ArticleBiological psychiatry2025
Machine Learning Analysis of the Orbitofrontal Cortex Transcriptome of Human Opioid Users Identifies Shisa7 as a Translational Target Relevant for Heroin Seeking Leveraging a Male Rat Model.
Article in Biological psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Proteomic Insights into Heroin Use: Links to Neurodegeneration.Molecular neurobiology · 2026Article
- Crosstalk Between Glycinergic and N-Methyl-D-Aspartate Receptor-Mediated Glutamatergic Transmission in Behaviours Associated with Opioid Use Disorder.International journal of molecular sciences · 2025Review
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Authors and funding
11 authors.
Funding
Abstract
backgroundIdentifying neurobiological targets predictive of the molecular neuropathophysiological signature of human opioid use disorder (OUD) could expedite new treatments. OUD is characterized by dysregulated cognition and goal-directed behavior mediated by the orbitofrontal cortex (OFC), and next-generation sequencing could provide insights regarding novel targets.
methodsHere, we used machine learning to evaluate human postmortem OFC RNA sequencing datasets from heroin users and control participants to identify transcripts that were predictive of heroin use. To determine a causal link to OUD-related behaviors, we examined the effects of overexpressing the top target gene in a translational rat model of heroin seeking and behavioral updating. Additionally, we determined the effects of overexpression on the rat OFC transcriptome compared with that of human heroin users. Co-immunoprecipitation/mass spectrometry (co-IP/MS) from the rat OFC elucidated the protein complex of the novel target.
resultsOur machine learning approach identified SHISA7 as predictive of human heroin users. Shisa7 is understudied but appears to be an auxiliary protein of GABA
conclusionsOur findings suggest that OFC Shisa7 is a critical driver of neurobehavioral pathology related to drug-seeking behavior and behavioral updating, thus identifying a potential therapeutic target for OUD.
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