Cantacessi, Cinzia and Gasser, Robin B. and Strube, Christina and Schnieder, Thomas and Jex, Aaron R. and Hall, Ross S. and Campbell, Bronwyn E. and Young, Neil D. and Ranganathan, Shoba and Sternberg, Paul W. and Mitreva, Makedonka (2011) Deep insights into Dictyocaulus viviparus transcriptomes provides unique prospects for new drug targets and disease intervention. Biotechnology Advances, 29 (3). pp. 261-271. ISSN 0734-9750 http://resolver.caltech.edu/CaltechAUTHORS:20110517-151915276
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The lungworm, Dictyocaulus viviparus, causes parasitic bronchitis in cattle, and is responsible for substantial economic losses in temperate regions of the world. Here, we undertake the first large-scale exploration of available transcriptomic data for this lungworm, examine differences in transcription between different stages/both genders and identify and prioritize essential molecules linked to fundamental metabolic pathways, which could represent novel drug targets. Approximately 3 million expressed sequence tags (ESTs), generated by 454 sequencing from third-stage larvae (L3s) as well as adult females and males of D. viviparus, were assembled and annotated. The assembly of these sequences yielded ~61,000 contigs, of which relatively large proportions encoded collagens (4.3%), ubiquitins (2.1%) and serine/threonine protein kinases (1.9%). Subtractive analysis in silico identified 6928 nucleotide sequences as being uniquely transcribed in L3, and 5203 and 7889 transcripts as being exclusive to the adult female and male, respectively. Most peptides predicted from the conceptual translations were nucleoplasmins (L3), serine/threonine protein kinases (female) and major sperm proteins (male). Additional analyses allowed the prediction of three drug target candidates, whose Caenorhabditis elegans homologues were linked to a lethal RNA interference phenotype. This detailed exploration, combined with future transcriptomic sequencing of all developmental stages of D. viviparus, will facilitate future investigations of the molecular biology of this parasitic nematode as well as genomic sequencing. These advances will underpin the discovery of new drug and/or vaccine targets, focused on biotechnological outcomes.
|Additional Information:||© 2010 Elsevier Inc. Received 6 September 2010; accepted 22 November 2010. Available online 21 December 2010. This research was supported by grants from the Australian Research Council, the Australian Academy of Science, the Australian–American Fulbright Commission (RBG) as well as the National Human Genome Research Institute and National Institutes of Health (MM). CC is the grateful recipient of an International Postgraduate Research Scholarship from the Australian Government and a fee-remission scholarship through the University of Melbourne as well as the Clunies Ross (2008) and Sue Newton (2009) awards from the School of Veterinary Science of the same university. ARJ is the recipient of a Career Developmental Award (CDA1) from the National Health and Medical Research Council (NHMRC). Support from the Victorian Life Sciences Computation Initiative (VLSCI) and IBM 'Collaboratory' is gratefully acknowledged (RBG).|
|Subject Keywords:||Dictyocaulus viviparus; Bovine lungworm; Next-generation sequencing; Bioinformatics; Transcriptome; Ancylostoma-secreted proteins; Drug target prediction|
|Official Citation:||Cinzia Cantacessi, Robin B. Gasser, Christina Strube, Thomas Schnieder, Aaron R. Jex, Ross S. Hall, Bronwyn E. Campbell, Neil D. Young, Shoba Ranganathan, Paul W. Sternberg, Makedonka Mitreva, Deep insights into Dictyocaulus viviparus transcriptomes provides unique prospects for new drug targets and disease intervention, Biotechnology Advances, Volume 29, Issue 3, May-June 2011, Pages 261-271, ISSN 0734-9750, DOI: 10.1016/j.biotechadv.2010.11.005.|
|Usage Policy:||No commercial reproduction, distribution, display or performance rights in this work are provided.|
|Deposited By:||Jason Perez|
|Deposited On:||19 May 2011 17:12|
|Last Modified:||19 May 2011 17:12|
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