MétaCan
Menu
Back to cohort
Record W4323531024 · doi:10.1038/s41467-023-36862-w

OTTERS: a powerful TWAS framework leveraging summary-level reference data

2023· article· en· W4323531024 on OpenAlexaff
Qile Dai, Geyu Zhou, Hongyu Zhao, Urmo Võsa, Lude Franke, Alexis Battle, Alexander Teumer, Terho Lehtimäki, Olli T. Raitakari, Tõnu Esko, Mawussé Agbessi, Habibul Ahsan, Isabel Alves, Anand Kumar Andiappan, Wibowo Arindrarto, Philip Awadalla, Frank Beutner, Marc Jan Bonder, Dorret I. Boomsma, Mark Christiansen, Annique Claringbould, Patrick Deelen, Marie-Julie Favé, Timothy M. Frayling, Sina A. Gharib, Greg Gibson, Bastiaan T. Heijmans, Gibran Hemani, Rick Jansen, Mika Kähönen, Anette Kalnapenkis, Silva Kasela, Johannes Kettunen, Yungil Kim, Holger Kirsten, Péter Kovács, Knut Krohn, Jaanika Kronberg, Viktorija Kukushkina, Zoltán Kutalik, Bernett Lee, Markus Loeffler, Urko M. Marigorta, Hailang Mei, Lili Milani, Grant W. Montgomery, Martina Müller‐Nurasyid, Matthias Nauck, Michel G. Nivard, Brenda W.J.H. Penninx, Markus Perola, Natalia Pervjakova, Brandon L. Pierce, Joseph E. Powell, Holger Prokisch, Bruce M. Psaty, Samuli Ripatti, Olaf Rötzschke, Sina Rüeger, Ashis Saha, Markus Scholz, Katharina Schramm, Ilkka Seppälä, P. Eline Slagboom, Coen D.A. Stehouwer, Michael Stümvoll, Patrick Sullivan, Peter A.C. ’t Hoen, Joachim Thiery, Tong Lin, Anke Tönjes, Jenny van Dongen, Maarten van Iterson, Joyce B. J. van Meurs, Jan H. Veldink, Joost Verlouw, Peter M. Visscher, Uwe Völker, Harm-Jan Westra, Cisca Wijmenga, Hanieh Yaghootka, Jian Yang, Biao Zeng, Futao Zhang, Michael P. Epstein, Jingjing Yang

Bibliographic record

VenueNature Communications · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGene expression and cancer classification
Canadian institutionsOntario Institute for Cancer Research
FundersNational Institute on AgingNational Center for Advancing Translational SciencesTaysPaavo Nurmen SäätiöNational Institute of General Medical SciencesTampereen TuberkuloosisäätiöSydäntutkimussäätiöJuho Vainion SäätiöAcademy of FinlandKelaIllinois Department of Public HealthEesti TeadusagentuurNational Institutes of HealthDiabetesliittoU.S. Department of Health and Human ServicesEmil Aaltosen SäätiöTranslational Genomics Research InstituteYrjö Jahnssonin SäätiöSigne ja Ane Gyllenbergin SäätiöSyöpäsäätiöFoundation for Cardiovascular ResearchSuomen Kulttuurirahasto
KeywordsComputer scienceReference dataData miningExpression quantitative trait lociBiology

Abstract

fetched live from OpenAlex

Most existing TWAS tools require individual-level eQTL reference data and thus are not applicable to summary-level reference eQTL datasets. The development of TWAS methods that can harness summary-level reference data is valuable to enable TWAS in broader settings and enhance power due to increased reference sample size. Thus, we develop a TWAS framework called OTTERS (Omnibus Transcriptome Test using Expression Reference Summary data) that adapts multiple polygenic risk score (PRS) methods to estimate eQTL weights from summary-level eQTL reference data and conducts an omnibus TWAS. We show that OTTERS is a practical and powerful TWAS tool by both simulations and application studies.

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 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)0.000
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: Not applicable · Consensus signal: Not applicable
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.599
Threshold uncertainty score0.479

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0020.002
Research integrity0.0000.001
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 head0.133
GPT teacher head0.383
Teacher spread0.250 · 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 teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNot applicable
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

Citations55
Published2023
Admission routes1
Has abstractyes

Explore more

Same venueNature CommunicationsSame topicGene expression and cancer classificationFrench-language works237,207