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首页> 外文期刊>Biotechnology Advances: An International Review Journal >Insights into the immuno-molecular biology of Angiostrongylus vasorum through transcriptomics-prospects for new interventions.
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Insights into the immuno-molecular biology of Angiostrongylus vasorum through transcriptomics-prospects for new interventions.

机译:通过转录组学深入了解血管圆线虫的免疫分子生物学-新干预措施的前景。

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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.
机译:血管圆线虫是在许多国家中具有重要临床重要性的狗和其他犬类的元线虫线虫。为了获得对该蠕虫的分子生物学的初步了解,我们对其蠕虫的转录组进行了首次大规模探索,并预测了与代谢和生物过程以及宿主免疫反应相关的必需分子。我们还预测并确定了药物靶标和候选药物的优先级。在Illumina测序(RNA-seq)之后,代表成人A. vasorum的5230万个序列读数被组装并注释。大会产生了20,033个重叠群,其在秀丽隐杆线虫中编码了具有11,505个同源物的蛋白质,并在各种其他寄生虫蠕虫中公开了另外的2252个同源物,其整理的数据集可公开获得。预测到11.752(58.6%)种蛋白质可实现功能注释,包括肽酶(4.5%)和肽酶抑制剂(1.6%),蛋白激酶(1.7%),G蛋白偶联受体(GPCR)(1.5%)和磷酸酶(1.2%)。编码排泄/分泌和免疫调节蛋白的重叠群代表一些转录程度最高的分子,而消化血红蛋白的编码酶在血管曲霉和其他食血线虫之间是保守的。使用基于本质的方法,可以预测A. vasorum中的药物靶标,包括神经递质受体,重要的化学感应离子通道和半胱氨酸蛋白酶-3,以及相关的小分子抑制剂/活化剂。将来对血管念珠菌的所有发育阶段进行的转录组学分析应有助于对该重要寄生线虫的分子生物学的深入研究,并支持其基因组测序。这些进展将为探索血管紧张症的免疫分子方面奠定基础,并有可能为发现新的干预方法奠定基础。

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