The Center for Genomic Sciences of the National Autonomous University of Mexico (UNAM) in Cuernavaca and a group of collaborators propose to further develop and enrich the RegulonDB database. RegulonDB contains the largest electronically-available regulatory network of any living organism, that of Escherichia coli K-12. In the project we will expand the design, implement computational and conceptual models, and generate annotations derived from original literature of the different components of the regulatory network. We will experimentally map promoters and transcription units under different conditions. This project expands a previous grant supporting RegulonDB. High quality manual curation is to be enriched beyond transcription initiation to include signal-transduction connecting sensing with regulation, as well as with natural language text processing tools. We propose to continue an exhaustive experimental mapping of all possible transcription initiation sites in the genome and to perform an exhaustive experimental identification of transcription units in different conditions. The core of RegulonDB (literature-based network and the graphic and browsing tools) will be linked and made accessible, as optional user selections, with high-throughput available experiments (microarrays and ChIP- chip) both as raw and pre-analyzed data, as well as with collections of computational predictions of all network elements (transcription factors, promoters, binding sites, operons, regulatory interactions). This will be based on track representations and compliant with international consortia normalized pathway exchange formats. The openness of RegulonDB data and internal structure will expand considerably, enhancing as well its availability to tools for analysis and representation.

Public Health Relevance

RegulonDB is a gold standard both in its conceptual and computational design, as well as in the amount and quality of data gathered on the largest and best characterized regulatory network of a single organism. The improvements and expansion of RegulonDB may accelerate research in other bacterial models, including pathogens. RegulonDB has served as a benchmark for a variety of computational predictive tools for components of the network. Furthermore, E.coli is at the forefront in systems biology as a proof-of-concept biological model to develop new methodologies in bioinformatics, representation and simulation, to overcome challenges in order to model and understand the functioning of a whole cell.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM071962-08
Application #
8127813
Study Section
Biodata Management and Analysis Study Section (BDMA)
Program Officer
Lyster, Peter
Project Start
2004-08-01
Project End
2013-08-31
Budget Start
2011-09-01
Budget End
2013-08-31
Support Year
8
Fiscal Year
2011
Total Cost
$382,052
Indirect Cost
Name
Center for Genomic Sciences
Department
Type
DUNS #
588238683
City
Cuernavaca
State
Country
Mexico
Zip Code
62210
Karp, Peter D; Weaver, Daniel; Paley, Suzanne et al. (2014) The EcoCyc Database. EcoSal Plus 6:
Martínez, Luary C; Martínez-Flores, Irma; Salgado, Heladia et al. (2014) In silico identification and experimental characterization of regulatory elements controlling the expression of the Salmonella csrB and csrC genes. J Bacteriol 196:325-36
Weiss, Verena; Medina-Rivera, Alejandra; Huerta, Araceli M et al. (2013) Evidence classification of high-throughput protocols and confidence integration in RegulonDB. Database (Oxford) 2013:bas059
Keseler, Ingrid M; Mackie, Amanda; Peralta-Gil, Martin et al. (2013) EcoCyc: fusing model organism databases with systems biology. Nucleic Acids Res 41:D605-12
Balderas-Martínez, Yalbi Itzel; Savageau, Michael; Salgado, Heladia et al. (2013) Transcription factors in Escherichia coli prefer the holo conformation. PLoS One 8:e65723
Salgado, Heladia; Peralta-Gil, Martin; Gama-Castro, Socorro et al. (2013) RegulonDB v8.0: omics data sets, evolutionary conservation, regulatory phrases, cross-validated gold standards and more. Nucleic Acids Res 41:D203-13
Gallego-Hernandez, A L; Hernandez-Lucas, I; De la Cruz, M A et al. (2012) Transcriptional regulation of the assT-dsbL-dsbI gene cluster in Salmonella enterica serovar Typhi IMSS-1 depends on LeuO, H-NS, and specific growth conditions. J Bacteriol 194:2254-64
Pauling, Josch; Rottger, Richard; Neuner, Andreas et al. (2012) On the trail of EHEC/EAEC--unraveling the gene regulatory networks of human pathogenic Escherichia coli bacteria. Integr Biol (Camb) 4:728-33
Salgado, Heladia; Martinez-Flores, Irma; Lopez-Fuentes, Alejandra et al. (2012) Extracting regulatory networks of Escherichia coli from RegulonDB. Methods Mol Biol 804:179-95
Massimelli, Maria J; Sánchez, Diego G; Buchieri, Maria V et al. (2011) Choline catabolism, ??? factor and NtrC are required for the full expression of the Pseudomonas aeruginosa phosphorylcholine phosphatase gene. Microbiol Res 166:380-90

Showing the most recent 10 out of 36 publications