Abstract
Orthology assignment is a key step of comparative genomic studies, for which many bioinformatic tools have been developed. However, all gene clustering pipelines are based on the analysis of protein distances, which are subject to many artifacts. In this article, we introduce Broccoli, a user-friendly pipeline designed to infer, with high precision, orthologous groups, and pairs of proteins using a phylogeny-based approach. Briefly, Broccoli performs ultrafast phylogenetic analyses on most proteins and builds a network of orthologous relationships. Orthologous groups are then identified from the network using a parameter-free machine learning algorithm. Broccoli is also able to detect chimeric proteins resulting from gene-fusion events and to assign these proteins to the corresponding orthologous groups. Tested on two benchmark data sets, Broccoli outperforms current orthology pipelines. In addition, Broccoli is scalable, with runtimes similar to those of recent distance-based pipelines. Given its high level of performance and efficiency, this new pipeline represents a suitable choice for comparative genomic studies. Broccoli is freely available at https://github.com/rderelle/Broccoli.
Highlights
Orthologous genes are genes originating from a speciation event, as opposed to paralogous genes originating from a gene duplication event (Koonin 2005)
Assigning gene orthology across distantly related species typically consists of identifying ancient speciation and gene duplication events from the comparisons of present gene or protein sequences
We compared Broccoli with two recent distance-based pipelines: OrthoFinder2 (Emms and Kelly 2019), which uses the MCL algorithm after distance corrections to mitigate the impact of evolutionary rate differences between species, and Sonicparanoid (Cosentino and Iwasaki 2019), which employs a BBH approach
Summary
Orthologous genes are genes originating from a speciation event, as opposed to paralogous genes originating from a gene duplication event (Koonin 2005). Assigning gene orthology across distantly related species typically consists of identifying ancient speciation and gene duplication events from the comparisons of present gene or protein sequences. This task is highly challenging for many reasons. The combination of successive speciation and gene duplication events, with the latter often being associated with gene losses and gene conversions (Kondrashov 2012; Pich and Kondrashov 2014; Harpak et al 2017), tends to blur the distinction between orthologs and paralogs. Incomplete lineage sorting (Maddison 1997), and the transfers of genetic material between species (i.e., lateral gene transfers) (Soucy et al 2015) and between genes (i.e., gene fusions)
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