PT  - JOURNAL ARTICLE
AU  - Manuel Lafond
AU  - Mona Meghdari Miardan
AU  - David Sankoff
TI  - Accurate prediction of orthologs in the presence of divergence after duplication
AID  - 10.1101/294405
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 294405
4099  - http://biorxiv.org/content/early/2018/04/04/294405.short
4100  - http://biorxiv.org/content/early/2018/04/04/294405.full
AB  - Motivation When gene duplication occurs, one of the copies may become free of selective pressure and evolve at an accelerated pace. This has important consequences on the prediction of orthology relationships, since two orthologous genes separated by divergence after duplication may differ in both sequence and function. In this work, we make the distinction between the primary orthologs, which have not been affected by accelerated mutation rates on their evolutionary path, and the secondary orthologs, which have. Similarity-based prediction methods will tend to miss secondary orthologs, whereas phylogeny-based methods cannot separate primary and secondary orthologs. However, both types of orthology have applications in important areas such as gene function prediction and phylogenetic reconstruction, motivating the need for methods that can distinguish the two types.Results We formalize the notion of divergence after duplication, and provide a theoretical basis for the inference of primary and secondary orthologs. We then put these ideas to practice with the HyPPO (Hybrid Prediction of Paralogs and Orthologs) framework, which combines ideas from both similarity and phylogeny approaches. We apply our method to simulated and empirical datasets, and show that we achieve superior accuracy in predicting primary orthologs, secondary orthologs and paralogs.Availability HyPPO is a modular framework with a core developed in Python, and is provided with a variety of C++ modules. The source code is available at https://github.com/manuellafond/HyPPO.Contact mlafond2{at}uOttawa.ca, mmegh021{at}uottawa.ca, sankoff{at}uottawa.ca