Functional genomics

English

United States, Boardman

Stanford University

数据描述

The ENCODE (Encyclopedia of DNA Elements) project provides functional genomics data, including functional characterization of genomic elements, data from cell lines, protein knockdown experiments, imputed experiments, and data from human donors, stem cell differentiation, immune cells, and mouse development. It encompasses ChIP-seq experiments, RNA-seq, and single-cell experiments, along with computational and integrative products.

www.encodeproject.org

IP: 34.211.244.144

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相关论文

243

Genetic variants affecting RNA stability influence complex traits and disease risk

Elaine Huang•Ting Fu•Ling Zhang•Guanao Yan•Ryo Yamamoto等 18 人

Nature Genetics

2025

•2025/9/5

•00 p.1-11

Gene expression is modulated jointly by transcriptional regulation and messenger RNA stability, yet the latter is often overlooked in studies on genetic variants. Here, leveraging metabolic labeling data (Bru/BruChase-seq) and a new computational pipeline, RNAtracker, we categorize genes as allele-s...

Gene expressionTranscriptomics

10.1038/S41588-025-02326-8

ISSN:1061-4036

The debranching enzyme Dbr1 regulates lariat turnover and intron splicing

Luke Buerer•Nathaniel E. Clark•Anastasia Welch•Chaorui Duan•Allison J. Taggart等 16 人

Nature Communications

2024

•2024/5/30

•Vol.15 No.1 p.1-13

The majority of genic transcription is intronic. Introns are removed by splicing as branched lariat RNAs which require rapid recycling. The branch site is recognized during splicing catalysis and later debranched by Dbr1 in the rate-limiting step of lariat turnover. Through generation of a viable DB...

BiochemistryMolecular biologyNucleasesRNA-binding proteinsRNA splicing

10.1038/S41467-024-48696-1

ISSN:2041-1723

Multimodal chromatin profiling using nanobody-based single-cell CUT&Tag

Bartosovic Marek•Castelo-Branco Gonçalo

Nature Biotechnology

2022

•2022/12/19

•00 p.1-12

Probing histone modifications at a single-cell level in thousands of cells has been enabled by technologies such as single-cell CUT&Tag. Here we describe nano-CUT&Tag (nano-CT), which allows simultaneous mapping of up to three epigenomic modalities at single-cell resolution using nanobody-Tn...

Cellular neuroscienceChromatin analysisEpigenomicsHistone post-translational modifications

10.1038/S41587-022-01535-4

ISSN:1087-0156

Mouse genome rewriting and tailoring of three important disease loci

Weimin Zhang•Ilona Golynker•Ran Brosh•Alvaro Fajardo•Yinan Zhu等 21 人

Nature

2023

•2023/11/1

•Vol.623 No.7986 p.423-431

Genetically engineered mouse models (GEMMs) help us to understand human pathologies and develop new therapies, yet faithfully recapitulating human diseases in mice is challenging. Advances in genomics have highlighted the importance of non-coding regulatory genome sequences, which control spatiotemp...

GeneticsSynthetic biology

10.1038/S41586-023-06675-4

ISSN:0028-0836

Denoising spatial epigenomic data via deep matrix factorization

Shuyan Wang•Hao Xu•Junyu Wang•Yao Xiao•Shanghao Dai等 9 人

Nature Computational Science

2026

•2026/1/13

•Vol.6 No.2 p.208-220

Spatial epigenomics (SE) technologies profile epigenomic landscapes within intact tissues, preserving spatial context and enabling the study of gene regulatory mechanisms in situ. However, current SE datasets typically suffer from low signal detection, substantial noise and extremely sparse peak mat...

Computational modelsEpigenomicsMachine learning

10.1038/S43588-025-00941-3

ISSN:2662-8457

Multiple stages of evolutionary change in anthrax toxin receptor expression in humans

Choate Lauren A.•Barshad Gilad•McMahon Pierce W.•Said Iskander•Rice Edward J.等 8 人

Nature Communications

2021

•2021/11/15

•Vol.12 No.1 p.1-12

The advent of animal husbandry and hunting increased human exposure to zoonotic pathogens. To understand how a zoonotic disease may have influenced human evolution, we study changes in human expression of anthrax toxin receptor 2 (ANTXR2), which encodes a cell surface protein necessary for Bacillus ...

Evolutionary geneticsQuantitative trait

10.1038/S41467-021-26854-Z

ISSN:2041-1723

A neurodevelopmental epigenetic programme mediated by SMARCD3–DAB1–Reelin signalling is hijacked to promote medulloblastoma metastasis

Zou Han•Poore Bradley•Brown Emily E.•Qian Jieqi•Xie Bin等 40 人

Nature Cell Biology

2023

•2023/2/27

•Vol.25 No.3 p.493-507

How abnormal neurodevelopment relates to the tumour aggressiveness of medulloblastoma (MB), the most common type of embryonal tumour, remains elusive. Here we uncover a neurodevelopmental epigenomic programme that is hijacked to induce MB metastatic dissemination. Unsupervised analyses of integrated...

Cancer epigeneticsCNS cancerDevelopmental neurogenesisMetastasis

10.1038/S41556-023-01093-0

ISSN:1465-7392

Noncanonical association of EZH2 with E2F1 promotes tumor proliferation through chromatin remodeling

Mijoung Yoo•Hyeonji Lee•Hyorim Park•Byunghee Kang•Hyo-Min Kim等 7 人

Experimental & Molecular Medicine

2025

•2025/12/19

•00 p.1-12

Enhancer of zeste homolog 2 (EZH2), the catalytic subunit of the polycomb repressive complex 2 (PRC2), which mediates transcriptional repression through histone H3 lysine 27 trimethylation (H3K27me3), is highly expressed in aggressive triple-negative breast cancer (TNBC). However, despite the elevat...

EpigenomicsGene regulation

10.1038/S12276-025-01603-0

ISSN:2092-6413

Unbiased discovery of cancer pathways and therapeutics using Pathway Ensemble Tool and Benchmark

Luopin Wang•Aryamav Pattnaik•Subhransu Sekhar Sahoo•Ella G. Stone•Yuxin Zhuang等 28 人

Nature Communications

2024

•2024/8/24

•Vol.15 No.1 p.1-16

Correctly identifying perturbed biological pathways is a critical step in uncovering basic disease mechanisms and developing much-needed therapeutic strategies. However, whether current tools are optimal for unbiased discovery of relevant pathways remains unclear. Here, we create “Benchmark” to crit...

Cancer genomicsComputational biology and bioinformaticsDrug discoveryPrognostic markersTumour biomarkers

10.1038/S41467-024-51859-9

ISSN:2041-1723

LINE-1 transcription activates long-range gene expression

Xiufeng Li•Luyao Bie•Yang Wang•Yaqiang Hong•Ziqiang Zhou等 19 人

Nature Genetics

2024

•2024/6/7

•00 p.1-9

Long interspersed nuclear element-1 (LINE-1 or L1) is a retrotransposon group that constitutes 17% of the human genome and shows variable expression across cell types. However, the control of L1 expression and its function in gene regulation are incompletely understood. Here we show that L1 transcri...

EmbryogenesisFunctional genomicsGenomicsHigh-throughput screening

10.1038/S41588-024-01789-5

ISSN:1061-4036

Predicting RNA-seq coverage from DNA sequence as a unifying model of gene regulation

Johannes Linder•Divyanshi Srivastava•Han Yuan•Vikram Agarwal•David R. Kelley

Nature Genetics

2025

•2025/1/8

•00 p.1-13

Sequence-based machine-learning models trained on genomics data improve genetic variant interpretation by providing functional predictions describing their impact on the cis-regulatory code. However, current tools do not predict RNA-seq expression profiles because of modeling challenges. Here, we in...

Functional genomicsGene regulationGenome informatics

10.1038/S41588-024-02053-6

ISSN:1061-4036

Recurrent noncoding U1 snRNA mutations drive cryptic splicing in SHH medulloblastoma

Hiromichi Suzuki•Sachin A. Kumar•Shimin Shuai•Ander Diaz-Navarro•Ana Gutierrez-Fernandez等 68 人

Nature

2019

•2019/10/9

•Vol.574 No.7780 p.707-711

In cancer, recurrent somatic single-nucleotide variants—which are rare in most paediatric cancers—are confined largely to protein-coding genes1–3. Here we report highly recurrent hotspot mutations (r.3A>G) of U1 spliceosomal small nuclear RNAs (snRNAs) in about 50% of Sonic hedgehog (SHH) medullobla...

Cancer genomicsCNS cancerPaediatric cancerRNA splicing

10.1038/S41586-019-1650-0

ISSN:0028-0836

Single-oocyte full-length isoform sequencing unveils the impact of transposable elements on RNA diversity and stability

Yuqian Wang•Wei Wang•Yujun Liu•Yiming He•Hongyu Song等 18 人

Nature Communications

2026

•2026/4/7

Oocyte-specific isoforms play crucial roles in oocyte maturation, while current understanding of the oocyte transcriptome is mainly focused on gene level. Here, we utilize single-cell full-length isoform sequencing to detect entire transcripts in human and mouse oocytes. Isoform diversity during ooc...

Gene expressionMeiosisOogenesisRNA sequencing

10.1038/S41467-026-71425-9

ISSN:2041-1723

The correlation between CpG methylation and gene expression is driven by sequence variants

Olafur Andri Stefansson•Brynja Dogg Sigurpalsdottir•Solvi Rognvaldsson•Gisli Hreinn Halldorsson•Kristinn Juliusson等 32 人

Nature Genetics

2024

•2024/7/24

•Vol.56 No.8 p.1624-1631

Gene promoter and enhancer sequences are bound by transcription factors and are depleted of methylated CpG sites (cytosines preceding guanines in DNA). The absence of methylated CpGs in these sequences typically correlates with increased gene expression, indicating a regulatory role for methylation....

DNA sequencingEpigeneticsGene expressionGenome-wide association studiesGenomics

10.1038/S41588-024-01851-2

ISSN:1061-4036

Meta-analysis of genome-wide associations and polygenic risk prediction for atrial fibrillation in more than 180,000 cases

Carolina Roselli•Ida Surakka•Morten S. Olesen•Gardar Sveinbjornsson•Nicholas A. Marston等 156 人

Nature Genetics

2025

•2025/3/6

•Vol.57 No.3 p.539-547

Atrial fibrillation (AF) is the most common heart rhythm abnormality and is a leading cause of heart failure and stroke. This large-scale meta-analysis of genome-wide association studies increased the power to detect single-nucleotide variant associations and found more than 350 AF-associated geneti...

Atrial fibrillationGenome-wide association studies

10.1038/S41588-024-02072-3

ISSN:1061-4036

LINE-1 retrotransposons contribute to mouse PV interneuron development

Gabriela O. Bodea•Juan M. Botto•Maria E. Ferreiro•Francisco J. Sanchez-Luque•Jose de los Rios Barreda等 28 人

Nature Neuroscience

2024

•2024/5/21

•00 p.1-11

Retrotransposons are mobile DNA sequences duplicated via transcription and reverse transcription of an RNA intermediate. Cis-regulatory elements encoded by retrotransposons can also promote the transcription of adjacent genes. Somatic LINE-1 (L1) retrotransposon insertions have been detected in mamm...

EpigenomicsGenetics of the nervous systemInhibitionNeuronal development

10.1038/S41593-024-01650-2

ISSN:1097-6256

5-Formylcytosine organizes nucleosomes and forms Schiff base interactions with histones in mouse embryonic stem cells

Eun-Ang Raiber•Guillem Portella•Sergio Martínez Cuesta•Robyn Hardisty•Pierre Murat等 14 人

Nature Chemistry

2018

•2018/10/22

•Vol.10 No.12 p.1258-1266

Nucleosomes are the basic unit of chromatin that help the packaging of genetic material while controlling access to the genetic information. The underlying DNA sequence, together with transcription-associated proteins and chromatin remodelling complexes, are important factors that influence the orga...

BiochemistryChromatinDNAEpigenetics

10.1038/S41557-018-0149-X

ISSN:1755-4330

Gapped-kmer sequence modeling robustly identifies regulatory vocabularies and distal enhancers conserved between evolutionarily distant mammals

Jin Woo Oh•Michael A. Beer

Nature Communications

2024

•2024/7/31

•Vol.15 No.1 p.1-16

Gene regulatory elements drive complex biological phenomena and their mutations are associated with common human diseases. The impacts of human regulatory variants are often tested using model organisms such as mice. However, mapping human enhancers to conserved elements in mice remains a challenge,...

Comparative genomicsEpigenomicsGene regulatory networks

10.1038/S41467-024-50708-Z

ISSN:2041-1723

Brain–heart–eye axis revealed by multi-organ imaging genetics and proteomics

Aleix Boquet-Pujadas•Filippos Anagnostakis•Michael R. Duggan•Cassandra M. Joynes•Arthur W. Toga等 9 人

Nature Biomedical Engineering

2025

•2025/9/30

•00 p.1-23

Multi-organ research investigates interconnections among multiple human organ systems, enhancing our understanding of human aging and disease mechanisms. Here we use multi-organ imaging, individual- and summary-level genetics, and proteomics data consolidated via the MULTI Consortium to delineate a ...

Genetics researchHeritable quantitative traitMachine learning

10.1038/S41551-025-01506-5

ISSN:2157-846X

An expanded registry of candidate cis-regulatory elements

Jill E. Moore•Henry E. Pratt•Kaili Fan•Nishigandha Phalke•Jonathan Fisher等 49 人

Nature

2026

•2026/1/7

•00 p.1-10

Mammalian genomes contain millions of regulatory elements that control the complex patterns of gene expression1. Previously, the ENCODE consortium mapped biochemical signals across hundreds of cell types and tissues and integrated these data to develop a registry containing 0.9 million human an...

Data integrationEpigenomicsGene regulationGenetic databasesTranscriptional regulatory elements

10.1038/S41586-025-09909-9

ISSN:0028-0836

Allele-specific binding of RNA-binding proteins reveals functional genetic variants in the RNA

Ei-Wen Yang•Jae Hoon Bahn•Esther Yun-Hua Hsiao•Boon Xin Tan•Yiwei Sun等 17 人

Nature Communications

2019

•2019/3/22

•Vol.10 No.1 p.1-15

Allele-specific protein-RNA binding is an essential aspect that may reveal functional genetic variants (GVs) mediating post-transcriptional regulation. Recently, genome-wide detection of in vivo binding of RNA-binding proteins is greatly facilitated by the enhanced crosslinking and immunoprecipitati...

Computational biology and bioinformaticsGene expressionGenetics

10.1038/S41467-019-09292-W

ISSN:2041-1723

53BP1 regulates heterochromatin through liquid phase separation

Zhang Lei•Geng Xinran•Wang Fangfang•Tang Jinshan•Ichida Yu等 19 人

Nature Communications

2022

•2022/1/18

•Vol.13 No.1 p.1-16

Human 53BP1 is primarily known as a key player in regulating DNA double strand break (DSB) repair choice; however, its involvement in other biological process is less well understood. Here, we report a previously uncharacterized function of 53BP1 at heterochromatin, where it undergoes liquid-liquid ...

Cell biologyMolecular biology

10.1038/S41467-022-28019-Y

ISSN:2041-1723

Multiplexed spatial mapping of chromatin features, transcriptome and proteins in tissues

Pengfei Guo•Liran Mao•Yufan Chen•Chin Nien Lee•Angelysia Cardilla等 8 人

Nature Methods

2025

•2025/1/27

•Vol.22 No.3 p.520-529

The phenotypic and functional states of cells are modulated by a complex interactive molecular hierarchy of multiple omics layers, involving the genome, epigenome, transcriptome, proteome and metabolome. Spatial omics approaches have enabled the study of these layers in tissue context but are often ...

EpigenomicsProteomic analysisTranscriptomics

10.1038/S41592-024-02576-0

ISSN:1548-7091

Spatiotemporal DNA methylome dynamics of the developing mouse fetus

Yupeng He•Manoj Hariharan•David U. Gorkin•Diane E. Dickel•Chongyuan Luo等 20 人

Nature

2020

•2020/7/29

•Vol.583 No.7818 p.752-759

Cytosine DNA methylation is essential for mammalian development but understanding of its spatiotemporal distribution in the developing embryo remains limited1,2. Here, as part of the mouse Encyclopedia of DNA Elements (ENCODE) project, we profiled 168 methylomes from 12 mouse tissues or organs at 9 ...

DNA methylationEpigenomicsGene regulation

10.1038/S41586-020-2119-X

ISSN:0028-0836

Transcription imparts architecture, function and logic to enhancer units

Nathaniel D. Tippens•Jin Liang•Alden King-Yung Leung•Shayne D. Wierbowski•Abdullah Ozer等 8 人

Nature Genetics

2020

•2020/9/21

•Vol.52 No.10 p.1067-1075

Distal enhancers play pivotal roles in development and disease yet remain one of the least understood regulatory elements. We used massively parallel reporter assays to perform functional comparisons of two leading enhancer models and find that gene-distal transcription start sites are robust predic...

Functional genomicsGene expressionGene regulationGenomics

10.1038/S41588-020-0686-2

ISSN:1061-4036

Cell cycle gene alterations associate with a redistribution of mutation risk across chromosomal domains in human cancers

Marina Salvadores•Fran Supek

Nature Cancer

2024

•2024/1/10

•00 p.1-17

Mutations in human cells exhibit increased burden in heterochromatic, late DNA replication time (RT) chromosomal domains, with variation in mutation rates between tissues mirroring variation in heterochromatin and RT. We observed that regional mutation risk further varies between individual tumors i...

Cancer genomicsChromatin remodellingEpigenomicsMutationTumour-suppressor proteins

10.1038/S43018-023-00707-8

ISSN:2662-1347

Dual DNA and protein tagging of open chromatin unveils dynamics of epigenomic landscapes in leukemia

Jonathan D. Lee•Joao A. Paulo•Ryan R. Posey•Vera Mugoni•Nikki R. Kong等 12 人

Nature Methods

2021

•2021/3/1

•Vol.18 No.3 p.293-302

The architecture of chromatin regulates eukaryotic cell states by controlling transcription factor access to sites of gene regulation. Here we describe a dual transposase–peroxidase approach, integrative DNA and protein tagging (iDAPT), which detects both DNA (iDAPT-seq) and protein (iDAPT-MS) assoc...

BiochemistryEpigenetics analysisFunctional genomicsProteomics

10.1038/S41592-021-01077-8

ISSN:1548-7091

Genome-wide associations of structural variants with human traits through imputation from long-read assemblies

Wei-Yang Bai•Shuli Liu•Zhongqu Duan•Ji-Jian Yang•Jie Chen等 10 人

Nature Genetics

2026

•2026/5/20

•00 p.1-10

Structural variants (SVs) are a major type of genetic variation, yet their role in human traits remains largely uncharacterized, primarily due to challenges in genotyping them on a genome-wide scale in large cohorts. Here we identified 171,233 high-quality, genome-wide SVs from 482 haplotype-resolve...

