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Record W2164802216 · doi:10.1038/srep15145

Synchronized age-related gene expression changes across multiple tissues in human and the link to complex diseases

2015· article· en· W2164802216 on OpenAlex
Jialiang Yang, Tao Huang, Francesca Petralia, Quan Long, Bin Zhang, Carmen Argmann, Yong Zhao, Charles V. Mobbs, Eric E. Schadt, Jun Zhu, Zhidong Tu, Kristin Ardlie, David S. DeLuca, Ayellet V. Segrè, Timothy J. Sullivan, Taylor Young, Ellen Gelfand, Casandra A. Trowbridge, Julian Maller, Taru Tukiainen, Monkol Lek, Lucas D. Ward, Pouya Kheradpour, Benjamin Iriarte, Yan Meng, Cameron D. Palmer, Wendy Winckler, Joel N. Hirschhorn, Manolis Kellis, Daniel G. MacArthur, Gad Getz, Andrey A. Shablin, Gen Li, Yi-Hui Zhou, Andrew B. Nobel, Ivan Rusyn, Fred A. Wright, Tuuli Lappalainen, Pedro G. Ferreira, Halit Ongen, Manuel A. Rivas, Alexis Battle, Sara Mostafavi, Jean Monlong, Michael Sammeth, Marta Melé, Ferrán Reverter, Jakob M. Goldmann, Daphne Koller, Roderic Guigó, Mark I. McCarthy, Emmanouil T. Dermitzakis, Eric R. Gamazon, Anuar Konkashbaev, Dan L. Nicolae, Nancy J. Cox, Timothée Flutre, Xiaoquan Wen, Matthew Stephens, Jonathan K. Pritchard, Luan Lin, Jun Liu, Amanda Brown, Bernadette Mestichelli, Denee Tidwell, Edmund Lo, Mike Salvatore, Saboor Shad, Jeffrey A. Thomas, John T. Lonsdale, Christopher Choi, Ellen Karasik, Kimberly Ramsey, Michael T. Moser, Barbara A. Foster, Bryan M. Gillard, John Syron, Johnelle Fleming, Harold I. Magazine, Rick Hasz, Gary Walters, Jason Bridge, Mark Miklos, Susan Sullivan, Laura K. Barker, Heather M. Traino, Magboeba Mosavel, Laura A. Siminoff, Dana R. Valley, Daniel C. Rohrer, Scott Jewel, Philip A. Branton, Leslie H. Sobin, Liqun Qi, Pushpa Hariharan, Shenpei Wu, David E. Tabor, Charles Shive, Anna M. Smith, Stephen A. Buia, Anita H. Undale, Karna Robinson, Nancy Roche, Kimberly M. Valentino, Angela Britton, Robin Burges, Debra Bradbury, Kenneth W. Hambright, John Seleski, Greg E. Korzeniewski, Kenyon Erickson, Yvonne Marcus, Jorge Tejada, Mehran Taherian, Chunrong Lu, Barnaby E. Robles, Margaret J. Basile, Deborah C. Mash, Simona Volpi, Jeff Struewing, Gary F. Temple, Joy T Boyer, Deborah Colantuoni, Susan E. Koester, NCI Latarsha J. Carithers, Helen M. Moore, Ping Guan, Carolyn C. Compton, Sherilyn J. Sawyer, Joanne P. Demchok, Jimmie B. Vaught, Chana A. Rabiner, Nicole C. Lockhart

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueScientific Reports · 2015
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetics, Aging, and Longevity in Model Organisms
Canadian institutionsMcGill UniversityMcGill Genome Centre
FundersCommon FundNational Institute of Neurological Disorders and StrokeNational Institute of Diabetes and Digestive and Kidney DiseasesNational Cancer InstituteNIH Office of the DirectorNational Human Genome Research InstituteNational Institute of Mental HealthNational Heart, Lung, and Blood InstituteNational Institutes of HealthUniversité de GenèveFondation LeducqBroad InstituteUniversity of ChicagoHarvard UniversityUniversity of PennsylvaniaNational Institute on Drug AbuseUniversity of Miami
KeywordsGene expressionTranscriptomeBiologyGeneRegulation of gene expressionGene expression profilingComputational biologyGenetics

Abstract

fetched live from OpenAlex

Aging is one of the most important biological processes and is a known risk factor for many age-related diseases in human. Studying age-related transcriptomic changes in tissues across the whole body can provide valuable information for a holistic understanding of this fundamental process. In this work, we catalogue age-related gene expression changes in nine tissues from nearly two hundred individuals collected by the Genotype-Tissue Expression (GTEx) project. In general, we find the aging gene expression signatures are very tissue specific. However, enrichment for some well-known aging components such as mitochondria biology is observed in many tissues. Different levels of cross-tissue synchronization of age-related gene expression changes are observed, and some essential tissues (e.g., heart and lung) show much stronger "co-aging" than other tissues based on a principal component analysis. The aging gene signatures and complex disease genes show a complex overlapping pattern and only in some cases, we see that they are significantly overlapped in the tissues affected by the corresponding diseases. In summary, our analyses provide novel insights to the co-regulation of age-related gene expression in multiple tissues; it also presents a tissue-specific view of the link between aging and age-related diseases.

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.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.075
Threshold uncertainty score0.453

Codex and Gemma teacher scores by category

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

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 head0.026
GPT teacher head0.289
Teacher spread0.263 · 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