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Record W4313544615 · doi:10.1038/s41586-022-05580-6

A DNA methylation atlas of normal human cell types

2023· article· en· W4313544615 on OpenAlexaff
Netanel Loyfer, Judith Magenheim, Ayelet Peretz, Gordon Cann, Joerg Bredno, Agnes Klochendler, Ilana Fox-Fisher, Sapir Shabi-Porat, Merav Hecht, Tsuria Pelet, Joshua Moss, Zeina Drawshy, Hamed Amini, Patriss W. Moradi, Sudharani Nagaraju, Dvora Bauman, David Shveiky, Shay Porat, Uri P. Dior, Gurion Rivkin, Omer Or, Nir Hirshoren, Einat Carmon, Alon J. Pikarsky, Abed Khalaileh, Gideon Zamir, Ronit Grinbaum, Machmud Abu Gazala, Ido Mizrahi, Noam Shussman, Amit Korach, Ori Wald, Uzi Izhar, Eldad Erez, Vladimir Yutkin, Yaacov Samet, Devorah Rotnemer Golinkin, Kirsty L. Spalding, Henrik Druid, Peter Arner, A. M. James Shapiro, Markus Grompe, Alex Aravanis, Oliver Venn, Arash Jamshidi, Ruth Shemer, Yuval Dor, Benjamin Gläser, Tommy Kaplan

Bibliographic record

VenueNature · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicEpigenetics and DNA Methylation
Canadian institutionsUniversity of Alberta
FundersLeibniz-GemeinschaftStichting Diabetes Onderzoek NederlandIsrael Science FoundationHuman Islet Research NetworkNational Institute of Diabetes and Digestive and Kidney DiseasesHadassah Medical OrganizationLeona M. and Harry B. Helmsley Charitable Trust
KeywordsDNA methylationBiologyChromatinEpigeneticsEpigenomicsCpG siteGeneticsEpigenetics of physical exerciseMethylationEnhancerDifferentially methylated regionsComputational biologyRegulation of gene expressionDNAGeneGene expression

Abstract

fetched live from OpenAlex

Abstract DNA methylation is a fundamental epigenetic mark that governs gene expression and chromatin organization, thus providing a window into cellular identity and developmental processes 1 . Current datasets typically include only a fraction of methylation sites and are often based either on cell lines that underwent massive changes in culture or on tissues containing unspecified mixtures of cells 2–5 . Here we describe a human methylome atlas, based on deep whole-genome bisulfite sequencing, allowing fragment-level analysis across thousands of unique markers for 39 cell types sorted from 205 healthy tissue samples. Replicates of the same cell type are more than 99.5% identical, demonstrating the robustness of cell identity programmes to environmental perturbation. Unsupervised clustering of the atlas recapitulates key elements of tissue ontogeny and identifies methylation patterns retained since embryonic development. Loci uniquely unmethylated in an individual cell type often reside in transcriptional enhancers and contain DNA binding sites for tissue-specific transcriptional regulators. Uniquely hypermethylated loci are rare and are enriched for CpG islands, Polycomb targets and CTCF binding sites, suggesting a new role in shaping cell-type-specific chromatin looping. The atlas provides an essential resource for study of gene regulation and disease-associated genetic variants, and a wealth of potential tissue-specific biomarkers for use in liquid biopsies.

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)0.000
metaresearch head score (Gemma)0.001
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: none
Teacher disagreement score0.006
Threshold uncertainty score0.019

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0030.003
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0010.001
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0060.003

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 head0.008
GPT teacher head0.276
Teacher spread0.268 · 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

Citations627
Published2023
Admission routes1
Has abstractyes

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