Precise generation of systems biology models from KEGG pathways

Abstract

BackgroundThe KEGG PATHWAY database provides a plethora of pathways for a diversity of organisms. All pathway components are directly linked to other KEGG databases, such as KEGG COMPOUND or KEGG REACTION. Therefore, the pathways can be extended with an enormous amount of information and provide a foundation for initial structural modeling approaches. As a drawback, KGML-formatted KEGG pathways are primarily designed for visualization purposes and often omit important details for the sake of a clear arrangement of its entries. Thus, a direct conversion into systems biology models would produce incomplete and erroneous models.ResultsHere, we present a precise method for processing and converting KEGG pathways into initial metabolic and signaling models encoded in the standardized community pathway formats SBML (Levels 2 and 3) and BioPAX (Levels 2 and 3). This method involves correcting invalid or incomplete KGML content, creating complete and valid stoichiometric reactions, translating relations to signaling models and augmenting the pathway content with various information, such as cross-references to Entrez Gene, OMIM, UniProt ChEBI, and many more.Finally, we compare several existing conversion tools for KEGG pathways and show that the conversion from KEGG to BioPAX does not involve a loss of information, whilst lossless translations to SBML can only be performed using SBML Level 3, including its recently proposed qualitative models and groups extension packages.ConclusionsBuilding correct BioPAX and SBML signaling models from the KEGG database is a unique characteristic of the proposed method. Further, there is no other approach that is able to appropriately construct metabolic models from KEGG pathways, including correct reactions with stoichiometry. The resulting initial models, which contain valid and comprehensive SBML or BioPAX code and a multitude of cross-references, lay the foundation to facilitate further modeling steps.

From word models to executable models of signaling networks using automated assembly

“…Several software tools have been developed to partially automate the construction of executable models from bioinformatics databases such as KEGG, Pathway Commons (Ruebenacker et al , ; Büchel et al , ; Wrzodek et al , ; Turei et al , ). Automating model translation in this way increases throughput and maintains links between model assumptions and curated findings in databases, eliminating the need for labor‐intensive annotations of hand‐built models (Le Novère et al , ).…”

“…Similarly, Cytoscape (Cline et al , ) makes it possible to import protein interactions from multiple databases and output the results to SBML. More recent one‐to‐many tools translate information from a single knowledge source into multiple output formats (Wrzodek et al , ), while many‐to‐one tools aggregate pathway information from many sources but target a single output format (Turei et al , ).…”

Pathways commonly dysregulated in mouse and human obese adipose tissue: FAT/CD36 modulates differentiation and lipogenesis

“…Human liver gene set was obtained in a previous study. 29 KEGG pathways gene number counts 69 were performed to raise gene datasets representative of either phenotypes or data sets (Supplementary Data 2).…”

Exploring the Genomic Roadmap and Molecular Phylogenetics Associated with MODY Cascades Using Computational Biology

“…Furthermore, unrooted phylogenetics tree such as circular alpha have been developed using software called interactive Tree Of Life (iTOL) which is an online tool for displaying the circular alpha tree and annotation [54]. We have generated Sequence logos using WebLogo software, which are used for graphical representation of amino acid for displaying the patterns in a set of aligned sequences [55,56]. Here, we have used all sequences to produce the sequence logos.…”