iTOP: inferring the topology of omics data

Motivation: In biology, we are often faced with multiple datasets recorded on the same set of objects, such as multi-omics and phenotypic data of the same tumors. These datasets are typically not independent from each other. For example, methylation may influence gene expression, which may, in turn, influence drug response. Such relationships can strongly affect analyses performed on the data, as we have previously shown for the identification of biomarkers of drug response. Therefore, it is important to be able to chart the relationships between datasets. Results: We present iTOP, a methodology to infer a topology of relationships between datasets. We base this methodology on the RV coefficient, a measure of matrix correlation, which can be used to determine how much information is shared between two datasets. We extended the RV coefficient for partial matrix correlations, which allows the use of graph reconstruction algorithms, such as the PC algorithm, to infer the topologies. In addition, since multi-omics data often contain binary data (e.g. mutations), we also extended the RV coefficient for binary data. Applying iTOP to pharmacogenomics data, we found that gene expression acts as a mediator between most other datasets and drug response: only proteomics clearly shares information with drug response that is not present in gene expression. Based on this result, we used TANDEM, a method for drug response prediction, to identify which variables predictive of drug response were distinct to either gene expression or proteomics.