Gene co-expression changes underlying the functional connectomic alterations in Alzheimer’s disease

作者：Bing He, Priyanka Gorijala, Linhui Xie, Sha Cao, Jingwen Yan · 发表于：BMC Medical Genomics · 年份：2022 · DOI：10.1186/s12920-022-01244-6 · 被引用次数：6 · 研究领域：Functional Brain Connectivity Studies、Bioinformatics and Genomic Networks、Alzheimer's disease research and treatments

BACKGROUND: There is growing evidence indicating that a number of functional connectivity networks are disrupted at each stage of the full clinical Alzheimer's disease spectrum. Such differences are also detectable in cognitive normal (CN) carrying mutations of AD risk genes, suggesting a substantial relationship between genetics and AD-altered functional brain networks. However, direct genetic effect on functional connectivity networks has not been measured. METHODS: Leveraging existing AD functional connectivity studies collected in NeuroSynth, we performed a meta-analysis to identify two sets of brain regions: ones with altered functional connectivity in resting state network and ones without. Then with the brain-wide gene expression data in the Allen Human Brain Atlas, we applied a new biclustering method to identify a set of genes with differential co-expression patterns between these two set of brain regions. RESULTS: Differential co-expression analysis using biclustering method led to a subset of 38 genes which showed distinctive co-expression patterns between AD-related and non AD-related brain regions in default mode network. More specifically, we observed 4 sub-clusters with noticeable co-expression difference, where the difference in correlations is above 0.5 on average. CONCLUSIONS: This work applies a new biclustering method to search for a subset of genes with altered co-expression patterns in AD-related default mode network regions. Compared with traditional di...