BriGHT: transcriptome-regularized multimodal neuroimaging for brain disorder prediction.
MOTIVATION Hypergraph-based models for brain disorder prediction mainly adopt imaging-derived hypergraphs as propagation backbones. However, the entanglement of topology construction and feature propagation leaves regional representations weakly constrained by underlying biological organization, making them vulnerable to subject-specific variation and noise, particularly in heterogeneous multimodal settings. RESULTS We present BriGHT, a Brain transcriptome-reGularized Hypergraph framework for mulTimodal disorder prediction. BriGHT employs a transcriptome-derived structural reference as a soft anchoring prior to regularize neuroimaging ROI embeddings, stabilizing representation geometry while preserving disease-relevant subject-specific variation. BriGHT further incorporates a reliability-aware fusion module to estimate subject-specific modality reliability from prediction confidence, cross-modal consistency, and decision certainty, enabling adaptive integration under heterogeneous modality quality. Experiments on three neuroimaging cohorts (ADNI, ADHD-200, REST-meta-MDD) and four modalities (VBM, fMRI, FDG, AV45) demonstrate that BriGHT consistently outperforms competing graph/hypergraph learning methods across six brain disorder prediction tasks. Perturbation analyses show that BriGHT benefits from the spatial correspondence between transcriptomic modules and imaging ROIs, rather than from arbitrary hypergraph regularization alone. Ablation and meta-analytic interpretability analyses support the contribution of transcriptomic anchoring and adaptive fusion to robust and biologically meaningful brain disorder prediction. AVAILABILITY The software is publicly available at: https://github.com/Yaolab-fantastic/BriGHT. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.