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Journal ArticleDOI

CARD 2020: antibiotic resistome surveillance with the comprehensive antibiotic resistance database

29 Oct 2019-Nucleic Acids Research (Oxford University Press)-Vol. 48

TL;DR: A new Resistomes & Variants module provides analysis and statistical summary of in silico predicted resistance variants from 82 pathogens and over 100 000 genomes, able to summarize predicted resistance using the information included in CARD, identify trends in AMR mobility and determine previously undescribed and novel resistance variants.

AbstractThe Comprehensive Antibiotic Resistance Database (CARD; https://card.mcmaster.ca) is a curated resource providing reference DNA and protein sequences, detection models and bioinformatics tools on the molecular basis of bacterial antimicrobial resistance (AMR). CARD focuses on providing high-quality reference data and molecular sequences within a controlled vocabulary, the Antibiotic Resistance Ontology (ARO), designed by the CARD biocuration team to integrate with software development efforts for resistome analysis and prediction, such as CARD's Resistance Gene Identifier (RGI) software. Since 2017, CARD has expanded through extensive curation of reference sequences, revision of the ontological structure, curation of over 500 new AMR detection models, development of a new classification paradigm and expansion of analytical tools. Most notably, a new Resistomes & Variants module provides analysis and statistical summary of in silico predicted resistance variants from 82 pathogens and over 100 000 genomes. By adding these resistance variants to CARD, we are able to summarize predicted resistance using the information included in CARD, identify trends in AMR mobility and determine previously undescribed and novel resistance variants. Here, we describe updates and recent expansions to CARD and its biocuration process, including new resources for community biocuration of AMR molecular reference data.

Topics: Resistome (51%)

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Citations
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Journal ArticleDOI
11 Dec 2020-Animal
TL;DR: (meta)proteomics analysis of bacterial compartment of raw milk is applied to obtain a method that provides a measurement of circulating AMR involved proteins and gathers information about the whole bacterial composition.
Abstract: The environment, including animals and animal products, is colonized by bacterial species that are typical and specific of every different ecological niche. Natural and human-related ecological pressure promotes the selection and expression of genes related to antimicrobial resistance (AMR). These genes might be present in a bacterial consortium but might not necessarily be expressed. Their expression could be induced by the presence of antimicrobial compounds that could originate from a given ecological niche or from human activity. In this work, we applied (meta)proteomics analysis of bacterial compartment of raw milk in order to obtain a method that provides a measurement of circulating AMR involved proteins and gathers information about the whole bacterial composition. Results from milk analysis revealed the presence of 29 proteins/proteoforms linked to AMR. The detection of mainly β-lactamases suggests the possibility of using the milk microbiome as a bioindicator for the investigation of AMR. Moreover, it was possible to achieve a culture-free qualitative and functional analysis of raw milk bacterial consortia.

112 citations


Cites methods from "CARD 2020: antibiotic resistome sur..."

  • ...Among other proteins with AMR potential identified using the CARD15 database there is an isoform of the Aminoglycoside N(6’)-acetyltransferase of Enterococcus hirae....

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  • ...In order to identify the whole bacterial proteome, the obtained MS datasets were analyzed using different databases: UniProt KB/Swiss-Prot restricted to all reviewed Bacteria protein sequences (UniProt KB) and the Comprehensive Antibiotic Resistance Database (CARD) [14]....

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  • ...Figure 3 shows the Venn diagram of the proteins identified in the two extractions using the CARD 15 database....

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  • ...The same raw MS dataset was then searched against the CARD 15 database....

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  • ...The qualitative identification of proteins was obtained by searching two different databases: (i) bacteria (UniProt KB/Swiss-Prot Protein Knowledgebase restricted to all Bacteria taxonomy) and (ii) The Comprehensive AMR Database (CARD, https://card.mcmaster.ca/) as FASTA files [13,14]....

