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      MEGARes 2.0: a database for classification of antimicrobial drug, biocide and metal resistance determinants in metagenomic sequence data

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          Abstract

          Antimicrobial resistance (AMR) is a threat to global public health and the identification of genetic determinants of AMR is a critical component to epidemiological investigations. High-throughput sequencing (HTS) provides opportunities for investigation of AMR across all microbial genomes in a sample (i.e. the metagenome). Previously, we presented MEGARes, a hand-curated AMR database and annotation structure developed to facilitate the analysis of AMR within metagenomic samples (i.e. the resistome). Along with MEGARes, we released AmrPlusPlus, a bioinformatics pipeline that interfaces with MEGARes to identify and quantify AMR gene accessions contained within a metagenomic sequence dataset. Here, we present MEGARes 2.0 ( https://megares.meglab.org), which incorporates previously published resistance sequences for antimicrobial drugs, while also expanding to include published sequences for metal and biocide resistance determinants. In MEGARes 2.0, the nodes of the acyclic hierarchical ontology include four antimicrobial compound types, 57 classes, 220 mechanisms of resistance, and 1,345 gene groups that classify the 7,868 accessions. In addition, we present an updated version of AmrPlusPlus (AMR ++ version 2.0), which improves accuracy of classifications, as well as expanding scalability and usability.

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          Most cited references53

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          Trimmomatic: a flexible trimmer for Illumina sequence data

          Motivation: Although many next-generation sequencing (NGS) read preprocessing tools already existed, we could not find any tool or combination of tools that met our requirements in terms of flexibility, correct handling of paired-end data and high performance. We have developed Trimmomatic as a more flexible and efficient preprocessing tool, which could correctly handle paired-end data. Results: The value of NGS read preprocessing is demonstrated for both reference-based and reference-free tasks. Trimmomatic is shown to produce output that is at least competitive with, and in many cases superior to, that produced by other tools, in all scenarios tested. Availability and implementation: Trimmomatic is licensed under GPL V3. It is cross-platform (Java 1.5+ required) and available at http://www.usadellab.org/cms/index.php?page=trimmomatic Contact: usadel@bio1.rwth-aachen.de Supplementary information: Supplementary data are available at Bioinformatics online.
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            The Sequence Alignment/Map format and SAMtools

            Summary: The Sequence Alignment/Map (SAM) format is a generic alignment format for storing read alignments against reference sequences, supporting short and long reads (up to 128 Mbp) produced by different sequencing platforms. It is flexible in style, compact in size, efficient in random access and is the format in which alignments from the 1000 Genomes Project are released. SAMtools implements various utilities for post-processing alignments in the SAM format, such as indexing, variant caller and alignment viewer, and thus provides universal tools for processing read alignments. Availability: http://samtools.sourceforge.net Contact: rd@sanger.ac.uk
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              BEDTools: a flexible suite of utilities for comparing genomic features

              Motivation: Testing for correlations between different sets of genomic features is a fundamental task in genomics research. However, searching for overlaps between features with existing web-based methods is complicated by the massive datasets that are routinely produced with current sequencing technologies. Fast and flexible tools are therefore required to ask complex questions of these data in an efficient manner. Results: This article introduces a new software suite for the comparison, manipulation and annotation of genomic features in Browser Extensible Data (BED) and General Feature Format (GFF) format. BEDTools also supports the comparison of sequence alignments in BAM format to both BED and GFF features. The tools are extremely efficient and allow the user to compare large datasets (e.g. next-generation sequencing data) with both public and custom genome annotation tracks. BEDTools can be combined with one another as well as with standard UNIX commands, thus facilitating routine genomics tasks as well as pipelines that can quickly answer intricate questions of large genomic datasets. Availability and implementation: BEDTools was written in C++. Source code and a comprehensive user manual are freely available at http://code.google.com/p/bedtools Contact: aaronquinlan@gmail.com; imh4y@virginia.edu Supplementary information: Supplementary data are available at Bioinformatics online.
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                Author and article information

                Journal
                Nucleic Acids Res
                Nucleic Acids Res
                nar
                Nucleic Acids Research
                Oxford University Press
                0305-1048
                1362-4962
                08 January 2020
                13 November 2019
                13 November 2019
                : 48
                : D1
                : D561-D569
                Affiliations
                [1 ] Veterinary Education, Research, and Outreach (VERO) Program, Texas A&M University and West Texas A&M University , Canyon, TX 79016, USA
                [2 ] Department of Veterinary Population Medicine, University of Minnesota , St. Paul, MN 55455, USA
                [3 ] Department of Microbiology, Immunology and Pathology, Colorado State University , Fort Collins, CO 80523, USA
                [4 ] Department of Clinical Sciences, Colorado State University , Fort Collins, CO 80523, USA
                [5 ] Department of Computer and Information Science and Engineering, University of Florida , Gainesville, FL 32611, USA
                [6 ] Department of Animal Sciences, Colorado State University , Fort Collins, CO 80523, USA
                Author notes
                To whom correspondence should be addressed. Tel: +1 970 219 6089; Email: pmorley@ 123456tamu.edu

                The authors wish it to be known that, in their opinion, the last two authors should be regarded as Joint Senior Authors.

                Author information
                http://orcid.org/0000-0002-3820-8988
                http://orcid.org/0000-0003-4277-746X
                http://orcid.org/0000-0001-6149-1008
                http://orcid.org/0000-0001-8138-2714
                Article
                gkz1010
                10.1093/nar/gkz1010
                7145535
                31722416
                c78d402a-9ae3-4db2-b5cf-67d61b3897fa
                © The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@ 123456oup.com

                History
                : 06 November 2019
                : 09 October 2019
                : 15 September 2019
                Page count
                Pages: 9
                Funding
                Funded by: USDA NIFA
                Award ID: 2015-68003-23048
                Award ID: 2018-51300-28563
                Funded by: College of Veterinary Medicine and Biomedical Sciences, Texas A and M University 10.13039/100013674
                Funded by: NIH 10.13039/100000002
                Award ID: R01 1R01AI141810-01
                Funded by: University of Minnesota 10.13039/100007249
                Categories
                Database Issue

                Genetics
                Genetics

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