Challenges in the analysis of viral metagenomes.

Challenges in the analysis of viral metagenomes.
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DOI:
10.1093/ve/vew022
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发表时间:
2016-07
期刊:
影响因子:
5.3
通讯作者:
Prosperi M
Prosperi M
中科院分区:
医学2区
文献类型:
--
作者:
Rose R;Constantinides B;Tapinos A;Robertson DL;Prosperi M

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基因组测序技术继续以惊人的速度发展,但从混合样本中重建和分类病毒基因组的分析方法在性能和可用性方面仍然有限。现有的解决方案通常针对专家用户,并且范围往往不明确,因此很难严格评估其性能。对于缺乏专业计算专业知识且适用于各种实验环境的研究人员来说,对直观分析工具的需求日益增长。显着的技术挑战阻碍了进展;例如,在临床和环境宏基因组中,病毒基因组的片段通常比宿主、细菌和/或其他生物体的片段少几个数量级;观察到的病毒基因组通常与参考基因组有很大偏差,需要使用详尽的比对方法;群体内病毒的高度多样性可能导致模糊的序列重建;最后,与不同病毒类群的估计数量相比,记录的病毒参考基因组相对较少,这使得分类存在问题。已经开发了各种软件工具来适应与表征病毒序列相关的独特挑战和用例;然而,这些工具的质量各不相同,并且它们的使用通常需要计算专业知识或使用功能强大的计算机,从而限制了它们对许多研究人员的用处。在这篇综述中,我们考虑了病毒测序和分析带来的一般性和特定应用的挑战,概述了可用工具和方法的前景,并提出了克服当前有效分析障碍的方法。
Genome sequencing technologies continue to develop with remarkable pace, yet analytical approaches for reconstructing and classifying viral genomes from mixed samples remain limited in their performance and usability. Existing solutions generally target expert users and often have unclear scope, making it challenging to critically evaluate their performance. There is a growing need for intuitive analytical tooling for researchers lacking specialist computing expertise and that is applicable in diverse experimental circumstances. Notable technical challenges have impeded progress; for example, fragments of viral genomes are typically orders of magnitude less abundant than those of host, bacteria, and/or other organisms in clinical and environmental metagenomes; observed viral genomes often deviate considerably from reference genomes demanding use of exhaustive alignment approaches; high intrapopulation viral diversity can lead to ambiguous sequence reconstruction; and finally, the relatively few documented viral reference genomes compared to the estimated number of distinct viral taxa renders classification problematic. Various software tools have been developed to accommodate the unique challenges and use cases associated with characterizing viral sequences; however, the quality of these tools varies, and their use often necessitates computing expertise or access to powerful computers, thus limiting their usefulness to many researchers. In this review, we consider the general and application-specific challenges posed by viral sequencing and analysis, outline the landscape of available tools and methodologies, and propose ways of overcoming the current barriers to effective analysis.
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