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Record W2173367702 · doi:10.1038/ncomms9570

The transcriptional landscape of age in human peripheral blood

2015· review· en· W2173367702 on OpenAlexaff
Marjolein J. Peters, Roby Joehanes, Luke C. Pilling, Claudia Schurmann, Karen N. Conneely, Joseph E. Powell, Eva Reinmaa, George L. Sutphin, Alexandra Zhernakova, Katharina Schramm, Yana A. Wilson, Sayuko Kobes, Taru Tukiainen, Michael A. Nalls, Dena Hernández, Mark Cookson, J. Raphael Gibbs, John Hardy, Adaikalavan Ramasamy, Alan B. Zonderman, Allissa Dillman, Bryan J. Traynor, Colin Smith, Dan L. Longo, Daniah Trabzuni, Juan C. Troncoso, Marcel van der Brug, Michael E. Weale, Richard M. O’Brien, Robert Johnson, Robert Walker, Ronald H. Zielke, Sampath Arepalli, Mina Ryten, Andrew Singleton, Y.F. Ramos, Harald H.H. Göring, Myriam Fornage, Ching‐Ti Liu, Sina A. Gharib, Barbara E. Stranger, Philip L. De Jager, Abraham Aviv, Daniel Levy, Joanne M. Murabito, Peter J. Munson, Tianxiao Huan, Albert Hofman, André G. Uitterlinden, Fernando Rivadeneira, Jeroen van Rooij, Lisette Stolk, Linda Broer, Michaël Verbiest, Mila Jhamai, Pascal Arp, Andres Metspalu, Liina Tserel, Lili Milani, Nilesh J. Samani, Pärt Peterson, Silva Kasela, Veryan Codd, Annette Peters, Cavin Ward‐Caviness, Christian Herder, Mélanie Waldenberger, Michael Roden, Paula Singmann, Sonja Zeilinger, Thomas Illig, Georg Homuth, Hans J. Grabe, Henry Völzke, Leif Steil, Thomas Kocher, Anna Murray, David Melzer, Hanieh Yaghootkar, Stefania Bandinelli, Eric K. Moses, Jack W. Kent, Joanne E. Curran, Matthew P. Johnson, Sarah Williams‐Blangero, Harm-Jan Westra, Allan F. McRae, Jennifer A. Smith, Sharon L. R. Kardia, Iiris Hovatta, Markus Perola, Samuli Ripatti, Veikko Salomaa, Anjali K. Henders, Nicholas G. Martin, Alicia K. Smith, Divya Mehta, Elisabeth B. Binder, K. Maria Nylocks, Elizabeth M. Kennedy, Torsten Klengel, Jingzhong Ding, Astrid M. Suchy‐Dicey, Daniel A. Enquobahrie, Jennifer A. Brody, Jerome I. Rotter, Yii‐Der Ida Chen, Jeanine J. Houwing‐Duistermaat, M. Kloppenburg, P. Eline Slagboom, Quinta Helmer, Wouter den Hollander, Shannon Bean, Towfique Raj, Noman Bakhshi, Qiao‐Ping Wang, Lisa J. Oyston, Bruce M. Psaty, Russell P. Tracy, Grant W. Montgomery, Stephen T. Turner, John Blangero, Ingrid Meulenbelt, Kerry J. Ressler, Jian Yang, Lude Franke, Johannes Kettunen, Peter M. Visscher, G. Gregory Neely, Ron Korstanje, Robert L. Hanson, Holger Prokisch, Luigi Ferrucci, Tõnu Esko, Alexander Teumer, Joyce B. J. van Meurs, Andrew D. Johnson

Bibliographic record

VenueNature Communications · 2015
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicEpigenetics and DNA Methylation
Canadian institutionsDiscovery Centre
FundersNational Center for Advancing Translational SciencesNational Institute on AgingNederlandse Organisatie voor Wetenschappelijk OnderzoekEuropean CommissionNational Institute of Diabetes and Digestive and Kidney DiseasesNational Heart, Lung, and Blood InstituteNational Institute for Health and Care Research
KeywordsTranscriptomeEpigeneticsDNA methylationCpG siteAgeingBiologyMethylationGeneGene expressionGeneticsRegulation of gene expressionComputational biologyBioinformatics

Abstract

fetched live from OpenAlex

Disease incidences increase with age, but the molecular characteristics of ageing that lead to increased disease susceptibility remain inadequately understood. Here we perform a whole-blood gene expression meta-analysis in 14,983 individuals of European ancestry (including replication) and identify 1,497 genes that are differentially expressed with chronological age. The age-associated genes do not harbor more age-associated CpG-methylation sites than other genes, but are instead enriched for the presence of potentially functional CpG-methylation sites in enhancer and insulator regions that associate with both chronological age and gene expression levels. We further used the gene expression profiles to calculate the 'transcriptomic age' of an individual, and show that differences between transcriptomic age and chronological age are associated with biological features linked to ageing, such as blood pressure, cholesterol levels, fasting glucose, and body mass index. The transcriptomic prediction model adds biological relevance and complements existing epigenetic prediction models, and can be used by others to calculate transcriptomic age in external cohorts.

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)0.001
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: Review · Consensus signal: Review
Teacher disagreement score0.001
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

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

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 head0.048
GPT teacher head0.372
Teacher spread0.324 · 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
GenreReview

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

Citations760
Published2015
Admission routes1
Has abstractyes

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