Large Collection of Diverse Gene Set Search Queries Recapitulate Known Protein-Protein Interactions and Gene-Gene Functional Associations

TL;DR

This study leverages a large collection of user-submitted gene sets from Enrichr to construct a gene-gene association network that recapitulates known biological interactions and offers predictive insights into gene functions.

Contribution

It introduces a novel approach of using crowdsourced gene set queries to infer a comprehensive gene association network with biological relevance.

Findings

The network recapitulates known protein-protein interactions.

It predicts novel gene-gene associations.

A new visualization algorithm preserves network structure.

Abstract

Popular online enrichment analysis tools from the field of molecular systems biology provide users with the ability to submit their experimental results as gene sets for individual analysis. Such queries are kept private, and have never before been considered as a resource for integrative analysis. By harnessing gene set query submissions from thousands of users, we aim to discover biological knowledge beyond the scope of an individual study. In this work, we investigated a large collection of gene sets submitted to the tool Enrichr by thousands of users. Based on co-occurrence, we constructed a global gene-gene association network. We interpret this inferred network as providing a summary of the structure present in this crowdsourced gene set library, and show that this network recapitulates known protein-protein interactions and functional associations between genes. This finding implies that this network also offers predictive value. Furthermore, we visualize this gene-gene association network using a new edge-pruning algorithm that retains both the local and global structures of large-scale networks. Our ability to make predictions for currently unknown gene associations, that may not be captured by individual researchers and data sources, is a demonstration of the potential of harnessing collective knowledge from users of popular tools in the field of molecular systems biology.