Genome-wide association studiesGenomics

10.1038/S41588-026-02612-Z

ISSN:1061-4036

Multi-ancestry genome-wide study identifies effector genes and druggable pathways for coronary artery calcification

Maryam Kavousi•Maxime M. Bos•Hanna J. Barnes•Christian L. Lino Cardenas•Doris Wong等 89 人

Nature Genetics

2023

•2023/9/28

•00 p.1-14

Coronary artery calcification (CAC), a measure of subclinical atherosclerosis, predicts future symptomatic coronary artery disease (CAD). Identifying genetic risk factors for CAC may point to new therapeutic avenues for prevention. Currently, there are only four known risk loci for CAC identified fr...

CalcificationGenome-wide association studies

10.1038/S41588-023-01518-4

ISSN:1061-4036

Genetic profiling of the circulating proteome in common diseases suggests causal proteins and improves risk prediction

Qianying Ma•Yimin Cai•Chunyi He•Yanmin Li•Caibo Ning等 20 人

Nature Communications

2025

•2025/12/12

Elucidating the genetic regulation of protein expression in specific disease states is important for understanding how genetic variation impact disease pathology. To this end, we conduct a large-scale genome-proteome-wide pQTL analysis on 2901 plasma proteins among 7626 healthy individuals and 28,06...

Gene regulationProteomicsQuantitative trait

10.1038/S41467-025-67238-X

ISSN:2041-1723

Genome-wide association meta-analysis of spontaneous coronary artery dissection identifies risk variants and genes related to artery integrity and tissue-mediated coagulation

David Adlam•Takiy-Eddine Berrandou•Adrien Georges•Christopher P. Nelson•Eleni Giannoulatou等 52 人

Nature Genetics

2023

•2023/5/29

•00 p.1-9

Spontaneous coronary artery dissection (SCAD) is an understudied cause of myocardial infarction primarily affecting women. It is not known to what extent SCAD is genetically distinct from other cardiovascular diseases, including atherosclerotic coronary artery disease (CAD). Here we present a genome...

Genome-wide association studiesMyocardial infarction

10.1038/S41588-023-01410-1

ISSN:1061-4036

Validation of human telomere length multi-ancestry meta-analysis association signals identifies POP5 and KBTBD6 as human telomere length regulation genes

Rebecca Keener•Surya B. Chhetri•Carla J. Connelly•Margaret A. Taub•Matthew P. Conomos等 98 人

Nature Communications

2024

•2024/5/24

•Vol.15 No.1 p.1-21

Genome-wide association studies (GWAS) have become well-powered to detect loci associated with telomere length. However, no prior work has validated genes nominated by GWAS to examine their role in telomere length regulation. We conducted a multi-ancestry meta-analysis of 211,369 individuals and ide...

AgeingGenetic variationGenome-wide association studiesQuantitative trait loci

10.1038/S41467-024-48394-Y

ISSN:2041-1723

An integrative ENCODE resource for cancer genomics

Jing Zhang•Donghoon Lee•Vineet Dhiman•Peng Jiang•Jie Xu等 58 人

Nature Communications

2020

•2020/7/29

•Vol.11 No.1 p.1-11

ENCODE comprises thousands of functional genomics datasets, and the encyclopedia covers hundreds of cell types, providing a universal annotation for genome interpretation. However, for particular applications, it may be advantageous to use a customized annotation. Here, we develop such a custom anno...

Cancer genomicsData integrationGene regulatory networks

10.1038/S41467-020-14743-W

ISSN:2041-1723

Quantifying negative selection in human 3ʹ UTRs uncovers constrained targets of RNA-binding proteins

Scott D. Findlay•Lindsay Romo•Christopher B. Burge

Nature Communications

2024

•2024/1/2

•Vol.15 No.1 p.1-15

Many non-coding variants associated with phenotypes occur in 3ʹ untranslated regions (3ʹ UTRs), and may affect interactions with RNA-binding proteins (RBPs) to regulate gene expression post-transcriptionally. However, identifying functional 3ʹ UTR variants has proven difficult. We use allele fr...

Genetic variationMolecular biologyMolecular evolution

10.1038/S41467-023-44456-9

ISSN:2041-1723

Genomic landscape of multiple myeloma and its precursor conditions

Jean-Baptiste Alberge•Ankit K. Dutta•Andrea Poletti•Tim H. H. Coorens•Elizabeth D. Lightbody等 38 人

Nature Genetics

2025

•2025/5/21

•00 p.1-11

Reliable strategies to capture patients at risk of progression from precursor stages of multiple myeloma (MM) to overt disease are still missing. We assembled a comprehensive collection of MM genomic data comprising 1,030 patients (218 with precursor conditions) that we used to identify recurrent co...

GenomicsMyeloma

10.1038/S41588-025-02196-0

ISSN:1061-4036

Single-cell long-read sequencing-based mapping reveals specialized splicing patterns in developing and adult mouse and human brain

Anoushka Joglekar•Wen Hu•Bei Zhang•Oleksandr Narykov•Mark Diekhans等 15 人

Nature Neuroscience

2024

•2024/4/9

•00 p.1-13

RNA isoforms influence cell identity and function. However, a comprehensive brain isoform map was lacking. We analyze single-cell RNA isoforms across brain regions, cell subtypes, developmental time points and species. For 72% of genes, full-length isoform expression varies along one or more axes. S...

Computational modelsGenetics of the nervous systemRNA splicing

10.1038/S41593-024-01616-4

ISSN:1097-6256

The chronODE framework for modelling multi-omic time series with ordinary differential equations and machine learning

Beatrice Borsari•Mor Frank•Eve S. Wattenberg•Ke Xu•Susanna X. Liu等 7 人

Nature Communications

2025

•2025/8/19

•Vol.16 No.1 p.1-16

Many genome-wide studies capture isolated moments in cell differentiation or organismal development. Conversely, longitudinal studies provide a more direct way to study these kinetic processes. Here, we present an approach for modeling gene-expression and chromatin kinetics from such studies: chronO...

Computational modelsMachine learning

10.1038/S41467-025-61921-9

ISSN:2041-1723

Human genome-wide measurement of drug-responsive regulatory activity

Graham D. Johnson•Alejandro Barrera•Ian C. McDowell•Anthony M. D’Ippolito•William H. Majoros等 9 人

Nature Communications

2018

•2018/12/21

•Vol.9 No.1 p.1-9

Environmental stimuli commonly act via changes in gene regulation. Human-genome-scale assays to measure such responses are indirect or require knowledge of the transcription factors (TFs) involved. Here, we present the use of human genome-wide high-throughput reporter assays to measure environmental...

EpigenomicsTranscriptional regulatory elements

10.1038/S41467-018-07607-X

ISSN:2041-1723

Long non-coding RNA HIF1A-As2 and MYC form a double-positive feedback loop to promote cell proliferation and metastasis in KRAS-driven non-small cell lung cancer

Yang Kaixin•Zhang Wenyang•Zhong Linghui•Xiao Yinan•Sahoo Sudhakar等 10 人

Cell Death & Differentiation

2023

•2023/4/11

•00 p.1-17

Lung cancer is the leading cause of cancer-related deaths worldwide. KRAS is the main oncogenic driver in lung cancer that can be activated by gene mutation or amplification, but whether long non-coding RNAs (lncRNAs) regulate its activation remains unknown. Through gain and loss of function approac...

Genetics researchMetastasis

10.1038/S41418-023-01160-X

ISSN:1350-9047

Promoter-proximal CTCF binding promotes distal enhancer-dependent gene activation

Naoki Kubo•Haruhiko Ishii•Xiong Xiong•Simona Bianco•Franz Meitinger等 16 人

Nature Structural & Molecular Biology

2021

•2021/1/4

•Vol.28 No.2 p.152-161

The CCCTC-binding factor (CTCF) works together with the cohesin complex to drive the formation of chromatin loops and topologically associating domains, but its role in gene regulation has not been fully defined. Here, we investigated the effects of acute CTCF loss on chromatin architecture and tran...

Chromatin structureEpigeneticsEpigenomicsTranscription

10.1038/S41594-020-00539-5

ISSN:1545-9993

Dynamic changes in the epigenomic landscape regulate human organogenesis and link to developmental disorders

Dave T. Gerrard•Andrew A. Berry•Rachel E. Jennings•Matthew J. Birket•Peyman Zarrineh等 17 人

Nature Communications

2020

•2020/8/6

•Vol.11 No.1 p.1-15

How the genome activates or silences transcriptional programmes governs organ formation. Little is known in human embryos undermining our ability to benchmark the fidelity of stem cell differentiation or cell programming, or interpret the pathogenicity of noncoding variation. Here, we study histone ...

AnatomyOrganogenesis

10.1038/S41467-020-17305-2

ISSN:2041-1723

Predictive analyses of regulatory sequences with EUGENe

Adam Klie•David Laub•James V. Talwar•Hayden Stites•Tobias Jores等 8 人

Nature Computational Science

2023

•2023/11/16

•00 p.1-11

Deep learning has become a popular tool to study cis-regulatory function. Yet efforts to design software for deep-learning analyses in regulatory genomics that are findable, accessible, interoperable and reusable (FAIR) have fallen short of fully meeting these criteria. Here we present elucidating t...

Genome informaticsMachine learningSoftware

10.1038/S43588-023-00544-W

ISSN:2662-8457

Machine learning uncovers cell identity regulator by histone code

Bo Xia•Dongyu Zhao•Guangyu Wang•Min Zhang•Jie Lv等 13 人

Nature Communications

2020

•2020/6/1

•Vol.11 No.1 p.1-12

Conversion between cell types, e.g., by induced expression of master transcription factors, holds great promise for cellular therapy. Our ability to manipulate cell identity is constrained by incomplete information on cell identity genes (CIGs) and their expression regulation. Here, we develop CEFCI...

Data miningDifferentiation

10.1038/S41467-020-16539-4

ISSN:2041-1723

Multi-organ AI endophenotypes chart the heterogeneity of brain, eye and heart pan-disease

Aleix Boquet-Pujadas•Filippos Anagnostakis•Zhijian Yang•Ye Ella Tian•Michael R. Duggan等 14 人

Nature Mental Health

2026

•2026/1/6

•Vol.4 No.2 p.203-230

Disease heterogeneity and commonality pose critical challenges to precision medicine, as traditional approaches frequently focus on single disease entities and overlook shared mechanisms across conditions. Here, inspired by pan-cancer and multi-organ research, we introduce the concept of ‘pan-diseas...

Computational modelsGenetics research

10.1038/S44220-025-00560-X

ISSN:2731-6076

Integrative genomic analyses of promoter G-quadruplexes reveal their selective constraint and association with gene activation

Guangyue Li•Gongbo Su•Yunxuan Wang•Wenmeng Wang•Jinming Shi等 7 人

Communications Biology

2023

•2023/6/10

•Vol.6 No.1 p.1-17

G-quadruplexes (G4s) regulate DNA replication and gene transcription, and are enriched in promoters without fully appreciated functional relevance. Here we show high selection pressure on putative G4 (pG4) forming sequences in promoters through investigating genetic and genomic data. Analyses of 76,...

Functional genomicsGenome informatics

10.1038/S42003-023-05015-6

ISSN:2399-3642

Crosstalk between RNA m6A and DNA methylation regulates transposable element chromatin activation and cell fate in human pluripotent stem cells

Tongyu Sun•Yueyuan Xu•Yu Xiang•Jianhong Ou•Erik J. Soderblom等 6 人

Nature Genetics

2023

•2023/7/20

•00 p.1-12

Transposable elements (TEs) are parasitic DNA sequences accounting for over half of the human genome. Tight control of the repression and activation states of TEs is critical for genome integrity, development, immunity and diseases, including cancer. However, precisely how this regulation is achieve...

Cell biologyEpigenomics

10.1038/S41588-023-01452-5

ISSN:1061-4036

DeepSTARR predicts enhancer activity from DNA sequence and enables the de novo design of synthetic enhancers

de Almeida Bernardo P.•Reiter Franziska•Pagani Michaela•Stark Alexander

Nature Genetics

2022

•2022/5/12

•00 p.1-12

Enhancer sequences control gene expression and comprise binding sites (motifs) for different transcription factors (TFs). Despite extensive genetic and computational studies, the relationship between DNA sequence and regulatory activity is poorly understood, and de novo enhancer design has been chal...

Computational biology and bioinformaticsGene regulationHigh-throughput screeningMutagenesis

10.1038/S41588-022-01048-5

ISSN:1061-4036

Data navigation on the ENCODE portal

Meenakshi S. Kagda•Bonita Lam•Casey Litton•Corinn Small•Cricket A. Sloan等 29 人

Nature Communications

2025

•2025/10/30

•Vol.16 No.1 p.1-11

Spanning two decades, the collaborative ENCODE project aims to identify all the functional elements within human and mouse genomes. To best serve the scientific community, the comprehensive ENCODE data including results from 23,000+ functional genomics experiments, 800+ functional elements character...

Data miningGenetic databasesGenomic analysis

10.1038/S41467-025-64343-9

ISSN:2041-1723

Multiomics data integration unveils core transcriptional regulatory networks governing cell-type identity

Sascha Jung•Antonio del Sol

Npj Systems Biology And Applications

2020

•2020/8/24

•Vol.6 No.1 p.1-4

A plethora of computational approaches have been proposed for reconstructing gene regulatory networks (GRNs) from gene expression data. However, gene regulatory processes are often too complex to predict from the transcriptome alone. Here, we present a computational method, Moni, that systematically...

Molecular biologySoftware

10.1038/S41540-020-00148-4

ISSN:2056-7189

Genome-wide DNA methylation profiling in blood reveals epigenetic signature of incident acute coronary syndrome

Pinpin Long•Jiahui Si•Ziwei Zhu•Yi Jiang•Yufei Wang等 30 人

Nature Communications

2024

•2024/8/28

•Vol.15 No.1 p.1-11

DNA methylation (DNAm) has been implicated in acute coronary syndrome (ACS), but the causality remains unclear in cross-sectional studies. Here, we conduct a prospective epigenome-wide association study of incident ACS in two Chinese cohorts (discovery: 751 nested case-control pairs; replication: 47...

Acute coronary syndromesMolecular medicine

10.1038/S41467-024-51751-6

ISSN:2041-1723

A leukemia-protective germline variant mediates chromatin module formation via transcription factor nucleation

Llimos Gerard•Gardeux Vincent•Koch Ute•Kribelbauer Judith F.•Hafner Antonina等 21 人

Nature Communications

2022

•2022/4/19

•Vol.13 No.1 p.1-21

Non-coding variants coordinate transcription factor (TF) binding and chromatin mark enrichment changes over regions spanning >100 kb. These molecularly coordinated regions are named “variable chromatin modules” (VCMs), providing a conceptual framework of how regulatory variation might shape compl...

Chronic lymphocytic leukaemiaGene regulation

10.1038/S41467-022-29625-6

ISSN:2041-1723

EPInformer: scalable and integrative prediction of gene expression from promoter-enhancer sequences with multimodal epigenomic profiles

Jiecong Lin•Zhijian Li•Yajie Zhao•Ruibang Luo•Luca Pinello

Nature Communications

2026

•2026/3/14

Transcriptional regulation, critical for cellular differentiation and adaptation to environmental changes, involves coordinated interactions among DNA sequences, regulatory proteins, and chromatin architecture. Despite extensive chromatin profiles and gene expression data from consortia, understandi...

Computational modelsMachine learning

10.1038/S41467-026-70535-8

ISSN:2041-1723

Super-silencers are crucial for development and carcinogenesis in B cells

Di Huang•Hanna M. Petrykowska•Dhaneshwar Kumar•Lela Kardava•Susan Moir等 8 人

Nature Communications

2025

•2025/9/25

•Vol.16 No.1 p.1-16

The strength of the repressive histone H3K27me3 signal varies across silencers. Focusing on regions with unusually strong signals—super-silencers—we show that B-cell super-silencers are initially linked to gene upregulation in development, with target genes highly expressed in stem cells. About 13% ...

Cancer genomicsGene regulationGene regulatory networks

10.1038/S41467-025-63329-X

ISSN:2041-1723

Replication-stress-induced chromatin loops protect fork stability

Vincent Gaggioli•Kaustav Sengupta•Ashutosh Choudhury•Joanna Paulson•Raviprasad Kuthethur等 25 人

Nature

2026

•2026/7/1

•00 p.1-13

Replication stress poses a major threat to genome integrity, yet how higher-order chromatin organization contributes to replication fork protection remains unclear1,2. Here we show that replication stress induces the formation of transient chromatin loops that enclose de novo heterochromatin-enriche...

Chromatin structureStalled forks

10.1038/S41586-026-10695-1

ISSN:0028-0836

Single-cell eQTL mapping of human endogenous retroviruses reveals cell type-specific genetic regulation in autoimmune diseases

Fan Zhu•Yi Liu•Jiehao Lei•Xinxing Li•Zexu Jiang等 8 人

Nature Communications

2025

•2025/8/14

•Vol.16 No.1 p.1-14

Human endogenous retroviruses constitute a significant portion of the human genome and play complex roles in gene regulation and disease processes. However, the expression pattern and disease associations of specific retroviral loci remain pooly understood. This study examines the expression and reg...

Autoimmune diseasesDisease geneticsRetrovirus

10.1038/S41467-025-62779-7

ISSN:2041-1723

SMARCE1 promotes neuroblastoma tumorigenesis through assisting MYCN-mediated transcriptional activation

Hu Xiaosong•Liu Ruochen•Hou Jianbing•Peng Wen•Wan Sicheng等 11 人

Oncogene

2022

•2022/8/17

•Vol.41 No.37 p.4295-4306

SMARCE1 gene, encoding a core subunit of SWI/SNF chromatin remodeling complex, is situated on chromosome 17q21-ter region that is frequently gained in neuroblastoma. However, its role in the tumorigenesis remains unknown. Here, we showed that high expression of SMARCE1 was associated with poor progn...

Cell growthPaediatric cancerTranscriptionTumour biomarkers

10.1038/S41388-022-02428-1

ISSN:0950-9232

A rare variant of African ancestry activates 8q24 lncRNA hub by modulating cancer associated enhancer

Kaivalya Walavalkar•Bharath Saravanan•Anurag Kumar Singh•Ranveer Singh Jayani•Ashwin Nair等 14 人

Nature Communications

2020

•2020/7/17

•Vol.11 No.1 p.1-14

Genetic variation at the 8q24 locus is linked with the greater susceptibility to prostate cancer in men of African ancestry. One such African ancestry specific rare variant, rs72725854 (A>G/T) (~6% allele frequency) has been associated with a ~2-fold increase in prostate cancer risk. However, the fu...

Cancer epigeneticsChromatin structureFunctional genomics

10.1038/S41467-020-17325-Y

ISSN:2041-1723

Identification and analysis of splicing quantitative trait loci across multiple tissues in the human genome

Diego Garrido-Martín•Beatrice Borsari•Miquel Calvo•Ferran Reverter•Roderic Guigó

Nature Communications

2021

•2021/2/1

•Vol.12 No.1 p.1-16

Alternative splicing (AS) is a fundamental step in eukaryotic mRNA biogenesis. Here, we develop an efficient and reproducible pipeline for the discovery of genetic variants that affect AS (splicing QTLs, sQTLs). We use it to analyze the GTEx dataset, generating a comprehensive catalog of sQTLs in th...

