

The impact of rare germline variants on human somatic mutation processes

Vali-Pour MischanLehner BenSupek Fran
Nature Communications
2022
2022/6/28
Vol.13 No.1 p.1-21
Somatic mutations are an inevitable component of ageing and the most important cause of cancer. The rates and types of somatic mutation vary across individuals, but relatively few inherited influences on mutation processes are known. We perform a gene-based rare variant association study with divers...
Cancer geneticsCancer genomicsComputational biology and bioinformaticsRare variants
10.1038/S41467-022-31483-1
ISSN:2041-1723

A catalogue of early diverged contemporary human genome variation reveals distinct Khoe-San populations

Weerachai JaratlerdsiriPamela X. Y. SohTingting GongJue JiangZolani Simayi15
Nature Communications
2026
2026/2/10
Vol.17 No.1 p.25730
Creating a catalogue of early diverged genome variation is critical to determine the true extent of human diversity and associated medical impact. Generating deep whole genome data for 150 Khoe-San (12 groups, 1 unclassified), and 40 regionally comparative Southern Africans (3 groups), we identify ~...
Genetic variationGenetics research
10.1038/S41467-026-69269-4
ISSN:2041-1723

Systematic analysis of snRNA genes reveals frequent RNU2-2 variants in dominant and recessive developmental and epileptic encephalopathies

Elsa LeitãoAmandine SantiniBenjamin CogneMiriam EssidMaria Athanasiadou228
Nature Genetics
2026
2026/3/30
00 p.1-16
Small nuclear RNAs (snRNAs) are essential components of the spliceosome. De novo variants in snRNA genes RNU4-2 (ReNU syndrome), RNU5B-1 and RNU2-2 have been linked to dominant neurodevelopmental disorders (NDDs), revealing a large unexpected contribution of noncoding RNA genes to genetic diseases. ...
EpilepsyGenetics researchNeurodevelopmental disordersTranscriptomics
10.1038/S41588-026-02547-5
ISSN:1061-4036

Genomic profiling of T-cell activation suggests increased sensitivity of memory T cells to CD28 costimulation

Dafni A. GlinosBlagoje SoskicCayman WilliamsAlan KennedyLuke Jostins7
Genes & Immunity
2020
2020/11/23
Vol.21 No.6 p.390-408
T-cell activation is a critical driver of immune responses. The CD28 costimulation is an essential regulator of CD4 T-cell responses, however, its relative importance in naive and memory T cells is not fully understood. Using different model systems, we observe that human memory T cells are more sen...
Gene expression profilingImmunogenetics
10.1038/S41435-020-00118-0
ISSN:1466-4879

The co-evolution of the genome and epigenome in colorectal cancer

Heide TimonHouseham JacobCresswell George D.Spiteri InmaculadaLynn Claire31
Nature
2022
2022/10/26
Vol.611 No.7937 p.733-743
Colorectal malignancies are a leading cause of cancer-related death1 and have undergone extensive genomic study2,3. However, DNA mutations alone do not fully explain malignant transformation4–7. Here we investigate the co-evolution of the genome and epigenome of colorectal tumours at singl...
Cancer genomicsColorectal cancerComputational biology and bioinformaticsEpigenomicsTumour heterogeneity
10.1038/S41586-022-05202-1
ISSN:0028-0836

Multi-omic profiling highlights factors associated with resistance to immuno-chemotherapy in non-small-cell lung cancer

Yilv YanDongqing SunJunjie HuYue ChenLiangdong Sun21
Nature Genetics
2024
2024/12/10
00 p.1-14
Although immune checkpoint blockade (ICB) therapies have shifted the treatment paradigm for non-small-cell lung cancer (NSCLC), many patients remain resistant. Here we characterize the tumor cell states and spatial cellular compositions of the NSCLC tumor microenvironment (TME) by analyzing single-c...
Non-small-cell lung cancerRNA sequencing
10.1038/S41588-024-01998-Y
ISSN:1061-4036

Application of high-throughput single-nucleus DNA sequencing in pancreatic cancer

Zhang HaochenKarnoub Elias-RamzeyUmeda ShigeakiChaligné RonanMasilionis Ignas13
Nature Communications
2023
2023/2/10
Vol.14 No.1 p.1-14
Despite insights gained by bulk DNA sequencing of cancer it remains challenging to resolve the admixture of normal and tumor cells, and/or of distinct tumor subclones; high-throughput single-cell DNA sequencing circumvents these and brings cancer genomic studies to higher resolution. However, its ap...
Cancer genomicsEvolutionary biologyMetastasisNext-generation sequencingPancreatic cancer
10.1038/S41467-023-36344-Z
ISSN:2041-1723

Passenger mutations link cellular origin and transcriptional identity in human lung adenocarcinomas

Sukanya PanjaPadmaja MantriKofi Ennu JohnsonJuan Sebastian Andrade-MartinezSoo-Ryum Yang17
Nature Genetics
2025
2025/11/27
00 p.1-9
DNA damage is preferentially repaired in expressed genes; thus, genome-wide correlations between somatic mutation patterns and normal cell transcription may reflect tumor cell origins. Accordingly, we found that aggregate lung adenocarcinoma (LUAD) and squamous cancer (LUSC) somatic mutation density...
GenomicsNon-small-cell lung cancerTranscriptomics
10.1038/S41588-025-02418-5
ISSN:1061-4036

Functional footprints of homologous recombination deficiency in prostate cancer revealed by ctDNA fragmentation and transcription factor accessibility

Georgios VlachosTina MoserIsaac LazzeriMatthias J. MoserLisa Glawitch17
British Journal Of Cancer
2026
2026/1/9
Vol.134 No.6 p.949-960
Homologous recombination deficiency (HRD) is a predictive biomarker for response to PARP inhibitors and platinum-based therapies in prostate cancer (PCa). However, current diagnostic approaches, often limited to BRCA1/2 mutation testing or genomic scars, fail to capture the full spectrum of HRD. Tis...
Cancer epigeneticsDiagnostic markers
10.1038/S41416-025-03301-0
ISSN:0007-0920

The neuroactive potential of the human gut microbiota in quality of life and depression

Mireia Valles-ColomerGwen FalonyYoussef DarziEttje F. TigchelaarJun Wang15
Nature Microbiology
2019
2019/2/4
Vol.4 No.4 p.623-632
The relationship between gut microbial metabolism and mental health is one of the most intriguing and controversial topics in microbiome research. Bidirectional microbiota–gut–brain communication has mostly been explored in animal models, with human research lagging behind. Large-scale metagenomics ...
MetagenomicsMicrobiomeNeurology
10.1038/S41564-018-0337-X
ISSN:2058-5276

Mendelian randomization accounting for complex correlated horizontal pleiotropy while elucidating shared genetic etiology

Cheng QingZhang XiaoChen Lin S.Liu Jin
Nature Communications
2022
2022/10/30
Vol.13 No.1 p.1-13
Mendelian randomization (MR) harnesses genetic variants as instrumental variables (IVs) to study the causal effect of exposure on outcome using summary statistics from genome-wide association studies. Classic MR assumptions are violated when IVs are associated with unmeasured confounders, i.e., when...
Computational modelsGeneticsGenome-wide association studiesRisk factors
10.1038/S41467-022-34164-1
ISSN:2041-1723

Prediction of homologous recombination deficiency identifies colorectal tumors sensitive to PARP inhibition

Giorgio CortiKristi BuzoEnrico BerrinoMartina MiottoMaria Costanza Aquilano18
Npj Precision Oncology
2024
2024/10/14
Vol.8 No.1 p.1-9
The synthetic lethal effect observed with the use of PARP inhibitors (PARPi) with tumors characterized by the loss of key players in the homologous recombination (HR) pathway, commonly referred to as “BRCAness”, is maintaining high interest in oncology. While BRCAness is a well-established feature i...
CancerColon cancerHigh-throughput screeningMolecular medicine
10.1038/S41698-024-00706-7
ISSN:2397-768X

Mutational signature in colorectal cancer caused by genotoxic pks + E. coli

Cayetano Pleguezuelos-ManzanoJens PuschhofAxel Rosendahl HuberArne van HoeckHenry M. Wood17
Nature
2020
2020/2/27
Vol.580 No.7802 p.269-273
Various species of the intestinal microbiota have been associated with the development of colorectal cancer1,2, but it has not been demonstrated that bacteria have a direct role in the occurrence of oncogenic mutations. Escherichia coli can carry the pathogenicity island pks, which encodes a set of ...
Cancer geneticsCancer microenvironmentCancer modelsIntestinal stem cellsPathogens
10.1038/S41586-020-2080-8
ISSN:0028-0836

