Evaluation of Machine Learning Models for Predicting Antimicrobial Resistance of Actinobacillus pleuropneumoniae From Whole Genome Sequences

Abstract

Antimicrobial resistance (AMR) is becoming a huge problem in countries all over the world, and new approaches to identifying strains resistant or susceptible to certain antibiotics are essential in fighting against antibiotic-resistant pathogens. Genotype-based machine learning methods showed great promise as a diagnostic tool, due to the increasing availability of genomic datasets and AST phenotypes. In this artical, Support Vector Machine (SVM) and Set Covering Machine (SCM) models were used to learn and predict the resistance of the five drugs (Tetracycline, Ampicillin, Sulfisoxazole, Trimethoprim, Enrofloxacin). The SVM model used the number of co-occurring k-mers between the genome of the isolates and the reference resistance genes to learn and predict the phenotypes of the bacteria to a specific antimicrobial, while the SCM model uses a greedy approach to construct conjunction or disjunction of Boolean functions to find the most concise set of k-mers that allows for accurate prediction of the phenotype. Five-fold cross-validation was performed on the training set of the SVM and SCM model to select the best hyperparameter values to avoid model overfitting. The training accuracy (mean cross-validation score) and the testing accuracy of SVM and SCM models of 5 drugs were above 90% regardless of the resistant mechanism of which were acquired resistant or point mutation in the chromosome. The results of correlation between the phenotype and the model predictions of the 5 drugs indicated that both SVM and SCM models could significantly classify the resistant isolates from the sensitive isolates of the bacteria (p<0.01), and would be used as potential tools in antimicrobial resistance surveillance and clinical diagnosis in veterinary medicine.