Computational biology and bioinformaticsTranscriptomics

10.1038/S41467-020-20578-2

ISSN:2041-1723

DNMT3B supports meso-endoderm differentiation from mouse embryonic stem cells

Lauria Andrea•Meng Guohua•Proserpio Valentina•Rapelli Stefania•Maldotti Mara等 15 人

Nature Communications

2023

•2023/1/23

•Vol.14 No.1 p.1-18

The correct establishment of DNA methylation patterns during mouse early development is essential for cell fate specification. However, the molecular targets as well as the mechanisms that determine the specificity of the de novo methylation machinery during differentiation are not completely elucid...

DifferentiationEmbryonic stem cellsEpigenetic memory

10.1038/S41467-023-35938-X

ISSN:2041-1723

Identification and characterization of constrained non-exonic bases lacking predictive epigenomic and transcription factor binding annotations

Olivera Grujic•Tanya N. Phung•Soo Bin Kwon•Adriana Arneson•Yuju Lee等 7 人

Nature Communications

2020

•2020/12/2

•Vol.11 No.1 p.1-16

Annotations of evolutionary sequence constraint based on multi-species genome alignments and genome-wide maps of epigenomic marks and transcription factor binding provide important complementary information for understanding the human genome and genetic variation. Here we developed the Constrained N...

BioinformaticsComparative genomicsComputational biology and bioinformaticsEpigenomics

10.1038/S41467-020-19962-9

ISSN:2041-1723

scMultiMap: Cell-type-specific mapping of enhancers and target genes from single-cell multimodal data

Chang Su•Dongsoo Lee•Peng Jin•Jingfei Zhang

Nature Communications

2025

•2025/4/26

•Vol.16 No.1 p.1-12

Mapping enhancers and target genes in disease-related cell types provides critical insights into the functional mechanisms of genome-wide association studies (GWAS) variants. Single-cell multimodal data, which measure gene expression and chromatin accessibility in the same cells, enable the cell-typ...

EpigeneticsGene regulationGene regulatory networksStatistical methods

10.1038/S41467-025-59306-Z

ISSN:2041-1723

DNA methylation atlas of the mouse brain at single-cell resolution

Liu Hanqing•Zhou Jingtian•Tian Wei•Luo Chongyuan•Bartlett Anna等 29 人

Nature

2021

•2021/10/6

•Vol.598 No.7879 p.120-128

Mammalian brain cells show remarkable diversity in gene expression, anatomy and function, yet the regulatory DNA landscape underlying this extensive heterogeneity is poorly understood. Here we carry out a comprehensive assessment of the epigenomes of mouse brain cell types by applying single-nucleus...

Cellular neuroscienceDNA methylationEpigenetics in the nervous systemEpigenomics

10.1038/S41586-020-03182-8

ISSN:0028-0836

Disrupting the phase separation of KAT8–IRF1 diminishes PD-L1 expression and promotes antitumor immunity

Wu Yuanzhong•Zhou Liwen•Zou Yezi•Zhang Yijun•Zhang Meifang等 17 人

Nature Cancer

2023

•2023/3/9

•Vol.4 No.3 p.382-400

Immunotherapies targeting the PD-1/PD-L1 axis have become first-line treatments in multiple cancers. However, only a limited subset of individuals achieves durable benefits because of the elusive mechanisms regulating PD-1/PD-L1. Here, we report that in cells exposed to interferon-γ (IFNγ), KAT8 und...

AcetylationCancerCancer therapyGene regulationTumour immunology

10.1038/S43018-023-00522-1

ISSN:2662-1347

Single-cell parallel analysis of DNA damage and transcriptome reveals selective genome vulnerability

Dongsheng Bai•Zhenkun Cao•Nivedita Attada•Jinghui Song•Chenxu Zhu

Nature Methods

2025

•2025/3/24

•00 p.1-11

Maintenance of genome integrity is paramount to molecular programs in multicellular organisms. Throughout the lifespan, various endogenous and environmental factors pose persistent threats to the genome, which can result in DNA damage. Understanding the functional consequences of DNA damage requires...

Biological techniquesMolecular biology

10.1038/S41592-025-02632-3

ISSN:1548-7091

Nucleotide Transformer: building and evaluating robust foundation models for human genomics

Hugo Dalla-Torre•Liam Gonzalez•Javier Mendoza-Revilla•Nicolas Lopez Carranza•Adam Henryk Grzywaczewski等 15 人

Nature Methods

2024

•2024/11/28

•00 p.1-11

The prediction of molecular phenotypes from DNA sequences remains a longstanding challenge in genomics, often driven by limited annotated data and the inability to transfer learnings between tasks. Here, we present an extensive study of foundation models pre-trained on DNA sequences, named Nucleotid...

GenomicsMachine learningSoftware

10.1038/S41592-024-02523-Z

ISSN:1548-7091

Whole-genome sequencing analysis of suicide deaths integrating brain-regulatory eQTLs data to identify risk loci and genes

Seonggyun Han•Emily DiBlasi•Eric T. Monson•Andrey Shabalin•Elliott Ferris等 19 人

Molecular Psychiatry

2023

•2023/10/4

•00 p.1-11

Recent large-scale genome-wide association studies (GWAS) have started to identify potential genetic risk loci associated with risk of suicide; however, a large portion of suicide-associated genetic factors affecting gene expression remain elusive. Dysregulated gene expression, not assessed by GWAS,...

GeneticsNeuroscience

10.1038/S41380-023-02282-X

ISSN:1359-4184

Ultraconserved enhancer function does not require perfect sequence conservation

Valentina Snetkova•Athena R. Ypsilanti•Jennifer A. Akiyama•Brandon J. Mannion•Ingrid Plajzer-Frick等 21 人

Nature Genetics

2021

•2021/3/29

•00 p.1-8

Ultraconserved enhancer sequences show perfect conservation between human and rodent genomes, suggesting that their functions are highly sensitive to mutation. However, current models of enhancer function do not sufficiently explain this extreme evolutionary constraint. We subjected 23 ultraconserve...

Functional genomicsGene regulationGenomics

10.1038/S41588-021-00812-3

ISSN:1061-4036

Min Qin•Xiaoxue Tian•Qili Wu•Qian Zhu•Meiling Yu等 13 人

Nature Communications

2025

•2025/12/12

Adverse outcomes including myocardial infarction (MI) and stroke render coronary artery disease (CAD) a leading cause of death worldwide. DNA methylation markers may alert such adversity ahead of the events. We profiled DNA methylation of blood leukocytes in 933 Chinese CAD patients with up-to-13-ye...

Cardiovascular diseasesPrognostic markers

10.1038/S41467-025-66204-X

ISSN:2041-1723

An epigenome atlas of neural progenitors within the embryonic mouse forebrain

Rhodes Christopher T.•Thompson Joyce J.•Mitra Apratim•Asokumar Dhanya•Lee Dongjin R.等 11 人

Nature Communications

2022

•2022/7/20

•Vol.13 No.1 p.1-17

A comprehensive characterization of epigenomic organization in the embryonic mouse forebrain will enhance our understanding of neurodevelopment and provide insight into mechanisms of neurological disease. Here we collected single-cell chromatin accessibility profiles from four distinct neurogenic re...

Developmental neurogenesisEpigenetics and plasticityNeuronal development

10.1038/S41467-022-31793-4

ISSN:2041-1723

Functional variants at 1p36.23 confer risk of schizophrenia through modulating RERE

Yixing Liu•Junyang Wang•Hong Yang•Yifan Li•Changgai Mu等 16 人

Nature Communications

2026

•2026/1/24

•Vol.17 No.1 p.17420

Genome-wide association studies have identified 1p36.23 as a schizophrenia risk locus. However, the functional variants and genes driving the association remain unknown. Here, we identified two functional variants (i.e., rs159961 and rs301792) at the 1p36.23 risk locus. Both variants reside introns ...

Disease geneticsFunctional genomicsGenetics of the nervous systemSchizophrenia

10.1038/S41467-026-68449-6

ISSN:2041-1723

Context transcription factors establish cooperative environments and mediate enhancer communication

Judith F. Kribelbauer-Swietek•Olga Pushkarev•Vincent Gardeux•Katerina Faltejskova•Julie Russeil等 7 人

Nature Genetics

2024

•2024/10/3

•00 p.1-14

Many enhancers control gene expression by assembling regulatory factor clusters, also referred to as condensates. This process is vital for facilitating enhancer communication and establishing cellular identity. However, how DNA sequence and transcription factor (TF) binding instruct the formation o...

Computational biology and bioinformaticsFunctional genomicsGene regulationMolecular biology

10.1038/S41588-024-01892-7

ISSN:1061-4036

Retrospective analysis of enhancer activity and transcriptome history

Boers Ruben•Boers Joachim•Tan Beatrice•van Leeuwen Marieke E.•Wassenaar Evelyne等 14 人

Nature Biotechnology

2023

•2023/2/23

•00 p.1-11

Cell state changes in development and disease are controlled by gene regulatory networks, the dynamics of which are difficult to track in real time. In this study, we used an inducible DCM–RNA polymerase subunit b fusion protein which labels active genes and enhancers with a bacterial methylation ma...

Assay systemsStem-cell differentiationTime seriesTranscriptomics

10.1038/S41587-023-01683-1

ISSN:1087-0156

Natural Killer cells demonstrate distinct eQTL and transcriptome-wide disease associations, highlighting their role in autoimmunity

Gilchrist James J.•Makino Seiko•Naranbhai Vivek•Sharma Piyush K.•Koturan Surya等 18 人

Nature Communications

2022

•2022/7/14

•Vol.13 No.1 p.1-13

Natural Killer cells are innate lymphocytes with central roles in immunosurveillance and are implicated in autoimmune pathogenesis. The degree to which regulatory variants affect Natural Killer cell gene expression is poorly understood. Here we perform expression quantitative trait locus mapping of ...

Disease geneticsGene regulationInnate immunityQuantitative trait

10.1038/S41467-022-31626-4

ISSN:2041-1723

Effective gene expression prediction from sequence by integrating long-range interactions

Avsec Žiga•Agarwal Vikram•Visentin Daniel•Ledsam Joseph R.•Grabska-Barwinska Agnieszka等 10 人

Nature Methods

2021

•2021/10/4

•Vol.18 No.10 p.1196-1203

How noncoding DNA determines gene expression in different cell types is a major unsolved problem, and critical downstream applications in human genetics depend on improved solutions. Here, we report substantially improved gene expression prediction accuracy from DNA sequences through the use of a de...

Gene expressionMachine learningSoftwareTranscriptomics

10.1038/S41592-021-01252-X

ISSN:1548-7091

Decoding gene regulation in the fly brain

Janssens Jasper•Aibar Sara•Taskiran Ibrahim Ihsan•Ismail Joy N.•Gomez Alicia Estacio等 19 人

Nature

2022

•2022/1/5

•00 p.1-7

The Drosophila brain is a frequently used model in neuroscience. Single-cell transcriptome analysis1–6, three-dimensional morphological classification7 and electron microscopy mapping of the connectome8,9 have revealed an immense diversity of neuronal and glial cell types that underlie an array of f...

Cellular neuroscienceDevelopmental neurogenesisGene regulationGene regulatory networks

10.1038/S41586-021-04262-Z

ISSN:0028-0836

A cytosolic surveillance mechanism activates the mitochondrial UPR

F. X. Reymond Sutandy•Ines Gößner•Georg Tascher•Christian Münch

Nature

2023

•2023/6/7

•Vol.618 No.7966 p.849-854

The mitochondrial unfolded protein response (UPRmt) is essential to safeguard mitochondria from proteotoxic damage by activating a dedicated transcriptional response in the nucleus to restore proteostasis1,2. Yet, it remains unclear how the information on mitochondria misfolding stress (MMS) is sign...

ChaperonesMitochondriaProtein aggregationStress signalling

10.1038/S41586-023-06142-0

ISSN:0028-0836

Mitochondrial clonal mosaicism encodes a biphasic molecular clock of aging

Zhenguo Wang•Zhe Li•Hongyu Liu•Chenghua Yang•Xin Li

Nature Aging

2025

•2025/5/27

•00 p.1-15

Mitochondria rapidly accumulate mutations throughout a lifetime, potentially acting as a molecular clock for aging and disease. We profiled mitochondrial RNA across 47 human tissues from 838 individuals, revealing rapid development of clonal mosaicism with two distinct tissue-specific aging signatur...

BiomarkersGenetics

10.1038/S43587-025-00890-6

ISSN:2662-8465

The transcriptional regulator ZNF398 mediates pluripotency and epithelial character downstream of TGF-beta in human PSCs

Irene Zorzan•Marco Pellegrini•Mattia Arboit•Danny Incarnato•Mara Maldotti等 11 人

Nature Communications

2020

•2020/5/12

•Vol.11 No.1 p.1-16

Human pluripotent stem cells (hPSCs) have the capacity to give rise to all differentiated cells of the adult. TGF-beta is used routinely for expansion of conventional hPSCs as flat epithelial colonies expressing the transcription factors POU5F1/OCT4, NANOG, SOX2. Here we report a global analysis of ...

Embryonic stem cellsGrowth factor signallingPluripotencyReprogramming

10.1038/S41467-020-16205-9

ISSN:2041-1723

CRISPR tiling deletion screens reveal functional enhancers and allelic compensation effects (ACE) on SIN3A transcription

Xingjie Ren•Lina Zheng•Yuxi Liu•Lenka Maliskova•Tsz Wai Tam等 14 人

Nature Communications

2026

•2026/3/25

Precise transcriptional regulation is critical for cellular function and development, yet the mechanism of this process remains poorly understood for many genes. To gain a deeper understanding of the regulation of neuropsychiatric disease risk genes, we identify a total of 39 functional enhancers fo...

CRISPR-Cas9 genome editingFunctional genomicsTranscriptional regulatory elements

10.1038/S41467-026-70933-Y

ISSN:2041-1723

Unveiling causal regulatory mechanisms through cell-state parallax

Alexander P. Wu•Rohit Singh•Christopher A. Walsh•Bonnie Berger

Nature Communications

2025

•2025/8/29

•Vol.16 No.1 p.1-15

Genome-wide association studies (GWAS) identify numerous disease-linked genetic variants at noncoding genomic loci, yet therapeutic progress is hampered by the challenge of deciphering the regulatory roles of these loci in tissue-specific contexts. Single-cell multimodal assays that simultaneously p...

Machine learningTranscriptional regulatory elements

10.1038/S41467-025-61337-5

ISSN:2041-1723

USF2 and TFEB compete in regulating lysosomal and autophagy genes

Jaebeom Kim•Young Suk Yu•Yehwa Choi•Do Hui Lee•Soobin Han等 13 人

Nature Communications

2024

•2024/9/27

•Vol.15 No.1 p.1-17

Autophagy, a highly conserved self-digestion process crucial for cellular homeostasis, is triggered by various environmental signals, including nutrient scarcity. The regulation of lysosomal and autophagy-related processes is pivotal to maintaining cellular homeostasis and basal metabolism. The cons...

AutophagyChromatinEpigeneticsTranscription

10.1038/S41467-024-52600-2

ISSN:2041-1723

Machine learning prediction of prime editing efficiency across diverse chromatin contexts

Nicolas Mathis•Ahmed Allam•András Tálas•Lucas Kissling•Elena Benvenuto等 15 人

Nature Biotechnology

2024

•2024/6/21

•00 p.1-8

The success of prime editing depends on the prime editing guide RNA (pegRNA) design and target locus. Here, we developed machine learning models that reliably predict prime editing efficiency. PRIDICT2.0 assesses the performance of pegRNAs for all edit types up to 15 bp in length in mismatch repair-...

ChromatinEpigeneticsGenetic engineeringHigh-throughput screeningMachine learning

10.1038/S41587-024-02268-2

ISSN:1087-0156

KARR-seq reveals cellular higher-order RNA structures and RNA–RNA interactions

Tong Wu•Anthony Youzhi Cheng•Yuexiu Zhang•Jiayu Xu•Jinjun Wu等 15 人

Nature Biotechnology

2024

•2024/1/18

•00 p.1-12

RNA fate and function are affected by their structures and interactomes. However, how RNA and RNA-binding proteins (RBPs) assemble into higher-order structures and how RNA molecules may interact with each other to facilitate functions remain largely unknown. Here we present KARR-seq, which uses N3-k...

RNARNA metabolismRNA sequencing

10.1038/S41587-023-02109-8

ISSN:1087-0156

Noncoding variants alter GATA2 expression in rhombomere 4 motor neurons and cause dominant hereditary congenital facial paresis

Alan P. Tenney•Silvio Alessandro Di Gioia•Bryn D. Webb•Wai-Man Chan•Elke de Boer等 58 人

Nature Genetics

2023

•2023/6/29

•00 p.1-15

Hereditary congenital facial paresis type 1 (HCFP1) is an autosomal dominant disorder of absent or limited facial movement that maps to chromosome 3q21-q22 and is hypothesized to result from facial branchial motor neuron (FBMN) maldevelopment. In the present study, we report that HCFP1 results from ...

Gene regulationNeurodevelopmental disordersNeurogenesisNeurological disordersTranscriptomics

10.1038/S41588-023-01424-9

ISSN:1061-4036

Increased enhancer–promoter interactions during developmental enhancer activation in mammals

Zhuoxin Chen•Valentina Snetkova•Grace Bower•Sandra Jacinto•Benjamin Clock等 14 人

Nature Genetics

2024

•2024/3/20

•00 p.1-11

Remote enhancers are thought to interact with their target promoters via physical proximity, yet the importance of this proximity for enhancer function remains unclear. Here we investigate the three-dimensional (3D) conformation of enhancers during mammalian development by generating high-resolution...

EpigenomicsGene regulation

10.1038/S41588-024-01681-2

ISSN:1061-4036

Supervised enhancer prediction with epigenetic pattern recognition and targeted validation

Anurag Sethi•Mengting Gu•Emrah Gumusgoz•Landon Chan•Koon-Kiu Yan等 25 人

Nature Methods

2020

•2020/7/29

•Vol.17 No.8 p.807-814

Enhancers are important non-coding elements, but they have traditionally been hard to characterize experimentally. The development of massively parallel assays allows the characterization of large numbers of enhancers for the first time. Here, we developed a framework using Drosophila STARR-seq to c...

Computational modelsEpigeneticsGene regulationStatistical methods

10.1038/S41592-020-0907-8

ISSN:1548-7091

BET bromodomain inhibitors regulate keratinocyte plasticity

Gabi Schutzius•Christian Kolter•Sebastian Bergling•Federico Tortelli•Florian Fuchs等 51 人

Nature Chemical Biology

2021

•2021/1/18

•Vol.17 No.3 p.280-290

Although most acute skin wounds heal rapidly, non-healing skin ulcers represent an increasing and substantial unmet medical need that urgently requires effective therapeutics. Keratinocytes resurface wounds to re-establish the epidermal barrier by transitioning to an activated, migratory state, but ...

