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Record W4323849257 · doi:10.1101/2023.03.09.531574

Evolutionary constraint and innovation across hundreds of placental mammals

2023· preprint· en· W4323849257 on OpenAlexaff
Matthew J. Christmas, Irene M. Kaplow, Diane P. Genereux, Michael X. Dong, Graham M. Hughes, Xue Li, Patrick F. Sullivan, Allyson G. Hindle, Gregory Andrews, Joel Armstrong, Matteo Bianchi, Ana M. Breit, Mark Diekhans, Cornelia Fanter, Nicole M. Foley, Daniel B. Goodman, Linda Goodman, Kathleen C. Keough, Bogdan Kirilenko, Amanda Kowalczyk, Colleen Lawless, Abigail Lind, Jennifer R. S. Meadows, Lucas R. Moreira, Ruby Redlich, Louise Ryan, Ross Swofford, Alejandro Valenzuela, Franziska Wagner, Ola Wallerman, Ashley R. Brown, Joana Damas, Kaili Fan, John Gatesy, Jenna Grimshaw, Jeremy Johnson, Sergey V. Kozyrev, Alyssa J. Lawler, Voichita D. Marinescu, Kathleen M. Morrill, Austin Osmanski, Nicole S. Paulat, BaDoi N. Phan, Steven K. Reilly, Daniel E. Schäffer, Cynthia Steiner, Megan A. Supple, Aryn P. Wilder, Morgan Wirthlin, James R. Xue, Bruce W. Birren, Steven Gazal, Robert Hubley, Klaus‐Peter Koepfli, Tomàs Marquès‐Bonet, Wynn K. Meyer, Martin Nweeia, Pardis C. Sabeti, Beth Shapiro, Arian F. A. Smit, Mark S. Springer, Emma C. Teeling, Zhiping Weng, Michael Hiller, Danielle L. Levesque, Harris A. Lewin, William J. Murphy, Arcadi Navarro, Benedict Paten, Katherine S. Pollard, David A. Ray, Irina Ruf, Oliver A. Ryder, Andreas R. Pfenning, Kerstin Lindblad‐Toh, Elinor K. Karlsson

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2023
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenomics and Phylogenetic Studies
Canadian institutionsCanadian Museum of Nature
FundersHigh Performance Research Computing, Texas A and M UniversityScience for Life LaboratoryBroad Institute
KeywordsBiologyEvolutionary biologyGenomeConstraint (computer-aided design)PhylogeneticsComputational biologyPhenotypeGeneGenetics

Abstract

fetched live from OpenAlex

Abstract Evolutionary constraint and acceleration are powerful, cell-type agnostic measures of functional importance. Previous studies in mammals were limited by species number and reliance on human-referenced alignments. We explore the evolution of placental mammals, including humans, through reference-free whole-genome alignment of 240 species and protein-coding alignments for 428 species. We estimate 10.7% of the human genome is evolutionarily constrained. We resolve constraint to single nucleotides, pinpointing functional positions, and refine and expand by over seven-fold the catalog of ultraconserved elements. Overall, 48.5% of constrained bases are as yet unannotated, suggesting yet-to-be-discovered functional importance. Using species-level phenotypes and an updated phylogeny, we associate coding and regulatory variation with olfaction and hibernation. Focusing on biodiversity conservation, we identify genomic metrics that predict species at risk of extinction.

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)0.003
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 score0.009

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.003
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0020.002
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0030.000

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 head0.020
GPT teacher head0.247
Teacher spread0.227 · 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

Citations24
Published2023
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicGenomics and Phylogenetic StudiesFrench-language works237,207