PPIA-coExp: Discovering Context-Specific Biomarkers Based on Protein–Protein Interactions, Co-Expression Networks, and Expression Data

Identifying a small set of effective biomarkers from multi-omics data is important for the discrimination of different cell types and helpful for the early detection diagnosis of complex diseases. However, it is challenging to identify optimal biomarkers from the high throughput molecular data. Here, we present a method called protein-protein interaction affinity and co-expression network (PPIA-coExp), a linear programming model designed to discover context-specific biomarkers based on co-expressed networks and protein-protein interaction affinity (PPIA), which was used to estimate the concentrations of protein complexes based on the law of mass action. The performance of PPIA-coExp excelled over the traditional node-based approaches in both the small and large samples. We applied PPIA-coExp to human aging and Alzheimer's disease (AD) and discovered some important biomarkers. In addition, we performed the integrative analysis of transcriptome and epigenomic data, revealing the correlation between the changes in gene expression and different histone modification distributions in human aging and AD.