Identification of upstream transcription factor binding sites in orthologous genes using mixed Student’s t-test statistics

Abstract

Background Transcription factor (TF) regulates the transcription of DNA to messenger RNA by binding to upstream sequence motifs. Identifying the locations of known motifs in whole genomes is computationally intensive. Methodology/Principal findings This study presents a computational tool, named “Grit”, for screening TF-binding sites (TFBS) by coordinating transcription factors to their promoter sequences in orthologous genes. This tool employs a newly developed mixed Student’s t-test statistical method that detects high-scoring binding sites utilizing conservation information among species. The program performs sequence scanning at a rate of 3.2 Mbp/s on a quad-core Amazon server and has been benchmarked by the well-established ChIP-Seq datasets, putting Grit amongst the top-ranked TFBS predictors. It significantly outperforms the well-known transcription factor motif scanning tools, Pscan (4.8%) and FIMO (17.8%), in analyzing well-documented ChIP-Atlas human genome Chip-Seq datasets. Significance Grit is a good alternative to current available motif scanning tools.