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首页> 外文期刊>BMC Genomics >An analysis of the transcriptome of Teladorsagia circumcincta: its biological and biotechnological implications
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An analysis of the transcriptome of Teladorsagia circumcincta: its biological and biotechnological implications

机译：圆角拟南芥转录组的分析：其生物学和生物技术意义

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Background Teladorsagia circumcincta (order Strongylida) is an economically important parasitic nematode of small ruminants (including sheep and goats) in temperate climatic regions of the world. Improved insights into the molecular biology of this parasite could underpin alternative methods required to control this and related parasites, in order to circumvent major problems associated with anthelmintic resistance. The aims of the present study were to define the transcriptome of the adult stage of T. circumcincta and to infer the main pathways linked to molecules known to be expressed in this nematode. Since sheep develop acquired immunity against T. circumcincta , there is some potential for the development of a vaccine against this parasite. Hence, we infer excretory/secretory molecules for T. circumcincta as possible immunogens and vaccine candidates. Results A total of 407,357 ESTs were assembled yielding 39,852 putative gene sequences. Conceptual translation predicted 24,013 proteins, which were then subjected to detailed annotation which included pathway mapping of predicted proteins (including 112 excreted/secreted [ES] and 226 transmembrane peptides), domain analysis and GO annotation was carried out using InterProScan along with BLAST2GO. Further analysis was carried out for secretory signal peptides using SignalP and non-classical sec pathway using SecretomeP tools. For ES proteins, key pathways, including Fc epsilon RI, T cell receptor, and chemokine signalling as well as leukocyte transendothelial migration were inferred to be linked to immune responses, along with other pathways related to neurodegenerative diseases and infectious diseases, which warrant detailed future studies. KAAS could identify new and updated pathways like phagosome and protein processing in endoplasmic reticulum. Domain analysis for the assembled dataset revealed families of serine, cysteine and proteinase inhibitors which might represent targets for parasite intervention. InterProScan could identify GO terms pertaining to the extracellular region. Some of the important domain families identified included the SCP-like extracellular proteins which belong to the pathogenesis-related proteins (PRPs) superfamily along with C-type lectin, saposin-like proteins. The 'extracellular region' that corresponds to allergen V5/Tpx-1 related, considered important in parasite-host interactions, was also identified. Six cysteine motif (SXC1) proteins, transthyretin proteins, C-type lectins, activation-associated secreted proteins (ASPs), which could represent potential candidates for developing novel anthelmintics or vaccines were few other important findings. Of these, SXC1, protein kinase domain-containing protein, trypsin family protein, trypsin-like protease family member (TRY-1), putative major allergen and putative lipid binding protein were identified which have not been reported in the published T. circumcincta proteomics analysis. Detailed analysis of 6,058 raw EST sequences from dbEST revealed 315 putatively secreted proteins. Amongst them, C-type single domain activation associated secreted protein ASP3 precursor, activation-associated secreted proteins (ASP-like protein), cathepsin B-like cysteine protease, cathepsin L cysteine protease, cysteine protease, TransThyretin-Related and Venom-Allergen-like proteins were the key findings. Conclusions We have annotated a large dataset ESTs of T. circumcincta and undertaken detailed comparative bioinformatics analyses. The results provide a comprehensive insight into the molecular biology of this parasite and disease manifestation which provides potential focal point for future research. We identified a number of pathways responsible for immune response. This type of large-scale computational scanning could be coupled with proteomic and metabolomic studies of this parasite leading to novel therapeutic intervention and disease control strategies. We have also successfully affirmed the use of bioinformatics tools, for the study of ESTs, which could now serve as a benchmark for the development of new computational EST analysis pipelines.
机译：背景技术Teladorsagia circumcincta（Strongylida）是世界上温带气候地区的一种小型反刍动物（包括绵羊和山羊）的重要经济寄生线虫。对这种寄生虫的分子生物学的深入了解可能会成为控制该寄生虫和相关寄生虫所需的替代方法的基础，以规避与驱虫药耐药性相关的重大问题。本研究的目的是确定成年的T.circumcincta的转录组，并推断与已知在该线虫中表达的分子相关的主要途径。由于绵羊获得了针对Circumcincta的免疫力，因此有可能开发出针对这种寄生虫的疫苗。因此，我们推断出T.circumcincta的排泄/分泌分子可能是免疫原和候选疫苗。结果总共407,357个EST被组装，产生了39,852个推定的基因序列。概念翻译预测了24,013个蛋白质，然后进行了详细注释，包括对预测蛋白质（包括112个分泌/分泌的[ES]和226个跨膜肽）的路径作图，结构域分析和GO注释使用InterProScan和BLAST2GO进行。使用SignalP对分泌信号肽进行了进一步分析，并使用SecretomeP工具对非经典sec途径进行了分析。对于ES蛋白，可以推断出关键途径，包括FcεRI，T细胞受体和趋化因子信号传导以及白细胞跨内皮迁移，都与免疫反应相关，以及与神经退行性疾病和传染性疾病有关的其他途径也有待进一步详细研究。学习。 KAAS可以识别内质网中吞噬体和蛋白质加工等新的和更新的途径。对组装数据集的域分析显示了丝氨酸，半胱氨酸和蛋白酶抑制剂家族，它们可能代表寄生虫干预的目标。 InterProScan可以识别与细胞外区域有关的GO术语。鉴定出的一些重要结构域家族包括与发病相关蛋白（PRPs）超家族一样的SCP样细胞外蛋白，以及C型凝集素，鞘脂蛋白样蛋白。还确定了与变应原V5 / Tpx-1相关的“细胞外区域”，在寄生虫-宿主相互作用中被认为是重要的。六种半胱氨酸基序（SXC1）蛋白，运甲状腺素蛋白蛋白，C型凝集素，激活相关分泌蛋白（ASPs）可能代表开发新型驱虫药或疫苗的潜在候选者，其他几个重要发现却很少。其中，已鉴定的SXC1，含蛋白激酶结构域的蛋白质，胰蛋白酶家族蛋白，胰蛋白酶样蛋白酶家族成员（TRY-1），推定的主要变应原和推定的脂质结合蛋白尚未在已公开的T.circumcincta蛋白质组学中报道。分析。对dbEST中6,058个原始EST序列的详细分析揭示了315种假定分泌的蛋白质。其中，C型单域激活相关的分泌蛋白ASP3前体，激活相关的分泌蛋白（ASP类蛋白），组织蛋白酶B类半胱氨酸蛋白酶，组织蛋白酶L半胱氨酸蛋白酶，半胱氨酸蛋白酶，与甲状腺素相关的和毒液变应原蛋白质是关键发现。结论我们已经注释了一个大型的Circumcincta数据集EST，并进行了详细的比较生物信息学分析。结果提供了对该寄生虫和疾病表现的分子生物学的全面了解，为将来的研究提供了潜在的焦点。我们确定了许多负责免疫反应的途径。这种类型的大规模计算扫描可以与这种寄生虫的蛋白质组学和代谢组学研究相结合，从而产生新颖的治疗干预和疾病控制策略。我们还成功肯定了使用生物信息学工具进行EST的研究，现在可以将其用作开发新的计算EST分析管道的基准。

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