Personal and panel references for improved alignment

项目摘要 下一代测序在生物学和疾病研究中无处不在。分析的第一步- 测序数据集是读段比对：确定测序的每个片段 数据（“读取”）来自参考基因组。目前，基因组学研究受到阻碍 通过使用一个单一的，任意的引用。这并不能解释存在的巨大的遗传多样性 在人类和模式生物中。此外，它可能导致“参考偏差”，进而导致错误或错误的结果。 误导性的科学结果。 我们提出了一个三个目标的项目，解决多方面的参考偏差问题。在 目标1，我们将开发新的方法和一个新的软件工具，称为biastools总结和 可视化参考偏差。在目标2中，我们将开发新的软件和方法， 通过与多个代表性的参考基因组进行比对来进行偏倚。在一个子项目中，我们将使用 基因型插补，以在大量参考单倍型的帮助下推断个性化基因组。 在第二个子项目中，我们将使用小的代表性基因组集合连接在一个“队列”中， 图”，以便最终相对于最适当的参考来分析读数。的方法 这两个分项目中所述的信息和通信技术将作为称为帕尔斯的新软件工具的一部分加以实施。作为一部分， 为了实现这一目标，我们将发布一个名为jector的软件库和工具， 坐标系到另一个。最后，对于目标3，我们应用了一种新的文本索引方法， r-索引，以使读段能够与大的参考单倍型组进行比对。我们将发布软件 as a software软件library图书馆and tool工具called叫pandex潘德克斯. 该项目的成功完成将为社会提供新的方法和参考 利用我们从大规模基因分型研究中收集的遗传信息， 长读程序集。所有软件都将在开源许可证下提供。

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.