Aberrant neural activity in the peritumoral cortex underlies the progression of tumor-associated seizures

Bibi L. J. BouwenAnne BolleboomYuanhong TangZhaofei YuAnna van der Stap13
Nature Communications
2025
2025/12/2
Vol.16 No.1 p.108460
Seizures are frequent complications in brain tumor patients, yet the underlying neuronal mechanisms remain poorly defined. Here, we examined pathophysiological alterations in the peritumoral cortex of patients undergoing tumor resection. The synaptic activity, dendritic spine density, and gene expre...
Cancer in the nervous systemCNS cancerEpilepsy
10.1038/S41467-025-66226-5
ISSN:2041-1723

Homologous recombination DNA repair deficiency and PARP inhibition activity in primary triple negative breast cancer

Neha ChopraHolly ToveyAlex PearsonRos CuttsChristy Toms22
Nature Communications
2020
2020/5/29
Vol.11 No.1 p.1-12
Triple negative breast cancer (TNBC) encompasses molecularly different subgroups, with a subgroup harboring evidence of defective homologous recombination (HR) DNA repair. Here, within a phase 2 window clinical trial, RIO trial (EudraCT 2014-003319-12), we investigate the activity of PARP inhibitors...
Breast cancerCancer screening
10.1038/S41467-020-16142-7
ISSN:2041-1723

Huntington’s disease age at motor onset is modified by the tandem hexamer repeat in TCERG1

Lobanov Sergey V.McAllister BranduffMcDade-Kumar MiaLandwehrmeyer G. BernhardOrth Michael16
Npj Genomic Medicine
2022
2022/9/5
Vol.7 No.1 p.1-9
Huntington’s disease is caused by an expanded CAG tract in HTT. The length of the CAG tract accounts for over half the variance in age at onset of disease, and is influenced by other genetic factors, mostly implicating the DNA maintenance machinery. We examined a single nucleotide variant, rs7972779...
Genetic association studyGenetic predisposition to disease
10.1038/S41525-022-00317-W
ISSN:2056-7944

Meta-analysis of sub-Saharan African studies provides insights into genetic architecture of lipid traits

Choudhury AnanyoBrandenburg Jean-TristanChikowore TinasheSengupta DhritiBoua Palwende Romuald22
Nature Communications
2022
2022/5/11
Vol.13 No.1 p.1-13
Genetic associations for lipid traits have identified hundreds of variants with clear differences across European, Asian and African studies. Based on a sub-Saharan-African GWAS for lipid traits in the population cross-sectional AWI-Gen cohort (N = 10,603) we report a novel LDL-C association in the ...
Cardiovascular diseasesGenome-wide association studiesQuantitative traitRisk factors
10.1038/S41467-022-30098-W
ISSN:2041-1723

Development and testing of a polygenic risk score for breast cancer aggressiveness

Yiwey ShiehJacquelyn RogerChristina YauDenise M. WolfGillian L. Hirst23
Npj Precision Oncology
2023
2023/5/15
Vol.7 No.1 p.1-11
Aggressive breast cancers portend a poor prognosis, but current polygenic risk scores (PRSs) for breast cancer do not reliably predict aggressive cancers. Aggressiveness can be effectively recapitulated using tumor gene expression profiling. Thus, we sought to develop a PRS for the risk of recurrenc...
Breast cancerCancer epidemiologyCancer genetics
10.1038/S41698-023-00382-Z
ISSN:2397-768X

Chromosome arm aneuploidies shape tumour evolution and drug response

Ankit ShuklaThu H. M. NguyenSarat B. MokaJonathan J. EllisJohn P. Grady13
Nature Communications
2020
2020/1/23
Vol.11 No.1 p.1-14
Chromosome arm aneuploidies (CAAs) are pervasive in cancers. However, how they affect cancer development, prognosis and treatment remains largely unknown. Here, we analyse CAA profiles of 23,427 tumours, identifying aspects of tumour evolution including probable orders in which CAAs occur and CAAs p...
Cancer therapeutic resistanceChemotherapyMachine learningMetastasisSystems biology
10.1038/S41467-020-14286-0
ISSN:2041-1723

Interethnic analyses of blood pressure loci in populations of East Asian and European descent

Fumihiko TakeuchiMasato AkiyamaNana MatobaTomohiro KatsuyaMasahiro Nakatochi94
Nature Communications
2018
2018/11/28
Vol.9 No.1 p.1-16
Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, we perform a multi-stage genome-wide association study for BP (max N = 289,038) principally in East Asians and meta-analysis in East Asians and Europeans. We repor...
Cardiovascular geneticsCirculationGenome-wide association studiesHypertension
10.1038/S41467-018-07345-0
ISSN:2041-1723

Chemokine expression predicts T cell-inflammation and improved survival with checkpoint inhibition across solid cancers

Joan Miguel RomeroEmma TitmussYifan WangJames VafiadisAlain Pacis18
Npj Precision Oncology
2023
2023/8/9
Vol.7 No.1 p.1-14
Immune checkpoint inhibitors (ICI) are highly effective in specific cancers where canonical markers of antitumor immunity are used for patient selection. Improved predictors of T cell-inflammation are needed to identify ICI-responsive tumor subsets in additional cancer types. We investigated associa...
Cancer genomicsCancer microenvironmentPrognostic markersTumour immunology
10.1038/S41698-023-00428-2
ISSN:2397-768X

Apparent latent structure within the UK Biobank sample has implications for epidemiological analysis

Simon HaworthRuth MitchellLaura CorbinKaitlin H. WadeTom Dudding13
Nature Communications
2019
2019/1/18
Vol.10 No.1 p.1-9
Large studies use genotype data to discover genetic contributions to complex traits and infer relationships between those traits. Co-incident geographical variation in genotypes and health traits can bias these analyses. Here we show that single genetic variants and genetic scores composed of multip...
EpidemiologyGenetic association studyGenome-wide association studiesPopulation genetics
10.1038/S41467-018-08219-1
ISSN:2041-1723

Genetic determinants of mannose-binding lectin activity predispose to thromboembolic complications in critical COVID-19

Hultström MichaelFrithiof RobertGrip JonathanLindelöf LinneaRooijackers Olav15
Nature Immunology
2022
2022/5/27
00 p.1-4
InfectionViral infection
10.1038/S41590-022-01227-W
ISSN:1529-2908

Disentangling genetic effects on transcriptional and post-transcriptional gene regulation through integrating exon and intron expression QTLs

Anneke BrümmerSven Bergmann
Nature Communications
2024
2024/5/6
Vol.15 No.1 p.1-13
Expression quantitative trait loci (eQTL) studies typically consider exon expression of genes and discard intronic RNA sequencing reads despite their information on RNA metabolism. Here, we quantify genetic effects on exon and intron levels of genes and their ratio in lymphoblastoid cell lines, reve...
Functional genomicsGene expressionGene regulationGenetic association studyTranscriptomics
10.1038/S41467-024-48244-X
ISSN:2041-1723

Hypothesis-free phenotype prediction within a genetics-first framework

Lu ChangZaucha JanGam RihabFang HaiBen Smithers18
Nature Communications
2023
2023/2/17
Vol.14 No.1 p.1-14
Cohort-wide sequencing studies have revealed that the largest category of variants is those deemed ‘rare’, even for the subset located in coding regions (99% of known coding variants are seen in less than 1% of the population. Associative methods give some understanding how rare genetic variants inf...
Computational biology and bioinformaticsGenetics
10.1038/S41467-023-36634-6
ISSN:2041-1723

Genome-wide association study identifies common variants associated with breast cancer in South African Black women

Mahtaab HayatWenlong C. ChenChantal Babb de VilliersSang Hyuck LeeCharles Curtis15
Nature Communications
2025
2025/4/14
Vol.16 No.1 p.1-11
Genome-wide association studies (GWAS) have characterized the contribution of common variants to breast cancer (BC) risk in populations of European ancestry, however GWAS have not been reported in resident African populations. This GWAS included 2485 resident African BC cases and 1101 population mat...
Cancer genomicsComputational biology and bioinformatics
10.1038/S41467-025-58789-0
ISSN:2041-1723

The cellular and molecular cardiac tissue responses in human inflammatory cardiomyopathies after SARS-CoV-2 infection and COVID-19 vaccination

