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Transcription Factors Across the Escherichia coli Pangenome: A 3D Perspective

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Comparative Genomics (RECOMB-CG 2024)

Part of the book series: Lecture Notes in Computer Science ((LNBI,volume 14616))

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Abstract

Identification of complete sets of transcription factors (TFs) is a foundational step in the inference of genetic regulatory networks. The availability of high-quality predictions of protein three-dimensional structures (3D), has made it possible to use structural similarities for the inference of homology beyond what is possible from sequence analyses alone. This work explores the potential to use such 3D structures for the identification of TFs in the Escherichia coli pangenome. Comparisons between predicted structures and their experimental counterparts confirmed the high-quality of predicted structures, with most 3D structural alignments showing TM-scores well above established structural similarity thresholds, though the quality seemed slightly lower for TFs than for other proteins. As expected, structural similarity decreased with sequence similarity, though most TM-scores still remained well above the structural similarity threshold. This was true regardless of the aligned structures being experimental or predicted. Results at the lowest sequence identity levels revealed potential for 3D structural comparisons to extend homology inferences below the “twilight zone” of sequence-based methods. The body of predicted 3D structures covered 99.7% of available proteins from the E. coli pangenome, missing only two of those matching TF domain sequence profiles. After cleaning out potential false positives, structural comparisons increased the number of inferred TFs in the pangenome by 50% over those obtained with sequence profiles alone, which translated into around 20% more TFs per genome.

Supported by the Natural Sciences and Engineering Research Council of Canada (NSERC).

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Authors and Affiliations

  1. Wilfrid Laurier University, Waterloo, ON, N2L 3C5, Canada

    Gabriel Moreno-Hagelsieb

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  1. Gabriel Moreno-Hagelsieb
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Correspondence to Gabriel Moreno-Hagelsieb .

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Editors and Affiliations

  1. CNRS, University of Montpellier, Montpellier, France

    Celine Scornavacca

  2. Center for Research and Advanced Studies, Irapuato, Mexico

    Maribel Hernández-Rosales

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Moreno-Hagelsieb, G. (2024). Transcription Factors Across the Escherichia coli Pangenome: A 3D Perspective. In: Scornavacca, C., Hernández-Rosales, M. (eds) Comparative Genomics. RECOMB-CG 2024. Lecture Notes in Computer Science(), vol 14616. Springer, Cham. https://doi.org/10.1007/978-3-031-58072-7_11

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