CARD 2017: expansion and model-centric curation of the comprehensive antibiotic resistance database

Abstract

The Comprehensive Antibiotic Resistance Database (CARD; http://arpcard.mcmaster.ca) is a manually curated resource containing high quality reference data on the molecular basis of antimicrobial resistance (AMR), with an emphasis on the genes, proteins and mutations involved in AMR. CARD is ontologically structured, model centric, and spans the breadth of AMR drug classes and resistance mechanisms, including intrinsic, mutation-driven and acquired resistance. It is built upon the Antibiotic Resistance Ontology (ARO), a custom built, interconnected and hierarchical controlled vocabulary allowing advanced data sharing and organization. Its design allows the development of novel genome analysis tools, such as the Resistance Gene Identifier (RGI) for resistome prediction from raw genome sequence. Recent improvements include extensive curation of additional reference sequences and mutations, development of a unique Model Ontology and accompanying AMR detection models to power sequence analysis, new visualization tools, and expansion of the RGI for detection of emergent AMR threats. CARD curation is updated monthly based on an interplay of manual literature curation, computational text mining, and genome analysis.

Figure 1.

Example of an ARO term (NDM-1 β-lactamase). Each ARO term in CARD incorporates a definition, its parent and sub-terms within the ARO, relevant peer-reviewed publications, and links to protein or chemical structure information (if available).

Figure 2.

The Protein Homolog detection model for NDM-1 β-lactamase, involving a curated reference sequence and BLASTP cut-off to limit hits to functional homologs.

Figure 3.

The Protein Variant detection model for Mycobacterium tuberculosis gyrA conferring resistance to fluoroquinolones, involving a curated reference sequence, BLASTP cut-off, and a catalogue of positional single nucleotide polymorphisms (SNPs) that confer resistance to fluoroquinolones. Locations of resistance SNPs are highlighted red in the reference sequence.

Figure 4.

Resistance Gene Identifier visualizations available at the CARD website, based on analysis of a recent clinical MDR Klebsiella pneumoniae isolate. (A) Individual AMR genes detected, based on ‘Perfect’ (green) matches or ‘Strict’ (blue) hits to CARD reference amino acid sequences, including secondary screening for AMR-conferring mutations where appropriate. Strict hits are defined as being within the similarity cut-offs of the individual AMR detection models and represent likely (but not tested) homologs of AMR genes. (B) The same results organized by Antibiotic Resistance Ontology functional categories, reflecting both drug classes and resistance mechanisms. Hits with weak similarity (i.e. ‘Loose’) are not shown. Images provided by the CARD web interface—full details are available by mouse hover as well as by clicking on terms.