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A Critical Evaluation of Background Gene Omission in Imaging Transcriptomics

dc.contributor.authorZhipeng Cao
dc.contributor.authorLi Bao
dc.contributor.authorJinmei Qin
dc.contributor.authorGuilai Zhan
dc.contributor.otherShanghai Xuhui Mental Health Center, Shanghai, China; School of Mental Health, Wenzhou Medical University, Zhejiang Province, China; Address correspondence to Zhipeng Cao, Ph.D.
dc.contributor.otherShanghai Xuhui Mental Health Center, Shanghai, China
dc.contributor.otherShanghai Xuhui Mental Health Center, Shanghai, China
dc.contributor.otherShanghai Xuhui Mental Health Center, Shanghai, China; Guilai Zhan, Ph.D.
dc.date.accessioned2025-08-27T04:50:42Z
dc.date.accessioned2025-10-08T08:27:11Z
dc.date.available2025-10-08T08:27:11Z
dc.date.issued01-11-2025
dc.identifier.urihttp://digilib.fisipol.ugm.ac.id/repo/handle/15717717/35927
dc.description.abstractImaging 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.
dc.language.isoEN
dc.publisherElsevier
dc.subject.lccPsychiatry
dc.titleA Critical Evaluation of Background Gene Omission in Imaging Transcriptomics
dc.typeArticle
dc.description.keywordsAllen Human Brain Atlas
dc.description.keywordsBackground gene selection
dc.description.keywordsEnrichment analysis
dc.description.keywordsFalse positives
dc.description.keywordsImaging transcriptomics
dc.description.keywordsOverrepresentation analysis
dc.description.doi10.1016/j.bpsgos.2025.100568
dc.title.journalBiological Psychiatry Global Open Science
dc.identifier.e-issn2667-1743
dc.identifier.oai8ac21e2b177040eab794a7451f694ef2
dc.journal.infoVolume 5, Issue 6


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