Post-translational modificationsScreeningSmall moleculesStem cells

10.1038/S41589-020-00716-Z

ISSN:1552-4450

The pancancer overexpressed NFYC Antisense 1 controls cell cycle mitotic progression through in cis and in trans modes of action

Cecilia Pandini•Giulia Pagani•Martina Tassinari•Emanuele Vitale•Eugenia Bezzecchi等 12 人

Cell Death & Disease

2024

•2024/3/11

•Vol.15 No.3 p.1-14

Antisense RNAs (asRNAs) represent an underappreciated yet crucial layer of gene expression regulation. Generally thought to modulate their sense genes in cis through sequence complementarity or their act of transcription, asRNAs can also regulate different molecular targets in trans, in the nucleus ...

Long non-coding RNAsNon-small-cell lung cancerSmall-cell lung cancer

10.1038/S41419-024-06576-Y

ISSN:2041-4889

Response splicing quantitative trait loci in primary human chondrocytes identify putative osteoarthritis risk genes

Seyoun Byun•Jacqueline Shine•Philip Coryell•Nicole E. Kramer•Susan D’Costa等 11 人

Nature Communications

2025

•2025/8/26

•Vol.16 No.1 p.1-17

Osteoarthritis affects millions worldwide, yet effective treatments remain elusive due to poorly understood molecular mechanisms. While genome-wide association studies (GWAS) have identified hundreds of osteoarthritis-associated loci, identifying the genes impacted at each locus remains challenging....

CartilageRNA splicing

10.1038/S41467-025-63299-0

ISSN:2041-1723

PARP14 inhibition restores PD-1 immune checkpoint inhibitor response following IFNγ-driven acquired resistance in preclinical cancer models

Chun Wai Wong•Christos Evangelou•Kieran N. Sefton•Rotem Leshem•Wei Zhang等 24 人

Nature Communications

2023

•2023/9/26

•Vol.14 No.1 p.1-21

Resistance mechanisms to immune checkpoint blockade therapy (ICBT) limit its response duration and magnitude. Paradoxically, Interferon γ (IFNγ), a key cytokine for cellular immunity, can promote ICBT resistance. Using syngeneic mouse tumour models, we confirm that chronic IFNγ exposure confers resi...

Cancer therapeutic resistanceTumour immunology

10.1038/S41467-023-41737-1

ISSN:2041-1723

Structure-based prediction and characterization of photo-crosslinking in native protein–RNA complexes

Huijuan Feng•Xiang-Jun Lu•Suvrajit Maji•Linxi Liu•Dmytro Ustianenko等 7 人

Nature Communications

2024

•2024/3/13

•Vol.15 No.1 p.1-14

UV-crosslinking of protein and RNA in direct contacts has been widely used to study protein-RNA complexes while our understanding of the photo-crosslinking mechanisms remains poor. This knowledge gap is due to the challenge of precisely mapping the crosslink sites in protein and RNA simultaneously i...

Computational biology and bioinformaticsRNARNA-binding proteinsStructural biology

10.1038/S41467-024-46429-Y

ISSN:2041-1723

Regulation associated modules reflect 3D genome modularity associated with chromatin activity

Zheng Lina•Wang Wei

Nature Communications

2022

•2022/9/8

•Vol.13 No.1 p.1-11

The 3D genome has been shown to be organized into modules including topologically associating domains (TADs) and compartments that are primarily defined by spatial contacts from Hi-C. There exists a gap to investigate whether and how the spatial modularity of the chromatin is related to the function...

Computational biology and bioinformaticsEpigeneticsEpigenomicsFunctional clustering

10.1038/S41467-022-32911-Y

ISSN:2041-1723

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

Megan E. McNamara•Sidharth S. Jain•Kesha Oza•Vinona Muralidaran•Amber J. Kiliti等 12 人

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

Chromatin structure dynamics during the mitosis-to-G1 phase transition

Haoyue Zhang•Daniel J. Emerson•Thomas G. Gilgenast•Katelyn R. Titus•Yemin Lan等 13 人

Nature

2019

•2019/11/27

•Vol.576 No.7785 p.158-162

Features of higher-order chromatin organization—such as A/B compartments, topologically associating domains and chromatin loops—are temporarily disrupted during mitosis1,2. Because these structures are thought to influence gene regulation, it is important to understand how they are re-established af...

Chromatin structureEpigeneticsMitosis

10.1038/S41586-019-1778-Y

ISSN:0028-0836

Regulation of RNA editing by RNA-binding proteins in human cells

Giovanni Quinones-Valdez•Stephen S. Tran•Hyun-Ik Jun•Jae Hoon Bahn•Ei-Wen Yang等 13 人

Communications Biology

2019

•2019/1/14

•Vol.2 No.1 p.1-14

Adenosine-to-inosine (A-to-I) editing, mediated by the ADAR enzymes, diversifies the transcriptome by altering RNA sequences. Recent studies reported global changes in RNA editing in disease and development. Such widespread editing variations necessitate an improved understanding of the regulatory m...

Computational biology and bioinformaticsMolecular biology

10.1038/S42003-018-0271-8

ISSN:2399-3642

Functional analysis of cancer-associated germline risk variants

Laura N. Kellman•Poornima H. Neela•Suhas Srinivasan•Zurab Siprashvili•Ronald L. Shanderson等 27 人

Nature Genetics

2025

•2025/2/17

•Vol.57 No.3 p.718-728

Single-nucleotide variants (SNVs) in regulatory DNA are linked to inherited cancer risk. Massively parallel reporter assays of 4,041 SNVs linked to 13 neoplasms comprising >90% of human malignancies were performed in pertinent primary human cell types and then integrated with matching chromatin a...

CancerFunctional genomics

10.1038/S41588-024-02070-5

ISSN:1061-4036

DNA methylation at the suppressor of cytokine signaling 3 (SOCS3) gene influences height in childhood

Prachand Issarapu•Manisha Arumalla•Hannah R. Elliott•Suraj S. Nongmaithem•Alagu Sankareswaran等 25 人

Nature Communications

2023

•2023/8/25

•Vol.14 No.1 p.1-16

Human height is strongly influenced by genetics but the contribution of modifiable epigenetic factors is under-explored, particularly in low and middle-income countries (LMIC). We investigate links between blood DNA methylation and child height in four LMIC cohorts (n = 1927) and identify a robust a...

DevelopmentDNA methylationEpigenomics

10.1038/S41467-023-40607-0

ISSN:2041-1723

Multiplexed transcriptome discovery of RNA-binding protein binding sites by antibody-barcode eCLIP

Lorenz Daniel A.•Her Hsuan-Lin•Shen Kylie A.•Rothamel Katie•Hutt Kasey R.等 11 人

Nature Methods

2022

•2022/12/22

•Vol.20 No.1 p.65-69

Ultraviolet crosslinking and immunoprecipitation (CLIP) methodologies enable the identification of RNA binding sites of RNA-binding proteins (RBPs). Despite improvements in the library preparation of RNA fragments, the enhanced CLIP (eCLIP) protocol requires 4 days of hands-on time and lacks the abi...

Gene expression analysisGene regulatory networksTranscriptomics

10.1038/S41592-022-01708-8

ISSN:1548-7091

Massively parallel genomic perturbations with multi-target CRISPR interrogates Cas9 activity and DNA repair at endogenous sites

Zou Roger S.•Marin-Gonzalez Alberto•Liu Yang•Liu Hans B.•Shen Leo等 9 人

Nature Cell Biology

2022

•2022/9/5

•Vol.24 No.9 p.1433-1444

Here we present an approach that combines a clustered regularly interspaced short palindromic repeats (CRISPR) system that simultaneously targets hundreds of epigenetically diverse endogenous genomic sites with high-throughput sequencing to measure Cas9 dynamics and cellular responses at scale. This...

CRISPR-Cas9 genome editingDNA damage responseDouble-strand DNA breaks

10.1038/S41556-022-00975-Z

ISSN:1465-7392

Impact of rare non-coding variants on human diseases through alternative polyadenylation outliers

Xudong Zou•Zhaozhao Zhao•Yu Chen•Kewei Xiong•Zeyang Wang等 12 人

Nature Communications

2025

•2025/1/16

•Vol.16 No.1 p.1-17

Although rare non-coding variants (RVs) play crucial roles in complex traits and diseases, understanding their mechanisms and identifying disease-associated RVs continue to be major challenges. Here we constructed a comprehensive atlas of alternative polyadenylation (APA) outliers (aOutliers), inclu...

Data miningGene regulation

10.1038/S41467-024-55407-3

ISSN:2041-1723

The dopamine transporter antagonist vanoxerine inhibits G9a and suppresses cancer stem cell functions in colon tumors

Christopher J. Bergin•Aïcha Zouggar•Amanda Mendes da Silva•Tanguy Fenouil•Joshua R. Haebe等 13 人

Nature Cancer

2024

•2024/2/13

•00 p.1-18

Cancer stem cells (CSCs), functionally characterized by self-renewal and tumor-initiating activity, contribute to decreased tumor immunogenicity, while fostering tumor growth and metastasis. Targeting G9a histone methyltransferase (HMTase) effectively blocks CSC functions in colorectal tumors by alt...

CancerCancer stem cellsColon cancerDrug development

10.1038/S43018-024-00727-Y

ISSN:2662-1347

A pan-cancer analysis of CpG Island gene regulation reveals extensive plasticity within Polycomb target genes

Yueyuan Zheng•Guowei Huang•Tiago C. Silva•Qian Yang•Yan-Yi Jiang等 8 人

Nature Communications

2021

•2021/4/30

•Vol.12 No.1 p.1-16

CpG Island promoter genes make up more than half of human genes, and a subset regulated by Polycomb-Repressive Complex 2 (PRC2+-CGI) become DNA hypermethylated and silenced in cancer. Here, we perform a systematic analysis of CGI genes across TCGA cancer types, finding that PRC2+-CGI genes are frequ...

Cancer genomicsEpigenomics

10.1038/S41467-021-22720-0

ISSN:2041-1723

Joint profiling of histone modifications and transcriptome in single cells from mouse brain

Chenxu Zhu•Yanxiao Zhang•Yang Eric Li•Jacinta Lucero•M. Margarita Behrens等 6 人

Nature Methods

2021

•2021/2/15

•Vol.18 No.3 p.283-292

Genome-wide profiling of histone modifications can reveal not only the location and activity state of regulatory elements, but also the regulatory mechanisms involved in cell-type-specific gene expression during development and disease pathology. Conventional assays to profile histone modifications ...

EpigenomicsGenomics

10.1038/S41592-021-01060-3

ISSN:1548-7091

Chromatin environment-dependent effects of DOT1L on gene expression in male germ cells

Manon Coulée•Alberto de la Iglesia•Mélina Blanco•Clara Gobé•Clémentine Lapoujade等 12 人

Communications Biology

2025

•2025/1/28

•Vol.8 No.1 p.1-17

The H3K79 methyltransferase DOT1L is essential for multiple aspects of mammalian development where it has been shown to regulate gene expression. Here, by producing and integrating epigenomic and spike-in RNA-seq data, we decipher the molecular role of DOT1L during mouse spermatogenesis and show tha...

EpigenomicsHistone post-translational modificationsSpermatogenesis

10.1038/S42003-024-07393-X

ISSN:2399-3642

Nucleosome wrapping states encode principles of 3D genome organization

Zengqi Wen•Ruixin Fang•Ruxin Zhang•Xinqian Yu•Fanli Zhou等 6 人

Nature Communications

2025

•2025/1/3

•Vol.16 No.1 p.1-11

Nucleosome is the basic structural unit of the genome. During processes like DNA replication and gene transcription, the conformation of nucleosomes undergoes dynamic changes, including DNA unwrapping and rewrapping, as well as histone disassembly and assembly. However, the wrapping characteristics ...

Chromatin analysisNucleosomes

10.1038/S41467-024-54735-8

ISSN:2041-1723

Transposable elements-mediated recruitment of KDM1A epigenetically silences HNF4A expression to promote hepatocellular carcinoma

Tiantian Jing•Dianhui Wei•Xiaoli Xu•Chengsi Wu•Lili Yuan等 9 人

Nature Communications

2024

•2024/7/4

•Vol.15 No.1 p.1-21

Transposable elements (TEs) contribute to gene expression regulation by acting as cis-regulatory elements that attract transcription factors and epigenetic regulators. This research aims to explore the functional and clinical implications of transposable element-related molecular events in hepatocel...

Gene silencingHepatocellular carcinomaOncogenes

10.1038/S41467-024-49926-2

ISSN:2041-1723

Predicting 3D genome folding from DNA sequence with Akita

Geoff Fudenberg•David R. Kelley•Katherine S. Pollard

Nature Methods

2020

•2020/10/12

•Vol.17 No.11 p.1111-1117

In interphase, the human genome sequence folds in three dimensions into a rich variety of locus-specific contact patterns. Cohesin and CTCF (CCCTC-binding factor) are key regulators; perturbing the levels of either greatly disrupts genome-wide folding as assayed by chromosome conformation capture me...

Chromatin structureEpigenomicsGenome informaticsGenomicsMachine learning

10.1038/S41592-020-0958-X

ISSN:1548-7091

Annotation of chromatin states in 66 complete mouse epigenomes during development

Arjan van der Velde•Kaili Fan•Junko Tsuji•Jill E. Moore•Michael J. Purcaro等 7 人

Communications Biology

2021

•2021/2/22

•Vol.4 No.1 p.1-15

The morphologically and functionally distinct cell types of a multicellular organism are maintained by their unique epigenomes and gene expression programs. Phase III of the ENCODE Project profiled 66 mouse epigenomes across twelve tissues at daily intervals from embryonic day 11.5 to birth. Applyin...

Epigenetic memoryEpigenomicsGene regulationGenome informatics

10.1038/S42003-021-01756-4

ISSN:2399-3642

G-quadruplexes promote the motility in MAZ phase-separated condensates to activate CCND1 expression and contribute to hepatocarcinogenesis

Wenmeng Wang•Dangdang Li•Qingqing Xu•Jiahui Cheng•Zhiwei Yu等 12 人

Nature Communications

2024

•2024/2/5

•Vol.15 No.1 p.1-17

G-quadruplexes (G4s) can recruit transcription factors to activate gene expression, but detailed mechanisms remain enigmatic. Here, we demonstrate that G4s in the CCND1 promoter propel the motility in MAZ phase-separated condensates and subsequently activate CCND1 transcription. Zinc finger (ZF) 2 o...

Intrinsically disordered proteinsOncogenesTranscriptional regulatory elements

10.1038/S41467-024-45353-5

ISSN:2041-1723

Exploring the roles of RNAs in chromatin architecture using deep learning

Shuzhen Kuang•Katherine S. Pollard

Nature Communications

2024

•2024/7/29

•Vol.15 No.1 p.1-14

Recent studies have highlighted the impact of both transcription and transcripts on 3D genome organization, particularly its dynamics. Here, we propose a deep learning framework, called AkitaR, that leverages both genome sequences and genome-wide RNA-DNA interactions to investigate the roles of chro...

Computational modelsData miningMachine learning

10.1038/S41467-024-50573-W

ISSN:2041-1723

The genetic architecture of DNA replication timing in human pluripotent stem cells

Ding Qiliang•Edwards Matthew M.•Wang Ning•Zhu Xiang•Bracci Alexa N.等 18 人

Nature Communications

2021

•2021/11/19

•Vol.12 No.1 p.1-18

DNA replication follows a strict spatiotemporal program that intersects with chromatin structure but has a poorly understood genetic basis. To systematically identify genetic regulators of replication timing, we exploited inter-individual variation in human pluripotent stem cells from 349 individual...

DNA replicationEpigeneticsGenomePopulation genetics

10.1038/S41467-021-27115-9

ISSN:2041-1723

The HAPSTR2 retrogene buffers stress signaling and resilience in mammals

Amici David R.•Cingoz Harun•Alasady Milad J.•Alhayek Sammy•Phoumyvong Claire M.等 8 人

Nature Communications

2023

•2023/1/11

•Vol.14 No.1 p.1-12

We recently identified HAPSTR1 (C16orf72) as a key component in a novel pathway which regulates the cellular response to molecular stressors, such as DNA damage, nutrient scarcity, and protein misfolding. Here, we identify a functional paralog to HAPSTR1: HAPSTR2. HAPSTR2 formed early in mammalian e...

Evolutionary geneticsStress signalling

10.1038/S41467-022-35697-1

ISSN:2041-1723

Disease-linked regulatory DNA variants and homeostatic transcription factors in epidermis

Douglas F. Porter•Robin M. Meyers•Weili Miao•David L. Reynolds•Audrey W. Hong等 30 人

Nature Communications

2025

•2025/9/25

•Vol.16 No.1 p.1-28

Identifying noncoding single nucleotide variants (SNVs) in regulatory DNA linked to polygenic disease risk, the transcription factors (TFs) they bind, and the genes they dysregulate is a goal in polygenic disease research. Here, we use massively parallel reporter analysis of 3451 SNVs linked to risk...

Biological techniquesGeneticsTranscriptional regulatory elements

10.1038/S41467-025-63070-5

ISSN:2041-1723

Targeting polyamine metabolism and ferroptosis enhances the efficacy of KRAS-targeted therapy depending on KEAP1 status

Yunyi Bian•Guangyao Shan•Guoshu Bi•Zhijie Xu•Jiaqi Liang等 16 人

Nature Communications

2025

•2025/11/11

•Vol.16 No.1 p.99230

The resistance to KRAS-targeted therapies, particularly due to co-occurring gene mutations, remains a significant challenge. Through a metabolite library screening, we reveal that polyamines sensitize KRAS inhibitors only in KRASMU/KEAP1WT cells but not in KRASMU/KEAP1MU cells. Transcriptome sequenc...

Cancer metabolismCancer therapeutic resistanceNon-small-cell lung cancer

10.1038/S41467-025-65441-4

ISSN:2041-1723

Asymmetric distribution of parental H3K9me3 in S phase silences L1 elements

Zhiming Li•Shoufu Duan•Xu Hua•Xiaowei Xu•Yinglu Li等 11 人

Nature

2023

•2023/11/8

•00 p.1-9

In eukaryotes, repetitive DNA sequences are transcriptionally silenced through histone H3 lysine 9 trimethylation (H3K9me3). Loss of silencing of the repeat elements leads to genome instability and human diseases, including cancer and ageing1–3. Although the role of H3K9me3 in the establishment and ...

ChromatinDNA replicationEpigenetics

10.1038/S41586-023-06711-3

ISSN:0028-0836

MOCCASIN: a method for correcting for known and unknown confounders in RNA splicing analysis

Barry Slaff•Caleb M. Radens•Paul Jewell•Anupama Jha•Nicholas F. Lahens等 9 人

Nature Communications

2021

•2021/6/7

•Vol.12 No.1 p.1-9

The effects of confounding factors on gene expression analysis have been extensively studied following the introduction of high-throughput microarrays and subsequently RNA sequencing. In contrast, there is a lack of equivalent analysis and tools for RNA splicing. Here we first assess the effect of c...

