Traceability, reproducibility and wiki-exploration for “à-la-carte” reconstructions of genome-scale metabolic models

Abstract

Genome-scale metabolic models have become the tool of choice for the global analysis of microorganism metabolism, and their reconstruction has attained high standards of quality and reliability. Improvements in this area have been accompanied by the development of some major platforms and databases, and an explosion of individual bioinformatics methods. Consequently, many recent models result from “à la carte” pipelines, combining the use of platforms, individual tools and biological expertise to enhance the quality of the reconstruction. Although very useful, introducing heterogeneous tools, that hardly interact with each other, causes loss of traceability and reproducibility in the reconstruction process. This represents a real obstacle, especially when considering less studied species whose metabolic reconstruction can greatly benefit from the comparison to good quality models of related organisms. This work proposes an adaptable workspace, AuReMe, for sustainable reconstructions or improvements of genome-scale metabolic models involving personalized pipelines. At each step, relevant information related to the modifications brought to the model by a method is stored. This ensures that the process is reproducible and documented regardless of the combination of tools used. Additionally, the workspace establishes a way to browse metabolic models and their metadata through the automatic generation of ad-hoc local wikis dedicated to monitoring and facilitating the process of reconstruction. AuReMe supports exploration and semantic query based on RDF databases. We illustrate how this workspace allowed handling, in an integrated way, the metabolic reconstructions of non-model organisms such as an extremophile bacterium or eukaryote algae. Among relevant applications, the latter reconstruction led to putative evolutionary insights of a metabolic pathway.

Memote: A community driven effort towards a standardized genome-scale metabolic model test suite

“…AuReMe, follows a similar approach, by allowing users to interact with a database through automatically generated wikis 55 . While databases offer greater capacity and speed than single, large data files, the programmatic or form-based interaction required for databases may not be most immediately accessible to a broad community.…”

Inferring biochemical reactions and metabolite structures to cope with metabolic pathway drift

“…Genome-scale metabolic network reconstruction was performed using the AuReMe pipeline [55]. A set of 89 targets coming from the literature was used as an input and is provided in S3 Table. Orphan metabolites that are experimentally supported but do not have a MetaCyc ID are listed in S4 Table. The process encompassed the following steps:…”

“…This G. sulphuraria annotation-based network was then used as a template to generate a C. crispus network using Pantograph. 28 4) an orthology-based network was also generated using the protein sequences from the version 2 of the annotated genome of E. siliculosus [76], as well as version 2 of its metabolic network [55]. 5) the four preliminary networks were merged together in the AuReMe environment, and an additional gap-filling step was performed using Meneco [77], constraining the network to produce the 84 metabolites from the literature that were indexed in the Metacyc database.…”

“…reinhardtii are respectively from KEGG [79] and BiGG [80]. To get access to MetaCyc pathway information for A. thaliana and C. reinhardtii, their networks were mapped using the sbml_mapping function implemented in the AuReMe workflow [55]. This function provides a dictionary of corresponding reactions from a database to an other one using the MetaNetX…”

“…sbml_mapping function implemented in the AuReMe workflow [55]. This function provides a dictionary of corresponding reactions from a database to an other one using the MetaNetX cross-reference database [81].…”