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      Recent advances in candidate-gene and whole-genome approaches to the discovery of anthelmintic resistance markers and the description of drug/receptor interactions

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          Highlights

          • We report on the Consortium for Anthelmintic Resistance and Susceptibility 2013 meeting.

          • Recent advances in the identification of markers for anthelmintic resistance are described.

          • The use of markers for benzimidazole resistance in field studies with veterinary and human nematodes.

          • The application of the newest high-throughput sequencing technologies to the study of anthelmintic resistance.

          Abstract

          Anthelmintic resistance has a great impact on livestock production systems worldwide, is an emerging concern in companion animal medicine, and represents a threat to our ongoing ability to control human soil-transmitted helminths. The Consortium for Anthelmintic Resistance and Susceptibility (CARS) provides a forum for scientists to meet and discuss the latest developments in the search for molecular markers of anthelmintic resistance. Such markers are important for detecting drug resistant worm populations, and indicating the likely impact of the resistance on drug efficacy. The molecular basis of resistance is also important for understanding how anthelmintics work, and how drug resistant populations arise. Changes to target receptors, drug efflux and other biological processes can be involved. This paper reports on the CARS group meeting held in August 2013 in Perth, Australia. The latest knowledge on the development of molecular markers for resistance to each of the principal classes of anthelmintics is reviewed. The molecular basis of resistance is best understood for the benzimidazole group of compounds, and we examine recent work to translate this knowledge into useful diagnostics for field use. We examine recent candidate-gene and whole-genome approaches to understanding anthelmintic resistance and identify markers. We also look at drug transporters in terms of providing both useful markers for resistance, as well as opportunities to overcome resistance through the targeting of the transporters themselves with inhibitors. Finally, we describe the tools available for the application of the newest high-throughput sequencing technologies to the study of anthelmintic resistance.

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          Most cited references156

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          De novo assembly and analysis of RNA-seq data.

          We describe Trans-ABySS, a de novo short-read transcriptome assembly and analysis pipeline that addresses variation in local read densities by assembling read substrings with varying stringencies and then merging the resulting contigs before analysis. Analyzing 7.4 gigabases of 50-base-pair paired-end Illumina reads from an adult mouse liver poly(A) RNA library, we identified known, new and alternative structures in expressed transcripts, and achieved high sensitivity and specificity relative to reference-based assembly methods.
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            T-Coffee: a web server for the multiple sequence alignment of protein and RNA sequences using structural information and homology extension

            This article introduces a new interface for T-Coffee, a consistency-based multiple sequence alignment program. This interface provides an easy and intuitive access to the most popular functionality of the package. These include the default T-Coffee mode for protein and nucleic acid sequences, the M-Coffee mode that allows combining the output of any other aligners, and template-based modes of T-Coffee that deliver high accuracy alignments while using structural or homology derived templates. These three available template modes are Expresso for the alignment of protein with a known 3D-Structure, R-Coffee to align RNA sequences with conserved secondary structures and PSI-Coffee to accurately align distantly related sequences using homology extension. The new server benefits from recent improvements of the T-Coffee algorithm and can align up to 150 sequences as long as 10 000 residues and is available from both http://www.tcoffee.org and its main mirror http://tcoffee.crg.cat.
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              Assessment of transcript reconstruction methods for RNA-seq

              RNA sequencing (RNA-seq) is transforming genome biology, enabling comprehensive transcriptome profiling with unprecendented accuracy and detail. Due to technical limitations of current high-throughput sequencing platforms, transcript identity, structure and expression level must be inferred programmatically from partial sequence reads of fragmented gene products. We evaluated 24 protocol variants of 14 independent computational methods for exon identification, transcript reconstruction and expression level quantification from RNA-seq data. Our results show that most algorithms are able to identify discrete transcript components with high success rates, but that assembly of complete isoform structures poses a major challenge even when all constituent elements are identified. Expression level estimates also varied widely across methods, even when based on similar transcript models. Consequently, the complexity of higher eukaryotic genomes imposes severe limitations in transcript recall and splice product discrimination that are likely to remain limiting factors for the analysis of current-generation RNA-seq data.
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                Author and article information

                Contributors
                Journal
                Int J Parasitol Drugs Drug Resist
                Int J Parasitol Drugs Drug Resist
                International Journal for Parasitology: Drugs and Drug Resistance
                Elsevier
                2211-3207
                13 August 2014
                13 August 2014
                December 2014
                : 4
                : 3
                : 164-184
                Affiliations
                [a ]CSIRO Animal, Food and Health Sciences, Brisbane, QLD, Australia
                [b ]CSIRO Animal, Food and Health Sciences, Armidale, NSW, Australia
                [c ]Parasitology Division, Moredun Research Institute, Penicuik, Midlothian, UK
                [d ]Institute for Parasitology and Tropical Veterinary Medicine, Freie Universitat Berlin, Berlin, Germany
                [e ]Department of Biomedical Sciences, Iowa State University, Ames, IA, USA
                [f ]Novartis Centre de Recherche Sante Animale, St. Aubin, Switzerland
                [g ]Veterinary Parasitology, Institute of Infection and Global Health, University of Liverpool, Liverpool, UK
                [h ]INRA, Toxalim, Research Centre in Food Toxicology, Toulouse, France
                [i ]Faculty of Veterinary Science, University of Melbourne, Parkville, VIC, Australia
                [j ]Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada
                [k ]Institute of Parasitology, McGill University, QC, Canada
                [l ]Department of Infectious Diseases & Center for Tropical and Emerging Global Disease, University of Georgia, Athens, GA, USA
                [m ]INRA, Infectiologie et Santé Publique, Nouzilly, France
                [n ]Université François Rabelais de Tours, Infectiologie et Santé Publique, Tours, France
                Author notes
                [* ]Corresponding author. Address: CSIRO Animal, Food and Health Sciences, 306 Carmody Rd, St. Lucia, Brisbane, QLD, Australia. andrew.kotze@ 123456csiro.au
                Article
                S2211-3207(14)00020-7
                10.1016/j.ijpddr.2014.07.007
                4266812
                25516826
                1e6b5478-cb87-47c4-aa98-53e902c997f2
                © 2014 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

                History
                : 29 May 2014
                : 25 July 2014
                : 29 July 2014
                Categories
                Review

                anthelmintic resistance,anthelmintic drugs,molecular markers,anthelmintic targets,receptors

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