ArticleBiological psychiatry global open science2025
A Critical Evaluation of Background Gene Omission in Imaging Transcriptomics.
Article in Biological psychiatry global open science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
3 citing papers in PubMed.
- Altered seed-to-whole-brain functional connectivity of goal-directed/habitual systems in obsessive-compulsive disorder: associated genes and preliminary classification potential.European archives of psychiatry and clinical neuroscience · 2026Article
- BrainEnrich: Revealing Biological Insights for Imaging-Derived Phenotypes Through Transcriptomic Enrichment.Human brain mapping · 2026Article
- Rethinking network analysis in ethnopharmacology: a multi-omics and AI roadmap to overcome conceptual and methodological biases.Frontiers in pharmacology · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Imaging transcriptomics integrates spatial gene expression data with imaging-derived phenotypes (IDPs) to elucidate molecular mechanisms that underlie brain structure and function. Overrepresentation analysis (ORA) is widely used to annotate IDP-related genes; however, many studies have overlooked appropriate background gene selection. Here, we critically evaluated the impact of omitting a proper background on ORA findings. A systematic review of 152 imaging transcriptomics studies (2015-2024) revealed that 84.9% did not report background genes, and only 5.26% used the Allen Human Brain Atlas (AHBA) genes as background. Simulations showed that ORA significance increased with background size. In realistic simulations, default backgrounds (e.g., all protein-coding genes) inflated pathway significance by up to 50-fold, with probabilities reaching 0.97, particularly for frequently reported pathways related to synaptic signaling and neurotransmission. In contrast, using AHBA genes as the background maintained the significance probabilities near 0.05. These findings highlight the need for appropriate background selection and transparent reporting and we provide practical guidance for ORA in imaging transcriptomics.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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 OpenQuestion graph.