Publications (44)221.74 Total impact
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Article: Prevention of canine leishmaniosis in a hyper-endemic area using a combination of 10% imidacloprid/4.5% flumethrin.
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ABSTRACT: BACKGROUND: Dogs are the main reservoir hosts of , the agent of human zoonotic visceral leishmaniosis. This study investigated the efficacy of a polymer matrix collar containing a combination of 10% imidacloprid and 4.5% flumethrin as a novel prophylactic measure to prevent infections in young dogs from a hyper-endemic area of southern Italy, with a view towards enhancing current control strategies against both human and canine leishmaniosis. METHODOLOGYPRINCIPAL FINDINGS: The study was carried out on 124 young dogs, of which 63 were collared (Group A) while 61 were left untreated (Group B), from March-April 2011 until March 2012. Blood and skin samples were collected at baseline (April 2011) and at the first, second, third and fourth follow-up time points (July, September 2011 and November 2011, and March 2012, respectively). Bone marrow and conjunctiva were sampled at baseline and at the fourth follow-up. Serological, cytological and molecular tests were performed to detect the presence of in the different tissues collected. At the end of the trial, no dog from Group A proved positive for at any follow-up, whereas 22 dogs from Group B were infected (incidence density rate = 45.1%); therefore, the combination of 10% imidacloprid and 4.5% flumethrin was 100% efficacious for the prevention of infection in young dogs prior to their first exposure to the parasite in a hyper-endemic area for CanL. CONCLUSIONS: The use of collars containing 10% imidacloprid and 4.5% flumethrin conferred long-term protection against infection by to dogs located in a hyper-endemic area, thus representing a reliable and sustainable strategy to decrease the frequency and spread of this disease among the canine population which will ultimately result in the reduction of associated risks to human health.PLoS ONE 01/2013; 8(2):e56374. · 4.09 Impact Factor -
Article: Getting the most out of parasitic helminth transcriptomes using HelmDB: Implications for biology and biotechnology.
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ABSTRACT: Compounded by a massive global food shortage, many parasitic diseases have a devastating, long-term impact on animal and human health and welfare worldwide. Parasitic helminths (worms) affect the health of billions of animals. Unlocking the systems biology of these neglected pathogens will underpin the design of new and improved interventions against them. Currently, the functional annotation of genomic and transcriptomic sequence data for socio-economically important parasitic worms relies almost exclusively on comparative bioinformatic analyses using model organism- and other databases. However, many genes and gene products of parasitic helminths (often > 50%) cannot be annotated using this approach, because they are specific to parasites and/or do not have identifiable homologues in other organisms for which sequence data are available. This inability to fully annotate transcriptomes and predicted proteomes is a major challenge and constrains our understanding of the biology of parasites, interactions with their hosts and of parasitism and the pathogenesis of disease on a molecular level. In the present article, we compiled transcriptomic data sets of key, socioeconomically important parasitic helminths, and constructed and validated a curated database, called HelmDB (www.helmdb.org). We demonstrate how this database can be used effectively for the improvement of functional annotation by employing data integration and clustering. Importantly, HelmDB provides a practical and user-friendly toolkit for sequence browsing and comparative analyses among divergent helminth groups (including nematodes and trematodes), and should be readily adaptable and applicable to a wide range of other organisms. This web-based, integrative database should assist 'systems biology' studies of parasitic helminths and the discovery and prioritization of novel drug and vaccine targets. This focus provides a pathway toward developing new and improved approaches for the treatment and control of parasitic diseases, with the potential for important biotechnological outcomes.Biotechnology advances 12/2012; · 8.25 Impact Factor -
Article: First laboratory culture of Phortica variegata (Diptera, Steganinae), a vector of Thelazia callipaeda.
Journal of Vector Ecology 12/2012; 37(2):458-461. · 0.88 Impact Factor -
Article: A deep exploration of the transcriptome and "excretory/secretory" proteome of adult Fascioloides magna.
