Clinical PathoScope: rapid alignment and filtration for accurate pathogen identification in clinical samples using unassembled sequencing data.

Clinical PathoScope: rapid alignment and filtration for accurate pathogen identification in clinical samples using unassembled sequencing data.
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DOI:
10.1186/1471-2105-15-262
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发表时间:
2014-08-04
期刊:
影响因子:
3
通讯作者:
Johnson WE
Johnson WE
中科院分区:
生物学4区
文献类型:
--
作者:
Byrd AL;Perez-Rogers JF;Manimaran S;Castro-Nallar E;Toma I;McCaffrey T;Siegel M;Benson G;Crandall KA;Johnson WE

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使用测序技术来研究样品的微生物组可以通过为个性化疾病治疗提供治疗靶点来积极影响患者的医疗保健。然而,这些样本含有来自各种来源的基因组序列,使病原体的鉴定复杂化。在这里,我们提出了临床病理镜,一个管道,以快速,准确地消除主机污染,分离微生物读数,并确定潜在的致病病原体。我们已经完成了临床病理镜开发过程中的三项基本任务。首先,我们开发了一个优化的框架,用于病原体鉴定,使用计算减法方法与读段修剪和模糊读段重新分配一致。其次,我们已经证明了我们的方法能够识别单个临床样本中的多种病原体,准确识别亚种水平的病原体,并使用真实的临床测序数据确定新型或高度突变病原体的最近系统发育邻居。最后,我们已经表明,临床PathoScope优于以前发表的病原体识别方法的计算速度,灵敏度和特异性。Clinical PathoScope是目前唯一可用的病原体鉴定方法,可以从混合样本中鉴定多种病原体,并区分样本中非常密切相关的物种和菌株,每个病原体的读数很少。此外,Clinical PathoScope不依赖于基因组组装,因此与当前基于组装的方法相比,可以更快地完成临床样本的分析。Clinical PathoScope可在http://sourceforge.net/projects/pathoscope/上免费获得。本文的在线版本(doi:10.1186/1471-2105-15-262)包含补充材料,可供授权用户使用。
The use of sequencing technologies to investigate the microbiome of a sample can positively impact patient healthcare by providing therapeutic targets for personalized disease treatment. However, these samples contain genomic sequences from various sources that complicate the identification of pathogens. Here we present Clinical PathoScope, a pipeline to rapidly and accurately remove host contamination, isolate microbial reads, and identify potential disease-causing pathogens. We have accomplished three essential tasks in the development of Clinical PathoScope. First, we developed an optimized framework for pathogen identification using a computational subtraction methodology in concordance with read trimming and ambiguous read reassignment. Second, we have demonstrated the ability of our approach to identify multiple pathogens in a single clinical sample, accurately identify pathogens at the subspecies level, and determine the nearest phylogenetic neighbor of novel or highly mutated pathogens using real clinical sequencing data. Finally, we have shown that Clinical PathoScope outperforms previously published pathogen identification methods with regard to computational speed, sensitivity, and specificity. Clinical PathoScope is the only pathogen identification method currently available that can identify multiple pathogens from mixed samples and distinguish between very closely related species and strains in samples with very few reads per pathogen. Furthermore, Clinical PathoScope does not rely on genome assembly and thus can more rapidly complete the analysis of a clinical sample when compared with current assembly-based methods. Clinical PathoScope is freely available at: http://sourceforge.net/projects/pathoscope/. The online version of this article (doi:10.1186/1471-2105-15-262) contains supplementary material, which is available to authorized users.
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