FungalRV: adhesin prediction and immunoinformatics portal for human fungal pathogens

Abstract

Background: The availability of sequence data of human pathogenic fungi generates opportunities to develop Bioinformatics tools and resources for vaccine development towards benefitting at-risk patients.

Description: We have developed a fungal adhesin predictor and an immunoinformatics database with predicted adhesins. Based on literature search and domain analysis, we prepared a positive dataset comprising adhesin protein sequences from human fungal pathogens Candida albicans, Candida glabrata, Aspergillus fumigatus, Coccidioides immitis, Coccidioides posadasii, Histoplasma capsulatum, Blastomyces dermatitidis, Pneumocystis carinii, Pneumocystis jirovecii and Paracoccidioides brasiliensis. The negative dataset consisted of proteins with high probability to function intracellularly. We have used 3945 compositional properties including frequencies of mono, doublet, triplet, and multiplets of amino acids and hydrophobic properties as input features of protein sequences to Support Vector Machine. Best classifiers were identified through an exhaustive search of 588 parameters and meeting the criteria of best Mathews Correlation Coefficient and lowest coefficient of variation among the 3 fold cross validation datasets. The "FungalRV adhesin predictor" was built on three models whose average Mathews Correlation Coefficient was in the range 0.89-0.90 and its coefficient of variation across three fold cross validation datasets in the range 1.2% - 2.74% at threshold score of 0. We obtained an overall MCC value of 0.8702 considering all 8 pathogens, namely, C. albicans, C. glabrata, A. fumigatus, B. dermatitidis, C. immitis, C. posadasii, H. capsulatum and P. brasiliensis thus showing high sensitivity and specificity at a threshold of 0.511. In case of P. brasiliensis the algorithm achieved a sensitivity of 66.67%. A total of 307 fungal adhesins and adhesin like proteins were predicted from the entire proteomes of eight human pathogenic fungal species. The immunoinformatics analysis data on these proteins were organized for easy user interface analysis. A Web interface was developed for analysis by users. The predicted adhesin sequences were processed through 18 immunoinformatics algorithms and these data have been organized into MySQL backend. A user friendly interface has been developed for experimental researchers for retrieving information from the database.

Conclusion: FungalRV webserver facilitating the discovery process for novel human pathogenic fungal adhesin vaccine has been developed.

Figure 1

Support Vector Machine (SVM) run flowchart. SVM was trained and tested following this flow process, and the best classifiers were selected.

Figure 2

Receiver operating characteristic curve. The selected optimal threshold value (marked by arrow) for "FungalRV adhesin predictor" is shown.

Figure 3

FungalRV adhesin predictor Web site. Users can paste or upload sequences in FASTA format for human pathogenic fungal adhesin and adhesin-like proteins prediction.

Figure 4

FungalRV Immunoinformatics Web site. Users can query FungalRV Immunoinformatics database for data useful from reverse vaccinology point of view corresponding to the predicted 307 adhesin and adhesin like proteins and known vaccine candidates.

Figure 5

Number of Sequence Pairs in the shown ClustalW score (percent Identity) ranges. This graph was plotted for the 307 predicted fungal adhesins and adhesin like protein sequences from the selected eight human pathogenic fungal species. This data includes sequences from the training set.

Figure 6

Overall FungalRV Layout: The proteomes of eight human pathogenic fungal species listed in the diagram were run through "FungalRV adhesin predictor" obtaining a list of 307 fungal adhesins and adhesin like proteins. The diagram provides a layout of analysis of the predicted proteins. All data are organized in relation to the primary key ORF ID. The analysis data obtained was arranged into FungalRV Database providing users' facility to query and export results into tab delimited text format.