Dataset Information

VAMPr: VAriant Mapping and Prediction of antibiotic resistance via explainable features and machine learning.

ABSTRACT: Antimicrobial resistance (AMR) is an increasing threat to public health. Current methods of determining AMR rely on inefficient phenotypic approaches, and there remains incomplete understanding of AMR mechanisms for many pathogen-antimicrobial combinations. Given the rapid, ongoing increase in availability of high-density genomic data for a diverse array of bacteria, development of algorithms that could utilize genomic information to predict phenotype could both be useful clinically and assist with discovery of heretofore unrecognized AMR pathways. To facilitate understanding of the connections between DNA variation and phenotypic AMR, we developed a new bioinformatics tool, variant mapping and prediction of antibiotic resistance (VAMPr), to (1) derive gene ortholog-based sequence features for protein variants; (2) interrogate these explainable gene-level variants for their known or novel associations with AMR; and (3) build accurate models to predict AMR based on whole genome sequencing data. We curated the publicly available sequencing data for 3,393 bacterial isolates from 9 species that contained AMR phenotypes for 29 antibiotics. We detected 14,615 variant genotypes and built 93 association and prediction models. The association models confirmed known genetic antibiotic resistance mechanisms, such as blaKPC and carbapenem resistance consistent with the accurate nature of our approach. The prediction models achieved high accuracies (mean accuracy of 91.1% for all antibiotic-pathogen combinations) internally through nested cross validation and were also validated using external clinical datasets. The VAMPr variant detection method, association and prediction models will be valuable tools for AMR research for basic scientists with potential for clinical applicability.

SUBMITTER: Kim J

PROVIDER: S-EPMC7015433 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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VAMPr: VAriant Mapping and Prediction of antibiotic resistance via explainable features and machine learning.

Kim Jiwoong J Greenberg David E DE Pifer Reed R Jiang Shuang S Xiao Guanghua G Shelburne Samuel A SA Koh Andrew A Xie Yang Y Zhan Xiaowei X

PLoS computational biology 20200113 1

Antimicrobial resistance (AMR) is an increasing threat to public health. Current methods of determining AMR rely on inefficient phenotypic approaches, and there remains incomplete understanding of AMR mechanisms for many pathogen-antimicrobial combinations. Given the rapid, ongoing increase in availability of high-density genomic data for a diverse array of bacteria, development of algorithms that could utilize genomic information to predict phenotype could both be useful clinically and assist w ...[more]

PMID: 31929521

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Project description:Artificial intelligence and machine learning techniques have proved fertile methods for attacking difficult problems in medicine and public health. These techniques have garnered strong interest for the analysis of the large, multi-domain open science datasets that are increasingly available in health research. Discovery science in large datasets is challenging given the unconstrained nature of the learning environment where there may be a large number of potential predictors and appropriate ranges for model hyperparameters are unknown. As well, it is likely that explainability is at a premium in order to engage in future hypothesis generation or analysis. Here, we present a novel method that addresses these challenges by exploiting evolutionary algorithms to optimize machine learning discovery science while exploring a large solution space and minimizing bias. We demonstrate that our approach, called integrated evolutionary learning (IEL), provides an automated, adaptive method for jointly learning features and hyperparameters while furnishing explainable models where the original features used to make predictions may be obtained even with artificial neural networks. In IEL the machine learning algorithm of choice is nested inside an evolutionary algorithm which selects features and hyperparameters over generations on the basis of an information function to converge on an optimal solution. We apply IEL to three gold standard machine learning algorithms in challenging, heterogenous biobehavioral data: deep learning with artificial neural networks, decision tree-based techniques and baseline linear models. Using our novel IEL approach, artificial neural networks achieved ≥ 95% accuracy, sensitivity and specificity and 45-73% R 2 in classification and substantial gains over default settings. IEL may be applied to a wide range of less- or unconstrained discovery science problems where the practitioner wishes to jointly learn features and hyperparameters in an adaptive, principled manner within the same algorithmic process. This approach offers significant flexibility, enlarges the solution space and mitigates bias that may arise from manual or semi-manual hyperparameter tuning and feature selection and presents the opportunity to select the inner machine learning algorithm based on the results of optimized learning for the problem at hand.

Dataset Information

VAMPr: VAriant Mapping and Prediction of antibiotic resistance via explainable features and machine learning.

Publications

VAMPr: VAriant Mapping and Prediction of antibiotic resistance via explainable features and machine learning.

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