An Integrative Approach for Identifying Network Biomarkers of Breast Cancer Subtypes Using Genomic, Interactomic, and Transcriptomic Data

Abstract

Breast cancer is a complex disease that can be classified into at least 10 different molecular subtypes. Appropriate diagnosis of specific subtypes is critical for ensuring the best possible patient treatment and response to therapy. Current computational methods for determining the subtypes are based on identifying differentially expressed genes (i.e., biomarkers) that can best discriminate the subtypes. Such approaches, however, are known to be unreliable since they yield different biomarker sets when applied to data sets from different studies. Gathering knowledge about the functional relationship among genes will identify "network biomarkers" that will enrich the criteria for biomarker selection. Cancer network biomarkers are subnetworks of functionally related genes that "work in concert" to perform functions associated with a tumorigenic. We propose a machine learning framework that can be used to identify network biomarkers and driver genes for each specific breast cancer subtype. Our results show that the resulting network biomarkers can separate one subtype from the others with very high accuracy.

Keywords: breast cancer; copy number aberration; protein–protein interactions; subtyping..