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Published on: March 3, 2023
Systematic analysis of supervised machine learning as an effective approach to predicate β-lactam resistance
Chaodong Zhang1,2, Yingjiao Ju1,3, Na Tang1,3
1State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Abstract:
Streptococcus pneumoniae is the most common human respiratory pathogen, and β-lactam antibiotics have been employed to treat infections caused by S. pneumoniae for decades. β-lactam resistance is steadily increasing in pneumococci and is mainly associated with the alteration in penicillin-binding proteins (PBPs) that reduce binding affinity of antibiotics to PBPs. However, the high variability of PBPs in clinical isolates and their mosaic gene structure hamper the predication of resistance level according to the PBP gene sequences. In this study, we developed a systematic strategy for applying supervised machine learning to predict S. pneumoniae antimicrobial susceptibility to β-lactam antibiotics. We combined published PBP sequences with minimum inhibitory concentration (MIC) values as labelled data and the sequences from NCBI database without MIC values as unlabelled data to develop an approach, using only a fragment from pbp2x (750 bp) and a fragment from pbp2b (750 bp) to predicate the cefuroxime and amoxicillin resistance. We further validated the performance of the supervised learning model by constructing mutants containing the randomly selected pbps and testing more clinical strains isolated from Chinese hospital. In addition, we established the association between resistance phenotypes and serotypes and sequence type of S. pneumoniae using our approach, which facilitate the understanding of the worldwide epidemiology of S. pneumonia.
Insights
Machine learning accurately predicts Streptococcus pneumoniae resistance to beta-lactam antibiotics using penicillin-binding protein gene fragments. This approach aids in understanding antimicrobial resistance and pneumococcal epidemiology.
Area of Science:
- Microbiology
- Genetics
- Computational Biology
Background:
- Streptococcus pneumoniae is a major human respiratory pathogen.
- Increasing beta-lactam antibiotic resistance in S. pneumoniae is linked to altered penicillin-binding proteins (PBPs).
- PBP variability and mosaic gene structures complicate resistance prediction.
Purpose of the Study:
- To develop a machine learning strategy for predicting S. pneumoniae antimicrobial susceptibility to beta-lactam antibiotics.
- To identify key PBP gene fragments for accurate resistance prediction.
- To associate resistance phenotypes with serotypes and sequence types for epidemiological insights.
Main Methods:
- Utilized supervised machine learning with published PBP sequences and minimum inhibitory concentration (MIC) values as labeled data.
- Incorporated unlabeled PBP sequences from the NCBI database.
- Focused on specific fragments of pbp2x and pbp2b genes to predict resistance to cefuroxime and amoxicillin.
Main Results:
- Developed a predictive model for S. pneumoniae beta-lactam resistance using limited PBP gene fragments.
- Validated the model's performance through mutant construction and testing of clinical isolates.
- Established associations between resistance phenotypes, serotypes, and sequence types.
Conclusions:
- Supervised machine learning offers a robust method for predicting antimicrobial susceptibility in S. pneumoniae.
- This approach simplifies resistance prediction by using specific PBP gene fragments.
- The findings contribute to understanding pneumococcal epidemiology and guiding treatment strategies.
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