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Concordance of gene expression in human protein complexes reveals tissue specificity and pathology.
|Publication Type||Journal Article|
|Authors||Börnigen, D., Pers TH, Thorrez L., Huttenhower C., Moreau Y., and Brunak S.|
|Abstract||Disease-causing variants in human genes usually lead to phenotypes specific to only a few tissues. Here, we present a method for predicting tissue specificity based on quantitative deregulation of protein complexes. The underlying assumption is that the degree of coordinated expression among proteins in a complex within a given tissue may pinpoint tissues that will be affected by a mutation in the complex and coordinated expression may reveal the complex to be active in the tissue. We identified known disease genes and their protein complex partners in a high-quality human interactome. Each susceptibility gene's tissue involvement was ranked based on coordinated expression with its interaction partners in a non-disease global map of human tissue-specific expression. The approach demonstrated high overall area under the curve (0.78) and was very successfully benchmarked against a random model and an approach not using protein complexes. This was illustrated by correct tissue predictions for three case studies on leptin, insulin-like-growth-factor 2 and the inhibitor of NF-κB kinase subunit gamma that show high concordant expression in biologically relevant tissues. Our method identifies novel gene-phenotype associations in human diseases and predicts the tissues where associated phenotypic effects may arise.|
|Year of Publication||2013|
|Journal||Nucleic acids research|
|Date Published (YYYY/MM/DD)||2013/08/05|