A two-way rectification method for identifying differentially expressed genes by maximizing the co-function relationship

Background: The identification of differentially expressed genes (DEGs) is an important task in many biological studies. The currently widely used methods often calculate a score for each gene by estimating the significance level in terms of the differential expression. However, biological experiments often have only three duplications, plus plenty of noises contain in gene expression datasets, which brings a great challenge to statistical analysis methods. Moreover, the abundance of gene expression levels are not evenly distributed. Thus, those low expressed genes are more easily to be detected by fold-change based methods, which may results in high false positives among the DEG list. Since phenotypical changes result from DEGs should be strongly related to several distinct cellular functions, a more robust method should be designed to increase the true positive rate of the functional related DEGs. Results: In this study, we propose a two-way rectification method for identifying DEGs by maximizing the co-function relationships between genes and their enriched cellular pathways. An iteration strategy is employed to sequentially narrow down the group of identified DEGs and their associated biological functions. Functional analyses reveal that the identified DEGs are well organized in the form of functional modules, and the enriched pathways are very significant with lower p-value and larger gene count. Conclusions: An integrative rectification method was proposed to identify key DEGs and their related functions simultaneously. The experimental validations demonstrate that the method has high interpretability and feasibility. It performs very well in terms of the identification of remarkable functional related genes.