Epione application: An integrated web‑toolkit of clinical genomics and personalized medicine in systemic lupus erythematosus

Abstract

Genome wide association studies (GWAS) have identified autoimmune disease‑associated loci, a number of which are involved in numerous disease‑associated pathways. However, much of the underlying genetic and pathophysiological mechanisms remain to be elucidated. Systemic lupus erythematosus (SLE) is a chronic, highly heterogeneous autoimmune disease, characterized by differences in autoantibody profile, serum cytokines and a multi‑system involvement. This study presents the Epione application, an integrated bioinformatics web‑toolkit, designed to assist medical experts and researchers in more accurately diagnosing SLE. The application aims to identify the most credible gene variants and single nucleotide polymorphisms (SNPs) associated with SLE susceptibility, by using patient's genomic data to aid the medical expert in SLE diagnosis. The application contains useful knowledge of >70,000 SLE‑related publications that have been analyzed, using data mining and semantic techniques, towards extracting the SLE‑related genes and the corresponding SNPs. Probable genes associated with the patient's genomic profile are visualized with several graphs, including chromosome ideograms, statistic bars and regulatory networks through data mining studies with relative publications, to obtain a representative number of the most credible candidate genes and biological pathways associated with the SLE. Furthermore, an evaluation study was performed on a patient diagnosed with SLE and is presented herein. Epione has also been expanded in family‑related candidate patients to evaluate its predictive power. All the recognized gene variants that were previously considered to be associated with SLE were accurately identified in the output profile of the patient, and by comparing the results, novel findings have emerged. The Epione application may assist and facilitate in early stage diagnosis by using the patients' genomic profile to compare against the list of the most predictable candidate gene variants related to SLE. Its diagnosis‑oriented output presents the user with a structured set of results on variant association, position in genome and links to specific bibliography and gene network associations. The overall aim of the present study was to provide a reliable tool for the most effective study of SLE. This novel and accessible webserver tool of SLE is available at http://geneticslab.aua.gr/epione/.

Keywords: bioinformatics; clinical informatics; data mining; genomics; systemic lupus erythematosus; variant analysis; whole exome sequencing; whole genome sequencing.

Figure 1

Epione application webserver pipeline. Left to right: Input parameters (FASTA or VCF file and a selected reference genome), Epione application pipeline, output files (SNP analysis results, candidate variants, patient profile and statistics charts, chromosome ideograms, relative publications with candidate variants and regulatory networks). VCF, Variant Call Format; SNPs, single nucleotide polymorphisms; SLE, systemic lupus erythematosus; dbSNP, Single Nucleotide Polymorphism Database.

Figure 2

Epione application presenting the systemic lupus erythematosus database. SNP, single nucleotide polymorphism; dbSNP, Single Nucleotide Polymorphism Database; OMIM, Online Mendelian Inheritance in Man.

Figure 3

Database analysis results. (A) 'X1', 'X2', 'X3' corresponds to the number of affected regions per SNP. (B) The five identified categories within the Epione database. (C) The identified types of SNPs within the Epione database. (D) The two major categories of the genomic regions within the Epione database. SNPs, single nucleotide polymorphisms; N/A, not applicable; LOC, locations; LINC, long intergenic non-coding; MIR, microRNA.

Figure 4

Selection of genes, alleles, pseudogenes and transcription factors for data mining and semantic analysis. SLE, systemic lupus erythematosus; MeSH, Medical Subject Headings.

Figure 5

Systemic lupus erythematosus gene regulatory network of the class 'Strong-associated SNPs' in a graph representation. SNPs, single nucleotide polymorphisms.

Figure 6

Epione application user interface. VCF, Variant Call Format.

Figure 7

Example of Epione application output part A. SLE, systemic lupus erythematosus; SNPs, single nucleotide polymorphisms.

Figure 8

Example of Epione application output part B. SNPs, single nucleotide polymorphisms; GWAS, genome wide association studies.

Figure 9

Example of Epione application output part C. SLE, systemic lupus erythematosus; SNPs, single nucleotide polymorphisms.