Development of a computational approach to accurately detect gene losses in genome sequences

生物学中的一个重要问题是，物种之间的表型差异涉及到哪些DNA变化。案例研究发现，在进化过程中，基因的丢失对表型的丢失和获得都很重要。该项目的目标是开发一种生物信息学方法，该方法使用比较基因组系统地检测给定物种基因组中丢失的基因。我们的主要重点是提高特异性，从而减少假阳性率，在某种程度上，不需要人工管理基因丢失候选基因，这是将这种方法应用于许多基因组的关键。我们的初步工作清楚地确定了哪些过滤步骤和序列比对方法需要实现，以达到这种高精度。利用这种方法，我们将检测寿命较短的脊椎动物物种的基因损失，以发现影响衰老的候选基因。此外，我们将使用这种方法来创建脊椎动物，果蝇和线虫的基因丢失目录。这将形成系统研究基因丢失如何影响表型差异进化的基础。

An important question in biology is what are the DNA changes that are involved in phenotypic differences between species. Case studies found that the loss of genes can be important for both the loss and gain of phenotypes during evolution. The goal of this project is the development of a bioinformatics method that uses comparative genomes to systematically detect genes that are lost in the genomes of a given species. Our main focus is to increase the specificity and thus reduce the false positive rate to an extent that no manual curation of gene loss candidates is necessary, which is key to apply this approach to many genomes. Our preliminary work clearly identified which filtering steps and sequence alignment approaches need to be implemented in order to achieve this high accuracy. Using this method, we will then detect gene losses in vertebrate species with short lifespans to uncover candidate genes that influence aging. Furthermore, we will use this method to create a catalog of gene losses in vertebrates, fruit flies and nematodes. This will form the basis to systematically study how gene loss had an impact on the evolution of phenotypic differences.