Integrated meta-analysis and machine learning approach identifies acyl-CoA thioesterase with other novel genes responsible for biofilm development in Staphylococcus aureus.

Abstract

Biofilm forming Staphylococcus aureus is a major threat to the health-care industry. It is important to understand the differences between planktonic and biofilm growth forms in the pathogen since conventional treatments targeting the planktonic forms are not effective against biofilms. The current study conducts a meta-analysis of three public transcriptomic profiles to examine the differences in gene expression between the planktonic and biofilm states of S. aureus using random-effects modeling. Mean effect sizes were calculated for 2847 genes among which 726 differentially expressed genes were taken for further analysis. Major genes that are discriminatory between the two conditions were mined using supervised learning techniques and validated by high-accuracy classifiers. Ten different feature selection algorithms were applied and used to rank the most important genes in S. aureus biofilms. Finally, an optimal set of 36 genes are presented as candidate genes in biofilm formation or development while throwing light on the novel roles of an acyl-CoA thioesterase enzyme and 10 hypothetical proteins in biofilms. The relevance of the identified gene set was further validated by building five different classification models using SVM, RF, kNN, NB and DT algorithms that were compared with models built from other relevant gene sets and by reviewing the functional role of 25 previously known genes in biofilm development. The study combines meta-analysis of differential expression with supervised machine learning strategies and feature selection for the first time to identify and validate a discriminatory set of genes important in biofilms of S. aureus. The functional roles of the identified genes predicted to be important in biofilms are further scrutinized and can be considered as a signature target list to develop anti-biofilm therapeutics in S. aureus.