An integrative and applicable phylogenetic footprinting framework for cis-regulatory motifs identification in prokaryotic genomes

Authors

Bingqiang Liu, Shandong University
Hanyuan Zhang, University of Nebraska-Lincoln
Chuan Zhou, Shandong University
Guojun Li, Shandong UniversityFollow
Anne Fennell, South Dakota State University
Guanghui Wang, Shandong University
Yu Kang, Beijing Institute of Genomics of CAS
Qi Liu, Tongji University
Qin Ma, South Dakota State University

Document Type

Article

Date of this Version

2016

Citation

Liu et al. BMC Genomics (2016) 17:578

Comments

© 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License

Abstract

Background: Phylogenetic footprinting is an important computational technique for identifying cis-regulatory motifs in orthologous regulatory regions from multiple genomes, as motifs tend to evolve slower than their surrounding non-functional sequences. Its application, however, has several difficulties for optimizing the selection of orthologous data and reducing the false positives in motif prediction.

Results: Here we present an integrative phylogenetic footprinting framework for accurate motif predictions in prokaryotic genomes (MP³). The framework includes a new orthologous data preparation procedure, an additional promoter scoring and pruning method and an integration of six existing motif finding algorithms as basic motif search engines. Specifically, we collected orthologous genes from available prokaryotic genomes and built the orthologous regulatory regions based on sequence similarity of promoter regions. This procedure made full use of the large-scale genomic data and taxonomy information and filtered out the promoters with limited contribution to produce a high quality orthologous promoter set. The promoter scoring and pruning is implemented through motif voting by a set of complementary predicting tools that mine as many motif candidates as possible and simultaneously eliminate the effect of random noise. We have applied the framework to Escherichia coli k12 genome and evaluated the prediction performance through comparison with seven existing programs. This evaluation was systematically carried out at the nucleotide and binding site level, and the results showed that MP³ consistently outperformed other popular motif finding tools. We have integrated MP³ into our motif identification and analysis server DMINDA, allowing users to efficiently identify and analyze motifs in 2,072 completely sequenced prokaryotic genomes.

Conclusion: The performance evaluation indicated that MP³ is effective for predicting regulatory motifs in prokaryotic genomes. Its application may enhance progress in elucidating transcription regulation mechanism, thus provide benefit to the genomic research community and prokaryotic genome researchers in particular.