Enhancing the biological relevance of machine learning classifiers for reverse vaccinology

Ashley I. Heinson, Yawwani Gunawardana, Bastiaan Moesker, Carmen C. Denman Hume, Elena Vataga, Yper Hall, Elena Stylianou, Helen McShane, Ann Williams, Mahesan Niranjan, Christopher H. Woelk

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Reverse vaccinology (RV) is a bioinformatics approach that can predict antigens with protective potential from the protein coding genomes of bacterial pathogens for subunit vaccine design. RV has become firmly established following the development of the BEXSERO® vaccine against Neisseria meningitidis serogroup B. RV studies have begun to incorporate machine learning (ML) techniques to distinguish bacterial protective antigens (BPAs) from non-BPAs. This research contributes significantly to the RV field by using permutation analysis to demonstrate that a signal for protective antigens can be curated from published data. Furthermore, the effects of the following on an ML approach to RV were also assessed: nested cross-validation, balancing selection of non-BPAs for subcellular localization, increasing the training data, and incorporating greater numbers of protein annotation tools for feature generation. These enhancements yielded a support vector machine (SVM) classifier that could discriminate BPAs (n = 200) from non-BPAs (n = 200) with an area under the curve (AUC) of 0.787. In addition, hierarchical clustering of BPAs revealed that intracellular BPAs clustered separately from extracellular BPAs. However, no immediate benefit was derived when training SVM classifiers on data sets exclusively containing intra- or extracellular BPAs. In conclusion, this work demonstrates that ML classifiers have great utility in RV approaches and will lead to new subunit vaccines in the future.

Original languageEnglish
Article number312
JournalInternational Journal of Molecular Sciences
Volume18
Issue number2
DOIs
Publication statusPublished - 1 Feb 2017

Keywords

  • Bacterial pathogen
  • Bacterial protective antigen
  • Machine learning
  • Reverse vaccinology
  • Support vector machine

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