Enabling Precision Medicine through Integrative Network Models

Abstract

A key challenge in precision medicine lies in understanding molecular-level underpinnings of complex human disease. Biological networks in multicellular organisms can generate hypotheses about disease genes, pathways, and their behavior in disease-related tissues. Diverse functional genomic data, including expression, protein–protein interaction, and relevant sequence and literature information, can be utilized to build integrative networks that provide both genome-wide coverage as well as contextual specificity and accuracy. By carefully extracting the relevant signal in thousands of heterogeneous functional genomics experiments through integrative analysis, these networks model how genes work together in specific contexts to carry out cellular processes, thereby contributing to a molecular-level understanding of complex human disease and paving the way toward better therapy and drug treatment. Here, we discuss current methods to build context-specific integrative networks, focusing on tissue-specific networks. We highlight applications of these networks in predicting tissue-specific molecular response, identifying candidate disease genes, and increasing power by amplifying the disease signal in quantitative genetics data. Altogether, these exciting developments enable biomedical scientists to characterize disease from pathophysiology to cellular system and, finally, to specific gene alterations—making significant strides toward the goal of precision medicine.