| Summary: | <p>Abstract</p> <p>Thanks to advances in next-generation technologies, genome sequences are now being generated at breadth (<it>e.g.</it> across environments) and depth (thousands of closely related strains, individuals or samples) unimaginable only a few years ago. <it>Phylogenomics</it> – the study of evolutionary relationships based on comparative analysis of genome-scale data – has so far been developed as industrial-scale molecular phylogenetics, proceeding in the two classical steps: multiple alignment of homologous sequences, followed by inference of a tree (or multiple trees). However, the algorithms typically employed for these steps scale poorly with number of sequences, such that for an increasing number of problems, high-quality phylogenomic analysis is (or soon will be) computationally infeasible. Moreover, next-generation data are often incomplete and error-prone, and analysis may be further complicated by genome rearrangement, gene fusion and deletion, lateral genetic transfer, and transcript variation. Here we argue that next-generation data require next-generation phylogenomics, including so-called <it>alignment-free</it> approaches.</p> <p>Reviewers</p> <p>Reviewed by Mr Alexander Panchin (nominated by Dr Mikhail Gelfand), Dr Eugene Koonin and Prof Peter Gogarten. For the full reviews, please go to the Reviewers’ comments section.</p>
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