RNA splicingSoftwareTranscriptomics

10.1038/S41467-021-23608-9

ISSN:2041-1723

Widespread perturbation of ETS factor binding sites in cancer

Carrasco Pro Sebastian•Hook Heather•Bray David•Berenzy Daniel•Moyer Devlin等 10 人

Nature Communications

2023

•2023/2/17

•Vol.14 No.1 p.1-15

Although >90% of somatic mutations reside in non-coding regions, few have been reported as cancer drivers. To predict driver non-coding variants (NCVs), we present a transcription factor (TF)-aware burden test based on a model of coherent TF function in promoters. We apply this test to NCVs from ...

Cancer genomicsGene expression profilingHigh-throughput screeningTranscriptional regulatory elements

10.1038/S41467-023-36535-8

ISSN:2041-1723

Symmetric inheritance of parental histones contributes to safeguarding the fate of mouse embryonic stem cells during differentiation

Qing Wen•Jiaqi Zhou•Congcong Tian•Xinran Li•Guibing Song等 23 人

Nature Genetics

2023

•2023/9/4

•Vol.55 No.9 p.1555-1566

Parental histones, the carriers of posttranslational modifications, are deposited evenly onto the replicating DNA of sister chromatids in a process dependent on the Mcm2 subunit of DNA helicase and the Pole3 subunit of leading-strand DNA polymerase. The biological significance of parental histone pr...

EpigeneticsEpigenomicsStem cells

10.1038/S41588-023-01477-W

ISSN:1061-4036

Chromatin modifier MTA1 regulates mitotic transition and tumorigenesis by orchestrating mitotic mRNA processing

Jian Liu•Chunxiao Li•Jinsong Wang•Dongkui Xu•Haijuan Wang等 18 人

Nature Communications

2020

•2020/9/8

•Vol.11 No.1 p.1-17

Dysregulated alternative splicing (AS) driving carcinogenetic mitosis remains poorly understood. Here, we demonstrate that cancer metastasis-associated antigen 1 (MTA1), a well-known oncogenic chromatin modifier, broadly interacts and co-expresses with RBPs across cancers, contributing to cancerous ...

Oncogenes

10.1038/S41467-020-18259-1

ISSN:2041-1723

Molecular glue degraders of HuR suppress BRAF-mutant colorectal cancer

Xiaocui Lu•Xiuyun Wang•Zheng Yang•Xusheng Wang•Lin Wang等 21 人

Nature

2026

•2026/6/10

•00 p.1-10

BRAF gain-of-function mutations, particularly BRAF(V600E), affect roughly 10% of all patients with colorectal cancer (CRC), and portend poor prognosis with limited therapeutic interventions. BRAF inhibitors such as encorafenib are ineffective due to MAPK pathway reactivation driven by BRAF dimerizat...

Targeted therapies

10.1038/S41586-026-10613-5

ISSN:0028-0836

SMYD5 catalyzes histone H3 lysine 36 trimethylation at promoters

Zhang Yanjun•Fang Yuan•Tang Yin•Han Shixun•Jia Junqi等 10 人

Nature Communications

2022

•2022/6/9

•Vol.13 No.1 p.1-19

Histone marks, carriers of epigenetic information, regulate gene expression. In mammalian cells, H3K36me3 is mainly catalyzed by SETD2 at gene body regions. Here, we find that in addition to gene body regions, H3K36me3 is enriched at promoters in primary cells. Through screening, we identify SMYD5, ...

Embryonic stem cellsEpigeneticsHistone post-translational modifications

10.1038/S41467-022-30940-1

ISSN:2041-1723

STR mutations on chromosome 15q cause thyrotropin resistance by activating a primate-specific enhancer of MIR7-2/MIR1179

Helmut Grasberger•Alexandra M. Dumitrescu•Xiao-Hui Liao•Elliott G. Swanson•Roy E. Weiss等 22 人

Nature Genetics

2024

•2024/5/7

•00 p.1-12

Thyrotropin (TSH) is the master regulator of thyroid gland growth and function. Resistance to TSH (RTSH) describes conditions with reduced sensitivity to TSH. Dominantly inherited RTSH has been linked to a locus on chromosome 15q, but its genetic basis has remained elusive. Here we show that non-cod...

Genetics researchThyroid diseases

10.1038/S41588-024-01717-7

ISSN:1061-4036

Photoselective sequencing: microscopically guided genomic measurements with subcellular resolution

Mangiameli Sarah M.•Chen Haiqi•Earl Andrew S.•Dobkin Julie A.•Lesman Daniel等 7 人

Nature Methods

2023

•2023/4/27

•00 p.1-9

In biological systems, spatial organization and function are interconnected. Here we present photoselective sequencing, a new method for genomic and epigenomic profiling within morphologically distinct regions. Starting with an intact biological specimen, photoselective sequencing uses targeted illu...

Genomic analysisGenomicsImaging

10.1038/S41592-023-01845-8

ISSN:1548-7091

Differential cofactor dependencies define distinct types of human enhancers

Neumayr Christoph•Haberle Vanja•Serebreni Leonid•Karner Katharina•Hendy Oliver等 16 人

Nature

2022

•2022/6/1

•00 p.1-8

All multicellular organisms rely on differential gene transcription regulated by genomic enhancers, which function through cofactors that are recruited by transcription factors1,2. Emerging evidence suggests that not all cofactors are required at all enhancers3–5, yet whether these observations refl...

Functional genomicsGene regulationHigh-throughput screeningTranscriptional regulatory elementsTranscriptomics

10.1038/S41586-022-04779-X

ISSN:0028-0836

A comprehensive benchmarking with interpretation and operational guidance for the hierarchy of topologically associating domains

Jingxuan Xu•Xiang Xu•Dandan Huang•Yawen Luo•Lin Lin等 14 人

Nature Communications

2024

•2024/5/23

•Vol.15 No.1 p.1-19

Topologically associating domains (TADs), megabase-scale features of chromatin spatial architecture, are organized in a domain-within-domain TAD hierarchy. Within TADs, the inner and smaller subTADs not only manifest cell-to-cell variability, but also precisely regulate transcription and differentia...

Data integrationEpigeneticsEpigenomicsGenome informaticsSoftware

10.1038/S41467-024-48593-7

ISSN:2041-1723

A regulatory variant at 19p13.3 is associated with primary biliary cholangitis risk and ARID3A expression

Li You•Li Zhiqiang•Chen Ruiling•Lian Min•Wang Hanxiao等 25 人

Nature Communications

2023

•2023/3/28

•Vol.14 No.1 p.1-14

Genome-wide association studies have identified 19p13.3 locus associated with primary biliary cholangitis (PBC). Here we aim to identify causative variant(s) and initiate efforts to define the mechanism by which the 19p13.3 locus variant(s) contributes to the pathogenesis of PBC. A genome-wide meta-...

Gene regulationGenome-wide association studiesPrimary biliary cirrhosis

10.1038/S41467-023-37213-5

ISSN:2041-1723

Male-specific lethal 1 (MSL1) promotes Erastin-induced ferroptosis in colon cancer cells by regulating the KCTD12-SLC7A11 axis

Lifu Luo•Qingzhi Zhao•Xueli Cui•Shijiao Dong•Yong Wang等 9 人

Cell Death & Disease

2025

•2025/4/12

•Vol.16 No.1 p.1-12

MSL1, a scaffold protein of the MSL histone acetyltransferase complex, is crucial for its structural integrity and enzymatic activity. While MSL1 is highly expressed in various tumors, its role in tumor progression and cell death remains unclear. Here, we provide evidence of a negative regulatory re...

Colon cancerPreclinical research

10.1038/S41419-025-07555-7

ISSN:2041-4889

A KRAS -responsive long non-coding RNA controls microRNA processing

Lei Shi•Peter Magee•Matteo Fassan•Sudhakar Sahoo•Hui Sun Leong等 18 人

Nature Communications

2021

•2021/4/1

•Vol.12 No.1 p.1-19

Wild-type KRAS (KRASWT) amplification has been shown to be a secondary means of KRAS activation in cancer and associated with poor survival. Nevertheless, the precise role of KRASWT overexpression in lung cancer progression is largely unexplored. Here, we identify and characterize a KRAS-responsive ...

Long non-coding RNAsNon-small-cell lung cancer

10.1038/S41467-021-22337-3

ISSN:2041-1723

Structural variation of the coding and non-coding human pharmacogenome

Roman Tremmel•Yitian Zhou•Matthias Schwab•Volker M. Lauschke

Npj Genomic Medicine

2023

•2023/9/8

•Vol.8 No.1 p.1-11

Genetic variants in drug targets and genes encoding factors involved in drug absorption, distribution, metabolism and excretion (ADME) can have pronounced impacts on drug pharmacokinetics, response, and toxicity. While the landscape of genetic variability at the level of single nucleotide variants (...

Functional genomicsMolecular medicinePredictive markers

10.1038/S41525-023-00371-Y

ISSN:2056-7944

m6Am-seq reveals the dynamic m6Am methylation in the human transcriptome

Sun Hanxiao•Li Kai•Zhang Xiaoting•Liu Jun’e•Zhang Meiling等 7 人

Nature Communications

2021

•2021/8/6

•Vol.12 No.1 p.1-12

N6,2′-O-dimethyladenosine (m6Am), a terminal modification adjacent to the mRNA cap, is a newly discovered reversible RNA modification. Yet, a specific and sensitive tool to directly map transcriptome-wide m6Am is lacking. Here, we report m6Am-seq, based on selective in vitro demethylation and RNA im...

MethylationRNARNA sequencing

10.1038/S41467-021-25105-5

ISSN:2041-1723

Loss of G9a preserves mutation patterns but increases chromatin accessibility, genomic instability and aggressiveness in skin tumours

Alexandra Avgustinova•Aikaterini Symeonidi•Andrés Castellanos•Uxue Urdiroz-Urricelqui•Llorenç Solé-Boldo等 11 人

Nature Cell Biology

2018

•2018/11/19

•Vol.20 No.12 p.1400-1409

Mutations in, and the altered expression of, epigenetic modifiers are pervasive in human tumours, making epigenetic factors attractive antitumour targets. The open-versus-closed chromatin state within the cells-of-origin of cancer correlates with the uneven distribution of mutations. However, the lo...

CancerCancer epigeneticsCancer genomicsSkin cancer

10.1038/S41556-018-0233-X

ISSN:1465-7392

Prioritizing disease and trait causal variants at the TNFAIP3 locus using functional and genomic features

John P. Ray•Carl G. de Boer•Charles P. Fulco•Caleb A. Lareau•Masahiro Kanai等 16 人

Nature Communications

2020

•2020/3/6

•Vol.11 No.1 p.1-13

Genome-wide association studies have associated thousands of genetic variants with complex traits and diseases, but pinpointing the causal variant(s) among those in tight linkage disequilibrium with each associated variant remains a major challenge. Here, we use seven experimental assays to characte...

CRISPR-Cas9 genome editingEpigenomicsFunctional genomicsImmunogenetics

10.1038/S41467-020-15022-4

ISSN:2041-1723

A FoxM1/Smad4 positive feedback loop promotes pancreatic cancer progression

Banzhan Ruan•Bingshu Wang•Xiaodian Zhang•Fujin Liu•Zhenling Wan等 11 人

Cell Death & Disease

2026

•2026/4/10

Pancreatic cancer is a highly lethal disease characterized by rapid onset, aggressive progression, and limited treatment options. The involvement of FoxM1 in the TGF-β/Smad signaling pathway has been linked to pancreatic cancer progression; however, the mechanisms behind the cooperative regulation o...

Mechanisms of diseaseOncogenes

10.1038/S41419-026-08697-Y

ISSN:2041-4889

Tumor-specific lncRNA IGF1R-AS1 trans-regulates chromatin interactions associated with oncogenic MYC signaling

Yongyong Yang•Ting-You Wang•Joshua Fry•Yingming Li•Qingshu Meng等 27 人

Nature Communications

2026

•2026/3/19

LncRNAs have emerged as pivotal regulators in the development and progression of various human cancers. However, understanding the precise mechanisms by which lncRNAs influence cancer progression remains a substantial challenge, largely due to their cell type- and tissue-specific expression patterns...

Cancer genomicsGene regulationGene regulatory networksProstate cancer

10.1038/S41467-026-70814-4

ISSN:2041-1723

Non-canonical functions of spliceosome components in cancer progression

Ivanova Olga M.•Anufrieva Ksenia S.•Kazakova Anastasia N.•Malyants Irina K.•Shnaider Polina V.等 7 人

Cell Death & Disease

2023

•2023/2/2

•Vol.14 No.2 p.1-17

Dysregulation of pre-mRNA splicing is a common hallmark of cancer cells and it is associated with altered expression, localization, and mutations of the components of the splicing machinery. In the last few years, it has been elucidated that spliceosome components can also influence cellular process...

CancerMechanisms of disease

10.1038/S41419-022-05470-9

ISSN:2041-4889

Linking regulatory variants to target genes by integrating single-cell multiome methods and genomic distance

Elizabeth Dorans•Karthik Jagadeesh•Kushal Dey•Alkes L. Price

Nature Genetics

2025

•2025/6/12

•00 p.1-10

Methods that analyze single-cell paired RNA sequencing (RNA-seq) and assay for transposase-accessible chromatin using sequencing (ATAC-seq) multiome data have shown promise in linking regulatory elements to genes. However, existing methods exhibit low concordance and do not capture the effects of ge...

Computational biology and bioinformaticsGene regulation

10.1038/S41588-025-02220-3

ISSN:1061-4036

Placental multi-omics integration identifies candidate functional genes for birthweight

Tekola-Ayele Fasil•Zeng Xuehuo•Chatterjee Suvo•Ouidir Marion•Lesseur Corina等 11 人

Nature Communications

2022

•2022/5/2

•Vol.13 No.1 p.1-12

Abnormal birthweight is associated with increased risk for cardiometabolic diseases in later life. Although the placenta is critical to fetal development and later life health, it has not been integrated into largescale functional genomics initiatives, and mechanisms of birthweight-associated varian...

Cardiovascular diseasesDevelopmental biologyEpigenomicsGene regulation

10.1038/S41467-022-30007-1

ISSN:2041-1723

Non-canonical functions of UHRF1 maintain DNA methylation homeostasis in cancer cells

Kosuke Yamaguchi•Xiaoying Chen•Brianna Rodgers•Fumihito Miura•Pavel Bashtrykov等 23 人

Nature Communications

2024

•2024/4/5

•Vol.15 No.1 p.1-18

DNA methylation is an essential epigenetic chromatin modification, and its maintenance in mammals requires the protein UHRF1. It is yet unclear if UHRF1 functions solely by stimulating DNA methylation maintenance by DNMT1, or if it has important additional functions. Using degron alleles, we show th...

Cancer epigeneticsDNA methylation

10.1038/S41467-024-47314-4

ISSN:2041-1723

MYC reshapes CTCF-mediated chromatin architecture in prostate cancer

Wei Zhao•Wang Song•Xu Yaning•Wang Wenzheng•Soares Fraser等 21 人

Nature Communications

2023

•2023/3/30

•Vol.14 No.1 p.1-15

MYC is a well characterized oncogenic transcription factor in prostate cancer, and CTCF is the main architectural protein of three-dimensional genome organization. However, the functional link between the two master regulators has not been reported. In this study, we find that MYC rewires prostate c...

Chromatin structureEpigenomicsProstate cancer

10.1038/S41467-023-37544-3

ISSN:2041-1723

System-wide analysis of RNA and protein subcellular localization dynamics

Eneko Villanueva•Tom Smith•Mariavittoria Pizzinga•Mohamed Elzek•Rayner M. L. Queiroz等 12 人

Nature Methods

2023

•2023/11/30

•00 p.1-12

Although the subcellular dynamics of RNA and proteins are key determinants of cell homeostasis, their characterization is still challenging. Here we present an integrative framework to simultaneously interrogate the dynamics of the transcriptome and proteome at subcellular resolution by combining tw...

Cell biologyProteomicsSequencing

10.1038/S41592-023-02101-9

ISSN:1548-7091

Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake

Alice Williamson•Dougall M. Norris•Xianyong Yin•K. Alaine Broadaway•Anne H. Moxley等 115 人

Nature Genetics

2023

•2023/6/8

•Vol.55 No.6 p.973-983

Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h af...

Gene expressionGenome-wide association studiesMetabolic disordersPopulation geneticsType 2 diabetes

10.1038/S41588-023-01408-9

ISSN:1061-4036

Interplay and cooperation between SREBF1 and master transcription factors regulate lipid metabolism and tumor-promoting pathways in squamous cancer

Li-Yan Li•Qian Yang•Yan-Yi Jiang•Wei Yang•Yuan Jiang等 23 人

Nature Communications

2021

•2021/7/16

•Vol.12 No.1 p.1-17

Squamous cell carcinomas (SCCs) comprise one of the most common histologic types of human cancer. Transcriptional dysregulation of SCC cells is orchestrated by tumor protein p63 (TP63), a master transcription factor (TF) and a well-researched SCC-specific oncogene. In the present study, both Gene Se...

Cancer epigeneticsGeneticsSquamous cell carcinoma

10.1038/S41467-021-24656-X

ISSN:2041-1723

Modeling tissue-specific breakpoint proximity of structural variations from whole-genomes to identify cancer drivers

Martinez-Fundichely Alexander•Dixon Austin•Khurana Ekta

Nature Communications

2022

•2022/9/26

•Vol.13 No.1 p.1-15

Structural variations (SVs) in cancer cells often impact large genomic regions with functional consequences. However, identification of SVs under positive selection is a challenging task because little is known about the genomic features related to the background breakpoint distribution in different...

Cancer genomicsEpigenomicsGenome informaticsOncogenesStructural variation

10.1038/S41467-022-32945-2

ISSN:2041-1723

Hepatic ARID3A facilitates liver cancer malignancy by cooperating with CEP131 to regulate an embryonic stem cell-like gene signature

Shen Mengting•Li Shengli•Zhao Yiming•Liu Yizhe•Liu Zhen等 11 人

Cell Death & Disease

2022

•2022/8/25

•Vol.13 No.8 p.1-13

Liver cancer stemness refers to the stem cell-like phenotype of hepatocarcinoma cells and is closely related to a high degree of tumour malignancy. Here, we identified AT-rich interacting domain 3A (ARID3A) as one of the most upregulated stemness-related transcription factors in liver cancer by an i...

Liver cancerMetastasisOncogenes

10.1038/S41419-022-05187-9

ISSN:2041-4889

The concurrence of DNA methylation and demethylation is associated with transcription regulation

Shi Jiejun•Xu Jianfeng•Chen Yiling Elaine•Li Jason Sheng•Cui Ya等 8 人

Nature Communications

2021

•2021/9/6

•Vol.12 No.1 p.1-12

The mammalian DNA methylome is formed by two antagonizing processes, methylation by DNA methyltransferases (DNMT) and demethylation by ten-eleven translocation (TET) dioxygenases. Although the dynamics of either methylation or demethylation have been intensively studied in the past decade, the direc...

Data miningDNA methylationEpigenomicsGene expressionGene regulation

10.1038/S41467-021-25521-7

ISSN:2041-1723

Multi-omic analysis reveals significantly mutated genes and DDX3X as a sex-specific tumor suppressor in cutaneous melanoma

Rached Alkallas•Mathieu Lajoie•Dan Moldoveanu•Karen Vo Hoang•Philippe Lefrançois等 12 人

Nature Cancer

2020

•2020/6/22

•Vol.1 No.6 p.635-652

The high background tumor mutation burden in cutaneous melanoma limits the ability to identify significantly mutated genes (SMGs) that drive this cancer. To address this, we performed a mutation significance study of over 1,000 melanoma exomes, combined with a multi-omic analysis of 470 cases from T...