Henrike MaatzEric L. LindbergEleonora AdamiNatalia López-AnguitaAlvaro Perdomo-Sabogal33
Nature Cardiovascular Research
2025
2025/2/24
Vol.4 No.3 p.330-345
Myocarditis, characterized by inflammatory cell infiltration, can have multiple etiologies, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or, rarely, mRNA-based coronavirus disease 2019 (COVID-19) vaccination. The underlying cellular and molecular mechanisms remain...
Cardiovascular diseasesTranscriptomics
10.1038/S44161-025-00612-6
ISSN:2731-0590

The genomic and immune landscape of long-term survivors of high-grade serous ovarian cancer

Garsed Dale W.Pandey AhwanFereday SianKennedy Catherine J.Takahashi Kazuaki40
Nature Genetics
2022
2022/12/1
Vol.54 No.12 p.1853-1864
Fewer than half of all patients with advanced-stage high-grade serous ovarian cancers (HGSCs) survive more than five years after diagnosis, but those who have an exceptionally long survival could provide insights into tumor biology and therapeutic approaches. We analyzed 60 patients with advanced-st...
DNA sequencingEpigenomicsOvarian cancerRNA sequencing
10.1038/S41588-022-01230-9
ISSN:1061-4036

Extrachromosomal circular DNA drives oncogenic genome remodeling in neuroblastoma

Richard P. KocheElias Rodriguez-FosKonstantin HelmsauerMartin BurkertIan C. MacArthur38
Nature Genetics
2019
2019/12/16
Vol.52 No.1 p.29-34
Extrachromosomal circularization of DNA is an important genomic feature in cancer. However, the structure, composition and genome-wide frequency of extrachromosomal circular DNA have not yet been profiled extensively. Here, we combine genomic and transcriptomic approaches to describe the landscape o...
Embryonal neoplasmsGenomics
10.1038/S41588-019-0547-Z
ISSN:1061-4036

Expanding the neurodevelopmental phenotypes of individuals with de novo KMT2A variants

Ada J. S. ChanCheryl CytrynbaumNy HoangPatricia M. AmbrozewiczRosanna Weksberg13
Npj Genomic Medicine
2019
2019/4/26
Vol.4 No.1 p.1-10
De novo loss-of-function (LoF) variants in the KMT2A gene are associated with Wiedemann−Steiner Syndrome (WSS). Recently, de novo KMT2A variants have been identified in sequencing studies of cohorts of individuals with neurodevelopmental disorders (NDDs). However, most of these studies lack the deta...
Autism spectrum disordersDisease genetics
10.1038/S41525-019-0083-X
ISSN:2056-7944

Mendelian randomization of immune cell phenotypes to discover potential drug targets for B-cell malignancy

Sina A. BeerMolly WentCharlie MillsCodie WoodAmit Sud8
Blood Cancer Journal
2025
2025/4/9
Vol.15 No.1 p.1-8
Although treatment options for B-cell malignancies have expanded, many patients continue to face limited response rates, highlighting an urgent need for new therapeutic targets. To prioritize candidate drug targets for B-cell malignancies, we employed Mendelian Randomization to estimate potentially ...
Cancer geneticsDrug development
10.1038/S41408-025-01277-X
ISSN:2044-5385

Bacterial SNPs in the human gut microbiome associate with host BMI

Liron ZahaviAmit LavonLee ReicherSaar ShoerAnastasia Godneva10
Nature Medicine
2023
2023/11/2
00 p.1-8
Genome-wide association studies (GWASs) have provided numerous associations between human single-nucleotide polymorphisms (SNPs) and health traits. Likewise, metagenome-wide association studies (MWASs) between bacterial SNPs and human traits can suggest mechanistic links, but very few such studies h...
Computational modelsMicrobiomeRisk factors
10.1038/S41591-023-02599-8
ISSN:1078-8956

Genome-wide survival study identifies a novel synaptic locus and polygenic score for cognitive progression in Parkinson’s disease

Ganqiang LiuJiajie PengZhixiang LiaoJoseph J. LocascioJean-Christophe Corvol39
Nature Genetics
2021
2021/5/6
Vol.53 No.6 p.787-793
A key driver of patients’ well-being and clinical trials for Parkinson’s disease (PD) is the course that the disease takes over time (progression and prognosis). To assess how genetic variation influences the progression of PD over time to dementia, a major determinant for quality of life, we perfor...
Genome-wide association studiesParkinson's disease
10.1038/S41588-021-00847-6
ISSN:1061-4036

Prevalence and correlates of common mental disorders among participants of the Uganda Genome Resource: Opportunities for psychiatric genetics research

Allan KalungiEugene KinyandaDickens Howard AkenaBizu GelayeWilber Ssembajjwe19
Molecular Psychiatry
2024
2024/7/14
00 p.1-9
Genetics research has potential to alleviate the burden of mental disorders in low- and middle-income-countries through identification of new mechanistic pathways which can lead to efficacious drugs or new drug targets. However, there is currently limited genetics data from Africa. The Uganda Genome...
ADHDGeneticsPsychiatric disorders
10.1038/S41380-024-02665-8
ISSN:1359-4184

RoCK and ROI: single-cell transcriptomics with multiplexed enrichment of selected transcripts and region-specific sequencing

Giulia MoroIzaskun MallonaMalwine J. BarzJoël MaillardMichael David Brügger17
Nature Communications
2025
2025/12/10
Vol.16 No.1 p.109910
Single-cell profiling technologies allow exploring molecular mechanisms that drive development, health, and disease. However, current methods still fall short of profiling single cell transcriptomes comprehensively, with one major challenge being high non-detection rates of specific transcripts and ...
Computational biology and bioinformaticsTranscriptomics
10.1038/S41467-025-66248-Z
ISSN:2041-1723

RBFOX2 deregulation promotes pancreatic cancer progression and metastasis through alternative splicing

Michelle MaurinMohammadreza RanjouriCristina Megino-LuqueJustin Y. NewbergDongliang Du18
Nature Communications
2023
2023/12/19
Vol.14 No.1 p.1-18
RNA splicing is an important biological process associated with cancer initiation and progression. However, the contribution of alternative splicing to pancreatic cancer (PDAC) development is not well understood. Here, we identify an enrichment of RNA binding proteins (RBPs) involved in splicing reg...
Pancreatic cancerRNA splicing
10.1038/S41467-023-44126-W
ISSN:2041-1723

Patterns of genomic change in residual disease after neoadjuvant chemotherapy for estrogen receptor-positive and HER2-negative breast cancer

Chatzipli AikateriniBonnefoi HervéMacGrogan GaetanSentis JulieCameron David7
British Journal Of Cancer
2021
2021/9/3
00 p.1-9
Treatment of patients with residual disease after neoadjuvant chemotherapy for breast cancer is an unmet clinical need. We hypothesised that tumour subclones showing expansion in residual disease after chemotherapy would contain mutations conferring drug resistance. We studied oestrogen receptor and...
Breast cancerCancer genomics
10.1038/S41416-021-01526-3
ISSN:0007-0920

Innate immune responsiveness predicts enhanced cellular immunity and symptomatic disease after controlled human influenza infection

Loukas PapargyrisJiayun XuClaire BroderickAo HuangTrupti Gore35
Nature Medicine
2026
2026/7/1
00 p.1-14
Controlled human influenza infection studies can uniquely interrogate the early immune factors associated with clinical outcome. In this study, 27 healthy volunteers with low strain-specific serum neutralizing antibody levels were challenged with influenza A/H3N2 virus. Twenty-two became infected, w...
InfectionInfluenza virusInnate immunity
10.1038/S41591-026-04483-7
ISSN:1078-8956

Integrative analysis of non-small cell lung cancer patient-derived xenografts identifies distinct proteotypes associated with patient outcomes

Mirhadi ShidehTam ShirleyLi QuanMoghal NadeemPham Nhu-An27
Nature Communications
2022
2022/4/5
Vol.13 No.1 p.1-17
Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths worldwide. Only a fraction of NSCLC harbor actionable driver mutations and there is an urgent need for patient-derived model systems that will enable the development of new targeted therapies. NSCLC and other cancers display pr...
Non-small-cell lung cancerTumour biomarkers
10.1038/S41467-022-29444-9
ISSN:2041-1723

Evolutionary dynamics of neoantigens in growing tumors

Eszter LakatosMarc J. WilliamsRyan O. SchenckWilliam C. H. CrossJacob Househam13
Nature Genetics
2020
2020/9/14
Vol.52 No.10 p.1057-1066
Cancers accumulate mutations that lead to neoantigens, novel peptides that elicit an immune response, and consequently undergo evolutionary selection. Here we establish how negative selection shapes the clonality of neoantigens in a growing cancer by constructing a mathematical model of neoantigen e...
CancerComputational scienceGenetics research
10.1038/S41588-020-0687-1
ISSN:1061-4036