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Journal ArticleDOI
TL;DR: This issue contains three breakthrough articles: AntiBodies Chemically Defined curates antibody sequences and their cognate antigens; SCOP returns with a new schema and breaks away from a purely hierarchical structure; while the new Alliance of Genome Resources brings together a number of Model Organism databases to pool knowledge and tools.
Abstract: The 2020 Nucleic Acids Research Database Issue contains 148 papers spanning molecular biology. They include 59 papers reporting on new databases and 79 covering recent changes to resources previously published in the issue. A further ten papers are updates on databases most recently published elsewhere. This issue contains three breakthrough articles: AntiBodies Chemically Defined (ABCD) curates antibody sequences and their cognate antigens; SCOP returns with a new schema and breaks away from a purely hierarchical structure; while the new Alliance of Genome Resources brings together a number of Model Organism databases to pool knowledge and tools. Major returning nucleic acid databases include miRDB and miRTarBase. Databases for protein sequence analysis include CDD, DisProt and ELM, alongside no fewer than four newcomers covering proteins involved in liquid-liquid phase separation. In metabolism and signaling, Pathway Commons, Reactome and Metabolights all contribute papers. PATRIC and MicroScope update in microbial genomes while human and model organism genomics resources include Ensembl, Ensembl genomes and UCSC Genome Browser. Immune-related proteins are covered by updates from IPD-IMGT/HLA and AFND, as well as newcomers VDJbase and OGRDB. Drug design is catered for by updates from the IUPHAR/BPS Guide to Pharmacology and the Therapeutic Target Database. The entire Database Issue is freely available online on the Nucleic Acids Research website (https://academic.oup.com/nar). The NAR online Molecular Biology Database Collection has been revised, updating 305 entries, adding 65 new resources and eliminating 125 discontinued URLs; so bringing the current total to 1637 databases. It is available at http://www.oxfordjournals.org/nar/database/c/.

45 citations


Cites background from "CARD 2020: antibiotic resistome sur..."

  • ...The very popular CARD database (48) reports on the challenges of coping with processing 5000 papers a year in the area of antimicrobial resistance and, among other innovations, now includes computationally predicted resistome data....

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Journal ArticleDOI
TL;DR: This review provides a detailed account of available bioinformatics platforms for identification and characterization of ARGs and associated genetic elements within single bacterial isolates and complex environmental samples, and focuses primarily on currently available ARG databases.
Abstract: Antibiotic or antimicrobial resistance (AR) facilitated by the vertical and/or horizontal transfer of antibiotic resistance genes (ARGs), is a serious global health challenge. While traditionally associated with pathogens in clinical environments, it is becoming increasingly clear that non-clinical environments may also be reservoirs of ARGs. The recent improvements in rapid and affordable next generation sequencing technologies along with sophisticated bioinformatics platforms has the potential to revolutionize diagnostic microbiology and microbial surveillance. Through the study and characterization of ARGs in bacterial genomes and complex metagenomes, we are now able to reveal the genetic scope of AR in single bacteria and complex communities, and obtain important insights into AR dynamics at species, population and community levels, providing novel epidemiological and ecological perspectives. A suite of bioinformatics pipelines and ARG databases are currently available for genomic and metagenomic data analyses. However, different platforms may significantly vary and therefore, it is crucial to choose the tools that are most suitable for the specific analysis being conducted. This review provides a detailed account of available bioinformatics platforms for identification and characterization of ARGs and associated genetic elements within single bacterial isolates and complex environmental samples. It focuses primarily on currently available ARG databases, employing a comprehensive benchmarking pipeline to identify ARGs in four bacterial genomes (Aeromonas salmonicida, Bacillus cereus, Burkholderia sp. and Escherichia coli) and three shotgun metagenomes (human gut, poultry litter and soil) providing insight into which databases should be used for different analytical scenarios.

23 citations


Journal ArticleDOI
TL;DR: A critical understanding of fate and toxicity of pharmaceutical compounds is provided and their vulnerability and occurrence in South Asia is highlighted and more in-depth and interdisciplinary understanding of the subject is developed.
Abstract: Pharmaceutically active compounds are newly recognized micropollutants which are ubiquitous in aquatic environment mainly due to direct discharge of treated and untreated wastewater from wastewater treatment plants These contaminants have attracted mounted attention due to their toxic effects on aquatic life They disrupt biological processes in non-target lower organisms upon exposure Biodegradation, photo-degradation, and sorption are key processes which determine their fate in the environment A variety of conventional and advanced treatment processes had been extensively investigated for the removal of pharmaceuticals from wastewater However, due to structural complexity and varying operating parameters, complete removal seems ideal Generally, due to high energy requirement of advanced treatment technology, it is considered cost ineffective Transport of pharmaceutical compounds occurs via aquatic channels whereas sediments and aquatic colloids play a significant role as sinks for these contaminants The current review provides a critical understanding of fate and toxicity of pharmaceutical compounds and highlights their vulnerability and occurrence in South Asia Antibiotics, analgesics, and psychiatric drugs were found predominantly in the water environment of South Asian regions Despite significant advances in understanding pharmaceuticals fate, toxicity, and associated risks since the 1990s, still substantial data gaps in terms of monitoring, human health risks, and legislation exist which presses the need to develop a more in-depth and interdisciplinary understanding of the subject

