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Record W4296460797 · doi:10.1101/2022.09.19.508480

Comparative transcriptomics reveals human-specific cortical features

2022· preprint· en· W4296460797 on OpenAlexaff
Nikolas L. Jorstad, Janet Song, David Exposito-Alonso, Hamsini Suresh, Nathan J. Castro, Fenna M. Krienen, Anna Marie Yanny, Jennie Close, Emily Gelfand, Kyle J. Travaglini, Soumyadeep Basu, Marc Beaudin, Darren Bertagnolli, Megan Crow, Song‐Lin Ding, Jeroen Eggermont, Alexandra Glandon, Jeff Goldy, Thomas Kroes, Brian Long, Delissa McMillen, Trangthanh Pham, Christine Rimorin, Kimberly Siletti, Saroja Somasundaram, Michael Tieu, Amy Torkelson, Katelyn Ward, Guoping Feng, William D. Hopkins, Thomas Höllt, C. Dirk Keene, Sten Linnarsson, Steven A. McCarroll, Boudewijn P. F. Lelieveldt, Chet C. Sherwood, Kimberly A. Smith, Christopher A. Walsh, Alexander Dobin, Jesse Gillis, Ed S. Lein, Rebecca D. Hodge, Trygve E. Bakken

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2022
Typepreprint
Languageen
FieldNeuroscience
TopicNeuroinflammation and Neurodegeneration Mechanisms
Canadian institutionsUniversity of Toronto
FundersDivision of Emerging FrontiersNederlandse Organisatie voor Wetenschappelijk OnderzoekNational Institute of Mental HealthNational Alliance for Research on Schizophrenia and DepressionNational Institutes of HealthNational Science Foundation
KeywordsBiologyMarmosetMacaqueCell typeHuman brainGorillaNeuroscienceLineage (genetic)TranscriptomeRhesus macaqueGeneEvolutionary biologyCellGene expressionGenetics

Abstract

fetched live from OpenAlex

Abstract Humans have unique cognitive abilities among primates, including language, but their molecular, cellular, and circuit substrates are poorly understood. We used comparative single nucleus transcriptomics in adult humans, chimpanzees, gorillas, rhesus macaques, and common marmosets from the middle temporal gyrus (MTG) to understand human-specific features of cellular and molecular organization. Human, chimpanzee, and gorilla MTG showed highly similar cell type composition and laminar organization, and a large shift in proportions of deep layer intratelencephalic-projecting neurons compared to macaque and marmoset. Species differences in gene expression generally mirrored evolutionary distance and were seen in all cell types, although chimpanzees were more similar to gorillas than humans, consistent with faster divergence along the human lineage. Microglia, astrocytes, and oligodendrocytes showed accelerated gene expression changes compared to neurons or oligodendrocyte precursor cells, indicating either relaxed evolutionary constraints or positive selection in these cell types. Only a few hundred genes showed human-specific patterning in all or specific cell types, and were significantly enriched near human accelerated regions (HARs) and conserved deletions (hCONDELS) and in cell adhesion and intercellular signaling pathways. These results suggest that relatively few cellular and molecular changes uniquely define adult human cortical structure, particularly by affecting circuit connectivity and glial cell function.

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: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
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 head0.058
GPT teacher head0.277
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 designObservational
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
Published2022
Admission routes1
Has abstractyes

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