Pathway Commons 2019 Update: integration, analysis and exploration of pathway data

Abstract

Pathway Commons (https://www.pathwaycommons.org) is an integrated resource of publicly available information about biological pathways including biochemical reactions, assembly of biomolecular complexes, transport and catalysis events and physical interactions involving proteins, DNA, RNA, and small molecules (e.g. metabolites and drug compounds). Data is collected from multiple providers in standard formats, including the Biological Pathway Exchange (BioPAX) language and the Proteomics Standards Initiative Molecular Interactions format, and then integrated. Pathway Commons provides biologists with (i) tools to search this comprehensive resource, (ii) a download site offering integrated bulk sets of pathway data (e.g. tables of interactions and gene sets), (iii) reusable software libraries for working with pathway information in several programming languages (Java, R, Python and Javascript) and (iv) a web service for programmatically querying the entire dataset. Visualization of pathways is supported using the Systems Biological Graphical Notation (SBGN). Pathway Commons currently contains data from 22 databases with 4794 detailed human biochemical processes (i.e. pathways) and ∼2.3 million interactions. To enhance the usability of this large resource for end-users, we develop and maintain interactive web applications and training materials that enable pathway exploration and advanced analysis.

Figure 1.

A summary of pathway and interaction databases in Pathway Commons Version 11, released February 2019. Participants are counts of ‘PhysicalEntity’ class instances from the BioPAX ontology, which includes the classes: complexes, DNA, DNARegion, Protein, RNA, RNARegion and SmallMolecule, including the possibility of multiple molecular states per gene (e.g. phosphorylated proteins, proteins in the nucleus). Citations for data providers: (20,30,61,67–84).

Figure 2.

From primary knowledge to end-user pathway tools. Pathway Commons (PC) aggregates and disseminates pathway and interaction knowledge from 22 databases (version 11). BioPAX files are downloaded directly from data providers and are subsequently validated, normalized and merged into PC. Data can be directly accessed programmatically via the web service or downloaded in bulk files. Exploration and analysis are aided by software tools, packages and web apps that are tailored to the use cases of computational and experimental researchers.

Figure 3.

Pathway Commons web apps. (A) Search provides integrated access to the entire collection of pathways and interactions in Pathway Commons. User queries are analyzed to select the type of search results they may find most useful, such as mentions of recognized genes along with link-outs to web apps and a ranked list of pathway search hits. (B) Each pathway search hit is linked to an interactive viewer, rendered using the Systems Biology Graphical Notation (SBGN) visual language. (C) The Interactions web app accessed from the search page links to an interactive network visualization showing relationships between one or more of genes recognized in a user query. (D) With longer lists of recognized genes, an Enrichment web app links to results of pathway enrichment analysis displayed as an interactive Enrichment Map network. Nodes represent pathways (GO: Biological Process, Reactome pathways) and edges connect similar pathways, as measured by the number of shared genes. All visualization features are built using the Cytoscape.js software library. (E) The Painter app, launched via the Enrichment Map app for Cytoscape desktop (not shown), projects quantitative gene expression data onto pathways. (F) A PCViz app accepts one or more query genes and displays a network of interactions between and around it.