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Record W4413189399 · doi:10.1101/2025.08.08.25333301

Translating the Transcriptome: A Connectomics Approach for Gene-Network Mapping and Clinical Application

2025· preprint· en· W4413189399 on OpenAlexaff
Clemens Neudorfer, Bassam Al‐Fatly, Barbara Hollunder, Ningfei Li, Garance M. Meyer, Nanditha Rajamani, Konstantin Butenko, Matteo Vissani, Alan Bush, Nathaniel Sisterson, Ehsan Tadayon, Frédéric Schaper, Julianna Pijar, Bahne H. Bahners, Lauren A. Hart, Savir Madan, Philip Mosley, Harith Akram, Nicola Acevedo, David Castle, Susan L. Rossell, Peter Bosanac, Jill L. Ostrem, Philip A. Starr, Vincent J.J. Odekerken, Rob M.A. de Bie, Juan A. Barcia, Himanshu Tyagi, Sameer A. Sheth, Wayne K. Goodman, Martijn Figee, Darin D. Dougherty, Veerle Visser‐Vandewalle, Ludvic Zrinzo, Eileen Joyce, Juho Joutsa, Thomas Picht, Katharina Faust, Andrea Kuehn, Christos Ganos, Jeremiah M. Scharf, Christine Klein, Michael Fox, R. Mark Richardson

Bibliographic record

VenuemedRxiv · 2025
Typepreprint
Languageen
FieldNeuroscience
TopicFunctional Brain Connectivity Studies
Canadian institutionsToronto Western HospitalCentre for Movement Disorders
FundersMedical Research CouncilNational Institutes of HealthDeutsches Zentrum für Luft- und RaumfahrtDeutsche ForschungsgemeinschaftUniversity College LondonNational Institute for Health and Care Research
KeywordsConnectomicsConnectomeComputational biologyGene regulatory networkComputer scienceGeneNeuroscienceTranscriptomeBiological networkBiologyArtificial intelligenceGene expressionFunctional connectivityGenetics

Abstract

fetched live from OpenAlex

Gene expression shapes the brain's functional connectome, yet it is unclear whether genes linked to the same disorder converge on shared networks. We introduce gene network mapping-a framework combining spatial transcriptomics with normative functional connectivity to identify networks associated with gene expression. By generating gene-network maps, we captured distributed connectivity patterns for individual genes. Aggregating these across genes implicated in the same disorder yielded disease-network maps that captured the cumulative genetic impact on brain networks. We validated these maps by comparing them to lesion-derived networks and testing whether modulation of these networks predicted outcomes in deep brain stimulation (DBS) cohorts. This framework offers a novel tool to study the molecular architecture of brain disorders and supports the network-informed diagnostics and therapeutics in precision medicine.

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: Simulation or modeling · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.005
Threshold uncertainty score0.017

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.006
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0020.002
Science and technology studies0.0010.001
Scholarly communication0.0020.001
Open science0.0010.002
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0050.001

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 head0.100
GPT teacher head0.330
Teacher spread0.230 · 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

Citations1
Published2025
Admission routes1
Has abstractyes

Explore more

Same venuemedRxiv→Same topicFunctional Brain Connectivity Studies→French-language works237,207→