The chromatin accessibility landscape of primary human cancers

Science, Journal Year: 2018, Volume and Issue: 362(6413)

Published: Oct. 26, 2018

Cancer chromatin accessibility landscape The Genome Atlas (TCGA) provides a high-quality resource of molecular data on large variety human cancers. Corces et al. used recently modified assay to profile determine the accessible in 410 TCGA samples from 23 cancer types (see Perspective by Taipale). When were integrated with other omics available for same tumor samples, inherited risk loci predisposition revealed, transcription factors and enhancers driving subtypes patient survival differences identified, noncoding mutations associated clinical prognosis discovered. Science , this issue p. eaav1898 ; see also 401

Language: Английский

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Comprehensive Analysis of Genetic Ancestry and Its Molecular Correlates in Cancer

Cancer Cell, Journal Year: 2020, Volume and Issue: 37(5), P. 639 - 654.e6

Published: May 1, 2020

Language: Английский

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Universal DNA methylation age across mammalian tissues

Nature Aging, Journal Year: 2023, Volume and Issue: 3(9), P. 1144 - 1166

Published: Aug. 10, 2023

Abstract Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation pan-tissue epigenetic clocks. Here, we demonstrate development universal pan-mammalian clocks, 11,754 arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate age with high accuracy ( r > 0.96). Age deviations correlate human mortality risk, mouse somatotropic axis mutations and caloric restriction. We identified specific cytosines levels that change numerous sites, highly enriched in polycomb repressive complex 2-binding locations, are near genes implicated development, cancer, obesity longevity. Our findings offer new evidence suggesting aging is evolutionarily conserved intertwined developmental processes all mammals.

Language: Английский

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A mammalian methylation array for profiling methylation levels at conserved sequences

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Feb. 10, 2022

Infinium methylation arrays are not available for the vast majority of non-human mammals. Moreover, even if species-specific were available, probe differences between them would confound cross-species comparisons. To address these challenges, we developed mammalian array, a single custom array that measures up to 36k CpGs per species well conserved across many species. We designed set probes can tolerate specific mutations. annotate in over 200 and report CpG island status chromatin states select Calibration experiments demonstrate high fidelity humans, rats, mice. The has several strengths: it applies all those have yet been sequenced, provides deep coverage cytosines facilitating development epigenetic biomarkers, increases probability biological insights gained one will translate others.

Language: Английский

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Meningioma DNA methylation groups identify biological drivers and therapeutic vulnerabilities

Nature Genetics, Journal Year: 2022, Volume and Issue: 54(5), P. 649 - 659

Published: May 1, 2022

Language: Английский

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Enhanced cell deconvolution of peripheral blood using DNA methylation for high-resolution immune profiling

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Feb. 9, 2022

Abstract DNA methylation microarrays can be employed to interrogate cell-type composition in complex tissues. Here, we expand reference-based deconvolution of blood include 12 leukocyte subtypes (neutrophils, eosinophils, basophils, monocytes, naïve and memory B cells, CD4 + CD8 T natural killer, regulatory cells). Including derived variables, our method provides 56 immune profile variables. The IDOL (IDentifying Optimal Libraries) algorithm was used identify libraries for data current previous platforms. accuracy estimates obtained using enhanced validated artificial mixtures whole-blood with known cellular from flow cytometry. We applied deconvolve cancer, aging, autoimmune disease datasets. In conclusion, these enable a detailed representation immune-cell profiles only facilitate standardized, thorough investigation human health disease.

Language: Английский

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In vivo partial reprogramming alters age-associated molecular changes during physiological aging in mice

Nature Aging, Journal Year: 2022, Volume and Issue: 2(3), P. 243 - 253

Published: March 7, 2022

Language: Английский

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Phase II clinical trial of metformin as a cancer stem cell-targeting agent in ovarian cancer

JCI Insight, Journal Year: 2020, Volume and Issue: unknown

Published: May 5, 2020

BACKGROUND. Epidemiologic studies suggest that metformin has antitumor effects. Laboratory indicate impacts cancer stem-like cells (CSCs). As part of a phase II trial, we evaluated the impact on CSC number and carcinoma-associated mesenchymal stem (CA-MSCs) clinical outcomes in nondiabetic patients with advanced-stage epithelial ovarian (EOC).

Language: Английский

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DNA methylation GrimAge version 2

Aging, Journal Year: 2022, Volume and Issue: unknown

Published: Dec. 14, 2022

Aging | doi:10.18632/aging.204434. Ake T. Lu, Alexandra M. Binder, Joshua Zhang, Qi Yan, Alex P. Reiner, Simon R. Cox, Janie Corley, Sarah E. Harris, Pei-Lun Kuo, Ann Z. Moore, Stefania Bandinelli, James D. Stewart, Cuicui Wang, Elissa J. Hamlat, S. Epel, Joel Schwartz, Eric A. Whitsel, Adolfo Correa, Luigi Ferrucci, Riccardo Marioni, Steve Horvath

Language: Английский

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Epigenomic and transcriptomic analyses define core cell types, genes and targetable mechanisms for kidney disease

Nature Genetics, Journal Year: 2022, Volume and Issue: 54(7), P. 950 - 962

Published: June 16, 2022

Language: Английский

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