Detecting Differentially Co-Expressed Gene Modules Via The Edge-Count Test

Background Gene expression profiling by microarray has been used to uncover molecular variations in many different diseases. Complementary to conventional differential expression analysis, differential co-expression analysis can identify gene markers from the systematic and granular level. There are three aspects for differential co-expression network analysis, including the network global topological comparison, differential co-expression cluster identification, and differential co-expressed genes and gene pair identification. To date, most of the methods available still rely on Pearson’s correlation coefficient despite its nonlinear insensitivity. Results Here we present an approach that is robust to nonlinearity by using the edge-count test for differential co-expression analysis. The performance of the new approach was tested with synthetic data and found to have significant results. For real data, we used a human cervical cancer data set prepared from 29 pairs of cervical tumor and matched normal tissue samples. Hierarchical cluster analysis resulted in the identification of clusters containing differentially co-expressed genes associated with the regulation of cervical cancer. Conclusion The proposed approach targets all different types of differential co-expression and it is sensitive to nonlinear relations. It is easy to implement and can be applied to any sequencing data to identify gene co-expression differences between multiple conditions

Network Medicine in the Age of Biomedical Big Data

Network medicine is an emerging area of research dealing with molecular and genetic interactions, network biomarkers of disease, and therapeutic target discovery. Large-scale biomedical data generation offers a unique opportunity to assess the effect and impact of cellular heterogeneity and environmental perturbations on the observed phenotype. Marrying the two, network medicine with biomedical data provides a framework to build meaningful models and extract impactful results at a network level. In this review, we survey existing network types and biomedical data sources. More importantly, we delve into ways in which the network medicine approach, aided by phenotype-specific biomedical data, can be gainfully applied. We provide three paradigms, mainly dealing with three major biological network archetypes: protein-protein interaction, expression-based, and gene regulatory networks. For each of these paradigms, we discuss a broad overview of philosophies under which various network methods work. We also provide a few examples in each paradigm as a test case of its successful application. Finally, we delineate several opportunities and challenges in the field of network medicine. We hope this review provides a lexicon for researchers from biological sciences and network theory to come on the same page to work on research areas that require interdisciplinary expertise. Taken together, the understanding gained from combining biomedical data with networks can be useful for characterizing disease etiologies and identifying therapeutic targets, which, in turn, will lead to better preventive medicine with translational impact on personalized healthcare