Orthology: Promises and challenges

Orthology is a cornerstone of comparative genomics and has numerous applications in current biology. In this chapter, we first introduce the concepts of orthology and paralogy. We then present the currently available orthology inference methods and the community-led efforts of standardization and benchmarking accompanying these developments. The large panel of available orthology resources is compared in terms of species coverage, access, contextual data and tools proposed to end-users to facilitate the analysis and exploitation of orthology data. We then review the importance of orthology applications, ranging from the study of protein families and information transfer to the comparison of genomes and genotype/phenotype correlations. Finally, we discuss the current challenges in the orthology field, faced with an ever-increasing number of proteomes of particularly heterogeneous quality. We highlight the urgent need of considering orthology at the protein domain and transcript levels and the conceptual and practical difficulties that this raises.