Analysis of cell free DNA to predict outcome to bevacizumab therapy in colorectal cancer patients

Tom VenkenIan S. MillerIngrid ArijsValentina ThomasAna Barat26
Npj Genomic Medicine
2024
2024/5/29
Vol.9 No.1 p.1-10
To predict outcome to combination bevacizumab (BVZ) therapy, we employed cell-free DNA (cfDNA) to determine chromosomal instability (CIN), nucleosome footprints (NF) and methylation profiles in metastatic colorectal cancer (mCRC) patients. Low-coverage whole-genome sequencing (LC-WGS) was performed ...
Cancer genomicsColon cancerPredictive markers
10.1038/S41525-024-00415-X
ISSN:2056-7944

Molecular medicine tumor board: whole-genome sequencing to inform on personalized medicine for a man with advanced prostate cancer

Andrew J. ArmstrongXiaotong LiMatthew TuckerShantao LiXinmeng Jasmine Mu9
Prostate Cancer And Prostatic Diseases
2021
2021/2/10
00 p.1-8
Molecular profiling of cancer is increasingly common as part of routine care in oncology, and germline and somatic profiling may provide insights and actionable targets for men with metastatic prostate cancer. However, all reported cases are of deidentified individuals without full medical and genom...
Cancer geneticsTranslational research
10.1038/S41391-021-00324-5
ISSN:1365-7852

A biobank of patient-derived pediatric brain tumor models

Sebastian BrabetzSarah E. S. LearySusanne N. GröbnerMadison W. NakamotoHuriye Şeker-Cin27
Nature Medicine
2018
2018/10/22
Vol.24 No.11 p.1752-1761
Brain tumors are the leading cause of cancer-related death in children. Genomic studies have provided insights into molecular subgroups and oncogenic drivers of pediatric brain tumors that may lead to novel therapeutic strategies. To evaluate new treatments, better preclinical models adequately refl...
Cancer genomicsCancer modelsCNS cancerPaediatric cancer
10.1038/S41591-018-0207-3
ISSN:1078-8956

Tobacco smoking and somatic mutations in human bronchial epithelium

Kenichi YoshidaKate H. C. GowersHenry Lee-SixDeepak P. ChandrasekharanTim Coorens21
Nature
2020
2020/1/29
Vol.578 No.7794 p.266-272
Tobacco smoking causes lung cancer1–3, a process that is driven by more than 60 carcinogens in cigarette smoke that directly damage and mutate DNA4,5. The profound effects of tobacco on the genome of lung cancer cells are well-documented6–10, but equivalent data for normal bronchial cells are lackin...
Cancer genomicsMutation
10.1038/S41586-020-1961-1
ISSN:0028-0836

Reconstructing single-cell karyotype alterations in colorectal cancer identifies punctuated and gradual diversification patterns

Yannik BollenEllen StellooPetra van LeenenMyrna van den BosBas Ponsioen26
Nature Genetics
2021
2021/7/1
00 p.1-9
Central to tumor evolution is the generation of genetic diversity. However, the extent and patterns by which de novo karyotype alterations emerge and propagate within human tumors are not well understood, especially at single-cell resolution. Here, we present 3D Live-Seq—a protocol that integrates l...
Colorectal cancerDNA sequencingTime-lapse imaging
10.1038/S41588-021-00891-2
ISSN:1061-4036

Lineage tracing of human development through somatic mutations

Michael Spencer ChapmanAnna Maria RanzoniBrynelle MyersNicholas WilliamsTim H. H. Coorens16
Nature
2021
2021/5/12
00 p.1-6
The ontogeny of the human haematopoietic system during fetal development has previously been characterized mainly through careful microscopic observations1. Here we reconstruct a phylogenetic tree of blood development using whole-genome sequencing of 511 single-cell-derived haematopoietic colonies f...
GenomicsHaematopoiesis
10.1038/S41586-021-03548-6
ISSN:0028-0836

PAX4 loss of function increases diabetes risk by altering human pancreatic endocrine cell development

Hwee Hui LauNicole A. J. KrentzFernando AbaituaMarta Perez-AlcantaraJun-Wei Chan20
Nature Communications
2023
2023/9/30
Vol.14 No.1 p.1-19
The coding variant (p.Arg192His) in the transcription factor PAX4 is associated with an altered risk for type 2 diabetes (T2D) in East Asian populations. In mice, Pax4 is essential for beta cell formation but its role on human beta cell development and/or function is unknown. Participants carrying t...
Disease modelType 2 diabetes
10.1038/S41467-023-41860-Z
ISSN:2041-1723

Tumor evolution metrics predict recurrence beyond 10 years in locally advanced prostate cancer

Javier Fernandez-MateosGeorge D. CresswellNicholas TrahearnKatharine WebbChirine Sakr27
Nature Cancer
2024
2024/7/12
00 p.1-18
Cancer evolution lays the groundwork for predictive oncology. Testing evolutionary metrics requires quantitative measurements in controlled clinical trials. We mapped genomic intratumor heterogeneity in locally advanced prostate cancer using 642 samples from 114 individuals enrolled in clinical tria...
CancerPhylogeneticsPrognostic markersProstate cancerTumour heterogeneity
10.1038/S43018-024-00787-0
ISSN:2662-1347

High-resolution analysis for urinary DNA jagged ends

Xie TingtingWang GuangyaDing Spencer C.Lee Wing-ShanCheng Suk Hang15
Npj Genomic Medicine
2022
2022/2/23
Vol.7 No.1 p.1-8
Single-stranded ends of double-stranded DNA (jagged ends) are more abundant in urinary DNA than in plasma DNA. However, the lengths of jagged ends in urinary DNA remained undetermined, as a previous method used for urinary DNA jagged end sequencing analysis (Jag-seq) relied on unmethylation at CpG s...
DNA sequencingTumour biomarkers
10.1038/S41525-022-00285-1
ISSN:2056-7944

Estimating narrow-sense heritability using family data from admixed populations

Georgios AthanasiadisDoug SpeedMette K. AndersenEmil V. R. AppelNiels Grarup11
Heredity
2020
2020/4/9
Vol.124 No.6 p.751-762
Estimating total narrow-sense heritability in admixed populations remains an open question. In this work, we used extensive simulations to evaluate existing linear mixed-model frameworks for estimating total narrow-sense heritability in two population-based cohorts from Greenland, and compared the r...
GeneticsHeritable quantitative trait
10.1038/S41437-020-0311-2
ISSN:0018-067X

NXPE1 alters the sialoglycome by acetylating sialic acids in the human colon

Bum Seok LeeAshley CookSurojit SurLaura DobbynMaria Popoli14
Nature Communications
2025
2025/5/27
Vol.16 No.1 p.1-14
Mild periodic acid Schiff staining (mPAS) of human colonic tissue has been used to answer a variety of fundamental questions in germline and somatic genetics. mPAS stains sialic acids except when these glycans are modified by O-acetylation, but a full accounting of the genes contributing to sialogly...
AcetylationAcetyltransferasesGenome-wide association studiesGlycobiologyNext-generation sequencing
10.1038/S41467-025-59671-9
ISSN:2041-1723

ERα-associated translocations underlie oncogene amplifications in breast cancer

Jake June-Koo LeeYoungsook Lucy JungTaek-Chin CheongJose Espejo Valle-InclanChong Chu15
Nature
2023
2023/5/17
00 p.1-9
Focal copy-number amplification is an oncogenic event. Although recent studies have revealed the complex structure1–3 and the evolutionary trajectories4 of oncogene amplicons, their origin remains poorly understood. Here we show that focal amplifications in breast cancer frequently derive from a mec...
Breast cancerCancer geneticsCancer genomicsStructural variation
10.1038/S41586-023-06057-W
ISSN:0028-0836

Residual ANTXR1+ myofibroblasts after chemotherapy inhibit anti-tumor immunity via YAP1 signaling pathway

Monika LicajRana MhaidlyYann KiefferHugo CroizerClaire Bonneau24
Nature Communications
2024
2024/2/12
Vol.15 No.1 p.1-27
Although cancer-associated fibroblast (CAF) heterogeneity is well-established, the impact of chemotherapy on CAF populations remains poorly understood. Here we address this question in high-grade serous ovarian cancer (HGSOC), in which we previously identified 4 CAF populations. While the global con...
Cancer microenvironmentOvarian cancerTumour heterogeneity
10.1038/S41467-024-45595-3
ISSN:2041-1723

