Denton James F, Lugo-Martinez Jose, Tucker Abraham E, Schrider Daniel R, Warren Wesley C, Hahn Matthew W
School of Informatics and Computing, Indiana University, Bloomington, Indiana.
Department of Biology, Indiana University, Bloomington, Indiana.
PLoS Comput Biol. 2014 Dec 4;10(12):e1003998. doi: 10.1371/journal.pcbi.1003998. eCollection 2014 Dec.
Current sequencing methods produce large amounts of data, but genome assemblies based on these data are often woefully incomplete. These incomplete and error-filled assemblies result in many annotation errors, especially in the number of genes present in a genome. In this paper we investigate the magnitude of the problem, both in terms of total gene number and the number of copies of genes in specific families. To do this, we compare multiple draft assemblies against higher-quality versions of the same genomes, using several new assemblies of the chicken genome based on both traditional and next-generation sequencing technologies, as well as published draft assemblies of chimpanzee. We find that upwards of 40% of all gene families are inferred to have the wrong number of genes in draft assemblies, and that these incorrect assemblies both add and subtract genes. Using simulated genome assemblies of Drosophila melanogaster, we find that the major cause of increased gene numbers in draft genomes is the fragmentation of genes onto multiple individual contigs. Finally, we demonstrate the usefulness of RNA-Seq in improving the gene annotation of draft assemblies, largely by connecting genes that have been fragmented in the assembly process.
当前的测序方法会产生大量数据,但基于这些数据的基因组组装往往极不完整。这些不完整且充满错误的组装会导致许多注释错误,尤其是基因组中基因的数量。在本文中,我们从总基因数量以及特定基因家族中基因的拷贝数这两个方面来研究该问题的严重程度。为此,我们将多个草图组装与相同基因组的高质量版本进行比较,使用了基于传统和新一代测序技术的鸡基因组的几个新组装,以及已发表的黑猩猩草图组装。我们发现,在草图组装中,超过40%的基因家族被推断基因数量错误,而且这些错误的组装既有基因的增加也有基因的减少。使用黑腹果蝇的模拟基因组组装,我们发现草图基因组中基因数量增加的主要原因是基因断裂成多个单独的重叠群。最后,我们证明了RNA测序在改善草图组装的基因注释方面的有用性,主要是通过连接在组装过程中已断裂的基因。
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