PathwayMatcher: proteoform-centric network construction enables fine-granularity multiomics pathway mapping

GigaScience
Luis Francisco Hernández SánchezMarc Vaudel

Abstract

Mapping biomedical data to functional knowledge is an essential task in bioinformatics and can be achieved by querying identifiers (e.g., gene sets) in pathway knowledge bases. However, the isoform and posttranslational modification states of proteins are lost when converting input and pathways into gene-centric lists. Based on the Reactome knowledge base, we built a network of protein-protein interactions accounting for the documented isoform and modification statuses of proteins. We then implemented a command line application called PathwayMatcher (github.com/PathwayAnalysisPlatform/PathwayMatcher) to query this network. PathwayMatcher supports multiple types of omics data as input and outputs the possibly affected biochemical reactions, subnetworks, and pathways. PathwayMatcher enables refining the network representation of pathways by including proteoforms defined as protein isoforms with posttranslational modifications. The specificity of pathway analyses is hence adapted to different levels of granularity, and it becomes possible to distinguish interactions between different forms of the same protein.

References

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Datasets Mentioned

BETA
GM114833

Software Mentioned

scico
ggplot2
graphlayouts
Apache
dplyr
purr
PRIDE Graph
Galaxy ToolShed
Docker
gtable

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