Molecularly matched targeted therapies plus radiotherapy in glioblastoma: the phase 1/2a N2M2 umbrella trial

Wolfgang WickLisa-Marie LanzAntje WickInga HartingSusan Dettmer25
Nature Medicine
2025
2025/9/5
00 p.1-8
Advances in molecular understanding and diagnostic precision of glioblastoma enable the identification of key genetic alterations in a timely manner and, in principle, allow treatments with targeted compounds based on molecular markers. Here we report the results of the phase 1/2 umbrella trial NCT ...
Drug developmentPredictive markers
10.1038/S41591-025-03928-9
ISSN:1078-8956

De novo variants in the splicing factor gene SF3B1 are associated with neurodevelopmental disorders

Kevin UguenTiffany BergotMarie-Pier Scott-BoyerSolène ChapalainCamille Desdouets67
Nature Communications
2026
2026/1/23
Vol.17 No.1 p.15690
SF3B1 is an essential and ubiquitous splicing factor that plays a pivotal role in the early steps of pre-mRNA splicing. Recurrent somatic missense mutations in SF3B1 are frequent in cancers, but no constitutional variant has been reported so far. We describe here a cohort of 26 individuals with neur...
Disease geneticsGenetics researchNeurodevelopmental disordersRNA splicingTranscriptomics
10.1038/S41467-026-68284-9
ISSN:2041-1723

Genetic substructure and complex demographic history of South African Bantu speakers

Dhriti SenguptaAnanyo ChoudhuryCesar Fortes-LimaShaun AronGavin Whitelaw17
Nature Communications
2021
2021/4/7
Vol.12 No.1 p.1-13
South Eastern Bantu-speaking (SEB) groups constitute more than 80% of the population in South Africa. Despite clear linguistic and geographic diversity, the genetic differences between these groups have not been systematically investigated. Based on genome-wide data of over 5000 individuals, represe...
Computational biology and bioinformaticsEvolutionary geneticsGenome-wide association studiesPopulation genetics
10.1038/S41467-021-22207-Y
ISSN:2041-1723

Genetic effects on the timing of parturition and links to fetal birth weight

Solé-Navais PolFlatley ChristopherSteinthorsdottir ValgerdurVaudel MarcJuodakis Julius85
Nature Genetics
2023
2023/4/3
00 p.1-9
The timing of parturition is crucial for neonatal survival and infant health. Yet, its genetic basis remains largely unresolved. We present a maternal genome-wide meta-analysis of gestational duration (n = 195,555), identifying 22 associated loci (24 independent variants) and an enrichment in genes ...
Genetics researchGenome-wide association studies
10.1038/S41588-023-01343-9
ISSN:1061-4036

In-depth inference of transcriptional regulatory networks reveals NPM1 as a therapeutic ribosomal regulator in MYC-amplified medulloblastoma

Tong ChenHuiyao ChenMingyang XiaYunfei LiaoHao Li8
Npj Precision Oncology
2025
2025/1/10
Vol.9 No.1 p.1-13
Medulloblastoma (MB) is an aggressive pediatric brain tumor with distinct molecular heterogeneity. Identifying subtype-specific signatures within Group 3 and Group 4 remains challenging due to shared cytogenetic alterations and limitations of conventional differential gene expression analysis. To un...
CNS cancerPaediatric cancer
10.1038/S41698-024-00792-7
ISSN:2397-768X

Patient-derived follicular lymphoma spheroids recapitulate lymph node signaling and immune profile uncovering galectin-9 as a novel immunotherapeutic target

Cèlia Dobaño-LópezJuan García ValeroFerran Araujo-AyalaFerran NadeuFabien Gava26
Blood Cancer Journal
2024
2024/5/2
Vol.14 No.1 p.1-14
Follicular lymphoma (FL), the most common indolent non-Hodgkin lymphoma, constitutes a paradigm of immune tumor microenvironment (TME) contribution to disease onset, progression, and heterogenous clinical outcome. Here we present the first FL-Patient Derived Lymphoma Spheroid (FL-PDLS), including fu...
B-cell lymphomaCancer immunotherapy
10.1038/S41408-024-01041-7
ISSN:2044-5385

Spatiotemporal dynamics of clonal selection and diversification in normal endometrial epithelium

Yamaguchi ManakoNakaoka HirofumiSuda KazuakiYoshihara KosukeIshiguro Tatsuya18
Nature Communications
2022
2022/2/17
Vol.13 No.1 p.1-18
It has become evident that somatic mutations in cancer-associated genes accumulate in the normal endometrium, but spatiotemporal understanding of the evolution and expansion of mutant clones is limited. To elucidate the timing and mechanism of the clonal expansion of somatic mutations in cancer-asso...
Cancer genomicsEndometrial cancerGene expressionGenome evolutionReproductive biology
10.1038/S41467-022-28568-2
ISSN:2041-1723

Multiomic neuropathology improves diagnostic accuracy in pediatric neuro-oncology

Sturm DominikCapper DavidAndreiuolo FelipeGessi MarcoKölsche Christian54
Nature Medicine
2023
2023/3/16
00 p.1-10
The large diversity of central nervous system (CNS) tumor types in children and adolescents results in disparate patient outcomes and renders accurate diagnosis challenging. In this study, we prospectively integrated DNA methylation profiling and targeted gene panel sequencing with blinded neuropath...
Cancer epidemiologyCancer epigeneticsCNS cancerDiagnostic markersPaediatric cancer
10.1038/S41591-023-02255-1
ISSN:1078-8956

Defective Epstein–Barr virus in chronic active infection and haematological malignancy

Yusuke OkunoTakayuki MurataYoshitaka SatoHideki MuramatsuYoshinori Ito38
Nature Microbiology
2019
2019/1/21
Vol.4 No.3 p.404-413
Epstein–Barr virus (EBV) infection is highly prevalent in humans and is implicated in various diseases, including cancer1,2. Chronic active EBV infection (CAEBV) is an intractable disease classified as a lymphoproliferative disorder in the 2016 World Health Organization lymphoma classification1,2. C...
Herpes virusTumour virus infections
10.1038/S41564-018-0334-0
ISSN:2058-5276

Metabolomic and microbiome profiling reveals personalized risk factors for coronary artery disease

Talmor-Barkan YeelaBar NoamShaul Aviv A.Shahaf NirGodneva Anastasia20
Nature Medicine
2022
2022/2/17
Vol.28 No.2 p.295-302
Complex diseases, such as coronary artery disease (CAD), are often multifactorial, caused by multiple underlying pathological mechanisms. Here, to study the multifactorial nature of CAD, we performed comprehensive clinical and multi-omic profiling, including serum metabolomics and gut microbiome dat...
Acute coronary syndromesBiomarkersMetabolomicsMicrobiome
10.1038/S41591-022-01686-6
ISSN:1078-8956

Accurate detection of circulating tumor DNA using nanopore consensus sequencing

Marcozzi AlessioJager MyrtheElferink MartinStraver Royvan Ginkel Joost H.15
Npj Genomic Medicine
2021
2021/12/9
Vol.6 No.1 p.1-11
Levels of circulating tumor DNA (ctDNA) in liquid biopsies may serve as a sensitive biomarker for real-time, minimally-invasive tumor diagnostics and monitoring. However, detecting ctDNA is challenging, as much fewer than 5% of the cell-free DNA in the blood typically originates from the tumor. To d...
Diagnostic markersDNA sequencing
10.1038/S41525-021-00272-Y
ISSN:2056-7944

Distinct genetic pathways define pre-malignant versus compensatory clonal hematopoiesis in Shwachman-Diamond syndrome

Alyssa L. KennedyKasiani C. MyersJames BowmanChristopher J. GibsonNicholas D. Camarda43
Nature Communications
2021
2021/2/26
Vol.12 No.1 p.1-15
To understand the mechanisms that mediate germline genetic leukemia predisposition, we studied the inherited ribosomopathy Shwachman-Diamond syndrome (SDS), a bone marrow failure disorder with high risk of myeloid malignancies at an early age. To define the mechanistic basis of clonal hematopoiesis ...
Cancer genomicsMedical genomics
10.1038/S41467-021-21588-4
ISSN:2041-1723

On-treatment measurements of circulating tumor DNA during FOLFOX therapy in patients with colorectal cancer