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ABSTRACT: Parasitic liver flukes of the family Fasciolidae are responsible for major socio-economic losses worldwide. However, at present, knowledge of the fundamental molecular biology of these organisms is scant. Here, we characterize, for the first time, the transcriptome and secreted proteome of the adult stage of the 'giant liver fluke', Fascioloides magna, using Illumina sequencing technology and one-dimensional SDS-PAGE and OFFGEL protein electrophoresis, respectively. A total of ~54,000,000 reads were generated and assembled into ~39,000 contiguous sequences (= contigs); ~20,000 peptides were predicted and classified based on homology searches, protein motifs, gene ontology and biological pathway mapping. From the predicted proteome, 48.1% proteins could be assigned to 384 biological pathway terms, including 'spliceosome', 'RNA transport' and 'endocytosis'. Putative proteins involved in amino acid degradation were most abundant. Of the 835 secreted proteins predicted from the transcriptome of F. magna, 80 were identified in the excretory/secretory products from this parasite. Highly represented were antioxidant proteins, followed by peptidases (particularly cathepsins) and proteins involved in carbohydrate metabolism. The integration of transcriptomic and proteomic datasets generated herein sets the scene for future studies, aimed at exploring the potential role/s that molecules may play at the host-parasite interface and for establishing novel strategies for the treatment or control of parasitic fluke infections.Molecular & Cellular Proteomics 08/2012; · 7.40 Impact Factor -
Article: Whole-genome sequence of Schistosoma haematobium.
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ABSTRACT: Schistosomiasis is a neglected tropical disease caused by blood flukes (genus Schistosoma; schistosomes) and affecting 200 million people worldwide. No vaccines are available, and treatment relies on one drug, praziquantel. Schistosoma haematobium has come into the spotlight as a major cause of urogenital disease, as an agent linked to bladder cancer and as a predisposing factor for HIV/AIDS. The parasite is transmitted to humans from freshwater snails. Worms dwell in blood vessels and release eggs that become embedded in the bladder wall to elicit chronic immune-mediated disease and induce squamous cell carcinoma. Here we sequenced the 385-Mb genome of S. haematobium using Illumina-based technology at 74-fold coverage and compared it to sequences from related parasites. We included genome annotation based on function, gene ontology, networking and pathway mapping. This genome now provides an unprecedented resource for many fundamental research areas and shows great promise for the design of new disease interventions.Nature Genetics 02/2012; 44(2):221-5. · 35.53 Impact Factor -
Article: SCP/TAPS proteins in helminths--where to from now?
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ABSTRACT: A diverse array of proteins belonging to the SCP/TAPS 'family' has been described for various eukaryotic organisms, including parasites. Although SCP/TAPS proteins have been hypothesized to play key roles in various fundamental biological processes, such as host-pathogen interactions and defence mechanisms, there is still a limited understanding of the precise roles of these proteins. Here, we review current knowledge of key SCP/TAPS proteins of helminths and their proposed roles in parasite-host interactions. Molecular investigations of these molecules in parasites and the integration of structural and functional data could lead to new and innovative approaches for the treatment and control of parasitic diseases, with important biotechnological outcomes.Molecular and Cellular Probes 02/2012; 26(1):54-9. · 2.08 Impact Factor -
Chapter: Recent progress in transcriptomics of key gastrointestinal nematodes in animals – fundamental research toward new intervention strategies
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ABSTRACT: Much remains to be understood about the fundamental biology of parasitic nematodes that cause serious disease in animals and humans world-wide. Unlocking the biology of these parasites using “omic” technologies will yield new and crucial knowledge of their molecular biology and biochemistry on a global scale. Here, we review progress on the transcriptomics of gastrointestinal nematodes of major socioeconomic importance, focusing on massively parallel (next-generation) sequencing technologies and the latest bioinformatic approaches. We predict exciting prospects for future systems biological explorations of these parasites and for the design of new drugs and/or vaccines.01/2012: pages 61-72; -
Article: Insights into SCP/TAPS proteins of liver flukes based on large-scale bioinformatic analyses of sequence datasets.