CancerCancer genomicsMelanoma

10.1038/S43018-020-0077-8

ISSN:2662-1347

Promoter G-quadruplexes and transcription factors cooperate to shape the cell type-specific transcriptome

Sara Lago•Matteo Nadai•Filippo M. Cernilogar•Maryam Kazerani•Helena Domíniguez Moreno等 7 人

Nature Communications

2021

•2021/6/23

•Vol.12 No.1 p.1-13

Cell identity is maintained by activation of cell-specific gene programs, regulated by epigenetic marks, transcription factors and chromatin organization. DNA G-quadruplex (G4)-folded regions in cells were reported to be associated with either increased or decreased transcriptional activity. By G4-C...

DNAGene expressionSarcomaTranscription

10.1038/S41467-021-24198-2

ISSN:2041-1723

A sense-antisense RNA interaction promotes breast cancer metastasis via regulation of NQO1 expression

Bruce Culbertson•Kristle Garcia•Daniel Markett•Hosseinali Asgharian•Li Chen等 14 人

Nature Cancer

2023

•2023/5/11

•00 p.1-17

Antisense RNAs are ubiquitous in human cells, yet their role is largely unexplored. Here we profiled antisense RNAs in the MDA-MB-231 breast cancer cell line and its highly lung metastatic derivative. We identified one antisense RNA that drives cancer progression by upregulating the redox enzyme NAD...

Breast cancerCancerGene expressionMechanisms of disease

10.1038/S43018-023-00554-7

ISSN:2662-1347

Integrating transcription factor occupancy with transcriptome-wide association analysis identifies susceptibility genes in human cancers

He Jingni•Wen Wanqing•Beeghly Alicia•Chen Zhishan•Cao Chen等 9 人

Nature Communications

2022

•2022/11/19

•Vol.13 No.1 p.1-15

Transcriptome-wide association studies (TWAS) have successfully discovered many putative disease susceptibility genes. However, TWAS may suffer from inaccuracy of gene expression predictions due to inclusion of non-regulatory variants. By integrating prior knowledge of susceptible transcription fact...

Cancer geneticsGenetic association studyStatistical methods

10.1038/S41467-022-34888-0

ISSN:2041-1723

Deep-learning augmented RNA-seq analysis of transcript splicing

Zijun Zhang•Zhicheng Pan•Yi Ying•Zhijie Xie•Samir Adhikari等 10 人

Nature Methods

2019

•2019/3/25

•Vol.16 No.4 p.307-310

A major limitation of RNA sequencing (RNA-seq) analysis of alternative splicing is its reliance on high sequencing coverage. We report DARTS (https://github.com/Xinglab/DARTS), a computational framework that integrates deep-learning-based predictions with empirical RNA-seq evidence to infer differen...

Machine learningRNA splicingSoftwareStatistical methodsTranscriptomics

10.1038/S41592-019-0351-9

ISSN:1548-7091

Direct characterization of cis-regulatory elements and functional dissection of complex genetic associations using HCR–FlowFISH

Reilly Steven K.•Gosai Sager J.•Gutierrez Alan•Mackay-Smith Ava•Ulirsch Jacob C.等 16 人

Nature Genetics

2021

•2021/7/29

•00 p.1-11

Effective interpretation of genome function and genetic variation requires a shift from epigenetic mapping of cis-regulatory elements (CREs) to characterization of endogenous function. We developed hybridization chain reaction fluorescence in situ hybridization coupled with flow cytometry (HCR–FlowF...

Biological techniquesFunctional genomicsGenetics

10.1038/S41588-021-00900-4

ISSN:1061-4036

AI-guided multi-omics analysis identifies NPC1-modulated susceptibility to SARS-CoV-2 infection under PM2.5 exposure

Guoqing Feng•Zheng Dong•Limei Ke•Weilai Zhou•Yu Tian等 19 人

Nature Communications

2026

•2026/3/30

Exposure to airborne fine particulate matter (PM2.5) has been linked to increased risk of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, yet the underlying mechanisms remain unclear. Here, by leveraging a fine-tuned foundation model of single-cell transcriptomics, we unc...

Environmental sciencesEpidemiologyGenetics researchRisk factorsViral infection

10.1038/S41467-026-71196-3

ISSN:2041-1723

Genome-wide association study identifies susceptibility loci for acute myeloid leukemia

Lin Wei-Yu•Fordham Sarah E.•Hungate Eric•Sunter Nicola J.•Elstob Claire等 83 人

Nature Communications

2021

•2021/10/29

•Vol.12 No.1 p.1-10

Acute myeloid leukemia (AML) is a hematological malignancy with an undefined heritable risk. Here we perform a meta-analysis of three genome-wide association studies, with replication in a fourth study, incorporating a total of 4018 AML cases and 10488 controls. We identify a genome-wide significant...

Acute myeloid leukaemiaCancer genomicsRisk factors

10.1038/S41467-021-26551-X

ISSN:2041-1723

Systematic characterization of cancer transcriptome at transcript resolution

Hu Wei•Wu Yangjun•Shi Qili•Wu Jingni•Kong Deping等 9 人

Nature Communications

2022

•2022/11/10

•Vol.13 No.1 p.1-16

Transcribed RNAs undergo various regulation and modification to become functional transcripts. Notably, cancer transcriptome has not been fully characterized at transcript resolution. Herein, we carry out a reference-based transcript assembly across >1000 cancer cell lines. We identify 498,255 tr...

Cancer genomicsCancer therapyData miningRegulatory networksTranscriptomics

10.1038/S41467-022-34568-Z

ISSN:2041-1723

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

Elsa Leitão•Amandine Santini•Benjamin Cogne•Miriam Essid•Maria Athanasiadou等 228 人

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

An encyclopedia of human enhancer–gene regulatory interactions

Andreas R. Gschwind•Kristy S. Mualim•Alireza Karbalayghareh•Maya U. Sheth•Kushal K. Dey等 46 人

Nature

2026

•2026/7/15

•00 p.1-12

Identifying transcriptional enhancers and their target genes is essential for understanding gene regulation and the effect of human genetic variation on disease1–6. Here we create and evaluate a resource of more than 92 million enhancer–gene regulatory interactions across 1,458 biosamples covering 3...

Chromatin structureComputational biology and bioinformaticsEpigenomicsFunctional genomicsGene regulation

10.1038/S41586-026-10781-4

ISSN:0028-0836

Systematic benchmarking of tools for CpG methylation detection from nanopore sequencing

Zaka Wing-Sze Yuen•Akanksha Srivastava•Runa Daniel•Dennis McNevin•Cameron Jack等 6 人

Nature Communications

2021

•2021/6/8

•Vol.12 No.1 p.1-12

DNA methylation plays a fundamental role in the control of gene expression and genome integrity. Although there are multiple tools that enable its detection from Nanopore sequencing, their accuracy remains largely unknown. Here, we present a systematic benchmarking of tools for the detection of CpG ...

DNA sequencingEpigenomicsGenome informaticsSoftware

10.1038/S41467-021-23778-6

ISSN:2041-1723

SCENIC+: single-cell multiomic inference of enhancers and gene regulatory networks

Carmen Bravo González-Blas•Seppe De Winter•Gert Hulselmans•Nikolai Hecker•Irina Matetovici等 10 人

Nature Methods

2023

•2023/7/13

•00 p.1-13

Joint profiling of chromatin accessibility and gene expression in individual cells provides an opportunity to decipher enhancer-driven gene regulatory networks (GRNs). Here we present a method for the inference of enhancer-driven GRNs, called SCENIC+. SCENIC+ predicts genomic enhancers along with ca...

EpigenomicsGene regulationGene regulatory networksSoftware

10.1038/S41592-023-01938-4

ISSN:1548-7091

PRO-IP-seq tracks molecular modifications of engaged Pol II complexes at nucleotide resolution

Anniina Vihervaara•Philip Versluis•Samu V. Himanen•John T. Lis

Nature Communications

2023

•2023/11/3

•Vol.14 No.1 p.1-19

RNA Polymerase II (Pol II) is a multi-subunit complex that undergoes covalent modifications as transcription proceeds through genes and enhancers. Rate-limiting steps of transcription control Pol II recruitment, site and degree of initiation, pausing duration, productive elongation, nascent transcri...

Gene expressionGene regulationGenome-wide analysis of gene expressionTranscriptional regulatory elements

10.1038/S41467-023-42715-3

ISSN:2041-1723

Epigenetic alterations affecting hematopoietic regulatory networks as drivers of mixed myeloid/lymphoid leukemia

Roger Mulet-Lazaro•Stanley van Herk•Margit Nuetzel•Aniko Sijs-Szabo•Noelia Díaz等 22 人

Nature Communications

2024

•2024/7/7

•Vol.15 No.1 p.1-22

Leukemias with ambiguous lineage comprise several loosely defined entities, often without a clear mechanistic basis. Here, we extensively profile the epigenome and transcriptome of a subgroup of such leukemias with CpG Island Methylator Phenotype. These leukemias exhibit comparable hybrid myeloid/ly...

Cancer genomicsDNA methylationLeukaemia

10.1038/S41467-024-49811-Y

ISSN:2041-1723

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

Valgerdur Steinthorsdottir•Ralph McGinnis•Nicholas O. Williams•Lilja Stefansdottir•Gudmar Thorleifsson等 75 人

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

Alternative promoters in CpG depleted regions are prevalently associated with epigenetic misregulation of liver cancer transcriptomes

Chirag Nepal•Jesper B. Andersen

Nature Communications

2023

•2023/5/11

•Vol.14 No.1 p.1-14

Transcriptional regulation is commonly governed by alternative promoters. However, the regulatory architecture in alternative and reference promoters, and how they differ, remains elusive. In 100 CAGE-seq libraries from hepatocellular carcinoma patients, here we annotate 4083 alternative promoters i...

Genome informaticsLiverLiver cancer

10.1038/S41467-023-38272-4

ISSN:2041-1723

Complex genomic patterns of abasic sites in mammalian DNA revealed by a high-resolution SSiNGLe-AP method

Cai Ye•Cao Huifen•Wang Fang•Zhang Yufei•Kapranov Philipp

Nature Communications

2022

•2022/10/5

•Vol.13 No.1 p.1-21

DNA damage plays a critical role in biology and diseases; however, how different types of DNA lesions affect cellular functions is far from clear mostly due to the paucity of high-resolution methods that can map their locations in complex genomes, such as those of mammals. Here, we present the devel...

AgeingDNA damage and repairGenomic analysis

10.1038/S41467-022-33594-1

ISSN:2041-1723

Cross-dataset pan-cancer detection by correlating cell-free DNA fragment coverage with open chromatin sites across cell types

Ludvig Renbo Olsen•Denis Odinokov•Jakob Qvortrup Holsting•Karoline Kondrup•Laura Iisager等 25 人

Nature Communications

2025

•2025/11/21

The fragmentation patterns of whole genome sequenced cell-free DNA are promising features for tumor-agnostic cancer detection. However, systematic biases challenge their cross-cohort generalization. We introduce LIONHEART, an open source cancer detection method specifically optimized to generalize a...

Cancer screeningMolecular medicinePredictive medicine

10.1038/S41467-025-66503-3

ISSN:2041-1723

The health impacts and genetic architecture of food liking in cardio-metabolic diseases

Wenbo Jiang•Hang Wang•Yiding Geng•Meijuan Guo•Yingdong Zuo等 16 人

Nature Communications

2025

•2025/5/23

•Vol.16 No.1 p.1-20

We evaluated temporal and genetic relationships between 176 food-liking-traits and cardio-metabolic diseases using data from the UK Biobank (N = 182,087) for observational analyses and summary-level GWAS data from FinnGen and other consortia (N = 406,565–977,323) for genetic analyses. Integrating ob...

CardiologyEndocrine system and metabolic diseasesRisk factors

10.1038/S41467-025-59945-2

ISSN:2041-1723

Long-read RNA-seq demarcates cis- and trans-directed alternative RNA splicing

Giovanni Quinones-Valdez•Kofi Amoah•Xinshu Xiao

Nature Communications

2025

•2025/10/30

•Vol.16 No.1 p.1-16

Genetic regulation of alternative splicing constitutes an important link between genetic variation and disease. Nonetheless, RNA splicing is regulated by both cis-acting elements and trans-acting splicing factors. Determining splicing events that are directed primarily by the cis- or trans-acting me...

Computational biology and bioinformaticsTranscriptomics

10.1038/S41467-025-64605-6

ISSN:2041-1723

A Bayesian model for unsupervised detection of RNA splicing based subtypes in cancers

Wang David•Quesnel-Vallieres Mathieu•Jewell San•Elzubeir Moein•Lynch Kristen等 7 人

Nature Communications

2023

•2023/1/4

•Vol.14 No.1 p.1-15

Identification of cancer sub-types is a pivotal step for developing personalized treatment. Specifically, sub-typing based on changes in RNA splicing has been motivated by several recent studies. We thus develop CHESSBOARD, an unsupervised algorithm tailored for RNA splicing data that captures “tile...

Cancer genomicsComputational biology and bioinformatics

10.1038/S41467-022-35369-0

ISSN:2041-1723

Sperm sequencing reveals extensive positive selection in the male germline

Matthew D. C. Neville•Andrew R. J. Lawson•Rashesh Sanghvi•Federico Abascal•My H. Pham等 21 人

Nature

2025

•2025/10/8

•00 p.1-8

Mutations that occur in the cell lineages of sperm or eggs can be transmitted to offspring. In humans, positive selection of driver mutations during spermatogenesis can increase the birth prevalence of certain developmental disorders1–3. Until recently, characterizing the extent of this selection in...

Disease geneticsGenome evolutionRare variants

10.1038/S41586-025-09448-3

ISSN:0028-0836

Integrated analysis of the complete sequence of a macaque genome

Shilong Zhang•Ning Xu•Lianting Fu•Xiangyu Yang•Kaiyue Ma等 38 人

Nature

2025

•2025/2/26

•00 p.1-8

The crab-eating macaques (Macaca fascicularis) and rhesus macaques (Macaca mulatta) are pivotal in biomedical and evolutionary research1–3. However, their genomic complexity and interspecies genetic differences remain unclear4. Here, we present a complete genome assembly of a crab-eating macaqu...

Comparative genomicsDNA sequencingEvolutionary geneticsGenome informatics

10.1038/S41586-025-08596-W

ISSN:0028-0836

Multi-omics single-cell data integration and regulatory inference with graph-linked embedding

Cao Zhi-Jie•Gao Ge

Nature Biotechnology

2022

•2022/5/2

•00 p.1-9

Despite the emergence of experimental methods for simultaneous measurement of multiple omics modalities in single cells, most single-cell datasets include only one modality. A major obstacle in integrating omics data from multiple modalities is that different omics layers typically have distinct fea...

Data integrationGene regulationMachine learningSoftware

10.1038/S41587-022-01284-4

ISSN:1087-0156

Reprogramming of the FOXA1 cistrome in treatment-emergent neuroendocrine prostate cancer

Sylvan C. Baca•David Y. Takeda•Ji-Heui Seo•Justin Hwang•Sheng Yu Ku等 41 人

Nature Communications

2021

•2021/3/30

•Vol.12 No.1 p.1-12

Lineage plasticity, the ability of a cell to alter its identity, is an increasingly common mechanism of adaptive resistance to targeted therapy in cancer. An archetypal example is the development of neuroendocrine prostate cancer (NEPC) after treatment of prostate adenocarcinoma (PRAD) with inhibito...

EpigenomicsProstate cancer

10.1038/S41467-021-22139-7

ISSN:2041-1723

Analysis of blood methylation quantitative trait loci in East Asians reveals ancestry-specific impacts on complex traits

Qianqian Peng•Xinxuan Liu•Wenran Li•Han Jing•Jiarui Li等 33 人

Nature Genetics

2024

•2024/4/19

•00 p.1-15

Methylation quantitative trait loci (mQTLs) are essential for understanding the role of DNA methylation changes in genetic predisposition, yet they have not been fully characterized in East Asians (EAs). Here we identified mQTLs in whole blood from 3,523 Chinese individuals and replicated them in ad...

Epigenetics

10.1038/S41588-023-01494-9

ISSN:1061-4036

EmbedTAD Using Graph Embedding and Unsupervised Learning to Identify TADs from High-Resolution Hi-C Data

H. M. A. Mohit Chowdhury•Oluwatosin Oluwadare

Communications Biology

2025

•2025/12/9

Topologically Associating Domains (TADs) serve a functional purpose as self-interacting regions whose boundaries are enriched with various proteins. Identifying these TAD regions is essential for examining several biological characteristics, including immune system function and chromosome organizati...

Data miningMachine learning

10.1038/S42003-025-09224-Z

ISSN:2399-3642

Structural basis for genome-wide site-specific DNA recognition by Nuclear Factor IA

Ci Zhu•Ding Xiao•Zhipu Luo•Jie Zhang•Shuang Liu等 13 人

Nature Communications

2025

•2025/12/15

Nuclear Factor IA, a member of the long-studied Nuclear Factor I family of DNA-binding proteins, plays pivotal roles in development and metabolism. Dysregulation or loss of Nuclear Factor IA is associated with severe neurological defects in humans and disruptions in fatty acid metabolism linked to c...

SAXSTranscriptional regulatory elementsX-ray crystallography

10.1038/S41467-025-67641-4

ISSN:2041-1723

Learning representations of chromatin contacts using a recurrent neural network identifies genomic drivers of conformation

Dsouza Kevin B.•Maslova Alexandra•Al-Jibury Ediem•Merkenschlager Matthias•Bhargava Vijay K.等 6 人

Nature Communications

2022

•2022/6/28

•Vol.13 No.1 p.1-19

Despite the availability of chromatin conformation capture experiments, discerning the relationship between the 1D genome and 3D conformation remains a challenge, which limits our understanding of their affect on gene expression and disease. We propose Hi-C-LSTM, a method that produces low-dimension...

EpigenomicsMachine learning

10.1038/S41467-022-31337-W

ISSN:2041-1723

An enhancer variant at 16q22.1 predisposes to hepatocellular carcinoma via regulating PRMT7 expression

Shen Ting•Ni Ting•Chen Jiaxuan•Chen Haitao•Ma Xiaopin等 23 人

Nature Communications

2022

•2022/3/9

•Vol.13 No.1 p.1-15

Most cancer causal variants are found in gene regulatory elements, e.g., enhancers. However, enhancer variants predisposing to hepatocellular carcinoma (HCC) remain unreported. Here we conduct a genome-wide survey of HCC-susceptible enhancer variants through a three-stage association study in 11,958...

EpigeneticsGenome-wide association studiesHepatocellular carcinoma

10.1038/S41467-022-28861-0

ISSN:2041-1723

The epigenomic landscape of transposable elements across normal human development and anatomy

Erica C. Pehrsson•Mayank N. K. Choudhary•Vasavi Sundaram•Ting Wang

Nature Communications

2019

•2019/12/10

•Vol.10 No.1 p.1-16

Transposable elements (TEs) have deposited functional regulatory elements throughout the human genome. Although most are silenced, certain TEs have been co-opted by the host. However, a comprehensive, multidimensional picture of the contribution of TEs to normal human gene regulation is still lackin...

