Identification of Highest-Affinity Binding Sites of Yeast Transcription Factor Families

J Chem Inf Model. 2020 Mar 23;60(3):1876-1883. doi: 10.1021/acs.jcim.9b01012. Epub 2020 Jan 28.

Abstract

Transcription factors (TFs) play a crucial role in controlling key cellular processes and responding to the environment. Yeast is a single-cell fungal organism that is a vital biological model organism for studying transcription and translation in basic biology. The transcriptional control process of yeast cells has been extensively calculated and studied using traditional methods and high-throughput technologies. However, the identities of transcription factors that regulate major functional categories of genes remain unknown. Due to the avalanche of biological data in the post-genomic era, it is an urgent need to develop automated computational methods to enable accurate identification of efficient transcription factor binding sites from the large number of candidates. In this paper, we analyzed high-resolution DNA-binding profiles and motifs for TFs, covering all possible contiguous 8-mers. First, we divided all 8-mer motifs into 16 various categories and selected all sorts of samples from each category by setting the threshold of E-score. Then, we employed five feature representation methods. Also, we adopted a total of four feature selection methods to filter out useless features. Finally, we used Extreme Gradient Boosting (XGBoost) as our base classifier and then utilized the one-vs-rest tactics to build 16 binary classifiers to solve this multiclassification problem. In the experiment, our method achieved the best performance with an overall accuracy of 79.72% and Mathew's correlation coefficient of 0.77. We found the similarity relationship among each category from different TF families and obtained sequence motif schematic diagrams via multiple sequence alignment. The complexity of DNA recognition may act as an important role in the evolution of gene regulation. Source codes are available at https://github.com/guofei-tju/tfbs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Computational Biology
  • Gene Expression Regulation
  • Protein Binding
  • Saccharomyces cerevisiae* / genetics
  • Saccharomyces cerevisiae* / metabolism
  • Transcription Factors* / genetics
  • Transcription Factors* / metabolism

Substances

  • Transcription Factors