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ABSTRACT: SCP/TAPS proteins of parasitic helminths have been proposed to play key roles in fundamental biological processes linked to the invasion of and establishment in their mammalian host animals, such as the transition from free-living to parasitic stages and the modulation of host immune responses. Despite the evidence that SCP/TAPS proteins of parasitic nematodes are involved in host-parasite interactions, there is a paucity of information on this protein family for parasitic trematodes of socio-economic importance. We conducted the first large-scale study of SCP/TAPS proteins of a range of parasitic trematodes of both human and veterinary importance (including the liver flukes Clonorchis sinensis, Opisthorchis viverrini, Fasciola hepatica and F. gigantica as well as the blood flukes Schistosoma mansoni, S. japonicum and S. haematobium). We mined all current transcriptomic and/or genomic sequence datasets from public databases, predicted secondary structures of full-length protein sequences, undertook systematic phylogenetic analyses and investigated the differential transcription of SCP/TAPS genes in O. viverrini and F. hepatica, with an emphasis on those that are up-regulated in the developmental stages infecting the mammalian host. This work, which sheds new light on SCP/TAPS proteins, guides future structural and functional explorations of key SCP/TAPS molecules associated with diseases caused by flatworms. Future fundamental investigations of these molecules in parasites and the integration of structural and functional data could lead to new approaches for the control of parasitic diseases.PLoS ONE 01/2012; 7(2):e31164. · 4.09 Impact Factor -
Article: Ascaris suum draft genome.
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ABSTRACT: Parasitic diseases have a devastating, long-term impact on human health, welfare and food production worldwide. More than two billion people are infected with geohelminths, including the roundworms Ascaris (common roundworm), Necator and Ancylostoma (hookworms), and Trichuris (whipworm), mainly in developing or impoverished nations of Asia, Africa and Latin America. In humans, the diseases caused by these parasites result in about 135,000 deaths annually, with a global burden comparable with that of malaria or tuberculosis in disability-adjusted life years. Ascaris alone infects around 1.2 billion people and, in children, causes nutritional deficiency, impaired physical and cognitive development and, in severe cases, death. Ascaris also causes major production losses in pigs owing to reduced growth, failure to thrive and mortality. The Ascaris-swine model makes it possible to study the parasite, its relationship with the host, and ascariasis at the molecular level. To enable such molecular studies, we report the 273 megabase draft genome of Ascaris suum and compare it with other nematode genomes. This genome has low repeat content (4.4%) and encodes about 18,500 protein-coding genes. Notably, the A. suum secretome (about 750 molecules) is rich in peptidases linked to the penetration and degradation of host tissues, and an assemblage of molecules likely to modulate or evade host immune responses. This genome provides a comprehensive resource to the scientific community and underpins the development of new and urgently needed interventions (drugs, vaccines and diagnostic tests) against ascariasis and other nematodiases.Nature 11/2011; 479(7374):529-33. · 36.28 Impact Factor -
Article: Heartworm genomics: unprecedented opportunities for fundamental molecular insights and new intervention strategies.
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ABSTRACT: Vector-borne diseases, including canine heartworm disease (CHWD), are of major socioeconomic and canine health importance worldwide. Although many studies have provided insights into CHWD, to date there has been limited study of fundamental molecular aspects of Dirofilaria immitis itself, its relationship with the canine host, its vectors, as well as the potential of drug resistance to emerge, using advanced -omic technologies. This article takes a prospective view of the benefits that advanced -omics technologies will have toward understanding D. immitis and CHWD. Tackling key biological questions using these technologies will provide a "systems biology" context and could lead to radically new intervention and management strategies against heartworm.Topics in Companion Animal Medicine 11/2011; 26(4):193-9. · 1.04 Impact Factor -
Article: Bovine theileriosis--an emerging problem in south-eastern Australia?
