skandiver: a divergence-based analysis tool for identifying intercellular mobile genetic elements

Xiaolei Brian Zhang, Grace Oualline, Jim Shaw, Yun William Yu
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Abstract

Mobile genetic elements (MGEs) are as ubiquitous in nature as they are varied in type, ranging from viral insertions to transposons to incorporated plasmids. Horizontal transfer of MGEs across bacterial species may also pose a significant threat to global health due to their capability to harbour antibiotic resistance genes. However, despite cheap and rapid whole genome sequencing, the varied nature of MGEs makes it difficult to fully characterize them, and existing methods for detecting MGEs often don't agree on what should count. In this manuscript, we first define and argue in favor of a divergence-based characterization of mobile-genetic elements. Using that paradigm, we present skandiver, a tool designed to efficiently detect MGEs from whole genome assemblies without the need for gene annotation or markers. skandiver determines mobile elements via genome fragmentation, average nucleotide identity (ANI), and divergence time. By building on the scalable skani software for ANI computation, skandiver can query hundreds of complete assemblies against $>$65,000 representative genomes in a few minutes and 19 GB memory, providing scalable and efficient method for elucidating mobile element profiles in incomplete, uncharacterized genomic sequences. For isolated and integrated large plasmids (>10kbp), skandiver's recall was 48\% and 47\%, MobileElementFinder was 59\% and 17\%, and geNomad was 86\% and 32\%, respectively. For isolated large plasmids, skandiver's recall (48\%) is lower than state-of-the-art reference-based methods geNomad (86\%) and MobileElementFinder (59\%). However, skandiver achieves higher recall on integrated plasmids and, unlike other methods, without comparing against a curated database, making skandiver suitable for discovery of novel MGEs. Availability: https://github.com/YoukaiFromAccounting/skandiver
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skandiver:用于识别细胞间移动遗传因子的基于分异的分析工具
移动遗传因子(MGEs)在自然界无处不在,其类型也多种多样,从病毒插入到转座子,再到整合质粒,不一而足。由于移动遗传因子能够携带抗生素耐药基因,因此它们在细菌物种间的水平转移也可能对全球健康构成重大威胁。然而,尽管全基因组测序既便宜又快速,但由于 MGEs 的性质各不相同,因此很难全面描述它们的特征,而且现有的 MGEs 检测方法往往对哪些应该被计算在内意见不一。在本手稿中,我们首先定义并支持基于发散性的移动遗传因子特征描述。利用这一范式,我们提出了 skandiver,这是一种无需基因注释或标记就能从全基因组组装中高效检测 MGE 的工具。skandiver 通过基因组片段、平均核苷酸同一性(ANI)和分歧时间来确定移动元素。skandiver通过基因组片段确定移动元素的平均核苷酸同一性(ANI)和分歧时间。通过利用可扩展的kani软件进行ANI计算,skandiver可以在几分钟内利用19 GB内存查询数百个完整的基因组组装和价值>65,000美元的代表性基因组,为阐明不完整、未定性基因组序列中的移动元素档案提供了可扩展的高效方法。对于分离的和整合的大质粒(>10kbp),skandiver的召回率分别为48%和47%,MobileElementFinder的召回率分别为59%和17%,geNomad的召回率分别为86%和32%。对于分离出的大质粒,skandiver的召回率(48%)低于最先进的基于参考的方法geNomad(86%)和MobileElementFinder(59%)。然而,skandiver 在整合质粒上的召回率更高,而且与其他方法不同的是,它不需要与已整合的数据库进行比较,这使得 skandiver 适合于发现新的 MGEs。可用性: https://github.com/YoukaiFromAccounting/skandiver
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