Personal and panel references for improved alignment

项目总结 下一代测序在生物学和疾病研究中无处不在。分析时的fi第一步- 确定测序数据集是读取对齐：确定每个测序片段的位置的过程 数据(“读”)来自参考基因组。目前，基因组学研究受到阻碍。 通过使用单一的、任意的引用。这不能解释现存的巨大的遗传多样性。 在人类和模型生物中。此外，它还可能导致“参考偏差”，进而导致错误或 误导性的科学fic结果。 我们提出了一个三个目标的项目，从多个方面解决了参考偏差问题。在……里面 目标1，我们将开发新的方法和新的软件工具，称为Biastools，用于总结和 形象化参考偏向。在目标2中，我们将开发新软件和方法来解决参考 通过与多个有代表性的参考基因组进行比对而产生偏倚。在一个子项目中，我们将使用 在一大组参考单倍型的帮助下，推断个性化的基因组的基因归因。 在第二个子项目中，我们将使用连接在“flow”中的具有代表性的基因组的小集合 图表，以便最终根据最合适的参考对阅读进行分析。这些方法 这两个子项目中描述的项目都将作为名为PALS的新软件工具的一部分实施。也可以作为一部分 为了实现这一目标，我们将发布一个名为射影的软件库和工具，用于将路线从 将坐标系参照到另一个坐标系。最后，对于目标3，我们应用了一种新的文本索引方法 R-INDEX可实现与大型参考单倍型仪表板的读数对齐。我们将发布该软件 作为一个称为Pandex的软件库和工具。 该项目的顺利完成将为社区提供新的方法和参考 这充分利用了我们从大规模基因分型研究和新的 长时间阅读的程序集。所有软件都将在开放源码许可证下提供。

PROJECT SUMMARY Next-generation sequencing is ubiquitous in the study of biology and disease. The first step when analyz- ing a sequencing dataset is read alignment: the process of determining where each snippet of sequencing data (“read”) came from with respect to a reference genome. Currently, genomics research is hampered by the use of a single, arbitrary reference. This fails to account for the vast genetic diversity that exists among humans and model organisms. Further, it can result in “reference bias,” in turn leading to false or misleading scientific results. We propose a three-aim project that addresses the reference bias problem on multiple fronts. In Aim 1, we will develop new methods and a new software tool called biastools for summarizing and visualizing reference bias. In Aim 2, we will develop new software and methods that address reference bias by enabling alignment to multiple representative reference genomes. In one subproject, we will use genotype imputation to infer a personalized genome with the help of a large panel of reference haplotypes. In a second subproject, we will use small collections of representative genomes connected in a “flow graph,” so that reads are ultimately analyzed with respect to the most appropriate reference. The methods described in both subprojects will be implemented as part of a new software tool called pals. Also as part of this aim, we will release a software library and tool called jector for transforming alignments from one reference coordinate system to another. Finally, for Aim 3, we apply a novel text-indexing method called r-index to enable alignment of reads to large panels of reference haplotypes. We will release the software as a software library and tool called pandex. Successful completion of the project will provide the community with new methods and references that leverage the genetic information we are gleaning from large-scale genotyping studies and from new long-read assemblies. All software will be made available under an open source license.