Inferring gene regulatory networks by an order independent algorithm using incomplete data sets

Analyzing incomplete data for inferring the structure of gene regulatory networks (GRNs) is a challenging task in bioinformatic. Bayesian network can be successfully used in this field. k -nearest neighbor, singular value decomposition (SVD)-based and multiple imputation by chained equations are three fundamental imputation methods to deal with missing values. Path consistency (PC) algorithm based on conditional mutual information (PCA--CMI) is a famous algorithm for inferring GRNs. This algorithm needs the data set to be complete. However, the problem is that PCA--CMI is not a stable algorithm and when applied on permuted gene orders, different networks are obtained. We propose an order independent algorithm, PCA--CMI--OI, for inferring GRNs. After imputation of missing data, the performances of PCA--CMI and PCA--CMI--OI are compared. Results show that networks constructed from data imputed by the SVD-based method and PCA--CMI--OI algorithm outperform other imputation methods and PCA--CMI. An undirected or partially directed network is resulted by PC-based algorithms. Mutual information test (MIT) score, which can deal with discrete data, is one of the famous methods for directing the edges of resulted networks. We also propose a new score, ConMIT, which is appropriate for analyzing continuous data. Results shows that the precision of directing the edges of skeleton is improved by applying the ConMIT score.