title: Comparative genomics approach to detecting split-coding regions in a low-coverage genome: lessons from the chimaera Callorhinchus milii (Holocephali, Chondrichthyes).
abstract: Recent development of deep sequencing technologies has facilitated de novo genome sequencing projects, now conducted even by individual laboratories. However, this will yield more and more genome sequences that are not well assembled, and will hinder thorough annotation when no closely related reference genome is available. One of the challenging issues is the identification of protein-coding sequences split into multiple unassembled genomic segments, which can confound orthology assignment and various laboratory experiments requiring the identification of individual genes. In this study, using the genome of a cartilaginous fish, Callorhinchus milii, as test case, we performed gene prediction using a model specifically trained for this genome. We implemented an algorithm, designated ESPRIT, to identify possible linkages between multiple protein-coding portions derived from a single genomic locus split into multiple unassembled genomic segments. We developed a validation framework based on an artificially fragmented human genome, improvements between early and recent mouse genome assemblies, comparison with experimentally validated sequences from GenBank, and phylogenetic analyses. Our strategy provided insights into practical solutions for efficient annotation of only partially sequenced (low-coverage) genomes. To our knowledge, our study is the first formulation of a method to link unassembled genomic segments based on proteomes of relatively distantly related species as references.
authors.affiliation: ETH Zurich, Computer Science, Universitätstrasse 6, 8092 Zurich, Switzerland. cdessimoz@inf.ethz.ch
authors.forename: Christophe
authors.initials: C
authors.lastname: Dessimoz
authors.forename: Stefan
authors.initials: S
authors.lastname: Zoller
authors.forename: Tereza
authors.initials: T
authors.lastname: Manousaki
authors.forename: Huan
authors.initials: H
authors.lastname: Qiu
authors.forename: Axel
authors.initials: A
authors.lastname: Meyer
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Kuraku
mesh_terms: D000465:Algorithms; D000818:Animals; D002678:Chimera / Q000235:genetics*; D030561:Databases, Nucleic Acid; D016678:Genome; D023281:Genomics / Q000379:methods*; D006801:Humans; D051379:Mice; D016366:Open Reading Frames; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA / Q000379:methods; D012754:Sharks / Q000235:genetics*