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Insights into the immuno-molecular biology of Angiostrongylus vasorum through transcriptomics—Prospects for new interventions

Ansell, Brendan R. E. and Schnyder, Manuela and Deplazes, Peter and Korhonen, Pasi K. and Young, Neil D. and Hall, Ross S. and Mangiola, Stefano and Boag, Peter R. and Hofmann, Andreas and Sternberg, Paul W. and Jex, Aaron R. and Gasser, Robin B. (2013) Insights into the immuno-molecular biology of Angiostrongylus vasorum through transcriptomics—Prospects for new interventions. Biotechnology Advances, 31 (8). pp. 1486-1500. ISSN 0734-9750. doi:10.1016/j.biotechadv.2013.07.006. https://resolver.caltech.edu/CaltechAUTHORS:20140214-093158107

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Abstract

Angiostrongylus vasorum is a metastrongyloid nematode of dogs and other canids of major clinical importance in many countries. In order to gain first insights into the molecular biology of this worm, we conducted the first large-scale exploration of its transcriptome, and predicted essential molecules linked to metabolic and biological processes as well as host immune responses. We also predicted and prioritized drug targets and drug candidates. Following Illumina sequencing (RNA-seq), 52.3 million sequence reads representing adult A. vasorum were assembled and annotated. The assembly yielded 20,033 contigs, which encoded proteins with 11,505 homologues in Caenorhabditis elegans, and additional 2252 homologues in various other parasitic helminths for which curated data sets were publicly available. Functional annotation was achieved for 11,752 (58.6%) proteins predicted for A. vasorum, including peptidases (4.5%) and peptidase inhibitors (1.6%), protein kinases (1.7%), G protein-coupled receptors (GPCRs) (1.5%) and phosphatases (1.2%). Contigs encoding excretory/secretory and immuno-modulatory proteins represented some of the most highly transcribed molecules, and encoded enzymes that digest haemoglobin were conserved between A. vasorum and other blood-feeding nematodes. Using an essentiality-based approach, drug targets, including neurotransmitter receptors, an important chemosensory ion channel and cysteine proteinase-3 were predicted in A. vasorum, as were associated small molecular inhibitors/activators. Future transcriptomic analyses of all developmental stages of A. vasorum should facilitate deep explorations of the molecular biology of this important parasitic nematode and support the sequencing of its genome. These advances will provide a foundation for exploring immuno-molecular aspects of angiostrongylosis and have the potential to underpin the discovery of new methods of intervention.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.biotechadv.2013.07.006DOIArticle
http://www.sciencedirect.com/science/article/pii/S0734975013001201PublisherArticle
ORCID:
AuthorORCID
Sternberg, Paul W.0000-0002-7699-0173
Additional Information:© 2013 Elsevier Inc. Received 2 May 2013; Received in revised form 28 June 2013; Accepted 16 July 2013; Available online 27 July 2013. This project was funded by the Australian Research Council and National Health and Medical Research Council (NHMRC) (R.B.G.), Howard Hughes Medical Institute (HHMI) and the National Institutes of Health (NIH) (P.W.S.). This project was also supported by a Victorian Life Sciences Computation Initiative (VLSCI) grant number VR0007 on its Peak Computing Facility at the University of Melbourne, an initiative of the Victorian Government. Other support from the Australian Academy of Science, the Australian–American Fulbright Commission, Alexander von Humboldt Foundation, Melbourne Water Corporation and the IBM Research Collaboratory for Life Sciences—Melbourne is gratefully acknowledged (R.B.G.). N.D.Y. is an NHMRC Early Career Research (ECR) Fellow. We also acknowledge the continued contributions of all staff at WormBase (www.wormbase.org). Nucleotide sequence data reported in this article are available in HelmDB (www.helmdb.org).
Funders:
Funding AgencyGrant Number
Australian Research CouncilUNSPECIFIED
National Health and Medical Research Council (NHMRC)UNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
NIHUNSPECIFIED
Victorian Life Sciences Computation Initiative (VLSCI)VR0007
Australian Academy of ScienceUNSPECIFIED
Australian–American Fulbright CommissionUNSPECIFIED
Alexander von Humboldt FoundationUNSPECIFIED
Melbourne Water CorporationUNSPECIFIED
IBM Research Collaboratory for Life Sciences—MelbourneUNSPECIFIED
NHMRC Early Career Research (ECR) FellowUNSPECIFIED
Subject Keywords:Angiostrongylus vasorum; Canine lungworm; Transcriptome; Bioinformatics; Molecular biology; Immunity; Intervention targets
Issue or Number:8
DOI:10.1016/j.biotechadv.2013.07.006
Record Number:CaltechAUTHORS:20140214-093158107
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20140214-093158107
Official Citation:Ansell, B. R. E., Schnyder, M., Deplazes, P., Korhonen, P. K., Young, N. D., Hall, R. S.,...Gasser, R. B. (2013). Insights into the immuno-molecular biology of Angiostrongylus vasorum through transcriptomics—Prospects for new interventions. Biotechnology Advances, 31(8), 1486-1500. doi: http://dx.doi.org/10.1016/j.biotechadv.2013.07.006
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:43830
Collection:CaltechAUTHORS
Deposited By: Jason Perez
Deposited On:18 Feb 2014 17:28
Last Modified:10 Nov 2021 16:43

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