<p>Whole-genome sequencing (WGS) data are an invaluable resource for understanding antimicrobial resistance (AMR) mechanisms. However, WGS data are high-dimensional and the lack of standardized genomic representations is a key barrier to AMR phenotype prediction. To fully explore these high-resolution data, we propose AMR-GNN, a graph deep learning-based framework that integrates multiple genomic representations with graph neural networks (GNN) to enable AMR phenotype prediction from genomic sequence data. We test AMR-GNN with <i>Pseudomonas aeruginosa</i>, a clinically relevant Gram-negative bacterial pathogen known for its complex AMR mechanisms. We present AMR-GNN as a proof-of-concept framework designed to address several key problems in AMR phenotype prediction with data-driven machine learning (ML) approaches, including using multiple genomic representations to enhance performance, to mitigate the influence of clonal relationships and to identify informative biomarkers to provide explainability. Follow-up validation on the largest publicly available dataset spanning both Gram-negative and Gram-positive pathogens highlights AMR-GNN’s broad applicability in detecting AMR in diverse and clinically relevant pathogen-drug combinations.</p>

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AMR-GNN: a multi-representation graph neural network framework to enable genomic antimicrobial resistance prediction

  • Hoai-An Nguyen,
  • Anton Y. Peleg,
  • Jessica A. Wisniewski,
  • Xiaoyu Wang,
  • Zhikang Wang,
  • Luke V. Blakeway,
  • Gnei Z. Badoordeen,
  • Ravali Theegala,
  • Nhu Quynh Doan,
  • Matthew H. Parker,
  • Anna G. Green,
  • Jiangning Song,
  • David L. Dowe,
  • Nenad Macesic

摘要

Whole-genome sequencing (WGS) data are an invaluable resource for understanding antimicrobial resistance (AMR) mechanisms. However, WGS data are high-dimensional and the lack of standardized genomic representations is a key barrier to AMR phenotype prediction. To fully explore these high-resolution data, we propose AMR-GNN, a graph deep learning-based framework that integrates multiple genomic representations with graph neural networks (GNN) to enable AMR phenotype prediction from genomic sequence data. We test AMR-GNN with Pseudomonas aeruginosa, a clinically relevant Gram-negative bacterial pathogen known for its complex AMR mechanisms. We present AMR-GNN as a proof-of-concept framework designed to address several key problems in AMR phenotype prediction with data-driven machine learning (ML) approaches, including using multiple genomic representations to enhance performance, to mitigate the influence of clonal relationships and to identify informative biomarkers to provide explainability. Follow-up validation on the largest publicly available dataset spanning both Gram-negative and Gram-positive pathogens highlights AMR-GNN’s broad applicability in detecting AMR in diverse and clinically relevant pathogen-drug combinations.