23 citations


Journal ArticleDOI
01 Oct 2020
TL;DR: Short-read MAG approaches are largely ineffective for the analysis of mobile genes, including those of public-health importance, such as AMR and VF genes, and it is proposed that researchers should explore developing methods that optimize for this issue.
Abstract: Metagenomic methods enable the simultaneous characterization of microbial communities without time-consuming and bias-inducing culturing. Metagenome-assembled genome (MAG) binning methods aim to reassemble individual genomes from this data. However, the recovery of mobile genetic elements (MGEs), such as plasmids and genomic islands (GIs), by binning has not been well characterized. Given the association of antimicrobial resistance (AMR) genes and virulence factor (VF) genes with MGEs, studying their transmission is a public-health priority. The variable copy number and sequence composition of MGEs makes them potentially problematic for MAG binning methods. To systematically investigate this issue, we simulated a low-complexity metagenome comprising 30 GI-rich and plasmid-containing bacterial genomes. MAGs were then recovered using 12 current prediction pipelines and evaluated. While 82-94 % of chromosomes could be correctly recovered and binned, only 38-44 % of GIs and 1-29 % of plasmid sequences were found. Strikingly, no plasmid-borne VF nor AMR genes were recovered, and only 0-45 % of AMR or VF genes within GIs. We conclude that short-read MAG approaches, without further optimization, are largely ineffective for the analysis of mobile genes, including those of public-health importance, such as AMR and VF genes. We propose that researchers should explore developing methods that optimize for this issue and consider also using unassembled short reads and/or long-read approaches to more fully characterize metagenomic data.

21 citations


References
More filters

Journal ArticleDOI
TL;DR: A new approach to rapid sequence comparison, basic local alignment search tool (BLAST), directly approximates alignments that optimize a measure of local similarity, the maximal segment pair (MSP) score.
Abstract: A new approach to rapid sequence comparison, basic local alignment search tool (BLAST), directly approximates alignments that optimize a measure of local similarity, the maximal segment pair (MSP) score. Recent mathematical results on the stochastic properties of MSP scores allow an analysis of the performance of this method as well as the statistical significance of alignments it generates. The basic algorithm is simple and robust; it can be implemented in a number of ways and applied in a variety of contexts including straight-forward DNA and protein sequence database searches, motif searches, gene identification searches, and in the analysis of multiple regions of similarity in long DNA sequences. In addition to its flexibility and tractability to mathematical analysis, BLAST is an order of magnitude faster than existing sequence comparison tools of comparable sensitivity.

81,150 citations


"CARD 2020: antibiotic resistome sur..." refers background in this paper

  • ...The latter is described by CARD’s Model Ontology (MO, Supplementary Figure S1), which includes reference nucleotide and protein sequences, as well as additional search parameters including mutations conferring AMR (if applicable) and curated BLAST(P/N) (34,35) bit score cut-offs....

    [...]


Journal ArticleDOI
TL;DR: Burrows-Wheeler Alignment tool (BWA) is implemented, a new read alignment package that is based on backward search with Burrows–Wheeler Transform (BWT), to efficiently align short sequencing reads against a large reference sequence such as the human genome, allowing mismatches and gaps.
Abstract: Motivation: The enormous amount of short reads generated by the new DNA sequencing technologies call for the development of fast and accurate read alignment programs. A first generation of hash table-based methods has been developed, including MAQ, which is accurate, feature rich and fast enough to align short reads from a single individual. However, MAQ does not support gapped alignment for single-end reads, which makes it unsuitable for alignment of longer reads where indels may occur frequently. The speed of MAQ is also a concern when the alignment is scaled up to the resequencing of hundreds of individuals. Results: We implemented Burrows-Wheeler Alignment tool (BWA), a new read alignment package that is based on backward search with Burrows–Wheeler Transform (BWT), to efficiently align short sequencing reads against a large reference sequence such as the human genome, allowing mismatches and gaps. BWA supports both base space reads, e.g. from Illumina sequencing machines, and color space reads from AB SOLiD machines. Evaluations on both simulated and real data suggest that BWA is ~10–20× faster than MAQ, while achieving similar accuracy. In addition, BWA outputs alignment in the new standard SAM (Sequence Alignment/Map) format. Variant calling and other downstream analyses after the alignment can be achieved with the open source SAMtools software package. Availability: http://maq.sourceforge.net Contact: [email protected]

35,234 citations


Journal ArticleDOI
TL;DR: The goals of the PDB are described, the systems in place for data deposition and access, how to obtain further information and plans for the future development of the resource are described.
Abstract: The Protein Data Bank (PDB; http://www.rcsb.org/pdb/ ) is the single worldwide archive of structural data of biological macromolecules. This paper describes the goals of the PDB, the systems in place for data deposition and access, how to obtain further information, and near-term plans for the future development of the resource.

