Comprehensive Analysis of Tissue-wide Gene Expression and Phenotype Data Reveals Tissues Affected in Rare Genetic Disorders.

ABSTRACT: Linking putatively pathogenic variants to the tissues they affect is necessary for determining the correct diagnostic workup and therapeutic regime in undiagnosed patients. Here, we explored how gene expression across healthy tissues can be used to infer this link. We integrated 6,665 tissue-wide transcriptomes with genetic disorder knowledge bases covering 3,397 diseases. Receiver-operating characteristics (ROC) analysis using expression levels in each tissue and across tissues indicated significant but modest associations between elevated expression and phenotype for most tissues (maximum area under ROC curve = 0.69). At extreme elevation, associations were marked. Upregulation of disease genes in affected tissues was pronounced for genes associated with autosomal dominant over recessive

SUBMITTER: Feiglin A 

PROVIDER: S-EPMC5928498 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature