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Record W4411942090 · doi:10.1101/2025.06.30.662193

A global genetic interaction map of a human cell reveals conserved principles of genetic networks

2025· preprint· en· W4411942090 on OpenAlexaff
Maximilian Billmann, Michael Costanzo, Xiang Zhang, Arshia Zernab Hassan, Mahfuzur Rahman, Kevin R. Brown, Katherine Chan, Amy H.Y. Tong, Carles Pons, Henry N. Ward, Catherine Ross, Jolanda van Leeuwen, Michael Aregger, Keith A. Lawson, Barbara Mair, Amy F. Roth, Duncan Forster, Guihong Tan, Patricia Mero, Sanna N. Masud, Yoonkyu Lee, Magali Aguilera-Uribe, Matej Ušaj, Luiz Gonzaga Paula de Almeida, Kamaldeep Aulakh, Urvi Bhojoo, Saba Birkadze, Nathaniel Budijono, Xunhui Cai, Joseph J. Caumanns, Megha Chandrashekhar, Daniel Chang, Ryan Climie, Kuheli Dasgupta, Adrian Drazic, José Rojas-Echenique, Rafael Gacesa, Adrian Granda Farias, Andrea Habsid, Ira Horecka, Kristin Kantautas, Fenghu Ji, Dae‐Kyum Kim, Seon Yong Lee, Wendy Liang, Julianne Lim, Kevin Lin, Xiaoyan Lu, Babak Nami, Allison M.L. Nixon, Nicholas Mikolajewicz, L. Nedyalkova, Thomas Rohde, M. Rodrigues, Martin Soste, Eric R. Schultz, Wen Wang, Ashwin Seetharaman, Emira Shuteriqi, Olga Sizova, Maria Tereshchenko, David Tieu, Jacob P. Turowec, Tajinder Ubhi, Sylvia Varland, Kyle Wang, Ziyang Wang, Jiarun Wei, Yu-Xi Xiao, Grant W. Brown, Benjamin F. Cravatt, Scott J. Dixon, Haley D.M. Wyatt, Hannes Röst, Frederick P. Roth, Tian Xia, Gary D. Bader, Robbie Loewith, Nicholas G. Davis, Brenda Andrews, Chad L. Myers, Jason Moffat, Charles Boone

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicBioinformatics and Genomic Networks
Canadian institutionsCanadian Institute for Advanced ResearchInstitute for Work & HealthToronto Rehabilitation InstituteMcGill University Health CentreAmgen (Canada)Hospital for Sick ChildrenUniversity of Toronto
FundersDeutsche Forschungsgemeinschaft
KeywordsEvolutionary biologyComputational biologyBiologyGenetics

Abstract

fetched live from OpenAlex

We generated a genome-scale, genetic interaction network from the analysis of more than 4 million double mutants in the haploid human cell line, HAP1. The network maps ~90,000 genetic interactions, including thousands of extreme synthetic lethal and genetic suppression interactions. Genetic interaction profiles enabled assembly of a hierarchical model of cell function, including modules corresponding to protein complexes, pathways, biological processes, and cellular compartments. Comparative analyses showed that general principles of genetic networks are conserved from yeast to human cells. A genetic interaction network mapped in a single genetic background complements the DepMap gene co-essentiality network, recapitulating many of the same biological connections and also capturing unique functional information to reveal roles of uncharacterized genes and molecular determinants of specific cancer cell line genetic dependencies.

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)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
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 head0.012
GPT teacher head0.231
Teacher spread0.219 · 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 designSimulation or modeling
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

Citations5
Published2025
Admission routes1
Has abstractyes

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