WholeCellKB: model organism databases for comprehensive whole-cell models

Abstract

Whole-cell models promise to greatly facilitate the analysis of complex biological behaviors. Whole-cell model development requires comprehensive model organism databases. WholeCellKB (http://wholecellkb.stanford.edu) is an open-source web-based software program for constructing model organism databases. WholeCellKB provides an extensive and fully customizable data model that fully describes individual species including the structure and function of each gene, protein, reaction and pathway. We used WholeCellKB to create WholeCellKB-MG, a comprehensive database of the Gram-positive bacterium Mycoplasma genitalium using over 900 sources. WholeCellKB-MG is extensively cross-referenced to existing resources including BioCyc, KEGG and UniProt. WholeCellKB-MG is freely accessible through a web-based user interface as well as through a RESTful web service.

Figure 1.

WholeCellKB-MG enables whole-cell modeling by integrating diverse data sources into a single database. (a) Currently, WholeCellKB-MG integrates >900 primary research articles, reviews, books and databases. (b) WholeCellKB-MG comprehensively represents all aspects of molecular physiology including metabolomics, genomics, transcriptomics and proteomics. (c) WholeCellKB-MG provides molecular data for whole-cell models.

Figure 2.

WholeCellKB aims to comprehensively describe cell physiology including the structure and dynamics of every metabolite, gene, RNA transcript and protein. Boxes illustrate several molecular properties represented by WholeCellKB.

Figure 3.

Detailed comparison of the content of WholeCellKB-MG and several existing biological databases. In addition to containing detailed descriptions of genetics, metabolism and transcriptional regulation comparable to existing resources such as BiGG (28), BioCyc (18) and CMR (4), WholeCellKB-MG has detailed representations of RNA degradation, RNA and protein maturation and protein translocation. Black boxes indicate physiology represented with fine granularity including the specific molecules involved in each specific interaction (e.g. specific metabolites involved in each metabolic reaction). Gray boxes indicate coarsely represented physiology, for example lumping families of similar reactions such as RNA methylation into a single database entry rather than representing the specific RNA bases involved in each individual reaction. White boxes indicate unrepresented physiology.