Techniques for multi-genome synteny analysis to overcome assembly limitations.
Techniques for multi-genome synteny analysis to overcome assembly limitations.
复制标题
DOI：
10.11234/gi1990.17.2_152
复制
发表时间：
2006
期刊：
影响因子：
--
通讯作者：
A. Bhutkar;Susan Russo;Temple F. Smith;W. Gelbart
中科院分区：
文献类型：
--
作者：
A. Bhutkar;Susan Russo;Temple F. Smith;W. Gelbart
基因组尺度的同线性分析，物种之间的相对基因顺序保守的分析，可以提供关键的见解进化染色体动力学，物种之间的重排率，物种形成分析。随着多个基因组的快速可用性，需要有效的解决方案来帮助比较同线分析。目前的方法依赖于同源性评估和基于多重比对的解决方案来确定物种之间的遗传标记的同源物并推断同线关系。多基因组共线性分析面临的主要挑战之一是由具有未测序缺口和可能的组装错误的基因组组装数据所带来的不确定性。目前，人工干预是必要的，以调整和校正的同源性评估和共线性推断的结果。本文提出了一种新的自动化方法来克服这些限制。它使用基于图的算法来推断表示同线性链的子图，其目标是在旁系同源物的存在下选择同源元件的最佳位置，以最大化同线性。这些同线性链通过基于用于微同线性加扰的各种用户定义的阈值合并子图来扩展。这种方法保留并适应组装中的重叠群和支架缺口，以确定可能落入未测序组装缺口或位于测序区段边缘或小片段上的同源遗传元件。此外，它还为断点分析和物种间染色体重排的比较研究提供了自动化解决方案。该方法被应用到果蝇.黑腹果蝇和果蝇.伪暗果蝇基因组的比较研究中，并在分析种间同线关系方面很有用。
Genome scale synteny analysis, the analysis of relative gene-order conservation between species, can provide key insights into evolutionary chromosomal dynamics, rearrangement rates between species, and speciation analysis. With the rapid availability of multiple genomes, there is a need for efficient solutions to aid in comparative syntenic analysis. Current methods rely on homology assessment and multiple alignment based solutions to determine homologs of genetic markers between species and to infer syntenic relationships. One of the primary challenges facing multi-genome syntenic analysis is the uncertainty posed by genome assembly data with un-sequenced gaps and possible assembly errors. Currently, manual intervention is necessary to tune and correct the results of homology assessment and synteny inference. This paper presents a novel automated approach to overcome some of these limitations. It uses a graph based algorithm to infer sub-graphs denoting synteny chains with the objective of choosing the best locations for homologous elements, in the presence of paralogs, in order to maximize synteny. These synteny chains are expanded by merging sub-graphs based on various user defined thresholds for micro-syntenic scrambling. This approach comprehends and accommodates for contig and scaffold gaps in the assembly to determine homologous genetic elements that might either fall in unsequenced assembly gaps or lie on the edges of sequenced segments or on small fragments. Furthermore, it provides an automated solution for breakpoint analysis and a comparative study of chromosomal rearrangements between species. This approach was applied to a comparative study involving Drosophila.melanogaster and Drosophila.pseudoobscura genomes, as an example, and has been useful in analyzing inter-species syntenic relationships.