Rapid and Accurate Discrimination of Mycobacterium abscessus Subspecies Based on Matrix-Assisted Laser Desorption Ionization-Time of Flight Spectrum and Machine Learning Algorithms.

Abstract

Mycobacterium abscessus complex (MABC) has been reported to cause complicated infections. Subspecies identification of MABC is crucial for adequate treatment due to different antimicrobial resistance properties amid subspecies. However, long incubation days are needed for the traditional antibiotic susceptibility testing (AST). Delayed effective antibiotics administration often causes unfavorable outcomes. Thus, we proposed a novel approach to identify subspecies and potential antibiotic resistance, guiding early and accurate treatment. Subspecies of MABC isolates were determined by secA1, rpoB, and hsp65. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) spectra were analyzed, and informative peaks were detected by random forest (RF) importance. Machine learning (ML) algorithms were used to build models for classifying MABC subspecies based on spectrum. The models were validated by repeated five-fold cross-validation to avoid over-fitting. In total, 102 MABC isolates (52 subspecies abscessus and 50 subspecies massiliense) were analyzed. Top informative peaks including m/z 6715, 4739, etc. were identified. RF model attained AUROC of 0.9166 (95% CI: 0.9072-0.9196) and outperformed other algorithms in discriminating abscessus from massiliense. We developed a MALDI-TOF based ML model for rapid and accurate MABC subspecies identification. Due to the significant correlation between subspecies and corresponding antibiotics resistance, this diagnostic tool guides a more precise and timelier MABC subspecies-specific treatment.