Precise Methods for Orthology Assessment in Large Data Sets Using Best Matches

同源性检测是基因组注释、基因命名和理解基因进化的重要任务。随着新基因组的快速加速，迫切需要高效的方法。正如大量文献所证明的那样，倒数最佳匹配方法相当准确，并且可以扩展到大数据集。然而，它们远非完美，并且容易出现假阳性和假阴性的正态调用。利用系统发育组合学的最新进展，我们在这里提出开发实用的方法来从相互的最佳命中（如通过序列（不）相似性评分）计算最接近的相关序列，即，在进化意义上的最佳匹配这些都直接关系到orthology。拟议工作的目标是开发一个软件库，实现这种数据校正，不仅在复制丢失的情况下，而且在水平基因转移的存在。为此，我们将再次利用最新的进展，在数学上的理解的orthology，和解之间的映射树，和事件的标签。我们将专注于实现一个开源软件库，而不是专注于另一个正字法评估工具，该软件库旨在使社区易于将新算法纳入自己的管道和工具中。作为一个展示应用程序，我们将开发一个新的后端ProteinOrtho，一个矫形评估工具，由Lechner集团在马尔堡。

Orthology detection is an important task for genome annotation, gene nomenclature, and the understanding of gene evolution. With the rapidly accelerating pace at which new genomes become available, highly efficient methods are urgently required. As demonstrated in a large body of literature, reciprocal best match methods are reasonably accurate and scale to large data sets. Nevertheless, they are far from perfect and prone to both false positive and false negative orthology calls. Drawing upon recent advances in phylogenetic combinatorics we propose here to develop practical methods to compute from reciprocal best hits (as scored by sequence (dis)similarity) the reciprocally most closely related sequences, i.e., the best matches in the proper evolutionary sense. These are directly related to orthology. The goal of the proposed work is to develop a softwarelibrary that implements this kind of data correction not only for the case of duplication-loss scenarios but also in the presence of horizontal gene transfer. To this end we will again make use of recent advances in the mathematical understanding of the orthology, reconciliation maps between trees, and event labelings. Instead of focusing on an yet another orthology assessment tool, we will focus on implementing an open source software library that is intended to make it easy for the community to include thenew algorithms into their own pipelines and tools. As a showcase application we will develop a new backend for ProteinOrtho, an orthology assessment tool maintained by the Lechner Group in Marburg.