RoDiCE: Robust differential protein co-expression analysis for cancer complexome

Abstract

MotivationThe full spectrum of abnormalities in cancer-associated protein complexes remains largely unknown. Comparing the co-expression structure of each protein complex between tumor and healthy cells may provide insights regarding cancer-specific protein dysfunction. However, the technical limitations of mass spectrometry-based proteomics, including contamination with biological protein variants, causes noise that leads to non-negligible over- (or under-) estimating co-expression. ResultsWe propose a robust algorithm for identifying protein complex aberrations in cancer based on differential protein co-expression testing. Our method based on a copula is sufficient for improving identification accuracy with noisy data compared to conventional linear correlation-based approaches. As an application, we use large-scale proteomic data from renal cancer to show that important protein complexes, regulatory signaling pathways, and drug targets can be identified. The proposed approach surpasses traditional linear correlations to provide insights into higher order differential co-expression structures. Availability and Implementationhttps://github.com/ymatts/RoDiCE.