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Transcriptomes of Trypanosoma brucei rhodesiense from sleeping sickness patients, rodents and culture: Effects of strain, growth conditions and RNA preparation methods
PLOS Neglected Tropical Diseases ( IF 3.8 ) Pub Date : 2018-02-23 , DOI: 10.1371/journal.pntd.0006280
Julius Mulindwa , Kevin Leiss , David Ibberson , Kevin Kamanyi Marucha , Claudia Helbig , Larissa Melo do Nascimento , Eleanor Silvester , Keith Matthews , Enock Matovu , John Enyaru , Christine Clayton

All of our current knowledge of African trypanosome metabolism is based on results from trypanosomes grown in culture or in rodents. Drugs against sleeping sickness must however treat trypanosomes in humans. We here compare the transcriptomes of Trypanosoma brucei rhodesiense from the blood and cerebrospinal fluid of human patients with those of trypanosomes from culture and rodents. The data were aligned and analysed using new user-friendly applications designed for Kinetoplastid RNA-Seq data. The transcriptomes of trypanosomes from human blood and cerebrospinal fluid did not predict major metabolic differences that might affect drug susceptibility. Usefully, there were relatively few differences between the transcriptomes of trypanosomes from patients and those of similar trypanosomes grown in rats. Transcriptomes of monomorphic laboratory-adapted parasites grown in in vitro culture closely resembled those of the human parasites, but some differences were seen. In poly(A)-selected mRNA transcriptomes, mRNAs encoding some protein kinases and RNA-binding proteins were under-represented relative to mRNA that had not been poly(A) selected; further investigation revealed that the selection tends to result in loss of longer mRNAs.



中文翻译:

来自昏睡病患者,啮齿动物和培养物的布氏锥虫锥虫的转录组:菌株,生长条件和RNA制备方法的影响

我们目前对非洲锥虫新陈代谢的所有知识都是基于在文化或啮齿动物中生长的锥虫的结果。然而,抗昏睡病的药物必须治疗人类的锥虫。我们在这里比较布氏锥虫锥虫的转录组从人类患者的血液和脑脊液中提取,以及来自培养物和啮齿动物的锥虫。使用针对运动质体RNA-Seq数据设计的新的用户友好应用程序对数据进行了对齐和分析。人血和脑脊液中锥虫的转录组不能预测可能影响药物敏感性的主要代谢差异。有用的是,来自患者的锥虫的转录组与在大鼠中生长的相似锥虫的转录组之间的差异相对较小。体外生长的单态实验室适应性寄生虫的转录组其文化与人类寄生虫极为相似,但仍存在一些差异。在poly(A)选择的mRNA转录组中,相对于尚未选择poly(A)的mRNA,编码某些蛋白激酶和RNA结合蛋白的mRNA的表达不足。进一步的研究表明,这种选择往往会导致更长的mRNA丢失。

更新日期:2018-02-24
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