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Practical Computational Methods for Regulatory Genomics: A cisGRN-Lexicon and cisGRN-Browser for Gene Regulatory Networks

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Computational Biology of Transcription Factor Binding

Part of the book series: Methods in Molecular Biology ((MIMB,volume 674))

Abstract

The CYRENE Project focuses on the study of cis-regulatory genomics and gene regulatory networks (GRN) and has three components: a cisGRN-Lexicon, a cisGRN-Browser, and the Virtual Sea Urchin software system. The project has been done in collaboration with Eric Davidson and is deeply inspired by his experimental work in genomic regulatory systems and gene regulatory networks. The current CYRENE cisGRN-Lexicon contains the regulatory architecture of 200 transcription factors encoding genes and 100 other regulatory genes in eight species: human, mouse, fruit fly, sea urchin, nematode, rat, chicken, and zebrafish, with higher priority on the first five species. The only regulatory genes included in the cisGRN-Lexicon (CYRENE genes) are those whose regulatory architecture is validated by what we call the Davidson Criterion: they contain functionally authenticated sites by site-specific mutagenesis, conducted in vivo, and followed by gene transfer and functional test. This is recognized as the most stringent experimental validation criterion to date for such a genomic regulatory architecture. The CYRENE cisGRN-Browser is a full genome browser tailored for cis-regulatory annotation and investigation. It began as a branch of the Celera Genome Browser (available as open source at http://sourceforge.net/projects/celeragb/) and has been transformed to a genome browser fully devoted to regulatory genomics. Its access paradigm for genomic data is zoom-to-the-DNA-base in real time. A more recent component of the CYRENE project is the Virtual Sea Urchin system (VSU), an interactive visualization tool that provides a four-dimensional (spatial and temporal) map of the gene regulatory networks of the sea urchin embryo.

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Acknowledgments

The support of the National Science Foundation under grant DBI 0645955 is acknowledged with gratitude. We would also like to acknowledge the tremendous impact on this work of our collaborator, Eric H. Davidson of the California Institute of Technology, who has guided every step of our efforts. This work would not have been possible without the contributions of three generations of annotators, most notably Tim Johnstone, Jake Halpert, and David Moskowitz. (The first generation was David Moskowitz, Rohan Madamsetti, and Sanjay Trehan; the second generation was Tamar Melman, Mark Grabiner, and Kyle Schutter; the third generation is Tim Johnstone, Jake Halpert, Mei Cao, Kenneth Estrellas, Nicole Noronha, and Daniel Yang.) We would also like to thank Andy Ransick, Andy Cameron and Russell Turner for many discussions and valuable suggestions. Last but not least, many thanks go to Erin Klopfenstein for her outstanding work and many valuable contributions to the CYRENE Project.

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Authors and Affiliations

  1. Department of Computer Science, Center for Computational Molecular Biology, Brown University, Providence, RI, USA

    Sorin Istrail, Ryan Tarpine & Derek Aguiar

  2. Department of Biomedical Engineering, Center for Computational Molecular Biology, Brown University, Providence, RI, USA

    Kyle Schutter

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  1. Sorin Istrail
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  2. Ryan Tarpine
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Correspondence to Sorin Istrail .

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  1. , Department of Statistics, University of Nebraska-Lincoln, Vine Street 1901, Lincoln, 68588-0665, Nebraska, USA

    Istvan Ladunga

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Istrail, S., Tarpine, R., Schutter, K., Aguiar, D. (2010). Practical Computational Methods for Regulatory Genomics: A cisGRN-Lexicon and cisGRN-Browser for Gene Regulatory Networks. In: Ladunga, I. (eds) Computational Biology of Transcription Factor Binding. Methods in Molecular Biology, vol 674. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-854-6_22

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  • DOI: https://doi.org/10.1007/978-1-60761-854-6_22

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