Tina MoserJulie Waldispuehl-GeiglJelena BelicSabrina WeberQing Zhou18
Npj Precision Oncology
2020
2020/11/13
Vol.4 No.1 p.1-7
We addressed a significant unknown feature of circulating tumor DNA (ctDNA), i.e., how ctDNA levels change during chemotherapy, by serially monitoring ctDNA in patients with colorectal cancer during the 48-h application of FOLFOX. Surprisingly, we did not observe a spike in ctDNA as a sign of a resp...
BiomarkersCancer
10.1038/S41698-020-00134-3
ISSN:2397-768X

Evolutionary history of transformation from chronic lymphocytic leukemia to Richter syndrome

Parry Erin M.Leshchiner IgnatyGuièze RomainJohnson ConnorTausch Eugen54
Nature Medicine
2023
2023/1/9
Vol.29 No.1 p.158-169
Richter syndrome (RS) arising from chronic lymphocytic leukemia (CLL) exemplifies an aggressive malignancy that develops from an indolent neoplasm. To decipher the genetics underlying this transformation, we computationally deconvoluted admixtures of CLL and RS cells from 52 patients with RS, evalua...
B-cell lymphomaCancer geneticsCancer genomicsChronic lymphocytic leukaemia
10.1038/S41591-022-02113-6
ISSN:1078-8956

Synonymous GATA2 mutations result in selective loss of mutated RNA and are common in patients with GATA2 deficiency

Emilia J. KozyraVictor B. PastorStylianos LefkopoulosSushree S. SahooHauke Busch39
Leukemia
2020
2020/6/18
Vol.34 No.10 p.2673-2687
Deficiency of the transcription factor GATA2 is a highly penetrant genetic disorder predisposing to myelodysplastic syndromes (MDS) and immunodeficiency. It has been recognized as the most common cause underlying primary MDS in children. Triggered by the discovery of a recurrent synonymous GATA2 var...
Genetics researchHaematological diseases
10.1038/S41375-020-0899-5
ISSN:0887-6924

5-Fluorouracil treatment induces characteristic T>G mutations in human cancer

Sharon ChristensenBastiaan Van der RoestNicolle BesselinkRoel JanssenSander Boymans11
Nature Communications
2019
2019/10/8
Vol.10 No.1 p.1-11
5-Fluorouracil (5-FU) is a chemotherapeutic drug commonly used for the treatment of solid cancers. It is proposed that 5-FU interferes with nucleotide synthesis and incorporates into DNA, which may have a mutational impact on both surviving tumor and healthy cells. Here, we treat intestinal organoid...
Cancer genomics
10.1038/S41467-019-12594-8
ISSN:2041-1723

Genomic characterization of metastatic breast cancers

François BertucciCharlotte K. Y. NgAnne PatsourisNathalie DroinSalvatore Piscuoglio28
Nature
2019
2019/5/22
Vol.569 No.7757 p.560-564
Metastasis is the main cause of death for patients with breast cancer. Many studies have characterized the genomic landscape of breast cancer during its early stages. However, there is evidence that genomic alterations are acquired during the evolution of cancers from their early to late stages, and...
Breast cancerTranslational research
10.1038/S41586-019-1056-Z
ISSN:0028-0836

Population dynamics of normal human blood inferred from somatic mutations

Henry Lee-SixNina Friesgaard ØbroMairi S. ShepherdSebastian GrossmannKevin Dawson16
Nature
2018
2018/9/5
Vol.561 No.7724 p.473-478
Haematopoietic stem cells drive blood production, but their population size and lifetime dynamics have not been quantified directly in humans. Here we identified 129,582 spontaneous, genome-wide somatic mutations in 140 single-cell-derived haematopoietic stem and progenitor colonies from a healthy 5...
LeukopoiesisPhylogenomics
10.1038/S41586-018-0497-0
ISSN:0028-0836

An organoid platform for ovarian cancer captures intra- and interpatient heterogeneity

Oded KopperChris J. de WitteKadi LõhmussaarJose Espejo Valle-InclanNizar Hami31
Nature Medicine
2019
2019/4/22
Vol.25 No.5 p.838-849
Ovarian cancer (OC) is a heterogeneous disease usually diagnosed at a late stage. Experimental in vitro models that faithfully capture the hallmarks and tumor heterogeneity of OC are limited and hard to establish. We present a protocol that enables efficient derivation and long-term expansion of OC ...
Cancer modelsOvarian cancer
10.1038/S41591-019-0422-6
ISSN:1078-8956

ERBB2 signaling drives immune cell evasion and resistance against immunotherapy in small cell lung cancer

Lydia MederCharlotte I. OrschelCyrielle L. BouchezRahil GholamipoorfardClaudia V. Orschel27
Nature Communications
2025
2025/12/9
Vol.16 No.1 p.109830
Small cell lung cancer (SCLC) is characterized by its highly aggressive phenotype and dismal outcome. Despite the benefit of adding immune checkpoint blockade to standard chemotherapy, tumors acquire the ability to evade immunosurveillance and develop resistance. To investigate these underlying mech...
Cancer immunotherapyLung cancerSmall-cell lung cancer
10.1038/S41467-025-66800-X
ISSN:2041-1723

Spatially resolved single-cell analyses of human meningioma identify novel cell states influencing tumor microenvironment and progression

Alexander P. LandryLeeor S. YefetJustin Z. WangAndrew AjisebutuChloe Gui18
Nature Genetics
2026
2026/6/9
Vol.58 No.6 p.1383-1395
Recent advances in our understanding of the molecular landscape of meningioma have generated new insights into the biology and heterogeneity of this disease, with demonstrated clinical value. However, there remains a need to understand tumor-intrinsic heterogeneity at single-cell resolution to infor...
CNS cancerComputational biology and bioinformatics
10.1038/S41588-026-02615-W
ISSN:1061-4036

Whole genome and transcriptome profiling in advanced pancreatic cancer patients on the COMPASS trial

Jennifer J. KnoxGun Ho JangRobert C. GrantAmy ZhangLucy Ma44
Nature Communications
2025
2025/7/1
Vol.16 No.1 p.1-14
Integrated whole genome and transcriptome sequencing can unveil distinct molecular subgroups in pancreatic cancer (PDAC). The COMPASS trial (NCT02750657) enrolled 268 patients with advanced PDAC; patients were given either modified (m) FOLFIRINOX or Gemcitabine-nab-paclitaxel (GnP) as per physicians...
CancerCancer genomicsMolecular medicinePancreatic cancer
10.1038/S41467-025-60808-Z
ISSN:2041-1723

Genome-wide association study meta-analysis of blood pressure traits and hypertension in sub-Saharan African populations: an AWI-Gen study

Surina SinghAnanyo ChoudhuryScott HazelhurstNigel J. CrowtherPalwendé R. Boua17
Nature Communications
2023
2023/12/16
Vol.14 No.1 p.1-14
Most hypertension-related genome-wide association studies (GWASs) focus on non-African populations, despite hypertension (a major risk factor for cardiovascular disease) being highly prevalent in Africa. The AWI-Gen study GWAS meta-analysis for blood pressure (BP)-related traits (systolic and diasto...
Genome-wide association studiesHypertension
10.1038/S41467-023-44079-0
ISSN:2041-1723

The longitudinal dynamics and natural history of clonal haematopoiesis

Fabre Margarete A.de Almeida José GuilhermeFiorillo EdoardoMitchell EmilyDamaskou Aristi21
Nature
2022
2022/6/1
00 p.1-8
Clonal expansions driven by somatic mutations become pervasive across human tissues with age, including in the haematopoietic system, where the phenomenon is termed clonal haematopoiesis1–4. The understanding of how and when clonal haematopoiesis develops, the factors that govern its behaviour, how ...
Acute myeloid leukaemiaComputational modelsMutationMyelodysplastic syndromeRisk factors
10.1038/S41586-022-04785-Z
ISSN:0028-0836

A single-cell atlas of non-haematopoietic cells in human lymph nodes and lymphoma reveals a landscape of stromal remodelling

Abe YoshiakiSakata-Yanagimoto MamikoFujisawa ManabuMiyoshi HiroakiSuehara Yasuhito23
Nature Cell Biology
2022
2022/3/24
00 p.1-14
The activities of non-haematopoietic cells (NHCs), including mesenchymal stromal cells and endothelial cells, in lymphomas are reported to underlie lymphomagenesis. However, our understanding of lymphoma NHCs has been hampered by unexplained NHC heterogeneity, even in normal human lymph nodes (LNs)....
Cancer microenvironmentTranscriptomicsTumour heterogeneity
10.1038/S41556-022-00866-3
ISSN:1465-7392

