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      Unlocking the Transcriptomes of Two Carcinogenic Parasites, Clonorchis sinensis and Opisthorchis viverrini

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          Abstract

          The two parasitic trematodes, Clonorchis sinensis and Opisthorchis viverrini, have a major impact on the health of tens of millions of humans throughout Asia. The greatest impact is through the malignant cancer ( = cholangiocarcinoma) that these parasites induce in chronically infected people. Therefore, both C. sinensis and O. viverrini have been classified by the World Health Organization (WHO) as Group 1 carcinogens. Despite their impact, little is known about these parasites and their interplay with the host at the molecular level. Recent advances in genomics and bioinformatics provide unique opportunities to gain improved insights into the biology of parasites as well as their relationships with their hosts at the molecular level. The present study elucidates the transcriptomes of C. sinensis and O. viverrini using a platform based on next-generation (high throughput) sequencing and advanced in silico analyses. From 500,000 sequences, >50,000 sequences were assembled for each species and categorized as biologically relevant based on homology searches, gene ontology and/or pathway mapping. The results of the present study could assist in defining molecules that are essential for the development, reproduction and survival of liver flukes and/or that are linked to the development of cholangiocarcinoma. This study also lays a foundation for future genomic and proteomic research of C. sinensis and O. viverrini and the cancers that they are known to induce, as well as novel intervention strategies.

          Author Summary

          The parasitic worms, Clonorchis sinensis and Opisthorchis viverrini, have a serious impact on the health of tens of millions of people throughout Asia. The greatest impact, however, is through the malignant, untreatable cancer (cholangiocarcinoma) that these parasites induce in chronically infected people. These liver flukes are officially classified by the World Health Organization (WHO) as Group 1 carcinogens. In spite of their massive impact on human health, little is known about these parasites and their relationship with the host at the molecular level. Here, we provide the first detailed insight into the transcriptomes of these flukes, providing a solid foundation for all of the molecular/-omic work required to understand their biology, but, more importantly, to elucidate key aspects of the induction of cholangiocarcinoma. Although our focus has been on the parasites, the implications will extend far beyond the study of parasitic disease. Importantly, insights into the pathogenesis of the infection are likely to have major implications for the study and understanding of other cancers.

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          Most cited references66

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          Reconstruction of biochemical networks in microorganisms.

          Systems analysis of metabolic and growth functions in microbial organisms is rapidly developing and maturing. Such studies are enabled by reconstruction, at the genomic scale, of the biochemical reaction networks that underlie cellular processes. The network reconstruction process is organism specific and is based on an annotated genome sequence, high-throughput network-wide data sets and bibliomic data on the detailed properties of individual network components. Here we describe the process that is currently used to achieve comprehensive network reconstructions and discuss how these reconstructions are curated and validated. This review should aid the growing number of researchers who are carrying out reconstructions for particular target organisms.
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            The Schistosoma japonicum genome reveals features of host-parasite interplay.

            (2009)
            Schistosoma japonicum is a parasitic flatworm that causes human schistosomiasis, which is a significant cause of morbidity in China and the Philippines. Here we present a draft genomic sequence for the worm. The genome provides a global insight into the molecular architecture and host interaction of this complex metazoan pathogen, revealing that it can exploit host nutrients, neuroendocrine hormones and signalling pathways for growth, development and maturation. Having a complex nervous system and a well-developed sensory system, S. japonicum can accept stimulation of the corresponding ligands as a physiological response to different environments, such as fresh water or the tissues of its intermediate and mammalian hosts. Numerous proteases, including cercarial elastase, are implicated in mammalian skin penetration and haemoglobin degradation. The genomic information will serve as a valuable platform to facilitate development of new interventions for schistosomiasis control.
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              ESTScan: a program for detecting, evaluating, and reconstructing potential coding regions in EST sequences.

              One of the problems associated with the large-scale analysis of unannotated, low quality EST sequences is the detection of coding regions and the correction of frameshift errors that they often contain. We introduce a new type of hidden Markov model that explicitly deals with the possibility of errors in the sequence to analyze, and incorporates a method for correcting these errors. This model was implemented in an efficient and robust program, ESTScan. We show that ESTScan can detect and extract coding regions from low-quality sequences with high selectivity and sensitivity, and is able to accurately correct frameshift errors. In the framework of genome sequencing projects, ESTScan could become a very useful tool for gene discovery, for quality control, and for the assembly of contigs representing the coding regions of genes.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, USA )
                1935-2727
                1935-2735
                June 2010
                22 June 2010
                : 4
                : 6
                : e719
                Affiliations
                [1 ]Department of Veterinary Science, The University of Melbourne, Werribee, Victoria, Australia
                [2 ]Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
                [3 ]Department of Parasitology and Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, Republic of Korea
                [4 ]Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
                [5 ]Queensland Tropical Health Alliance, James Cook University, Smithfield, Cairns, Queensland, Australia
                [6 ]Department of Microbiology, Immunology and Tropical Medicine, The George Washington University Medical Center, Washington, D. C., United States of America
                University of Queensland, Australia
                Author notes

                Conceived and designed the experiments: NDY. Performed the experiments: NDY. Analyzed the data: NDY BEC RSH ARJ CC. Contributed reagents/materials/analysis tools: TL WMS BS. Wrote the paper: NDY. Contributed to drafting the manuscript: ARJ TL PJB AL. Supervised the project: RBG.

                Article
                10-PNTD-RA-0899R2
                10.1371/journal.pntd.0000719
                2889816
                20582164
                b8b03370-d1f5-4e96-9555-6ae4d61cbf14
                Young et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 18 February 2010
                : 28 April 2010
                Page count
                Pages: 14
                Categories
                Research Article
                Computational Biology/Comparative Sequence Analysis
                Computational Biology/Genomics
                Computational Biology/Transcriptional Regulation
                Genetics and Genomics/Comparative Genomics

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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