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. 2016 Nov 29;10(1):129.
doi: 10.1186/s12918-016-0369-x.

The Quality of Metabolic Pathway Resources Depends on Initial Enzymatic Function Assignments: A Case for Maize

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Free PMC article

The Quality of Metabolic Pathway Resources Depends on Initial Enzymatic Function Assignments: A Case for Maize

Jesse R Walsh et al. BMC Syst Biol. .
Free PMC article

Abstract

Background: As metabolic pathway resources become more commonly available, researchers have unprecedented access to information about their organism of interest. Despite efforts to ensure consistency between various resources, information content and quality can vary widely. Two maize metabolic pathway resources for the B73 inbred line, CornCyc 4.0 and MaizeCyc 2.2, are based on the same gene model set and were developed using Pathway Tools software. These resources differ in their initial enzymatic function assignments and in the extent of manual curation. We present an in-depth comparison between CornCyc and MaizeCyc to demonstrate the effect of initial computational enzymatic function assignments on the quality and content of metabolic pathway resources.

Results: These two resources are different in their content. MaizeCyc contains GO annotations for over 21,000 genes that CornCyc is missing. CornCyc contains on average 1.6 transcripts per gene, while MaizeCyc contains almost no alternate splicing. MaizeCyc also does not match CornCyc's breadth in representing the metabolic domain; MaizeCyc has fewer compounds, reactions, and pathways than CornCyc. CornCyc's computational predictions are more accurate than those in MaizeCyc when compared to experimentally determined function assignments, demonstrating the relative strength of the enzymatic function assignment pipeline used to generate CornCyc.

Conclusions: Our results show that the quality of initial enzymatic function assignments primarily determines the quality of the final metabolic pathway resource. Therefore, biologists should pay close attention to the methods and information sources used to develop a metabolic pathway resource to gauge the utility of using such functional assignments to construct hypotheses for experimental studies.

Keywords: BioCyc; CornCyc; Database comparison; JavaCycO; MaizeCyc; Metabolic pathway databases.

Figures

Fig. 1
Fig. 1
Overview of the pipelines used to create CornCyc 4.0 and MaizeCyc 2.2. Green represents common components, and orange and blue CornCyc- and MaizeCyc-specific components respectively. CornCyc and MaizeCyc were both based on the B73 RefGen_v2 gene model. They mainly differed in different functional annotation prediction methods incorporated into their respective pipelines. Both databases used Pathway Tools and MetaCyc for their reaction and pathway inference. Since both databases were created at different times, they used different versions of MetaCyc. Finally, manual curation has been applied to both databases. In order to account for differences at the pathway and reaction inference steps as well as at the manual curation step, we propagated updates from the same version of MetaCyc to both databases and allowed the propagation utility to remove manually curated data
Fig. 2
Fig. 2
Performance comparison between CornCyc 4.0, MaizeCyc 2.2, and the union of both datasets based on 1,475 experimentally verified annotations across 1,450 genes
Fig. 3
Fig. 3
Comparison of a) GO annotated gene, b) reaction mapped gene, c) reaction mapped protein, d) compound, e) reaction, and f) pathway statistics between CornCyc 4.0 and MaizeCyc 2.2
Fig. 4
Fig. 4
Comparison of Reactions Sorted by EC Category between CornCyc 4.0, MaizeCyc 2.2, BRENDA (July 2015 Release), and MetaCyc 19.5. For CornCyc and MaizeCyc, reactions with no EC category are not included in the calculations. CornCyc unique reactions refer to all reactions that were unique to the CornCyc when compared to MaizeCyc, and vice versa. For MetaCyc and BRENDA, all reactions, including those not found in plants, were included
Fig. 5
Fig. 5
The gene-reaction relationships for reactions in the C4 photosynthesis pathway PWY-7115. While the pathway and reaction-pathway membership (above) remain the same for both resources, the gene-reaction relationships differ. Each gene-reaction pair (below) indicates if the pairing is found in CornCyc (yellow), MaizeCyc (green), or both resources (orange)

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