Ancient DNA reveals reproductive barrier despite shared Avar-period culture

Ke WangBendeguz TobiasDoris Pany-KuceraMargit BernerSabine Eggers25
Nature
2025
2025/1/15
00 p.1-8
After a long-distance migration, Avars with Eastern Asian ancestry arrived in Eastern Central Europe in 567 to 568 ce and encountered groups with very different European ancestry1,2. We used ancient genome-wide data of 722 individuals and fine-grained interdisciplinary analysis of large seventh- to ...
ArchaeologyBiological anthropologyComparative genomicsHistory
10.1038/S41586-024-08418-5
ISSN:0028-0836

Targeting TACC3 represents a novel vulnerability in highly aggressive breast cancers with centrosome amplification

Saatci OzgeAkbulut OzgeCetin MetinSikirzhytski VitaliUner Meral13
Cell Death & Differentiation
2023
2023/3/2
00 p.1-15
Centrosome amplification (CA) is a hallmark of cancer that is strongly associated with highly aggressive disease and worse clinical outcome. Clustering extra centrosomes is a major coping mechanism required for faithful mitosis of cancer cells with CA that would otherwise undergo mitotic catastrophe...
OncogenesTumour-suppressor proteins
10.1038/S41418-023-01140-1
ISSN:1350-9047

Diet–microbiome associations in 10,068 individuals from the Human Phenotype Project to guide personalized nutrition

Tomer SegevDaniel BarakLiron ZahaviAnastasia GodnevaMichal Rein10
Nature Medicine
2026
2026/3/23
00 p.1-11
Diet is a major environmental factor influencing the human gut microbiome. However, the effects of specific foods and dietary patterns on microbial composition, diversity and function is not fully understood, limiting progress toward personalized dietary strategies. Here, leveraging 10,068 participa...
Lifestyle modificationMicrobial ecologyMicrobiomePredictive markersPredictive medicine
10.1038/S41591-026-04312-X
ISSN:1078-8956

Benchmarking of analysis strategies for data-independent acquisition proteomics using a large-scale dataset comprising inter-patient heterogeneity

Fröhlich KlemensBrombacher EvaFahrner MatthiasVogele DanielKook Lucas12
Nature Communications
2022
2022/5/12
Vol.13 No.1 p.1-13
Numerous software tools exist for data-independent acquisition (DIA) analysis of clinical samples, necessitating their comprehensive benchmarking. We present a benchmark dataset comprising real-world inter-patient heterogeneity, which we use for in-depth benchmarking of DIA data analysis workflows f...
Data processingMass spectrometryProteomics
10.1038/S41467-022-30094-0
ISSN:2041-1723

An assessment of prognostic immunity markers in breast cancer

Benlong YangJeff ChouYaozhong TaoDengbin WuXinhong Wu16
Npj Breast Cancer
2018
2018/10/29
Vol.4 No.1 p.1-9
Tumor-infiltrating lymphocytes (TIL) and immunity gene signatures have been reported to be significantly prognostic in breast cancer but have not yet been applied for calculation of risk of recurrence in clinical assays. A compact set of 17 immunity genes was derived herein from an Affymetrix-derive...
Breast cancerPrognostic markers
10.1038/S41523-018-0088-0
ISSN:2374-4677

Whole-genome sequencing of 1,171 elderly admixed individuals from São Paulo, Brazil

Naslavsky Michel S.Scliar Marilia O.Yamamoto Guilherme L.Wang Jaqueline Yu TingZverinova Stepanka42
Nature Communications
2022
2022/3/4
Vol.13 No.1 p.1-11
As whole-genome sequencing (WGS) becomes the gold standard tool for studying population genomics and medical applications, data on diverse non-European and admixed individuals are still scarce. Here, we present a high-coverage WGS dataset of 1,171 highly admixed elderly Brazilians from a census-base...
Data publication and archivingHaplotypesMobile elementsRare variantsStructural variation
10.1038/S41467-022-28648-3
ISSN:2041-1723

Circulating cell-free DNA methylation patterns indicate cellular sources of allograft injury after liver transplant

Megan E. McNamaraSidharth S. JainKesha OzaVinona MuralidaranAmber J. Kiliti12
Nature Communications
2025
2025/6/17
Vol.16 No.1 p.1-17
Post-transplant complications reduce allograft and recipient survival. Current approaches for detecting allograft injury non-invasively are limited and do not differentiate between cellular mechanisms. Here, we monitor cellular damages after liver transplants from cell-free DNA (cfDNA) fragments rel...
ApoptosisDNA methylationTranslational research
10.1038/S41467-025-60507-9
ISSN:2041-1723

Identification of gut microbiome features associated with host metabolic health in a large population-based cohort

Ayya KeshetEran Segal
Nature Communications
2024
2024/10/29
Vol.15 No.1 p.1-13
The complex relationship between the gut microbiome and host metabolic health has been an emerging research area. Several recent studies have highlighted the potential effects of the microbiome’s diversity, composition and metabolic production capabilities on Body Mass Index (BMI), liver health, glu...
BacteriaDiabetes
10.1038/S41467-024-53832-Y
ISSN:2041-1723

Landscape and function of multiple mutations within individual oncogenes

Yuki SaitoJunji KoyaMitsugu ArakiYasunori KogureSumito Shingaki16
Nature
2020
2020/4/8
Vol.582 No.7810 p.95-99
Sporadic reports have described cancer cases in which multiple driver mutations (MMs) occur in the same oncogene1,2. However, the overall landscape and relevance of MMs remain elusive. Here we carried out a pan-cancer analysis of 60,954 cancer samples, and identified 14 pan-cancer and 6 cancer-type-...
Cancer genomicsOncogenes
10.1038/S41586-020-2175-2
ISSN:0028-0836

Integrative analysis of genomic and transcriptomic characteristics associated with progression of aggressive thyroid cancer

Seong-Keun YooYoung Shin SongEun Kyung LeeJinha HwangHwan Hee Kim16
Nature Communications
2019
2019/6/24
Vol.10 No.1 p.1-12
Anaplastic thyroid cancer (ATC) and advanced differentiated thyroid cancers (DTCs) show fatal outcomes, unlike DTCs. Here, we demonstrate mutational landscape of 27 ATCs and 86 advanced DTCs by massively-parallel DNA sequencing, and transcriptome of 13 ATCs and 12 advanced DTCs were profiled by RNA ...
Cancer genomicsThyroid cancer
10.1038/S41467-019-10680-5
ISSN:2041-1723

Evidence for dynastic succession among early Celtic elites in Central Europe

Joscha GretzingerFelicitas SchmittAngela MötschSelina CarlhoffThiseas Christos Lamnidis23
Nature Human Behaviour
2024
2024/6/3
00 p.1-14
The early Iron Age (800 to 450 BCE) in France, Germany and Switzerland, known as the ‘West-Hallstattkreis’, stands out as featuring the earliest evidence for supra-regional organization north of the Alps. Often referred to as ‘early Celtic’, suggesting tentative connections to later cultural phenome...
ArchaeologyBiological anthropologyHistoryPopulation genetics
10.1038/S41562-024-01888-7
ISSN:2397-3374

Subclonal reconstruction of tumors by using machine learning and population genetics

Giulio CaravagnaTimon HeideMarc J. WilliamsLuis ZapataDaniel Nichol15
Nature Genetics
2020
2020/9/2
Vol.52 No.9 p.898-907
Most cancer genomic data are generated from bulk samples composed of mixtures of cancer subpopulations, as well as normal cells. Subclonal reconstruction methods based on machine learning aim to separate those subpopulations in a sample and infer their evolutionary history. However, current approach...
CancerData processingGenomicsPopulation dynamics
10.1038/S41588-020-0675-5
ISSN:1061-4036

Human pancreatic islet three-dimensional chromatin architecture provides insights into the genetics of type 2 diabetes

Irene Miguel-EscaladaSilvia Bonàs-GuarchInês CebolaJoan Ponsa-CobasJulen Mendieta-Esteban36
Nature Genetics
2019
2019/6/28
Vol.51 No.7 p.1137-1148
Genetic studies promise to provide insight into the molecular mechanisms underlying type 2 diabetes (T2D). Variants associated with T2D are often located in tissue-specific enhancer clusters or super-enhancers. So far, such domains have been defined through clustering of enhancers in linear genome m...
EpigenomicsGenetics researchGenome-wide association studiesMetabolic disorders
10.1038/S41588-019-0457-0
ISSN:1061-4036

Parkinson’s families project: a UK-wide study of early onset and familial Parkinson’s disease

