Comparative Analysis of Human Tissue Interactomes Reveals Factors Leading to Tissue-Specific Manifestation of Hereditary Diseases
A. The tissue-distribution of hereditary diseases and their causal genes shows that diseases are manifested in few tissues, while most of their germline-aberrant causal genes are expressed in 10 tissues or more. The numbers of expressed causal genes across 1–16 tissues appear in Table S13. B. Causal genes tend to be more highly expressed in their disease tissues relative to other tissues in which they are expressed. We observed higher median expression levels in disease tissues for 128 out of the 203 germline-aberrant causal genes for which RPKM values were available (p-value<10−4). The box-plot diagram shows the quartiles (25%, 50% and 75%) of the median RPKM levels of causal genes; for each gene only tissues expressing the gene were considered. C. Causal genes involved in TS-PPI tend to have more TS-PPI in their disease tissues relative to other tissues. Out of 126 genes with TS-PPI, 58 genes had higher median TS-PPI in the disease tissue relative to non-disease tissues in which they are expressed (p-value<10−4). The box-plot diagram shows the quartiles (25%, 50% and 75%) of the median number of TS-PPI of causal genes, where for each gene only tissues expressing the gene were considered. The first (25%) and second (50%) quartiles of non-disease tissues were zero and therefore overlap with the X axis. D. The majority of the 303 hereditary diseases are associated with elevated expression and/or TS-PPIs of their causal genes in their disease tissues.