A matrix rank based concordance index for evaluating and detecting conditional specific co-expressed gene modules

Abstract

Background: Gene co-expression network analysis (GCNA) is widely adopted in bioinformatics and biomedical research with applications such as gene function prediction, protein-protein interaction inference, disease markers identification, and copy number variance discovery. Currently there is a lack of rigorous analysis on the mathematical condition for which the co-expressed gene module should satisfy. Methods: In this paper, we present a linear algebraic based Centralized Concordance Index (CCI) for evaluating the concordance of co-expressed gene modules from gene co-expression network analysis. The CCI can be used to evaluate the performance for co-expression network analysis algorithms as well as for detecting condition specific co-expression modules. We applied CCI in detecting lung tumor specific gene modules. Results and Discussion: Simulation showed that CCI is a robust indicator for evaluating the concordance of a group of co-expressed genes. The application to lung cancer datasets revealed interesting potential tumor specific genetic alterations including CNVs and even hints for gene-fusion. Deeper analysis required for understanding the molecular mechanisms of all such condition specific co-expression relationships. Conclusion: The CCI can be used to evaluate the performance for co-expression network analysis algorithms as well as for detecting condition specific co-expression modules. It is shown to be more robust to outliers and interfering modules than density based on Pearson correlation coefficients.