ArticleScience (New York, N.Y.)2024
Single-cell chromatin accessibility reveals malignant regulatory programs in primary human cancers.
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Article in Science (New York, N.Y.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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40citing papers in PubMed
–field-weighted citation impact
What it found
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Who cites it
40 citing papers in PubMed.
- IRP1/ARID3A complex promotes pancreatic cancer chemoresistance by suppressing CYGB-related ferroptosis.Genes & diseases · 2026Article
- Developmentally constrained plasticity as a therapeutic vulnerability in cancer.Neoplasia (New York, N.Y.) · 2026Review
- Single-cell multimodal profiling of pan-cancer cell lines uncovers gene regulatory principles underlying intrinsic cell states and environmental features.Nature communications · 2026Article
- A novel homozygous frameshift mutation in CFAP65 is associated with multiple morphological abnormalities of sperm flagella in a consanguineous Pakistani family.Basic and clinical andrology · 2026Article
- Robust and generalizable CNV detection for single-cell sequencing assays.Nucleic acids research · 2026Article
- Article
- RAD21 regulation of the enhancer-promoter chromatin loop of RAD51 promotes PARPi resistance in ovarian cancer.Journal of translational medicine · 2026Article
- Single-cell multimodal profiling of pan-cancer cell lines uncovers gene regulatory principles underlying intrinsic cell states and environmental features.bioRxiv : the preprint server for biology · 2026Article
- Spatial and single-cell characterization of human glioblastoma tumor microenvironment reveals malignant cellular communities.Nature neuroscience · 2026Article
- A lightweight deep learning model with channel attention for kidney cell classification from microscopy images.Scientific reports · 2026Article
- Epigenetic Regulation of Uterine Smooth Muscle Tumors: Histone Modifications in Uterine Fibroids and Leiomyosarcoma.Biology · 2026Review
- Inferring tumor absolute copy number and clonal substructure from single-cell chromatin accessibility.Briefings in bioinformatics · 2026Article
- Mapping functional non-coding variation in individual human genomes through haplotyping, multiomics, and deep learning.Nature communications · 2026Article
- Review
- Cell type annotation for scATAC-seq via DNA large language model and graph domain adaptation.PLoS computational biology · 2026Article
- Spatial Chromatin Accessibility Analysis of Intratumor Heterogeneity in Breast Cancer.Genomics, proteomics & bioinformatics · 2026Article
- Chromatin architecture and physical constriction cooperate in phenotype switching and cancer cell dissemination.bioRxiv : the preprint server for biology · 2026Article
- scAmp analyzes focal gene amplifications at single-cell resolution.bioRxiv : the preprint server for biology · 2026Article
- CHD4 epigenetically coordinates genomic instability and immunosuppression to drive pan-cancer progression and confer HDAC inhibitor sensitivity.Clinical and experimental medicine · 2026Article
- Single-nucleus multi-omics delineates distinct epigenetic programs associated with tumor progression in lung adenocarcinoma.Clinical epigenetics · 2026Article
Corrections and comments
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Authors and funding
50 authors.
Laksshman SundaramDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0002-8953-3940
Arvind Kumar *Illumina AI laboratory, Illumina Inc, Foster City, CA, USA.ORCID 0000-0002-1804-2343
Matthew Zatzman *Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID 0000-0001-5235-4116
Adriana SalcedoIllumina AI laboratory, Illumina Inc, Foster City, CA, USA.
Neal RavindraIllumina AI laboratory, Illumina Inc, Foster City, CA, USA.ORCID 0000-0001-5558-3758
Shadi ShamsDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0003-4334-2820
Bryan H LouieDepartment of Dermatology, Stanford University School of Medicine, Stanford, CA, USA.
S Tansu BagdatliDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
Matthew A MyersComputational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID 0000-0002-9337-5180
Shahab SarmashghiBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0003-0564-1643
Hyo Young ChoiDepartment of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.ORCID 0000-0002-7627-8493
Won-Young ChoiUTHSC Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN, USA.
Kathryn E YostDepartment of Dermatology, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0001-6807-950X
Yanding ZhaoDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
Jeffrey M GranjaDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
Toshinori HinoueCenter for Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA.ORCID 0000-0002-5078-5016
D Neil HayesDepartment of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.ORCID 0000-0001-6203-7771
Andrew CherniackBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0003-0470-0111
Ina FelauNational Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.ORCID 0000-0002-9005-0700
Hani ChoudhryDepartment of Biochemistry, Faculty of Science, Cancer and Mutagenesis Unit, King Fahd Center for Medical Research, King Abdulaziz University, Jeddah, Saudi Arabia.
Jean C ZenklusenNational Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.ORCID 0000-0002-9489-1873
Kyle Kai-How FarhIllumina AI laboratory, Illumina Inc, Foster City, CA, USA.ORCID 0000-0001-6947-8537
Andrew McPhersonComputational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID 0000-0002-5654-5101
Christina CurtisDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0003-0166-3802
Peter W LairdCenter for Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA.ORCID 0000-0001-9117-3641
Cancer Genome Atlas Analysis Network‡
John A DemchokCenter for Cancer Genomics, National Cancer Institute, Bethesda, MD 20892, USA.
Liming YangCenter for Cancer Genomics, National Cancer Institute, Bethesda, MD 20892, USA.
Roy TarnuzzerCenter for Cancer Genomics, National Cancer Institute, Bethesda, MD 20892, USA.
