Abstract

In systems biology, inference of functional associations among genes is compelling because the construction of functional association networks facilitates biomarker discovery. Specifically, such gene associations in human can help identify putative biomarkers that can be used as diagnostic tools in treating patients. Although biomedical literature is considered a valuable data source for this task, currently only a limited number of webservers are available for mining gene-gene associations from the vast amount of biomedical literature using text mining techniques. Moreover, these webservers often have limited coverage of biomedical literature and also lack efficient and user-friendly tools to interpret and visualize mined relationships among genes. To address these limitations, we developed GAIL (Gene-gene Association Inference based on biomedical Literature), an interactive webserver that infers human gene-gene associations from Gene Ontology (GO) guided biomedical literature mining and provides dynamic visualization of the resulting association networks and various gene set enrichment analysis tools. We evaluate the utility and performance of GAIL with applications to gene signatures associated with systemic lupus erythematosus and breast cancer. Results show that GAIL allows effective interrogation and visualization of gene-gene networks and their subnetworks, which facilitates biological understanding of gene-gene associations. GAIL is available at http://chunglab.io/GAIL/.

Highlights

  • Systems biology is currently believed to be dictated by ‘functional modules,’ groups of gene products that are functionally similar and together contribute to some high-level function [1]

  • The Network Query page is the main functionality of GAIL, and it allows users to input a list of genes and implements interactive visualization and inference of association network for the given genes

  • The user can investigate biological functions related to each community by clicking the “Gene Ontology (GO) Analysis” button

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Summary

Introduction

Systems biology is currently believed to be dictated by ‘functional modules,’ groups of gene products that are functionally similar and together contribute to some high-level function [1]. The major data sources to infer gene-gene association networks are experimental data such as gene coexpression and quantitative mass spectrometry on proteins, two hybrid screening [7, 8] and co-immunoprecipitation data [9, 10], as well as databases indicating biological pathway comembership between genes [11,12,13]. Another valuable data source to infer gene-gene association is the biomedical literature, including abstracts, full-length texts, and text annotations [14]. One of the most popular data sources for biomedical literature is the PubMed database (https://www.ncbi.nlm.nih.gov/pubmed), which contains more than 27 million articles

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