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Generalizing and learning protein-DNA binding sequence representations by an evolutionary algorithm

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Abstract

Protein-DNA bindings are essential activities. Understanding them forms the basis for further deciphering of biological and genetic systems. In particular, the protein-DNA bindings between transcription factors (TFs) and transcription factor binding sites (TFBSs) play a central role in gene transcription. Comprehensive TF-TFBS binding sequence pairs have been found in a recent study. However, they are in one-to-one mappings which cannot fully reflect the many-to-many mappings within the bindings. An evolutionary algorithm is proposed to learn generalized representations (many-to-many mappings) from the TF-TFBS binding sequence pairs (one-to-one mappings). The generalized pairs are shown to be more meaningful than the original TF-TFBS binding sequence pairs. Some representative examples have been analyzed in this study. In particular, it shows that the TF-TFBS binding sequence pairs are not presumably in one-to-one mappings. They can also exhibit many-to-many mappings. The proposed method can help us extract such many-to-many information from the one-to-one TF-TFBS binding sequence pairs found in the previous study, providing further knowledge in understanding the bindings between TFs and TFBSs.

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Notes

  1. As defined in Leung et al. (2010), a kmer is commonly found in a set of sequences if and only if it is a substring in more than or equal to half of the sequences.

  2. A TFBS kmer–TF kmer pair is considered binding for a PDB chain if and only if an atom of the TFBS kmer and an atom of the TF kmer are close to each other. Two atoms are considered close if and only if their distance is smaller than 3.5 angstrom. Leung et al. (2010).

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Acknowledgments

The authors are grateful to the anonymous reviewers for their valuable comments. They would like to thank Tak-Ming Chan for his help on surveying the related works. This research is partially supported by the grants from the Research Grants Council of the Hong Kong Special Administrative Region, China (Project Nos. 414107 and 414708).

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Authors and Affiliations

  1. Department of Computer Science and Engineering, The Chinese University of Hong Kong, Shatin, Hong Kong

    Ka-Chun Wong, Man-Hon Wong & Kwong-Sak Leung

  2. Mathematical and Computer Sciences and Engineering Division, King Abdullah University of Science and Technology, Jeddah, Kingdom of Saudi Arabia

    Ka-Chun Wong & Chengbin Peng

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Correspondence to Ka-Chun Wong.

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Wong, KC., Peng, C., Wong, MH. et al. Generalizing and learning protein-DNA binding sequence representations by an evolutionary algorithm. Soft Comput 15, 1631–1642 (2011). https://doi.org/10.1007/s00500-011-0692-5

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