ArticleNature communications2021
Overcoming false-positive gene-category enrichment in the analysis of spatially resolved transcriptomic brain atlas data.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers, 3 of them syntheses that pooled it.
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100 citing papers in PubMed, 3 syntheses or guidelines pooled it, 169 citations in OpenAlex.
- From risk to chronicity: genetic and neuroimaging insights into the evolving patterns of spontaneous brain activity in schizophrenia.Psychological medicine · 2025Pooled it
- Resting-State Brain Activity Changes and Their Genetic Correlates in Mild Traumatic Brain Injury.Human brain mapping · 2025Pooled it
- Transcriptome meta-analysis and validation to discovery of hub genes and pathways in focal and segmental glomerulosclerosis.BMC nephrology · 2024Pooled it
- Problems With GO Enrichment as an Endpoint for Ecological Omics Interpretation.Molecular ecology · 2026Article
- Diffusion MRI reveals amyloid plaque-associated cellular signatures through spatial transcriptomic integration.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Mapping the dual functional organization of the substantia nigra.Molecular psychiatry · 2026Article
- Assessing molecular, cellular and transcriptomic bases of laminar perfusion and cytoarchitecture coupling in the human cortex.Nature communications · 2026Article
- Cellular signatures underlying functional resilience in presymptomatic frontotemporal dementia.Brain : a journal of neurology · 2026Article
- Correlation of thalamic functional organization disturbances and genetic architecture in motor subtypes of Parkinson's disease.NPJ Parkinson's disease · 2026Article
- Imaging Genomics Across Primate Species: Advancing Understanding of Neurological and Psychiatric Disorders.Neuroscience bulletin · 2026Review
- Structural connectome architecture and biological vulnerability shape cortical atrophy in cocaine use disorder.BMC medicine · 2026Article
- Linking changes in sulcal morphometry to cognitive development from childhood to adolescence.Communications biology · 2026Article
- A data-driven framework linking the connectome to spatial gene expression gradients inspired by chemoaffinity theory.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Brain network dysfunction and treatment-induced network reorganization in major depressive disorder.Brain imaging and behavior · 2026Article
- Linking Cortical Morphometry in Self-Limited Epilepsy With Centrotemporal Spikes to Cognition, Function, and Molecular Architecture.CNS neuroscience & therapeutics · 2026Article
- Synapse types are spatially associated with regional hemodynamics in the mouse brain.PLoS biology · 2026Article
- HyperpolarizedImaging neuroscience (Cambridge, Mass.) · 2026Article
- Lifestyle and Transcriptional Signatures Associated with Ethnicity/Race-Related Variations in the Functional Connectome.Research (Washington, D.C.) · 2026Article
- Transcriptional and neurotransmitter signatures associated with regional gray matter alterations in juvenile myoclonic epilepsy.Frontiers in molecular neuroscience · 2026Article
- Transcriptional signatures of the cortical morphometric similarity network gradient in left temporal lobe epilepsy with different seizure symptoms.Frontiers in neuroscience · 2026Article
40 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transcriptomic atlases have improved our understanding of the correlations between gene-expression patterns and spatially varying properties of brain structure and function. Gene-category enrichment analysis (GCEA) is a common method to identify functional gene categories that drive these associations, using gene-to-category annotation systems like the Gene Ontology (GO). Here, we show that applying standard GCEA methodology to spatial transcriptomic data is affected by substantial false-positive bias, with GO categories displaying an over 500-fold average inflation of false-positive associations with random neural phenotypes in mouse and human. The estimated false-positive rate of a GO category is associated with its rate of being reported as significantly enriched in the literature, suggesting that published reports are affected by this false-positive bias. We show that within-category gene-gene coexpression and spatial autocorrelation are key drivers of the false-positive bias and introduce flexible ensemble-based null models that can account for these effects, made available as a software toolbox.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.