Contiguous and accurate de novo assembly of metazoan genomes with modest long read coverage
Contiguous and accurate de novo assembly of metazoan genomes with modest long read coverage
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DOI：
10.1093/nar/gkw654
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发表时间：
2016-11-02
影响因子：
14.9
通讯作者：
Emerson, J. J.
中科院分区：
文献类型：
--
作者：
Chakraborty, Mahul;Baldwin-Brown, James G.;Emerson, J. J.
准确、完整和连续的基因组组装对于鉴定基因组的重要结构和功能元件以及鉴定遗传变异是必不可少的。然而，大多数最近的基因组组装仍然是不完整和支离破碎的。虽然长分子测序有望提供更完整的基因组组装，但对错误率，低产量，严格的DNA要求和最佳实践的不确定性的担忧可能会阻止许多研究人员采用这项技术。在这里，结合白金标准果蝇参考基因组，我们分析了最近发表的长分子测序数据，以确定是什么支配基因组组装的完整性和连续性。我们还提出了一种混合元组装方法，实现了显着的装配连续性果蝇和人类组件只有适度的长分子测序覆盖。我们的研究结果激发了一组初步的最佳实践，以获得准确和连续的组件，一个“缺失的手册”，指导关键决策，在建设高质量的从头基因组组装，从DNA分离抛光组装。
Genome assemblies that are accurate, complete and contiguous are essential for identifying important structural and functional elements of genomes and for identifying genetic variation. Nevertheless, most recent genome assemblies remain incomplete and fragmented. While long molecule sequencing promises to deliver more complete genome assemblies with fewer gaps, concerns about error rates, low yields, stringent DNA requirements and uncertainty about best practices may discourage many investigators from adopting this technology. Here, in conjunction with the platinum standard Drosophila melanogaster reference genome, we analyze recently published long molecule sequencing data to identify what governs completeness and contiguity of genome assemblies. We also present a hybrid meta-assembly approach that achieves remarkable assembly contiguity for both Drosophila and human assemblies with only modest long molecule sequencing coverage. Our results motivate a set of preliminary best practices for obtaining accurate and contiguous assemblies, a 'missing manual' that guides key decisions in building high quality de novo genome assemblies, from DNA isolation to polishing the assembly.