Deep insights into Dictyocaulus viviparus transcriptomes provides unique prospects for new drug targets and disease intervention

Cantacessi, Cinzia, Gasser, Robin B., Strube, Christina, Schnieder, Thomas, Jex, Aaron R., Hall, Ross S., Campbell, Bronwyn E., Young, Neil D., Ranganathan, Shoba, 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.

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Abstract

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.

Item ID: 26450
Item Type: Article (Research - C1)
ISSN: 1873-1899
Keywords: Dictyocaulus viviparus, bovine lungworm, next-generation sequencing, bioinformatics, transcriptome, ancylostoma-secreted proteins, drug target prediction
Funders: Australian Research Council (ARC), Australian Academy of Science, Australian–American Fulbright Commission, National Human Genome Research Institute, National Institutes of Health
Date Deposited: 29 Apr 2013 01:19
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110309 Infectious Diseases @ 30%
06 BIOLOGICAL SCIENCES > 0604 Genetics > 060408 Genomics @ 60%
08 INFORMATION AND COMPUTING SCIENCES > 0803 Computer Software > 080301 Bioinformatics Software @ 10%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 60%
97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 30%
97 EXPANDING KNOWLEDGE > 970107 Expanding Knowledge in the Agricultural and Veterinary Sciences @ 10%
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