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Record W2076154138 · doi:10.1038/nature14248

Integrative analysis of 111 reference human epigenomes

2015· article· en· W2076154138 on OpenAlexaff
Anshul Kundaje, Wouter Meuleman, Jason Ernst, Misha Bilenky, Angela Yen, Alireza Heravi‐Moussavi, Pouya Kheradpour, Zhizhuo Zhang, Jianrong Wang, Michael J. Ziller, Viren Amin, John W. Whitaker, Matthew D. Schultz, Lucas D. Ward, Abhishek Sarkar, Gerald Quon, Richard Sandstrom, Matthew L. Eaton, Yi-Chieh Wu, Andreas R. Pfenning, Xinchen Wang, Melina Claussnitzer, Yaping Liu, Cristian Coarfa, R. Alan Harris, Noam Shoresh, Charles B. Epstein, Elizabeta Gjoneska, Danny Leung, Wei Xie, R. David Hawkins, Ryan Lister, Chibo Hong, Philippe Gascard, Andrew J. Mungall, Richard A. Moore, Eric Chuah, Angela Tam, Theresa K. Canfield, R. Scott Hansen, Rajinder Kaul, Peter J. Sabo, Mukul S. Bansal, Annaïck Carles, Jesse R. Dixon, Kai-How Farh, Soheil Feizi, Rosa Karlić, Ah-Ram Kim, Ashwinikumar Kulkarni, Daofeng Li, Rebecca F. Lowdon, GiNell Elliott, Tim R. Mercer, Shane Neph, Vitor Onuchic, Paz Polak, Nisha Rajagopal, Pradipta Ray, Richard Sallari, Kyle Siebenthall, Nicholas A. Sinnott‐Armstrong, Michael Stevens, Robert E. Thurman, Jie Wu, Bo Zhang, Xin Zhou, Arthur E. Beaudet, Laurie A. Boyer, Philip L. De Jager, Peggy Farnham, Susan J. Fisher, David Haussler, Steven J.M. Jones, Wei Li, Marco A. Marra, Michael T. McManus, Shamil Sunyaev, James A. Thomson, Thea D. Tlsty, Wei Wang, Robert A. Waterland, Michael Q. Zhang, Lisa H. Chadwick, B Bernstein, J Costello, Joseph R. Ecker, Martin Hirst, Alexander Meissner, Aleksandar Milosavljević, Bing Ren, J Stamatoyannopoulos, Ting Wang, Manolis Kellis

Bibliographic record

VenueNature · 2015
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicEpigenetics and DNA Methylation
Canadian institutionsSimon Fraser UniversityUniversity of British ColumbiaCanada's Michael Smith Genome Sciences CentreBC Cancer Agency
FundersEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentCommon FundNational Institute of Environmental Health SciencesNational Institute of Diabetes and Digestive and Kidney DiseasesNational Institute on Deafness and Other Communication DisordersNational Institute on Drug AbuseNational Institute of Mental HealthNational Heart, Lung, and Blood InstituteNational Institute on AgingTsinghua National Laboratory for Information Science and TechnologyNational Center for Advancing Translational SciencesNational Human Genome Research InstituteTsinghua UniversityNational Natural Science Foundation of ChinaNational Institutes of HealthNational Science FoundationWashington University in St. LouisNational Institute of Neurological Disorders and StrokeNational Institute of General Medical SciencesMassachusetts General HospitalHoward Hughes Medical Institute
KeywordsEpigenomicsDNA methylationComputational biologyBiologyHuman genomeGeneticsEpigenomeChromatinGenomeGeneGene expression

Abstract

fetched live from OpenAlex

The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease. This study describes the integrative analysis of 111 reference human epigenomes, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression; the results annotate candidate regulatory elements in diverse tissues and cell types, their candidate regulators, and the set of human traits for which they show genetic variant enrichment, providing a resource for interpreting the molecular basis of human disease. The goal of the NIH Roadmap Epigenomics Consortium was to generate a reference collection of human epigenomes for primary cells and tissues. This study describes the integrative analysis of 111 reference human epigenomes, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. The results show that disease and trait-associated genetic variants are enriched in predicted tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits and providing a resource for interpreting the molecular basis of human disease.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.009

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0020.003
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0030.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.024
GPT teacher head0.331
Teacher spread0.307 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations7,110
Published2015
Admission routes1
Has abstractyes

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