小柯机器人

美国加州大学Benedict Paten和Glenn Hickey共同合作，近期取得重要工作进展。他们研究利用Minigraph-Cactus基因组比对构建了泛基因组图谱。相关研究成果2023年5月10日在线发表于《自然—生物技术》杂志上。

据介绍，泛基因组参考通过存储一组具有代表性的不同单倍型及其比对来解决参考基因组的偏差，通常以图表的形式。由变异调用者确定的替代等位基因可用于构建泛基因组图，但长读测序的进步正在导致广泛可用的高质量相控组装。与变体调用相反，直接从程序集构建泛基因组图，可以利用图在不同尺度上表示变异的能力。

研究人员展示了Minigraph-Cactus泛基因组工具，它直接从全基因组比对中创建泛基因组，并展示了它扩展到来自人类泛基因组参考联盟的90种人类单倍型的能力。该方法构建包含所有形式遗传变异的图表，同时允许使用当前的图谱绘制和基因分型工具。研究人员测量了用于泛基因组分析的参考基因组的质量和完整性的影响，并表明使用端粒到端粒联盟的CHM13参考可以提高这一方法的准确性。此外，研究人员还展示了果蝇泛基因组的构建。

附：英文原文

Title: Pangenome graph construction from genome alignments with Minigraph-Cactus

Author: Hickey, Glenn, Monlong, Jean, Ebler, Jana, Novak, Adam M., Eizenga, Jordan M., Gao, Yan, Marschall, Tobias, Li, Heng, Paten, Benedict

Issue&Volume: 2023-05-10

Abstract: Pangenome references address biases of reference genomes by storing a representative set of diverse haplotypes and their alignment, usually as a graph. Alternate alleles determined by variant callers can be used to construct pangenome graphs, but advances in long-read sequencing are leading to widely available, high-quality phased assemblies. Constructing a pangenome graph directly from assemblies, as opposed to variant calls, leverages the graph’s ability to represent variation at different scales. Here we present the Minigraph-Cactus pangenome pipeline, which creates pangenomes directly from whole-genome alignments, and demonstrate its ability to scale to 90 human haplotypes from the Human Pangenome Reference Consortium. The method builds graphs containing all forms of genetic variation while allowing use of current mapping and genotyping tools. We measure the effect of the quality and completeness of reference genomes used for analysis within the pangenomes and show that using the CHM13 reference from the Telomere-to-Telomere Consortium improves the accuracy of our methods. We also demonstrate construction of a Drosophila melanogaster pangenome.

DOI: 10.1038/s41587-023-01793-w

Source: https://www.nature.com/articles/s41587-023-01793-w

Nature Biotechnology：《自然—生物技术》，创刊于1996年。隶属于施普林格·自然出版集团，最新IF：68.164
官方网址：https://www.nature.com/nbt/
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