VAMPr

VAMPr predicts antimicrobial resistance (AMR) phenotypes and maps gene-level sequence variants to identify genetic determinants of resistance from whole genome sequencing data.


Key Features:

  • Gene Ortholog-Based Sequence Feature Derivation: Derives gene ortholog-based sequence features for protein variants to enable detailed examination of genetic variations linked to antibiotic resistance.
  • Interrogation of Gene-Level Variants: Systematically interrogates explainable gene-level variants to identify known and novel associations with AMR.
  • Model Building for AMR Prediction: Constructs prediction models from whole genome sequencing data using curated sequences from 3,393 bacterial isolates across nine species with AMR phenotypes for 29 antibiotics.
  • High Accuracy and Validation: Achieves a mean prediction accuracy of 91.1% across antibiotic–pathogen combinations, validated by internal nested cross-validation and external clinical datasets.
  • Association Models: Produces association models that confirm known genetic resistance mechanisms, such as blaKPC linked to carbapenem resistance.

Scientific Applications:

  • Clinical Utility: Predicts AMR phenotypes from genomic data to aid diagnosis of resistant infections.
  • Research Advancements: Identifies previously unrecognized AMR mechanisms and supports basic research into resistance pathways.
  • Data Integration: Integrates publicly available sequencing data with phenotypic information as a resource for bacterial genomics and antibiotic resistance studies.

Methodology:

Detects variant genotypes from genomic sequences and derives gene ortholog-based sequence features for protein variants; builds association models linking genetic variations to known AMR mechanisms and constructs prediction models to forecast AMR phenotypes from whole genome sequencing data, with validation by nested cross-validation and external clinical datasets using curated sequencing data from 3,393 isolates across nine species covering 29 antibiotics.

Topics

Details

Programming Languages:
Perl
Added:
1/18/2021
Last Updated:
3/11/2021

Operations

Publications

Kim J, Greenberg DE, Pifer R, Jiang S, Xiao G, Shelburne SA, Koh A, Xie Y, Zhan X. VAMPr: VAriant Mapping and Prediction of antibiotic resistance via explainable features and machine learning. PLOS Computational Biology. 2020;16(1):e1007511. doi:10.1371/journal.pcbi.1007511. PMID:31929521. PMCID:PMC7015433.

PMID: 31929521
PMCID: PMC7015433
Funding: - National Institutes of Health: 1R01GM12647901A1, 5P30CA142543 - UTSW: DocStars Award - Cancer Prevention and Research Institute of Texas: RP150596, RP180319