30,190 citations


"CARD 2020: antibiotic resistome sur..." refers methods in this paper

  • ...In 2017, we described the CARD*Shark text-mining algorithm (26) for computer-assisted literature triage, which we have expanded based on the new ARO Drug Class classification tags....

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Journal ArticleDOI
TL;DR: Bowtie 2 combines the strengths of the full-text minute index with the flexibility and speed of hardware-accelerated dynamic programming algorithms to achieve a combination of high speed, sensitivity and accuracy.
Abstract: As the rate of sequencing increases, greater throughput is demanded from read aligners. The full-text minute index is often used to make alignment very fast and memory-efficient, but the approach is ill-suited to finding longer, gapped alignments. Bowtie 2 combines the strengths of the full-text minute index with the flexibility and speed of hardware-accelerated dynamic programming algorithms to achieve a combination of high speed, sensitivity and accuracy.

27,973 citations


"CARD 2020: antibiotic resistome sur..." refers methods in this paper

  • ...Metagenomics analysis (i.e. RGI bwt) uses Bowtie2 (40) or BWA (41) mapping of sequencing reads to CARD’s PHM reference sequences only, while annotation of genomes or assembly contigs predicts resistome using four of CARD’s AMR detection models: PHM, PVM, RVM and POM (note: RGI currently only scans for nonsynonymous substitutions; not frameshifts, deletions or insertions)....

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  • ...RGI bwt) uses Bowtie2 (40) or BWA (41) mapping of sequencing reads to CARD’s PHM reference sequences only, while annotation of genomes or assembly contigs predicts resistome using four of CARD’s AMR detection models: PHM, PVM, RVM and POM (note: RGI currently only scans for nonsynonymous substitutions; not frameshifts, deletions or insertions)....

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Journal ArticleDOI
TL;DR: The new BLAST command-line applications, compared to the current BLAST tools, demonstrate substantial speed improvements for long queries as well as chromosome length database sequences.
Abstract: Sequence similarity searching is a very important bioinformatics task. While Basic Local Alignment Search Tool (BLAST) outperforms exact methods through its use of heuristics, the speed of the current BLAST software is suboptimal for very long queries or database sequences. There are also some shortcomings in the user-interface of the current command-line applications. We describe features and improvements of rewritten BLAST software and introduce new command-line applications. Long query sequences are broken into chunks for processing, in some cases leading to dramatically shorter run times. For long database sequences, it is possible to retrieve only the relevant parts of the sequence, reducing CPU time and memory usage for searches of short queries against databases of contigs or chromosomes. The program can now retrieve masking information for database sequences from the BLAST databases. A new modular software library can now access subject sequence data from arbitrary data sources. We introduce several new features, including strategy files that allow a user to save and reuse their favorite set of options. The strategy files can be uploaded to and downloaded from the NCBI BLAST web site. The new BLAST command-line applications, compared to the current BLAST tools, demonstrate substantial speed improvements for long queries as well as chromosome length database sequences. We have also improved the user interface of the command-line applications.

9,783 citations


"CARD 2020: antibiotic resistome sur..." refers background or methods in this paper

  • ...The website also includes a built-in BLAST instance for comparing sequences to CARD reference sequences and a web instance of RGI for resistome prediction with data visualization tools (https:// card.mcmaster.ca/analyze)....

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  • ...The RVM is functionally similar to the PVM, except it works for rRNA mutations and therefore uses a nucleotide reference sequence and a BLASTN bit score cut-off....

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  • ...Briefly, RGI algorithmically predicts AMR genes and mutations from submitted genomes using a combination of open reading frame prediction with Prodigal (38), sequence alignment with BLAST (35) or DIAMOND (39), and curated resistance mutations included with the AMR detection model....

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  • ...In the same time period, the CARD website hosted ∼45 000 BLAST analyses, ∼220 000 RGI analyses, ∼64 000 data file downloads, and ∼10,000 RGI software downloads....

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  • ...We had determined that the asymptotic nature of the BLAST expectation value (E) gave it very low discriminatory power between different -lactamase gene families (nearly 13 of CARD’s content), but that the linear nature of the BLAST bit score (S′) allowed this level of discrimination....

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