Simultaneous gene finding in multiple genomes

Abstract

As whole genome sequencing is taking on ever-increasing dimensions, the new challenge is the accurate and consistent annotation of entire clades of genomes. We address this problem with a new approach to comparative gene finding that takes a multiple genome alignment of closely related species and simultaneously predicts the location and structure of protein-coding genes in all input genomes, thereby exploiting negative selection and sequence conservation. The model prefers potential gene structures in the different genomes that are in agreement with each other, or -if notwhere the exon gains and losses are plausible given the species tree. We formulate the multi-species gene finding problem as a binary labeling problem on a graph. The resulting optimization problem is NP hard, but can be efficiently approximated using a subgradient-based dual decomposition approach. The proposed method was tested on a whole-genome alignment of 12 Drosophila species and its accuracy evaluated on D. melanogaster. The method is being implemented as an extension to the gene finder AUGUSTUS.

Repeat associated mechanisms of genome evolution and function revealed by the Mus caroli and Mus pahari genomes

“…Mus caroli and Mus pahari genes were annotated using a combination of three annotation pipelines: TransMap (Stanke et al 2008), AUGUSTUS (Stanke et al 2006), and a new mode of AUGUSTUS called Comparative AUGUSTUS (AUGUSTUS-CGP) (Konig et al 2016). The GENCODE set of Mus musculus transcripts (M8 release) (Harrow et al 2012) was used with the TransMap pipeline.…”

“…We generated RNA-seq data from brain, liver, heart, and kidney in Mus caroli and Mus pahari to annotate the genes using an integration of TransMap (Stanke et al 2008), AUGUSTUS (Stanke et al 2006), and AUGUSTUS-CGP (Konig et al 2016) pipelines (Supplemental Methods SM1.7). This approach identified 20,323 and 20,029 protein-coding genes and 10,069 and 9336 noncoding genes, comparable to the mouse and rat reference genomes (Supplemental Fig.…”

Comparative Annotation Toolkit (CAT) - simultaneous clade and personal genome annotation

“…AUGUSTUS recently added a novel objective function parameterization option that makes use of whole genome alignments to predict coding genes simultaneously in every genome in the alignment [72] called Comparative AUGUSTUS or AugustusCGP.…”

“…For this purpose, AUGUSTUS is run in its new comparative mode (CGP) recently published [72]. This mode uses a novel objective function to simultaneously predict coding transcripts in every genome in a Cactus alignment, taking in extrinsic information from any provided existing annotations as well as RNA-seq and/or IsoSeq data in any of the aligned genomes.…”

“…In contrast to most earlier alignment methods [139,140,141], progressiveCactus alignments are not-reference based, include duplications, and are thus suitable for the annotation of many-to-many orthology relationships. We show how the output of this projected annotation set can be cleaned up and filtered through special application of AUGUSTUS [55], and how novel information can be introduced by combining the projected annotation set with predictions produced by Comparative Augustus [72]. These predictions can be further supplemented and validated by incorporating long range RNA-sequencing data such as those generated by the IsoSeq protocol [142].…”