VacSol: a high throughput in silico pipeline to predict potential therapeutic targets in prokaryotic pathogens using subtractive reverse vaccinology

Abstract

Background: With advances in reverse vaccinology approaches, a progressive improvement has been observed in the prediction of putative vaccine candidates. Reverse vaccinology has changed the way of discovery and provides a mean to propose target identification in reduced time and labour. In this regard, high throughput genomic sequencing technologies and supporting bioinformatics tools have greatly facilitated the prompt analysis of pathogens, where various predicted candidates have been found effective against certain infections and diseases. A pipeline, VacSol, is designed here based on a similar approach to predict putative vaccine candidates both rapidly and efficiently.

Results: VacSol, a new pipeline introduced here, is a highly scalable, multi-mode, and configurable software designed to automate the high throughput in silico vaccine candidate prediction process for the identification of putative vaccine candidates against the proteome of bacterial pathogens. Vaccine candidates are screened using integrated, well-known and robust algorithms/tools for proteome analysis, and the results from the VacSol software are presented in five different formats by taking proteome sequence as input in FASTA file format. The utility of VacSol is tested and compared with published data and using the Helicobacter pylori 26695 reference strain as a benchmark.

Conclusion: VacSol rapidly and efficiently screens the whole bacterial pathogen proteome to identify a few predicted putative vaccine candidate proteins. This pipeline has the potential to save computational costs and time by efficiently reducing false positive candidate hits. VacSol results do not depend on any universal set of rules and may vary based on the provided input. It is freely available to download from: https://sourceforge.net/projects/vacsol/ .

Keywords: Computational pipeline; PVCs; Reverse vaccinology; Subtractive proteomics; VacSol; Vaccine candidates.

Fig. 1

Schematic diagram of the protein prioritization process. Steps to prioritize proteins to identify PVCs include: (1) the complete bacterial proteome (sequences) subjected to the VacSol pipeline for identifying PVCs; (2) the complete proteome is searched for non-host homologous, essential, virulent proteins residing in the extracellular membrane with less than two transmembrane helices; (3) proteins that meet the selection criteria are considered to be PVC proteins; (4) prioritized proteins are further analyzed for antigenic B- and T-cell epitopes

Fig. 2

Schematic diagram of VacSol processing. VacSol is comprised of two working modes: (i) GUI, and (ii) Standalone. The software is highly flexible as it permits users to submit a FASTA proteome sequence in four different ways. Submitted input is validated through a FASTA validator, and then VacSol screens the whole proteome to prioritize proteins that have antigenic B- and T-cell epitopes. Individual tool results (Localizer, Blaster, Helicer, and Epitoper) and complete results are generated for prioritized proteins in five different formats

Fig. 3

VacSol-generated results. VacSol generated a summary report for the complete H. pylori proteome with prioritized proteins. Each protein is assigned a unique VacSol ID