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ABSTRACT: Bovine theileriosis is an arthropod-borne disease caused by one or more haemoprotozoan parasites of the genus Theileria. Traditionally, Theileria infection in cattle in Australia was largely asymptomatic and recognized to be associated with Theileria buffeli, now assigned to the Theileria orientalis-group. There have been some recent outbreaks of theileriosis in dairy and beef cattle, mainly in subtropical climatic zone (New South Wales) of Australia. Here, we provide the first published evidence of an outbreak of bovine theileriosis in the south-eastern Australia (state of Victoria) linked to the ikeda and chitose genotypes of T. orientalis. Future investigations should focus sharply on the elucidating the epidemiology and ecology of Theileria in this region to subvert the possible impact on the cattle industry.Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 08/2011; 11(8):2095-7. · 3.22 Impact Factor -
Article: Key strongylid nematodes of animals - Impact of next-generation transcriptomics on systems biology and biotechnology.
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ABSTRACT: The advent and integration of high-throughput 'omic technologies (e.g., genomics, transcriptomics, proteomics and metabolomics) are becoming instrumental to assist fundamental explorations of the systems biology of organisms. In particular, these technologies now provide unique opportunities for global, molecular investigations of parasites. For example, studies of the transcriptomes (all transcripts in an organism, tissue or cell) of different species and/or developmental stages of parasitic nematodes provide insights into aspects of gene expression, regulation and function, which is a major step to understanding their biology. The purpose of this article was to review salient aspects of the systematics and biology of selected species of parasitic nematodes (particularly key species of the order Strongylida) of socio-economic importance, to describe conventional and advanced sequencing technologies and bioinformatic tools for large-scale investigations of the transcriptomes of these parasites and to highlight the prospects and implications of these explorations for developing novel methods of parasite intervention.Biotechnology advances 08/2011; 30(3):469-88. · 8.25 Impact Factor -
Article: The transcriptome of Trichuris suis--first molecular insights into a parasite with curative properties for key immune diseases of humans.
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ABSTRACT: Iatrogenic infection of humans with Trichuris suis (a parasitic nematode of swine) is being evaluated or promoted as a biological, curative treatment of immune diseases, such as inflammatory bowel disease (IBD) and ulcerative colitis, in humans. Although it is understood that short-term T. suis infection in people with such diseases usually induces a modified Th2-immune response, nothing is known about the molecules in the parasite that induce this response. As a first step toward filling the gaps in our knowledge of the molecular biology of T. suis, we characterised the transcriptome of the adult stage of this nematode employing next-generation sequencing and bioinformatic techniques. A total of ∼65,000,000 reads were generated and assembled into ∼20,000 contiguous sequences ( = contigs); ∼17,000 peptides were predicted and classified based on homology searches, protein motifs and gene ontology and biological pathway mapping. These analyses provided interesting insights into a number of molecular groups, particularly predicted excreted/secreted molecules (n = 1,288), likely to be involved in the parasite-host interactions, and also various molecules (n = 120) linked to chemokine, T-cell receptor and TGF-β signalling as well as leukocyte transendothelial migration and natural killer cell-mediated cytotoxicity, which are likely to be immuno-regulatory or -modulatory in the infected host. This information provides a conceptual framework within which to test the immunobiological basis for the curative effect of T. suis infection in humans against some immune diseases. Importantly, the T. suis transcriptome characterised herein provides a curated resource for detailed studies of the immuno-molecular biology of this parasite, and will underpin future genomic and proteomic explorations.PLoS ONE 01/2011; 6(8):e23590. · 4.09 Impact Factor -
Article: A portrait of the transcriptome of the neglected trematode, Fasciola gigantica--biological and biotechnological implications.
