Target Gene Prediction of Transcription Factor Using a New Neighborhood-regularized Tri-factorization One-class Collaborative Filtering Algorithm.

Abstract

Identifying the target genes of transcription factors (TFs) is one of the key factors to understand transcriptional regulation. However, our understanding of genome-wide TF targeting profile is limited due to the cost of large scale experiments and intrinsic complexity. Thus, computational prediction methods are useful to predict the unobserved associations. Here, we developed a new one-class collaborative filtering algorithm tREMAP that is based on regularized, weighted nonnegative matrix tri-factorization. The algorithm predicts unobserved target genes for TFs using known gene-TF associations and protein-protein interaction network. Our benchmark study shows that tREMAP significantly outperforms its counterpart REMAP, a bi-factorization-based algorithm, for transcription factor target gene prediction in all four performance metrics AUC, MAP, MPR, and HLU. When evaluated by independent data sets, the prediction accuracy is 37.8% on the top 495 predicted associations, an enrichment factor of 4.19 compared with the random guess. Furthermore, many of the predicted novel associations by tREMAP are supported by evidence from literature. Although we only use canonical TF-target gene interaction data in this study, tREMAP can be directly applied to tissue-specific data sets. tREMAP provides a framework to integrate multiple omics data for the further improvement of TF target gene prediction. Thus, tREMAP is a potentially useful tool in studying gene regulatory networks. The benchmark data set and the source code of tREMAP are freely available at https://github.com/hansaimlim/REMAP/tree/master/TriFacREMAP.