Samantha J Caesar-JohnsonCenter for Cancer Genomics, National Cancer Institute, Bethesda, MD 20892, USA.
Zhining WangCenter for Biomedical Informatics and Information Technology, National Cancer Institute, NIH, 9609 Medical Center Drive, Rockville, MD 20850, USA.
Ashley S DoaneInstitute for Computational Biomedicine, Weill Cornell Medicine, New York, NY 10065, USA.
Ekta KhuranaInstitute for Computational Biomedicine, Weill Cornell Medicine, New York, NY 10065, USA.
Mauro A A CastroBioinformatics and Systems Biology Laboratory, Federal University of Paraná, Curitiba 81520-260, Brazil.
Alexander J LazarDepartments of Pathology & Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Bradley M BroomDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
John N WeinsteinDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Rehan AkbaniDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Shwetha V KumarDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Benjamin J RaphaelDepartment of Computer Science, Princeton University, 35 Olden Street, Princeton, NJ 08540.
Christopher K WongBiomolecular Engineering Department, School of Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
Joshua M StuartBiomolecular Engineering Department, School of Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
Rojin SafaviBiomolecular Engineering Department, School of Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
Christopher C BenzBuck Institute for Research on Aging, Novato, CA 94945, USA.
Benjamin K JohnsonCenter for Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA.
Cindy KyiCenter for Cancer Genomics, National Cancer Institute, Bethesda, MD 20892, USA.
Hui ShenCenter for Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA.
M Ryan CorcesDepartment of Dermatology, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0001-7465-7652
Howard Y ChangDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0002-9459-4393
William J GreenleafDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0003-1409-3095
Funding
The Patient-Reported Outcomes, Community-Engagement and Language (PRO-CEL) CoreP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · 1985 to 2025
$88.4MStanford Mendelian Genomics Research CenterU01HG011762 · STANFORD UNIVERSITY · 2025 to 2025
$2.8MStanford Center for Connecting DNA Variants to Function and PhenotypeUM1HG011972 · STANFORD UNIVERSITY · 2025 to 2025
$1.8MCombinatorial Cell State EngineeringDP1HG013599 · STANFORD UNIVERSITY · 2025 to 2025
$1.1MDefining and perturbing gene regulatory dynamics in the developing human heart to understand mechanisms of congenital heart defectsR01HL171611 · STANFORD UNIVERSITY · 2025 to 2025
$730kFast, powerful, scalable, usable, and distributable methods for multi-modal single cell analysesR01HG013317 · STANFORD UNIVERSITY · 2025 to 2025
$701kDefining and perturbing gene regulatory dynamics in the developing human brainR01NS128028 · STANFORD UNIVERSITY · 2025 to 2025
$598kStanford Tissue Mapping CenterU54HG012723 · STANFORD UNIVERSITY · 2025 to 2025
$500kIntegrative Cancer Epigenomic Data Analysis Center (ICE-DAC)U24CA264023 · VAN ANDEL RESEARCH INSTITUTE · 2025 to 2025
$456kThe MSK Genomic Data Analysis Center for Tumor EvolutionU24CA264028 · SLOAN-KETTERING INST CAN RESEARCH · 2025 to 2025
$425kA Genome Data Analysis Center Focused on Batch Effect Analysis and Data IntegrationU24CA264006 · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2025 to 2025
$403kCenter for the Comprehensive Analysis of Cancer Somatic Copy-Number Alterations, Rearrangements, and Long-Read Sequencing DataU24CA264029 · BROAD INSTITUTE, INC. · 2025 to 2025
$397kNCI NIH HHS P30 CA008748NCI NIH HHS U24 CA264006NCI NIH HHS U24 CA264009NCI NIH HHS U24 CA264021NCI NIH HHS U24 CA264023NCI NIH HHS U24 CA264027NCI NIH HHS U24 CA264028NCI NIH HHS U24 CA264029NCI NIH HHS U24 CA264032NCI NIH HHS U2C CA233311NHGRI NIH HHS DP1 HG013599NHGRI NIH HHS P50 HG007735NHGRI NIH HHS R01 HG013317NHGRI NIH HHS RM1 HG007735NHGRI NIH HHS U01 HG011762NHGRI NIH HHS U54 HG012723NHGRI NIH HHS UM1 HG009436NHGRI NIH HHS UM1 HG011972NHLBI NIH HHS R01 HL171611NIMH NIH HHS U01 MH116529NINDS NIH HHS R01 NS128028
Abstract
To identify cancer-associated gene regulatory changes, we generated single-cell chromatin accessibility landscapes across eight tumor types as part of The Cancer Genome Atlas. Tumor chromatin accessibility is strongly influenced by copy number alterations that can be used to identify subclones, yet underlying cis-regulatory landscapes retain cancer type-specific features. Using organ-matched healthy tissues, we identified the "nearest healthy" cell types in diverse cancers, demonstrating that the chromatin signature of basal-like-subtype breast cancer is most similar to secretory-type luminal epithelial cells. Neural network models trained to learn regulatory programs in cancer revealed enrichment of model-prioritized somatic noncoding mutations near cancer-associated genes, suggesting that dispersed, nonrecurrent, noncoding mutations in cancer are functional. Overall, these data and interpretable gene regulatory models for cancer and healthy tissue provide a framework for understanding cancer-specific gene regulation.
Indexed as
ChromatinGene Expression Regulation, NeoplasticNeoplasmsSingle-Cell AnalysisBreast NeoplasmsDNA Copy Number VariationsHumansMutationNeural Networks, ComputerChromatin
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.