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ABSTRACT: Fasciola gigantica (Digenea) is an important foodborne trematode that causes liver fluke disease (fascioliasis) in mammals, including ungulates and humans, mainly in tropical climatic zones of the world. Despite its socioeconomic impact, almost nothing is known about the molecular biology of this parasite, its interplay with its hosts, and the pathogenesis of fascioliasis. Modern genomic technologies now provide unique opportunities to rapidly tackle these exciting areas. The present study reports the first transcriptome representing the adult stage of F. gigantica (of bovid origin), defined using a massively parallel sequencing-coupled bioinformatic approach. From >20 million raw sequence reads, >30,000 contiguous sequences were assembled, of which most were novel. Relative levels of transcription were determined for individual molecules, which were also characterized (at the inferred amino acid level) based on homology, gene ontology, and/or pathway mapping. Comparisons of the transcriptome of F. gigantica with those of other trematodes, including F. hepatica, revealed similarities in transcription for molecules inferred to have key roles in parasite-host interactions. Overall, the present dataset should provide a solid foundation for future fundamental genomic, proteomic, and metabolomic explorations of F. gigantica, as well as a basis for applied outcomes such as the development of novel methods of intervention against this neglected parasite.PLoS Neglected Tropical Diseases 01/2011; 5(2):e1004. · 4.69 Impact Factor -
Article: Major prospects for exploring canine vector borne diseases and novel intervention methods using 'omic technologies.
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ABSTRACT: Canine vector-borne diseases (CVBDs) are of major socioeconomic importance worldwide. Although many studies have provided insights into CVBDs, there has been limited exploration of fundamental molecular aspects of most pathogens, their vectors, pathogen-host relationships and disease and drug resistance using advanced, 'omic technologies. The aim of the present article is to take a prospective view of the impact that next-generation, 'omics technologies could have, with an emphasis on describing the principles of transcriptomic/genomic sequencing as well as bioinformatic technologies and their implications in both fundamental and applied areas of CVBD research. Tackling key biological questions employing these technologies will provide a 'systems biology' context and could lead to radically new intervention and management strategies against CVBDs.Parasites & Vectors 01/2011; 4:53. · 2.94 Impact Factor -
Article: Atypical (RIO) protein kinases from Haemonchus contortus--promise as new targets for nematocidal drugs.
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ABSTRACT: Almost nothing is known about atypical kinases in multicellular organisms, including parasites. Supported by information and data available for the free-living nematode, Caenorhabditis elegans, and other eukaryotes, the present article describes three RIO kinase genes, riok-1, riok-2 and riok-3, from Haemonchus contortus, one of the most important parasitic nematodes of small ruminants. Analyses of these genes and their products predict that they each play critical roles in the developmental pathways of parasitic nematodes. The findings of this review indicate prospects for functional studies of these genes in C. elegans (as a surrogate) and opportunities for the design of a novel class of nematode-specific inhibitors of RIO kinases. The latter aspect is of paramount importance, given the serious problems linked to anthelmintic resistance in parasitic nematode populations of livestock.Biotechnology advances 01/2011; 29(3):338-50. · 8.25 Impact Factor -
Article: Cryptic parasite revealed improved prospects for treatment and control of human cryptosporidiosis through advanced technologies.
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ABSTRACT: Cryptosporidium is an important genus of parasitic protozoa of humans and other vertebrates and is a major cause of intestinal disease globally. Unlike many common causes of infectious enteritis, there are no widely available, effective vaccine or drug-based intervention strategies for Cryptosporidium, and control is focused mainly on prevention. This approach is particularly deficient for infections of severely immunocompromised and/or suppressed, the elderly or malnourished people. However, cryptosporidiosis also presents a significant burden on immunocompetent individuals, and can, for example have lasting effects on the physical and mental development of children infected at an early age. In the last few decades, our understanding of Cryptosporidium has expanded significantly in numerous areas, including the parasite life-cycle, the processes of excystation, cellular invasion and reproduction, and the interplay between parasite and host. Nonetheless, despite extensive research, many aspects of the biology of Cryptosporidium remain unknown, and treatment and control are challenging. Here, we review the current state of knowledge of Cryptosporidium, with a focus on major advances arising from the recently completed genome sequences of the two species of greatest relevance in humans, namely Cryptosporidium hominis and Cryptosporidium parvum. In addition, we discuss the potential of next-generation sequencing technologies, new advances in in silico analyses and progress in in vitro culturing systems to bridge these gaps and to lead toward effective treatment and control of cryptosporidiosis.Advances in Parasitology 01/2011; 77:141-73. · 4.39 Impact Factor -
Article: Deep insights into Dictyocaulus viviparus transcriptomes provides unique prospects for new drug targets and disease intervention.
