Systematic analysis of supervised machine learning as an effective approach to predicate β-lactam resistance phenotype in Streptococcus pneumoniae

Zhang，Chaodong1,2; Ju，Yingjiao1,3; Tang，Na1,3; Li，Yun4; Zhang，Gang1; Song，Yuqin1; Fang，Hailing1; Yang，Liang5; Feng，Jie1

2020-07-15

10.1093/bib/bbz056

BRIEFINGS IN BIOINFORMATICS   影响因子和分区

1467-5463

1477-4054

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.

Streptococcus pneumonia genotypic antimicrobial susceptibility testing penicillin-binding protein supervised machine learning β-lactam resistance

SCI

英语

其他

National Natural Science Foundation of China[31870134][81861138053] ; Beijing Municipal Science & Technology Commission[Z161100000116042]

Biochemistry & Molecular Biology ; Mathematical & Computational Biology

Biochemical Research Methods ; Mathematical & Computational Biology

WOS:000576139100018

OXFORD UNIV PRESS

COMPUTER SCIENCE

2-s2.0-85088265609

Scopus

1.State Key Laboratory of Microbial Resources,Institute of Microbiology,Chinese Academy of Sciences,China
2.Singapore Centre for Environmental Life Sciences Engineering,Nanyang Technological University 60 Nanyang Drive,Singapore
3.College of Life Science,University of Chinese Academy of Sciences,China
4.Institute of Clinical Pharmacology,Peking University First Hospital,China
5.School of Medicine,Southern University of Science and Technology,Guangdong Province,Shenzhen,China

Zhang，Chaodong,Ju，Yingjiao,Tang，Na,et al. Systematic analysis of supervised machine learning as an effective approach to predicate β-lactam resistance phenotype in Streptococcus pneumoniae[J]. BRIEFINGS IN BIOINFORMATICS,2020,21(4):1347-1355.

Zhang，Chaodong.,Ju，Yingjiao.,Tang，Na.,Li，Yun.,Zhang，Gang.,...&Feng，Jie.(2020).Systematic analysis of supervised machine learning as an effective approach to predicate β-lactam resistance phenotype in Streptococcus pneumoniae.BRIEFINGS IN BIOINFORMATICS,21(4),1347-1355.

Zhang，Chaodong,et al."Systematic analysis of supervised machine learning as an effective approach to predicate β-lactam resistance phenotype in Streptococcus pneumoniae".BRIEFINGS IN BIOINFORMATICS 21.4(2020):1347-1355.