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Record W4296666593 · doi:10.1101/2022.09.20.508736

Conserved coexpression at single cell resolution across primate brains

2022· preprint· en· W4296666593 on OpenAlexaff
Hamsini Suresh, Megan Crow, Nikolas L. Jorstad, Rebecca D. Hodge, Ed S. Lein, Alexander Dobin, Trygve E. Bakken, Jesse Gillis

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2022
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicSingle-cell and spatial transcriptomics
Canadian institutionsUniversity of Toronto
FundersNational Institutes of HealthNational Alliance for Research on Schizophrenia and Depression
KeywordsBiologyMacaquePrimateMarmosetPopulationNeuroscienceRhesus macaqueHuman brainEvolutionary biologyPhenotypeGeneGenetics

Abstract

fetched live from OpenAlex

Abstract Enhanced cognitive function in humans is hypothesized to result from cortical expansion and increased cellular diversity. However, the mechanisms that drive these phenotypic differences remain poorly understood, in part due to the lack of high-quality cellular resolution data in human and non-human primates. Here, we take advantage of single cell expression data from the middle temporal gyrus of five primates (human, chimp, gorilla, macaque and marmoset) to identify 57 homologous cell types and generate cell-type specific gene coexpression networks for comparative analysis. While ortholog expression patterns are generally well conserved, we find 24% of genes with extensive differences between human and non-human primates (3383/14,131), which are also associated with multiple brain disorders. To validate these observations, we perform a meta-analysis of coexpression networks across 19 animals, and find that a subset of these genes have deeply conserved coexpression across all non-human animals, and strongly divergent coexpression relationships in humans (139/3383, <1% of primate orthologs). Genes with human-specific cellular expression and coexpression networks (like NHEJ1, GTF2H2, C2 and BBS5 ) typically evolve under relaxed selective constraints and may drive rapid evolutionary change in brain function. One Sentence Summary Cross-primate middle temporal gyrus single cell expression data reveals patterns of conservation and divergence that can be validated with population coexpression networks.

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)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.063
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0010.000
Scholarly communication0.0000.000
Open science0.0010.002
Research integrity0.0010.001
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 head0.019
GPT teacher head0.237
Teacher spread0.217 · 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.

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

Citations4
Published2022
Admission routes1
Has abstractyes

Explore more

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