Systemic analysis of changes in protein modification and gene coexpression networks in cancer

Abstract

Perturbed posttranslational modification (PTM) landscapes and gene expression networks commonly cause pathological phenotypes. To elucidate altered PTM landscapes on a large scale, disease-associated mutations from TCGA, Uniprot, and dbSNP were integrated with PTM sites from PhosphoSitePlus. We characterized each dataset individually, compared somatic with germline mutations, and analyzed PTM sites intersecting directly with disease variants. To assess the impact of mutations in the flanking regions of phosphosites, we developed DeltaScansite, a pipeline that compares Scansite predictions on wild type versus mutated sequences. Disease mutations are also visualized in PhosphoSitePlus. TCGA also curates gene expression data from tumor and normal tissues, enabling us to calculate gene coexpression networks and apply graph algorithms in Neo4j.