BioinformaticsEpigeneticsEpigenetics analysisEpigenomicsGene regulation

10.1038/S41467-019-13555-X

ISSN:2041-1723

Systematic analysis of binding of transcription factors to noncoding variants

Jian Yan•Yunjiang Qiu•André M. Ribeiro dos Santos•Yimeng Yin•Yang E. Li等 18 人

Nature

2021

•2021/1/27

•Vol.591 No.7848 p.147-151

Many sequence variants have been linked to complex human traits and diseases1, but deciphering their biological functions remains challenging, as most of them reside in noncoding DNA. Here we have systematically assessed the binding of 270 human transcription factors to 95,886 noncoding variants in ...

Functional genomicsGene expressionGenome-wide association studiesTranscriptional regulatory elements

10.1038/S41586-021-03211-0

ISSN:0028-0836

A large-scale binding and functional map of human RNA-binding proteins

Eric L. Van Nostrand•Peter Freese•Gabriel A. Pratt•Xiaofeng Wang•Xintao Wei等 39 人

Nature

2020

•2020/7/29

•Vol.583 No.7818 p.711-719

Many proteins regulate the expression of genes by binding to specific regions encoded in the genome1. Here we introduce a new data set of RNA elements in the human genome that are recognized by RNA-binding proteins (RBPs), generated as part of the Encyclopedia of DNA Elements (ENCODE) project phase ...

Alternative splicingTranscriptomics

10.1038/S41586-020-2077-3

ISSN:0028-0836

The changing mouse embryo transcriptome at whole tissue and single-cell resolution

Peng He•Brian A. Williams•Diane Trout•Georgi K. Marinov•Henry Amrhein等 16 人

Nature

2020

•2020/7/29

•Vol.583 No.7818 p.760-767

During mammalian embryogenesis, differential gene expression gradually builds the identity and complexity of each tissue and organ system1. Here we systematically quantified mouse polyA-RNA from day 10.5 of embryonic development to birth, sampling 17 tissues and organs. The resulting developmental t...

Developmental biologyNetwork topologyTranscriptional regulatory elementsTranscriptomics

10.1038/S41586-020-2536-X

ISSN:0028-0836

Integrative proteogenomic analysis identifies COL6A3-derived endotrophin as a mediator of the effect of obesity on coronary artery disease

Satoshi Yoshiji•Tianyuan Lu•Guillaume Butler-Laporte•Julia Carrasco-Zanini-Sanchez•Chen-Yang Su等 29 人

Nature Genetics

2025

•2025/1/24

•Vol.57 No.2 p.345-357

Obesity strongly increases the risk of cardiometabolic diseases, yet the underlying mediators of this relationship are not fully understood. Given that obesity strongly influences circulating protein levels, we investigated proteins mediating the effects of obesity on coronary artery disease, stroke...

Cardiovascular diseasesDrug discoveryObesityPersonalized medicine

10.1038/S41588-024-02052-7

ISSN:1061-4036

Asymmetric predictive relationships across histone modifications

Li Hongyang•Guan Yuanfang

Nature Machine Intelligence

2022

•2022/3/21

•Vol.4 No.3 p.288-299

Decoding the epigenomic landscapes in diverse tissues and cell types is fundamental to understanding molecular mechanisms underlying many essential cellular processes and human diseases. Recent advances in artificial intelligence provide new methods and strategies for imputing unknown epigenomes bas...

EpigenomicsMachine learning

10.1038/S42256-022-00455-X

ISSN:2522-5839

Human papillomavirus-encoded circular RNA circE7 promotes immune evasion in head and neck squamous cell carcinoma

Junshang Ge•Yi Meng•Jiayue Guo•Pan Chen•Jie Wang等 19 人

Nature Communications

2024

•2024/10/4

•Vol.15 No.1 p.1-18

Immune evasion represents a crucial milestone in the progression of cancer and serves as the theoretical foundation for tumor immunotherapy. In this study, we reveal a negative association between Human Papillomavirus (HPV)-encoded circular RNA, circE7, and the infiltration of CD8+ T cells in head a...

Cancer epigeneticsHead and neck cancerTumour immunology

10.1038/S41467-024-52981-4

ISSN:2041-1723

Integrative analysis reveals RNA G-quadruplexes in UTRs are selectively constrained and enriched for functional associations

David S. M. Lee•Louis R. Ghanem•Yoseph Barash

Nature Communications

2020

•2020/1/27

•Vol.11 No.1 p.1-12

G-quadruplex (G4) sequences are abundant in untranslated regions (UTRs) of human messenger RNAs, but their functional importance remains unclear. By integrating multiple sources of genetic and genomic data, we show that putative G-quadruplex forming sequences (pG4) in 5’ and 3’ UTRs are selectively ...

Genetic association studyGenetic variationRNARNA folding

10.1038/S41467-020-14404-Y

ISSN:2041-1723

Placental genomics mediates genetic associations with complex health traits and disease

Bhattacharya Arjun•Freedman Anastasia N.•Avula Vennela•Harris Rebeca•Liu Weifang等 16 人

Nature Communications

2022

•2022/2/4

•Vol.13 No.1 p.1-15

As the master regulator in utero, the placenta is core to the Developmental Origins of Health and Disease (DOHaD) hypothesis but is historically understudied. To identify placental gene-trait associations (GTAs) across the life course, we perform distal mediator-enriched transcriptome-wide associati...

DevelopmentGene expressionGene regulation

10.1038/S41467-022-28365-X

ISSN:2041-1723

Base-excision repair pathway shapes 5-methylcytosine deamination signatures in pan-cancer genomes

André Bortolini Silveira•Alexandre Houy•Olivier Ganier•Begüm Özemek•Sandra Vanhuele等 16 人

Nature Communications

2024

•2024/11/14

•Vol.15 No.1 p.1-17

Transition of cytosine to thymine in CpG dinucleotides is the most frequent type of mutation in cancer. This increased mutability is commonly attributed to the spontaneous deamination of 5-methylcytosine (5mC), which is normally repaired by the base-excision repair (BER) pathway. However, the contri...

Base excision repairCancer genomics

10.1038/S41467-024-54223-Z

ISSN:2041-1723

Hi-Compass: a depth-aware deep learning framework for predicting cell-type-specific 3D genome organization from single-cell to spatial resolution

Yuan-Chen Sun•Wen-Jie Jiang•Kang-Wen Cai•Na-Na Wei•Fu-Ting Lai等 14 人

Nature Communications

2026

•2026/4/14

Three-dimensional genome organization controls cell-type-specific gene expression through chromatin interactions, yet systematic analysis across diverse cellular contexts remains limited by experimental constraints. Here we present Hi-Compass, a depth-aware deep learning framework that predicts cell...

Chromatin analysisChromatin remodellingComputational modelsEpigenomicsMachine learning

10.1038/S41467-026-71877-Z

ISSN:2041-1723

BAP1 is a haploinsufficient tumor suppressor linking chronic pancreatitis to pancreatic cancer in mice

Stephanie Perkail•Jaclyn Andricovich•Yan Kai•Alexandros Tzatsos

Nature Communications

2020

•2020/6/15

•Vol.11 No.1 p.1-17

Chronic pancreatitis represents a risk factor for the development of pancreatic cancer. We find that heterozygous loss of histone H2A lysine 119 deubiquitinase BAP1 (BRCA1 Associated Protein-1) associates with a history of chronic pancreatitis and occurs in 25% of pancreatic ductal adenocarcinomas a...

CancerGenetics

10.1038/S41467-020-16589-8

ISSN:2041-1723

Global reference mapping of human transcription factor footprints

Jeff Vierstra•John Lazar•Richard Sandstrom•Jessica Halow•Kristen Lee等 19 人

Nature

2020

•2020/7/29

•Vol.583 No.7818 p.729-736

Combinatorial binding of transcription factors to regulatory DNA underpins gene regulation in all organisms. Genetic variation in regulatory regions has been connected with diseases and diverse phenotypic traits1, but it remains challenging to distinguish variants that affect regulatory function2. G...

EpigenomicsFunctional genomicsGene regulation

10.1038/S41586-020-2528-X

ISSN:0028-0836

A disease model resource reveals core principles of tissue-specific cancer evolution

Sebastian Mueller•Niklas de Andrade Krätzig•Markus Tschurtschenthaler•Miguel G. Silva•Chiara Thordsen等 66 人

Nature

2026

•2026/2/25

•00 p.1-12

Oncogenes such as KRAS display marked tissue specificity in their oncogenic potential, genetic interactions and phenotypic effects, but the underlying determinants remain largely unresolved1–5. Here, to address these questions, we developed the Mouse Cancer Cell line Atlas, a broad-utility resource ...

Cancer geneticsCancer modelsOncogenes

10.1038/S41586-026-10187-2

ISSN:0028-0836

OncoMark: a high-throughput neural multi-task learning framework for comprehensive cancer hallmark quantification

Shreyansh Priyadarshi•Camellia Mazumder•Bhavesh Neekhra•Sayan Biswas•Debojyoti Chowdhury等 7 人

Communications Biology

2025

•2025/10/7

•Vol.8 No.1 p.1-12

Quantifying the biological processes that drive cancer progression remains a key challenge in oncology. Although the hallmarks of cancer provide a foundational framework for understanding tumor behavior, existing diagnostic tools rarely measure these hallmarks directly. Here we present a neural mult...

Cancer genomicsSoftware

10.1038/S42003-025-08727-Z

ISSN:2399-3642

Multi-omics analysis reveals contextual tumor suppressive and oncogenic gene modules within the acute hypoxic response

Zdenek Andrysik•Heather Bender•Matthew D. Galbraith•Joaquin M. Espinosa

Nature Communications

2021

•2021/3/2

•Vol.12 No.1 p.1-18

Cellular adaptation to hypoxia is a hallmark of cancer, but the relative contribution of hypoxia-inducible factors (HIFs) versus other oxygen sensors to tumorigenesis is unclear. We employ a multi-omics pipeline including measurements of nascent RNA to characterize transcriptional changes upon acute...

CancerTranscriptionTranscription factorsTranscriptomics

10.1038/S41467-021-21687-2

ISSN:2041-1723

Common variation in meiosis genes shapes human recombination and aneuploidy

Sara A. Carioscia•Arjun Biddanda•Margaret R. Starostik•Xiaona Tang•Eva R. Hoffmann等 7 人

Nature

2026

•2026/1/21

•Vol.651 No.8104 p.146-153

The leading cause of human pregnancy loss is aneuploidy, often tracing to errors in chromosome segregation during female meiosis1,2. Although abnormal crossover recombination is known to confer risk for aneuploidy3,4, limited data have hindered understanding of the potential shared genetic basis of ...

CytogeneticsDNA recombinationGene expressionGenome-wide association studiesMeiosis

10.1038/S41586-025-09964-2

ISSN:0028-0836

GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements

Dixon Peter H.•Levine Adam P.•Cebola Inês•Chan Melanie M. Y.•Amin Aliya S.等 22 人

Nature Communications

2022

•2022/8/17

•Vol.13 No.1 p.1-18

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse o...

Gene expression profilingGenome-wide association studiesLiver diseases

10.1038/S41467-022-29931-Z

ISSN:2041-1723

Prioritization of autoimmune disease-associated genetic variants that perturb regulatory element activity in T cells

Mouri Kousuke•Guo Michael H.•de Boer Carl G.•Lissner Michelle M.•Harten Ingrid A.等 14 人

Nature Genetics

2022

•2022/5/5

•00 p.1-10

Genome-wide association studies (GWASs) have uncovered hundreds of autoimmune disease-associated loci; however, the causal genetic variants within each locus are mostly unknown. Here, we perform high-throughput allele-specific reporter assays to prioritize disease-associated variants for five autoim...

Functional genomicsImmunogenetics

10.1038/S41588-022-01056-5

ISSN:1061-4036

Integrative analysis of the 3D genome and epigenome in mouse embryonic tissues

Miao Yu•Nathan R. Zemke•Ziyin Chen•Ivan Juric•Rong Hu等 21 人

Nature Structural & Molecular Biology

2024

•2024/12/16

•00 p.1-12

While a rich set of putative cis-regulatory sequences involved in mouse fetal development have been annotated recently on the basis of chromatin accessibility and histone modification patterns, delineating their role in developmentally regulated gene expression continues to be challenging. To fill t...

Chromatin structureDevelopmental biologyEpigenomicsTranscriptional regulatory elements

10.1038/S41594-024-01431-2

ISSN:1545-9993

Symmetric neural progenitor divisions require chromatin-mediated homologous recombination DNA repair by Ino80

Jason M. Keil•Daniel Z. Doyle•Adel Qalieh•Mandy M. Lam•Owen H. Funk等 10 人

Nature Communications

2020

•2020/7/31

•Vol.11 No.1 p.1-15

Chromatin regulates spatiotemporal gene expression during neurodevelopment, but it also mediates DNA damage repair essential to proliferating neural progenitor cells (NPCs). Here, we uncover molecularly dissociable roles for nucleosome remodeler Ino80 in chromatin-mediated transcriptional regulation...

Cell divisionChromatinNeuronal developmentTranscription

10.1038/S41467-020-17551-4

ISSN:2041-1723

Context-specific regulatory genetic variation in MTOR dampens neutrophil-T cell crosstalk in pneumonia-associated sepsis

Ping Zhang•Patrick MacLean•Alicia Jia•Callum R. O’Neill•Alice Allcock等 20 人

Nature Communications

2026

•2026/2/25

•Vol.17 No.1 p.32010

Sepsis is a heterogeneous clinical syndrome with a high mortality, requiring personalised stratification strategies. Here, we characterise genetic variation that modulates MTOR, a critical regulator of metabolism and immune responses in sepsis. The effects are context specific, involving a regulator...

EpigenomicsGenetics researchImmunogeneticsSepsis

10.1038/S41467-026-69919-7

ISSN:2041-1723

Disentangling oncogenic amplicons in esophageal adenocarcinoma

Alvin Wei Tian Ng•Dylan Peter McClurg•Ben Wesley•Shahriar A. Zamani•Emily Black等 18 人

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

N6-methyladenosine regulated FGFR4 attenuates ferroptotic cell death in recalcitrant HER2-positive breast cancer

Zou Yutian•Zheng Shaoquan•Xie Xinhua•Ye Feng•Hu Xiaoqian等 17 人

Nature Communications

2022

•2022/5/13

•Vol.13 No.1 p.1-18

Intrinsic and acquired anti-HER2 resistance remains a major hurdle for treating HER2-positive breast cancer. Using genome-wide CRISPR/Cas9 screening in vitro and in vivo, we identify FGFR4 as an essential gene following anti-HER2 treatment. FGFR4 inhibition enhances susceptibility to anti-HER2 thera...

CancerCancer therapeutic resistanceCancer therapyCell death

10.1038/S41467-022-30217-7

ISSN:2041-1723

Multidimensional chromatin profiling of zebrafish pancreas to uncover and investigate disease-relevant enhancers

Bordeira-Carriço Renata•Teixeira Joana•Duque Marta•Galhardo Mafalda•Ribeiro Diogo等 15 人

Nature Communications

2022

•2022/4/11

•Vol.13 No.1 p.1-17

The pancreas is a central organ for human diseases. Most alleles uncovered by genome-wide association studies of pancreatic dysfunction traits overlap with non-coding sequences of DNA. Many contain epigenetic marks of cis-regulatory elements active in pancreatic cells, suggesting that alterations in...

Animal disease modelsChromatin analysisEpigenomicsGene regulationGenetics research

10.1038/S41467-022-29551-7

ISSN:2041-1723

ORC1 binds to cis-transcribed RNAs for efficient activation of replication origins

Aina Maria Mas•Enrique Goñi•Igor Ruiz de los Mozos•Aida Arcas•Luisa Statello等 18 人

Nature Communications

2023

•2023/7/24

•Vol.14 No.1 p.1-19

Cells must coordinate the activation of thousands of replication origins dispersed throughout their genome. Active transcription is known to favor the formation of mammalian origins, although the role that RNA plays in this process remains unclear. We show that the ORC1 subunit of the human Origin R...

Molecular biologyNon-coding RNAsOrigin firing

10.1038/S41467-023-40105-3

ISSN:2041-1723

Getting personal with epigenetics: towards individual-specific epigenomic imputation with machine learning

Alex Hawkins-Hooker•Giovanni Visonà•Tanmayee Narendra•Mateo Rojas-Carulla•Bernhard Schölkopf等 6 人

Nature Communications

2023

•2023/8/7

•Vol.14 No.1 p.1-14

Epigenetic modifications are dynamic mechanisms involved in the regulation of gene expression. Unlike the DNA sequence, epigenetic patterns vary not only between individuals, but also between different cell types within an individual. Environmental factors, somatic mutations and ageing contribute to...

Histone post-translational modificationsMachine learningPost-translational modifications

10.1038/S41467-023-40211-2

ISSN:2041-1723

Cell-type-specific effects of genetic variation on chromatin accessibility during human neuronal differentiation

Dan Liang•Angela L. Elwell•Nil Aygün•Oleh Krupa•Justin M. Wolter等 17 人

Nature Neuroscience

2021

•2021/5/20

•00 p.1-13

Common genetic risk for neuropsychiatric disorders is enriched in regulatory elements active during cortical neurogenesis. However, it remains poorly understood as to how these variants influence gene regulation. To model the functional impact of common genetic variation on the noncoding genome duri...

Developmental neurogenesisEpigenomicsGene regulationGenome-wide association studies

10.1038/S41593-021-00858-W

ISSN:1097-6256

FreeHi-C simulates high-fidelity Hi-C data for benchmarking and data augmentation

Ye Zheng•Sündüz Keleş

Nature Methods

2019

•2019/11/11

•Vol.17 No.1 p.37-40

The ability to simulate high-throughput chromatin conformation (Hi-C) data is foundational for benchmarking Hi-C data analysis methods. Here we present a nonparametric strategy named FreeHi-C to simulate Hi-C data from the interacting genome fragments. Data from FreeHi-C exhibit high fidelity to bio...

Computational modelsSoftwareStatistical methods

10.1038/S41592-019-0624-3

ISSN:1548-7091

Common DNA methylation dynamics in endometriod adenocarcinoma and glioblastoma suggest universal epigenomic alterations in tumorigenesis

Jennifer A. Karlow•Benpeng Miao•Xiaoyun Xing•Ting Wang•Bo Zhang

Communications Biology

2021

•2021/5/21

•Vol.4 No.1 p.1-16

Trends in altered DNA methylation have been defined across human cancers, revealing global loss of methylation (hypomethylation) and focal gain of methylation (hypermethylation) as frequent cancer hallmarks. Although many cancers share these trends, little is known about the specific differences in ...

