Tracking disease progression by searching paths in a temporal network of biological processes

Abstract

Metabolic disorders such as obesity and diabetes are diseases which develop gradually over time through the perturbations of biological processes. These perturbed biological processes usually work in an interdependent way. Systematic experiments tracking disease progression at gene level are usually conducted through a temporal microarray data. There is a need for developing methods to analyze such highly complex data to capture disease progression at the molecular level. In the present study, we have considered temporal microarray data from an experiment conducted to study development of obesity and diabetes in mice. We first constructed a network between biological processes through common genes. We analyzed the data to obtain perturbed biological processes at each time point. Finally, we used the biological process network to find links between these perturbed biological processes. This enabled us to identify paths linking initial perturbed processes with final perturbed processes which capture disease progression. Using different datasets and statistical tests, we established that these paths are highly precise to the dataset from which these are obtained. We also established that the connecting genes present in these paths might contain some biological information and thus can be used for further mechanistic studies. The methods developed in our study are also applicable to a broad array of temporal data.