WikiPathways: a multifaceted pathway database bridging metabolomics to other omics research

Abstract

WikiPathways (wikipathways.org) captures the collective knowledge represented in biological pathways. By providing a database in a curated, machine readable way, omics data analysis and visualization is enabled. WikiPathways and other pathway databases are used to analyze experimental data by research groups in many fields. Due to the open and collaborative nature of the WikiPathways platform, our content keeps growing and is getting more accurate, making WikiPathways a reliable and rich pathway database. Previously, however, the focus was primarily on genes and proteins, leaving many metabolites with only limited annotation. Recent curation efforts focused on improving the annotation of metabolism and metabolic pathways by associating unmapped metabolites with database identifiers and providing more detailed interaction knowledge. Here, we report the outcomes of the continued growth and curation efforts, such as a doubling of the number of annotated metabolite nodes in WikiPathways. Furthermore, we introduce an OpenAPI documentation of our web services and the FAIR (Findable, Accessible, Interoperable and Reusable) annotation of resources to increase the interoperability of the knowledge encoded in these pathways and experimental omics data. New search options, monthly downloads, more links to metabolite databases, and new portals make pathway knowledge more effortlessly accessible to individual researchers and research communities.

Figure 1.

Overview of coverage of various gene spaces. WikiPathways (WP) currently covers 11 532 unique human genes. Venn diagram A shows that 50% of the protein coding genes (Ensembl: 22 376 genes) are found in WikiPathways. B shows the 66% coverage of all disease genes (OMIM: 15,262 genes), which also illustrates that the vast majority of genes in WikiPathways are associated with a disease. The C diagram shows that WikiPathways covers 71% of all genes known to be involved in human metabolism (GO metabolic process: 11 296 genes).

Figure 2.

Metabolite coverage growth in WikiPathways. Taking KEGG as the standard, we plot the growth of WikiPathways (WP) coverage over the past five years. WikiPathways and KEGG unique human metabolite counts were calculated by extracting identifiers from archived WikiPathways releases and unifying to, ideally, Wikidata ID, otherwise ChEBI or HMDB. About two-third of all identifiers (blue line) could be mapped to a Wikidata (red line). Metabolite IDs that could not be mapped to these three databases, have decreased over the last five years (unmapped, green line).

Figure 3.

Previous and updated Glucose-1-phosphate metabolism (Saccharomyces cerevisiae) pathway diagram: the original pathway (left, Heckman, J., Chichester, C. and Willighagen, E. (2016) Glucose-1-phosphate metabolism (Saccharomyces cerevisiae). wikipathways.org/instance/WP260_r89691) represented the reactions as five separate chemical reactions and with several metabolites as text labels. After curation, the improved pathway (right, Heckman, J., Chichester, C., Willighagen, E., Slenter, D. and Kutmon, M. (2017) Glucose-1-phosphate metabolism (S. cerevisiae). wikipathways.org/instance/WP260_r94487) shows connected reactions with annotated metabolites.