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Record W2799762305 · doi:10.1126/science.aao1729

Systematic analysis of complex genetic interactions

2018· article· en· W2799762305 on OpenAlexafffund
Elena Kuzmin, Benjamin VanderSluis, Wen Wang, Guihong Tan, Raamesh Deshpande, Yiqun Chen, Matej Ušaj, Attila Balint, Mojca Mattiazzi Ušaj, Jolanda van Leeuwen, Elizabeth N. Koch, Carles Pons, Andrius J. Dagilis, Michael Pryszlak, Jason Zi Yang Wang, Julia Hanchard, Margot Riggi, Kaicong Xu, Hamed Heydari, Bryan-Joseph San Luis, Ermira Shuteriqi, Hongwei Zhu, Nydia van Dyk, Sara Sharifpoor, Michael Costanzo, Robbie Loewith, Amy A. Caudy, Daniel I. Bolnick, Grant W. Brown, Brenda Andrews, Charles Boone, Chad L. Myers

Bibliographic record

VenueScience · 2018
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicBioinformatics and Genomic Networks
Canadian institutionsUniversity of Toronto
FundersNational Institute of General Medical SciencesNational Institute of Allergy and Infectious DiseasesNatural Sciences and Engineering Research Council of CanadaCanadian Institutes of Health ResearchSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungUniversity of MinnesotaCanton de GenèveNational Human Genome Research InstituteUniversity of TorontoNational Institutes of HealthNational Science Foundation
KeywordsBiologyGeneticsGeneInheritance (genetic algorithm)MutantPhenotypeEpistasisGene interactionGenetic analysisMutationInteraction networkComputational biology

Abstract

fetched live from OpenAlex

To systematically explore complex genetic interactions, we constructed ~200,000 yeast triple mutants and scored negative trigenic interactions. We selected double-mutant query genes across a broad spectrum of biological processes, spanning a range of quantitative features of the global digenic interaction network and tested for a genetic interaction with a third mutation. Trigenic interactions often occurred among functionally related genes, and essential genes were hubs on the trigenic network. Despite their functional enrichment, trigenic interactions tended to link genes in distant bioprocesses and displayed a weaker magnitude than digenic interactions. We estimate that the global trigenic interaction network is ~100 times as large as the global digenic network, highlighting the potential for complex genetic interactions to affect the biology of inheritance, including the genotype-to-phenotype relationship.

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)0.006
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.006
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0030.002
Science and technology studies0.0010.001
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0000.001
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 head0.014
GPT teacher head0.283
Teacher spread0.269 · 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 designBench or experimental
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

Citations314
Published2018
Admission routes2
Has abstractyes

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