Trustworthy Enhanced Multi-view Multi-modal Alzheimer’s Disease Prediction with Brain-wide Imaging Transcriptomics Data

Brain transcriptomics provides insights into the molecular mechanisms by which the brain coordinates its functions and processes. However, existing multimodal methods for predicting Alzheimer’s disease (AD) primarily rely on imaging and sometimes genetic data, often neglecting the transcriptomic basis of brain. Furthermore, while striving to integrate complementary information between modalities, most studies overlook the informativeness disparities between modalities. Here, we propose TMM, a trusted multiview multimodal graph attention framework for AD diagnosis, using extensive brain-wide transcriptomics and imaging data. First, we construct view-specific brain regional co-function networks (RRIs) from transcriptomics and multimodal radiomics data to incorporate interaction information from both biomolecular and imaging perspectives. Next, we apply graph attention (GAT) processing to each RRI network to produce graph embeddings and employ cross-modal attention to fuse transcriptomics-derived embedding with each imaging-derived embedding. Finally, a novel true-false-harmonized class probability (TFCP) strategy is designed to assess and adaptively adjust the prediction confidence of each modality for AD diagnosis. We evaluate TMM using the AHBA database with brain-wide transcriptomics data and the ADNI database with three imaging modalities (AV45-PET, FDG-PET, and VBM-MRI). The results demonstrate the superiority of our method in identifying AD, EMCI, and LMCI compared to state-of-the-arts. Code and data are available at https://github.com/Yaolab-fantastic/TMM.