CNS cancerDNA methylationEndometrial cancer

10.1038/S42003-021-02094-1

ISSN:2399-3642

Spatial transcriptomics reveals niche-specific enrichment and vulnerabilities of radial glial stem-like cells in malignant gliomas

Ren Yanming•Huang Zongyao•Zhou Lingling•Xiao Peng•Song Junwei等 29 人

Nature Communications

2023

•2023/2/23

•Vol.14 No.1 p.1-19

Diffuse midline glioma-H3K27M mutant (DMG) and glioblastoma (GBM) are the most lethal brain tumors that primarily occur in pediatric and adult patients, respectively. Both tumors exhibit significant heterogeneity, shaped by distinct genetic/epigenetic drivers, transcriptional programs including RNA ...

Cancer genomicsCancer modelsCNS cancer

10.1038/S41467-023-36707-6

ISSN:2041-1723

An integrated view of the structure and function of the human 4D nucleome

Job Dekker•Betul Akgol Oksuz•Yang Zhang•Ye Wang•Miriam K. Minsk等 90 人

Nature

2025

•2025/12/17

•00 p.1-18

The dynamic three-dimensional (3D) organization of the human genome (the 4D nucleome) is linked to genome function. Here we describe efforts by the 4D Nucleome Project1 to map and analyse the 4D nucleome in widely used H1 human embryonic stem cells and immortalized fibroblasts (HFFc6). We produced a...

Computational modelsEpigeneticsGenome

10.1038/S41586-025-09890-3

ISSN:0028-0836

Analysis of R-loop forming regions identifies RNU2-2 and RNU5B-1 as neurodevelopmental disorder genes

Adam Jackson•Nishi Thaker•Alexander Blakes•Gillian Rice•Sam Griffiths-Jones等 23 人

Nature Genetics

2025

•2025/5/29

•00 p.1-5

R-loops are DNA–RNA hybrid structures that may promote mutagenesis. However, their contribution to human Mendelian disorders is unexplored. Here we show excess de novo variants in genomic regions that form R-loops (henceforth, ‘R-loop regions’) and demonstrate enrichment of R-loop region variants (R...

Clinical geneticsNeurodevelopmental disorders

10.1038/S41588-025-02209-Y

ISSN:1061-4036

Sex-specific genetic architecture of blood pressure

Min-Lee Yang•Chang Xu•Trisha Gupte•Thomas J. Hoffmann•Carlos Iribarren等 7 人

Nature Medicine

2024

•2024/3/8

•00 p.1-11

The genetic and genomic basis of sex differences in blood pressure (BP) traits remain unstudied at scale. Here, we conducted sex-stratified and combined-sex genome-wide association studies of BP traits using the UK Biobank resource, identifying 1,346 previously reported and 29 new BP trait-associate...

Genetics researchGenome-wide association studies

10.1038/S41591-024-02858-2

ISSN:1078-8956

High-content single-cell combinatorial indexing

Ryan M. Mulqueen•Dmitry Pokholok•Brendan L. O’Connell•Casey A. Thornton•Fan Zhang等 11 人

Nature Biotechnology

2021

•2021/7/5

•00 p.1-7

Single-cell combinatorial indexing (sci) with transposase-based library construction increases the throughput of single-cell genomics assays but produces sparse coverage in terms of usable reads per cell. We develop symmetrical strand sci (‘s3’), a uracil-based adapter switching approach that improv...

EpigeneticsGenomics

10.1038/S41587-021-00962-Z

ISSN:1087-0156

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

Deepak N. Subramanian•Maia Zethoven•Kathleen I. Pishas•Evanny R. Marinović•Simone McInerny等 11 人

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

The mutational impact of culturing human pluripotent and adult stem cells

Ewart Kuijk•Myrthe Jager•Bastiaan van der Roest•Mauro D. Locati•Arne Van Hoeck等 11 人

Nature Communications

2020

•2020/5/19

•Vol.11 No.1 p.1-12

Genetic changes acquired during in vitro culture pose a risk for the successful application of stem cells in regenerative medicine. To assess the genetic risks induced by culturing, we determined all mutations in individual human stem cells by whole genome sequencing. Individual pluripotent, intesti...

Adult stem cellsComputational biology and bioinformaticsGenomicsMutationPluripotent stem cells

10.1038/S41467-020-16323-4

ISSN:2041-1723

Characterization of cis-regulatory elements and functional variants in colorectal cancer using epigenomics and CRISPRi screenings

Zequn Lu•Can Chen•Heng Zhang•Bin Li•Yizhuo Liu等 37 人

Nature Cancer

2025

•2025/8/25

•00 p.1-23

Genetic variants associated with colorectal cancer (CRC) are primarily noncoding and reside in cis-regulatory elements (CREs), yet their underlying mechanisms remain elusive. Here we established a dynamic epigenetic atlas using multiomics data from 533 colorectal tissues spanning normal to advanced ...

CancerCancer genomicsColorectal cancerGenome-wide association studies

10.1038/S43018-025-01031-Z

ISSN:2662-1347

Screening for functional circular RNAs using the CRISPR–Cas13 system

Siqi Li•Xiang Li•Wei Xue•Lin Zhang•Liang-Zhong Yang等 19 人

Nature Methods

2020

•2020/12/7

•Vol.18 No.1 p.51-59

Circular RNAs (circRNAs) produced from back-spliced exons are widely expressed, but individual circRNA functions remain poorly understood owing to the lack of adequate methods for distinguishing circRNAs from cognate messenger RNAs with overlapping exons. Here, we report that CRISPR–RfxCas13d can ef...

High-throughput screeningLong non-coding RNAs

10.1038/S41592-020-01011-4

ISSN:1548-7091

Temporally divergent regulatory mechanisms govern neuronal diversification and maturation in the mouse and marmoset neocortex

Yuan Wen•Ma Sai•Brown Juliana R.•Kim Kwanho•Murek Vanessa等 13 人

Nature Neuroscience

2022

•2022/8/1

•Vol.25 No.8 p.1049-1058

Mammalian neocortical neurons span one of the most diverse cell type spectra of any tissue. Cortical neurons are born during embryonic development, and their maturation extends into postnatal life. The regulatory strategies underlying progressive neuronal development and maturation remain unclear. H...

Cell type diversityEpigenetics in the nervous systemTranscriptomics

10.1038/S41593-022-01123-4

ISSN:1097-6256

Cochlear transcript diversity and its role in auditory functions implied by an otoferlin short isoform

Huihui Liu•Hongchao Liu•Longhao Wang•Lei Song•Guixian Jiang等 12 人

Nature Communications

2023

•2023/5/29

•Vol.14 No.1 p.1-19

Isoforms of a gene may contribute to diverse biological functions. In the cochlea, the repertoire of alternative isoforms remains unexplored. We integrated single-cell short-read and long-read RNA sequencing techniques and identified 236,012 transcripts, 126,612 of which were unannotated in the GENC...

Hair cellMolecular neuroscience

10.1038/S41467-023-38621-3

ISSN:2041-1723

Genetic variations of DNA bindings of FOXA1 and co-factors in breast cancer susceptibility

Wen Wanqing•Chen Zhishan•Bao Jiandong•Long Quan•Shu Xiao-ou等 7 人

Nature Communications

2021

•2021/9/13

•Vol.12 No.1 p.1-12

Identifying transcription factors (TFs) whose DNA bindings are altered by genetic variants that regulate susceptibility genes is imperative to understand transcriptional dysregulation in disease etiology. Here, we develop a statistical framework to analyze extensive ChIP-seq and GWAS data and identi...

Breast cancerCancer epigenetics

10.1038/S41467-021-25670-9

ISSN:2041-1723

In vivo mapping of mutagenesis sensitivity of human enhancers

Michael Kosicki•Boyang Zhang•Vivian Hecht•Anusri Pampari•Laura E. Cook等 20 人

Nature

2025

•2025/6/18

•00 p.1-8

Distant-acting enhancers are central to human development1. However, our limited understanding of their functional sequence features prevents the interpretation of enhancer mutations in disease2. Here we determined the functional sensitivity to mutagenesis of human developmental enhancers in vivo. F...

EmbryologyEpigenomicsGene regulationMachine learning

10.1038/S41586-025-09182-W

ISSN:0028-0836

Transcriptome variation in human tissues revealed by long-read sequencing

Glinos Dafni A.•Garborcauskas Garrett•Hoffman Paul•Ehsan Nava•Jiang Lihua等 24 人

Nature

2022

•2022/8/3

•Vol.608 No.7922 p.353-359

Regulation of transcript structure generates transcript diversity and plays an important role in human disease1–7. The advent of long-read sequencing technologies offers the opportunity to study the role of genetic variation in transcript structure8–16. In this Article, we present a large human long...

Gene expression profilingQuantitative trait lociRNA sequencingRNA splicingSoftware

10.1038/S41586-022-05035-Y

ISSN:0028-0836

Identification of LZTFL1 as a candidate effector gene at a COVID-19 risk locus

Downes Damien J.•Cross Amy R.•Hua Peng•Roberts Nigel•Schwessinger Ron等 19 人

Nature Genetics

2021

•2021/11/4

•Vol.53 No.11 p.1606-1615

The severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) disease (COVID-19) pandemic has caused millions of deaths worldwide. Genome-wide association studies identified the 3p21.31 region as conferring a twofold increased risk of respiratory failure. Here, using a combined multiomics and mac...

Gene regulationGenome-wide association studiesGenomicsRespiratory tract diseasesSARS-CoV-2

10.1038/S41588-021-00955-3

ISSN:1061-4036

MetaTiME integrates single-cell gene expression to characterize the meta-components of the tumor immune microenvironment

Yi Zhang•Guanjue Xiang•Alva Yijia Jiang•Allen Lynch•Zexian Zeng等 15 人

Nature Communications

2023

•2023/5/6

•Vol.14 No.1 p.1-12

Recent advances in single-cell RNA sequencing have shown heterogeneous cell types and gene expression states in the non-cancerous cells in tumors. The integration of multiple scRNA-seq datasets across tumors can indicate common cell types and states in the tumor microenvironment (TME). We develop a ...

Cancer microenvironmentClassification and taxonomyData integrationSoftwareTumour immunology

10.1038/S41467-023-38333-8

ISSN:2041-1723

Decoding chromatin states by proteomic profiling of nucleosome readers

Saulius Lukauskas•Andrey Tvardovskiy•Nhuong V. Nguyen•Mara Stadler•Peter Faull等 20 人

Nature

2024

•2024/3/6

•00 p.1-9

DNA and histone modifications combine into characteristic patterns that demarcate functional regions of the genome1,2. While many ‘readers’ of individual modifications have been described3–5, how chromatin states comprising composite modification signatures, histone variants and internucleosomal lin...

EpigeneticsHistone post-translational modificationsProtein databasesProtein–protein interaction networksProteome informatics

10.1038/S41586-024-07141-5

ISSN:0028-0836

Systematic assessment of long-read RNA-seq methods for transcript identification and quantification

Francisco J. Pardo-Palacios•Dingjie Wang•Fairlie Reese•Mark Diekhans•Sílvia Carbonell-Sala等 87 人

Nature Methods

2024

•2024/6/7

•00 p.1-15

The Long-read RNA-Seq Genome Annotation Assessment Project Consortium was formed to evaluate the effectiveness of long-read approaches for transcriptome analysis. Using different protocols and sequencing platforms, the consortium generated over 427 million long-read sequences from complementary DNA ...

Gene expression profilingRNA sequencingSequence annotationSoftware

10.1038/S41592-024-02298-3

ISSN:1548-7091

Transposable elements as tissue-specific enhancers in cancers of endodermal lineage

Konsta Karttunen•Divyesh Patel•Jihan Xia•Liangru Fei•Kimmo Palin等 7 人

Nature Communications

2023

•2023/9/1

•Vol.14 No.1 p.1-19

Transposable elements (TE) are repetitive genomic elements that harbor binding sites for human transcription factors (TF). A regulatory role for TEs has been suggested in embryonal development and diseases such as cancer but systematic investigation of their functions has been limited by their wides...

CancerCancer genomicsComputational biology and bioinformatics

10.1038/S41467-023-41081-4

ISSN:2041-1723

Oncogenic gene expression and epigenetic remodeling of cis-regulatory elements in ASXL1-mutant chronic myelomonocytic leukemia

Binder Moritz•Carr Ryan M.•Lasho Terra L.•Finke Christy M.•Mangaonkar Abhishek A.等 15 人

Nature Communications

2022

•2022/3/17

•Vol.13 No.1 p.1-14

Myeloid neoplasms are clonal hematopoietic stem cell disorders driven by the sequential acquisition of recurrent genetic lesions. Truncating mutations in the chromatin remodeler ASXL1 (ASXL1MT) are associated with a high-risk disease phenotype with increased proliferation, epigenetic therapeutic res...

Cancer genomicsEpigenomicsGene expressionGene regulationMyelodysplastic syndrome

10.1038/S41467-022-29142-6

ISSN:2041-1723

A generalizable Hi-C foundation model for chromatin architecture, single-cell and multiomics analysis across species

Xiao Wang•Yuanyuan Zhang•Suhita Ray•Anupama Jha•Tangqi Fang等 9 人

Nature Methods

2026

•2026/6/15

•00 p.1-15

Nuclear DNA is organized into a three-dimensional (3D) structure that impacts critical cellular processes. However, the integrative analysis of 3D structure (measured by high-throughput chromosome conformation capture (Hi-C)) and associated epigenomic regulation (for example, assay for transposase-a...

ChromosomesComputational modelsEpigenomicsMachine learningSoftware

10.1038/S41592-026-03097-8

ISSN:1548-7091

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

Anneke Brümmer•Sven 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

Population-specific putative causal variants shape quantitative traits

Satoshi Koyama•Xiaoxi Liu•Yoshinao Koike•Keiko Hikino•Masaru Koido等 30 人

Nature Genetics

2024

•2024/10/3

•00 p.1-9

Human genetic variants are associated with many traits through largely unknown mechanisms. Here, combining approximately 260,000 Japanese study participants, a Japanese-specific genotype reference panel and statistical fine-mapping, we identified 4,423 significant loci across 63 quantitative traits,...

Genome-wide association studiesPersonalized medicine

10.1038/S41588-024-01913-5

ISSN:1061-4036

Identifying the “stripe” transcription factors and cooperative binding related to DNA methylation

Ximei Luo•Quan Zou

Communications Biology

2024

•2024/10/5

•Vol.7 No.1 p.1-10

DNA methylation plays a critical role in gene regulation by modulating the DNA binding of transcription factors (TFs). This study integrates TFs’ ChIP-seq profiles with WGBS profiles to investigate how DNA methylation affects protein interactions. Statistical methods and a 5-letter DNA motif calling...

BioinformaticsDNA methylation

10.1038/S42003-024-06992-Y

ISSN:2399-3642

ChromatinHD connects single-cell DNA accessibility and conformation to gene expression through scale-adaptive machine learning

Wouter Saelens•Olga Pushkarev•Bart Deplancke

Nature Communications

2025

•2025/1/2

•Vol.16 No.1 p.1-18

Gene regulation is inherently multiscale, but scale-adaptive machine learning methods that fully exploit this property in single-nucleus accessibility data are still lacking. Here, we develop ChromatinHD, a pair of scale-adaptive models that uses the raw accessibility data, without peak-calling or w...

Chromatin remodellingComputational modelsRegulatory networksStatistical methods

10.1038/S41467-024-55447-9

ISSN:2041-1723

SnapHiC: a computational pipeline to identify chromatin loops from single-cell Hi-C data

Yu Miao•Abnousi Armen•Zhang Yanxiao•Li Guoqiang•Lee Lindsay等 14 人

Nature Methods

2021

•2021/8/26

•00 p.1-4

Single-cell Hi-C (scHi-C) analysis has been increasingly used to map chromatin architecture in diverse tissue contexts, but computational tools to define chromatin loops at high resolution from scHi-C data are still lacking. Here, we describe Single-Nucleus Analysis Pipeline for Hi-C (SnapHiC), a me...

ChromatinComputational models

10.1038/S41592-021-01231-2

ISSN:1548-7091

Tissue-specific multi-omics analysis of atrial fibrillation

Assum Ines•Krause Julia•Scheinhardt Markus O.•Müller Christian•Hammer Elke等 12 人

Nature Communications

2022

•2022/1/21

•Vol.13 No.1 p.1-15

Genome-wide association studies (GWAS) for atrial fibrillation (AF) have uncovered numerous disease-associated variants. Their underlying molecular mechanisms, especially consequences for mRNA and protein expression remain largely elusive. Thus, refined multi-omics approaches are needed for decipher...

Gene expressionGene regulatory networksGenome-wide association studiesGenomicsProteomics

10.1038/S41467-022-27953-1

ISSN:2041-1723

Growth differentiation factor 1-induced tumour plasticity provides a therapeutic window for immunotherapy in hepatocellular carcinoma

Cheng Wei•Li Hao-Long•Xi Shao-Yan•Zhang Xiao-Feng•Zhu Yun等 19 人

Nature Communications

2021

•2021/12/8

•Vol.12 No.1 p.1-14

Tumour lineage plasticity is an emerging hallmark of aggressive tumours. Tumour cells usually hijack developmental signalling pathways to gain cellular plasticity and evade therapeutic targeting. In the present study, the secreted protein growth and differentiation factor 1 (GDF1) is found to be clo...

Cancer stem cellsHepatocellular carcinomaTumour immunology

10.1038/S41467-021-27525-9

ISSN:2041-1723

An atlas of dynamic chromatin landscapes in mouse fetal development

David U. Gorkin•Iros Barozzi•Yuan Zhao•Yanxiao Zhang•Hui Huang等 43 人

Nature

2020

•2020/7/29

•Vol.583 No.7818 p.744-751

The Encyclopedia of DNA Elements (ENCODE) project has established a genomic resource for mammalian development, profiling a diverse panel of mouse tissues at 8 developmental stages from 10.5 days after conception until birth, including transcriptomes, methylomes and chromatin states. Here we systema...

DifferentiationEpigenomics

10.1038/S41586-020-2093-3

ISSN:0028-0836

The genetic architecture of biological age in nine human organ systems

Junhao Wen•Ye Ella Tian•Ioanna Skampardoni•Zhijian Yang•Yuhan Cui等 11 人

Nature Aging

2024

•2024/6/28

•00 p.1-18

Investigating the genetic underpinnings of human aging is essential for unraveling the etiology of and developing actionable therapies for chronic diseases. Here, we characterize the genetic architecture of the biological age gap (BAG; the difference between machine learning-predicted age and chrono...

AgeingData miningGenome-wide association studies

10.1038/S43587-024-00662-8

ISSN:2662-8465

Reconstruction of diploid higher-order human 3D genome interactions from noisy Pore-C data using Dip3D

Ying Chen•Zhuo-Bin Lin•Shao-Kai Wang•Bo Wu•Longjian Niu等 17 人

Nature Structural & Molecular Biology

2025

•2025/3/4

•00 p.1-13

Differential high-order chromatin interactions between homologous chromosomes affect many biological processes. Traditional chromatin conformation capture genome analysis methods mainly identify two-way interactions and cannot provide comprehensive haplotype information, especially for low-heterozyg...

EpigenomicsGenomic analysisGenomicsHigh-throughput screening

10.1038/S41594-025-01512-W

ISSN:1545-9993