Clodagh TownsZih-Hua FangManuela M. X. TanSimona JasaityteTheresa M. Schmaderer24
Npj Parkinson's Disease
2024
2024/10/17
Vol.10 No.1 p.1-13
The Parkinson’s Families Project is a UK-wide study aimed at identifying genetic variation associated with familial and early-onset Parkinson’s disease (PD). We recruited individuals with a clinical diagnosis of PD and age at motor symptom onset ≤45 years and/or a family history of PD in up to third...
Clinical geneticsParkinson's disease
10.1038/S41531-024-00778-Z
ISSN:2373-8057

A comprehensive spatio-cellular map of the human hypothalamus

John A. TadrossLukas SteuernagelGeorgina K. C. DowsettKatherine A. KentistouSofia Lundh17
Nature
2025
2025/2/5
Vol.639 No.8055 p.708-716
The hypothalamus is a brain region that plays a key role in coordinating fundamental biological functions1. However, our understanding of the underlying cellular components and neurocircuitries have, until recently, emerged primarily from rodent studies2,3. Here we combine single-nucleus sequencing ...
Neural circuitsObesity
10.1038/S41586-024-08504-8
ISSN:0028-0836

Assessment of candidate high-grade serous ovarian carcinoma predisposition genes through integrated germline and tumour sequencing

Deepak N. SubramanianMaia ZethovenKathleen I. PishasEvanny R. MarinovićSimone McInerny11
Npj Genomic Medicine
2025
2025/1/10
Vol.10 No.1 p.1-16
High-grade serous ovarian carcinoma (HGSOC) has a significant hereditary component, only half of which is explained. Previously, we performed germline exome sequencing on BRCA1 and BRCA2-negative HGSOC patients, revealing three proposed and 43 novel candidate genes enriched with rare loss-of-functio...
Cancer geneticsCancer genomicsGenetics researchOvarian cancer
10.1038/S41525-024-00447-3
ISSN:2056-7944

Single-cell somatic copy number variants in brain using different amplification methods and reference genomes

Ester Kalef-EzraZeliha Gozde TuranDiego Perez-RodriguezIda BomannSairam Behera11
Communications Biology
2024
2024/10/9
Vol.7 No.1 p.1-10
The presence of somatic mutations, including copy number variants (CNVs), in the brain is well recognized. Comprehensive study requires single-cell whole genome amplification, with several methods available, prior to sequencing. Here we compare PicoPLEX with two recent adaptations of multiple displa...
Data processingGenetics of the nervous systemGenomicsNeurodegenerative diseasesNext-generation sequencing
10.1038/S42003-024-06940-W
ISSN:2399-3642

Sequence variants influencing the regulation of serum IgG subclass levels

Thorunn A. OlafsdottirGudmar ThorleifssonAitzkoa Lopez de Lapuente PortillaStefan JonssonLilja Stefansdottir35
Nature Communications
2024
2024/9/14
Vol.15 No.1 p.1-13
Immunoglobulin G (IgG) is the main isotype of antibody in human blood. IgG consists of four subclasses (IgG1 to IgG4), encoded by separate constant region genes within the Ig heavy chain locus (IGH). Here, we report a genome-wide association study on blood IgG subclass levels. Across 4334 adults and...
Genome-wide association studiesImmunogeneticsInflammatory diseases
10.1038/S41467-024-52470-8
ISSN:2041-1723

Deciphering the genetics and mechanisms of predisposition to multiple myeloma

Molly WentLaura Duran-LozanoGisli H. HalldorssonAndrea GunnellNerea Ugidos-Damboriena50
Nature Communications
2024
2024/8/5
Vol.15 No.1 p.1-15
Multiple myeloma (MM) is an incurable malignancy of plasma cells. Epidemiological studies indicate a substantial heritable component, but the underlying mechanisms remain unclear. Here, in a genome-wide association study totaling 10,906 cases and 366,221 controls, we identify 35 MM risk loci, 12 of ...
Genetics researchMyeloma
10.1038/S41467-024-50932-7
ISSN:2041-1723

A rare human variant that disrupts GPR10 signalling causes weight gain in mice

Talbot FleurFeetham Claire H.Mokrosiński JacekLawler KatherineKeogh Julia M.19
Nature Communications
2023
2023/3/15
Vol.14 No.1 p.1-10
Disruption of brain-expressed G protein-coupled receptor-10 (GPR10) causes obesity in animals. Here, we identify multiple rare variants in GPR10 in people with severe obesity and in normal weight controls. These variants impair ligand binding and G protein-dependent signalling in cells. Transgenic m...
Clinical geneticsEndocrine system and metabolic diseases
10.1038/S41467-023-36966-3
ISSN:2041-1723

Clone copy number diversity is linked to survival in lung cancer

Piotr PawlikKristiana GrigoriadisAbigail BunkumHelena CogganAlexander M. Frankell14
Nature
2025
2025/8/13
00 p.1-8
Both single nucleotide variants (SNVs) and somatic copy number alterations (SCNAs) accumulate in cancer cells during tumour development, fuelling clonal evolution. However, accurate estimation of clone-specific copy numbers from bulk DNA-sequencing data is challenging. Here we present allele-specifi...
Computational modelsNon-small-cell lung cancerPhylogeny
10.1038/S41586-025-09398-W
ISSN:0028-0836

Epigenetic activation of a RAS/MYC axis in H3.3K27M-driven cancer

Sanja PajovicRobert SiddawayTaylor BridgeJaval ShethPatricia Rakopoulos16
Nature Communications
2020
2020/12/4
Vol.11 No.1 p.1-16
Histone H3 lysine 27 (H3K27M) mutations represent the canonical oncohistone, occurring frequently in midline gliomas but also identified in haematopoietic malignancies and carcinomas. H3K27M functions, at least in part, through widespread changes in H3K27 trimethylation but its role in tumour initia...
Cancer modelsEpigeneticsMechanisms of diseasePaediatric cancerPreclinical research
10.1038/S41467-020-19972-7
ISSN:2041-1723

Clinicopathologic and molecular predictors of survival in BRCA-deficient tubo-ovarian high-grade serous carcinoma

Tibor A. ZwimpferSian FeredayAhwan PandeyDinuka AriyaratneMadawa W. Jayawardana148
Nature Communications
2026
2026/4/1
0
BRCA-associated homologous recombination deficiency (HRD) is present in ~50% of high-grade serous carcinomas (HGSC) and predicts sensitivity to platinum-based therapy. However, there is little understanding of why some patients with BRCA-deficient tumors experience poor outcomes. In a large HGSC coh...
Cancer geneticsCancer genomicsDNA sequencingOvarian cancerRNA sequencing
10.1038/S41467-026-71134-3
ISSN:2041-1723

Interrogating breast cancer heterogeneity using single and pooled circulating tumor cell analysis

Rothé FrançoiseVenet DavidPeeters DieterRouas GhizlaneRediti Mattia12
Npj Breast Cancer
2022
2022/7/5
Vol.8 No.1 p.1-8
Single cell technologies allow the interrogation of tumor heterogeneity, providing insights into tumor evolution and treatment resistance. To better understand whether circulating tumor cells (CTCs) could complement metastatic biopsies for tumor genomic profiling, we characterized 11 single CTCs and...
Breast cancerTranslational researchTumour heterogeneity
10.1038/S41523-022-00445-7
ISSN:2374-4677

Single-cell genotyping and transcriptomic profiling of mosaic focal cortical dysplasia

Sara BaldassariEsther KlinglerLucia Gomez TeijeiroMarion DoladilheCorentin Raoux16
Nature Neuroscience
2025
2025/4/30
00 p.1-9
Focal cortical dysplasia type II (FCDII) is a cortical malformation causing refractory epilepsy. FCDII arises from developmental somatic activating mutations in mTOR pathway genes, leading to focal cortical dyslamination and abnormal cytomegalic cells. Which cell types carry pathogenic mutations and...
EpilepsyMolecular neuroscienceNeurodevelopmental disordersTranscriptomics
10.1038/S41593-025-01936-Z
ISSN:1097-6256

A reference map of potential determinants for the human serum metabolome

Noam BarTal KoremOmer WeissbrodDavid ZeeviDaphna Rothschild14
Nature
2020
2020/11/11
Vol.588 No.7836 p.135-140
The serum metabolome contains a plethora of biomarkers and causative agents of various diseases, some of which are endogenously produced and some that have been taken up from the environment1. The origins of specific compounds are known, including metabolites that are highly heritable2,3, or those t...
DatabasesMachine learningMetabolomicsMicrobiology
10.1038/S41586-020-2896-2
ISSN:0028-0836