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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.Biotechnology advances 12/2010; 29(3):261-71. · 8.25 Impact Factor -
Article: First transcriptomic analysis of the economically important parasitic nematode, Trichostrongylus colubriformis, using a next-generation sequencing approach.
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ABSTRACT: Trichostrongylus colubriformis (Strongylida), a small intestinal nematode of small ruminants, is a major cause of production and economic losses in many countries. The aims of the present study were to define the transcriptome of the adult stage of T. colubriformis, using 454 sequencing technology and bioinformatic analyses, and to predict the main pathways that key groups of molecules are linked to in this nematode. A total of 21,259 contigs were assembled from the sequence data produced from a normalized cDNA library; 7876 of these contigs had known orthologues in the free-living nematode Caenorhabditis elegans, and encoded, amongst others, proteins with 'transthyretin-like' (8.8%), 'RNA recognition' (8.4%) and 'metridin-like ShK toxin' (7.6%) motifs. Bioinformatic analyses inferred that relatively high proportions of the C. elegans homologues are involved in biological pathways linked to 'peptidases' (4%), 'ribosome' (3.6%) and 'oxidative phosphorylation' (3%). Highly represented were peptides predicted to be associated with the nervous system, digestion of host proteins or inhibition of host proteases. Probabilistic functional gene networking of the complement of C. elegans orthologues (n=2126) assigned significance to particular subsets of molecules, such as protein kinases and serine/threonine phosphatases. The present study represents the first, comprehensive insight into the transcriptome of adult T. colubriformis, which provides a foundation for fundamental studies of the molecular biology and biochemistry of this parasitic nematode as well as prospects for identifying targets for novel nematocides. Future investigations should focus on comparing the transcriptomes of different developmental stages, both genders and various tissues of this parasitic nematode for the prediction of essential genes/gene products that are specific to nematodes.Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 12/2010; 10(8):1199-207. · 3.22 Impact Factor -
Article: A practical, bioinformatic workflow system for large data sets generated by next-generation sequencing.
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ABSTRACT: Transcriptomics (at the level of single cells, tissues and/or whole organisms) underpins many fields of biomedical science, from understanding the basic cellular function in model organisms, to the elucidation of the biological events that govern the development and progression of human diseases, and the exploration of the mechanisms of survival, drug-resistance and virulence of pathogens. Next-generation sequencing (NGS) technologies are contributing to a massive expansion of transcriptomics in all fields and are reducing the cost, time and performance barriers presented by conventional approaches. However, bioinformatic tools for the analysis of the sequence data sets produced by these technologies can be daunting to researchers with limited or no expertise in bioinformatics. Here, we constructed a semi-automated, bioinformatic workflow system, and critically evaluated it for the analysis and annotation of large-scale sequence data sets generated by NGS. We demonstrated its utility for the exploration of differences in the transcriptomes among various stages and both sexes of an economically important parasitic worm (Oesophagostomum dentatum) as well as the prediction and prioritization of essential molecules (including GTPases, protein kinases and phosphatases) as novel drug target candidates. This workflow system provides a practical tool for the assembly, annotation and analysis of NGS data sets, also to researchers with a limited bioinformatic expertise. The custom-written Perl, Python and Unix shell computer scripts used can be readily modified or adapted to suit many different applications. This system is now utilized routinely for the analysis of data sets from pathogens of major socio-economic importance and can, in principle, be applied to transcriptomics data sets from any organism.Nucleic Acids Research 09/2010; 38(17):e171. · 8.03 Impact Factor
Top co-authors
Top Journals
Institutions
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2008–2013
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Università degli Studi di Bari Aldo Moro
- Dipartimento di Medicina Veterinaria
Bari, Apulia, Italy -
Queensland Institute of Medical Research
Brisbane, Queensland, Australia
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2012
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Victoria University Melbourne
Melbourne, Victoria, Australia
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2008–2012
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University of Melbourne
- Faculty of Veterinary Science
Melbourne, Victoria, Australia
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