title: Proteogenomics produces comprehensive and highly accurate protein-coding gene annotation in a complete genome assembly of Malassezia sympodialis.
abstract: Complete and accurate genome assembly and annotation is a crucial foundation for comparative and functional genomics. Despite this, few complete eukaryotic genomes are available, and genome annotation remains a major challenge. Here, we present a complete genome assembly of the skin commensal yeast Malassezia sympodialis and demonstrate how proteogenomics can substantially improve gene annotation. Through long-read DNA sequencing, we obtained a gap-free genome assembly for M. sympodialis (ATCC 42132), comprising eight nuclear and one mitochondrial chromosome. We also sequenced and assembled four M. sympodialis clinical isolates, and showed their value for understanding Malassezia reproduction by confirming four alternative allele combinations at the two mating-type loci. Importantly, we demonstrated how proteomics data could be readily integrated with transcriptomics data in standard annotation tools. This increased the number of annotated protein-coding genes by 14% (from 3612 to 4113), compared to using transcriptomics evidence alone. Manual curation further increased the number of protein-coding genes by 9% (to 4493). All of these genes have RNA-seq evidence and 87% were confirmed by proteomics. The M. sympodialis genome assembly and annotation presented here is at a quality yet achieved only for a few eukaryotic organisms, and constitutes an important reference for future host-microbe interaction studies.
authors.affiliation: Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, 17121 Solna, Sweden.
authors.forename: Yafeng
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, 17121 Solna, Sweden.
authors.forename: Pär G
authors.initials: PG
authors.lastname: Engström
authors.affiliation: National Genomics Infrastructure, Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, 75108 Uppsala, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Tellgren-Roth
authors.affiliation: Department of Biology, Saint Louis University, St. Louis, MO 63103, USA.
authors.forename: Charles D
authors.initials: CD
authors.lastname: Baudo
authors.affiliation: Department of Biology, Saint Louis University, St. Louis, MO 63103, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Kennell
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Sheng
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: R Blake
authors.initials: RB
authors.lastname: Billmyre
authors.affiliation: School of Biomedical and Biomolecular Science, Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Markus S
authors.initials: MS
authors.lastname: Schröder
authors.affiliation: Department of Medicine Solna, Translational Immunology Unit, Karolinska Institutet and University Hospital, 17177 Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Andersson
authors.affiliation: Department of Medicine Solna, Translational Immunology Unit, Karolinska Institutet and University Hospital, 17177 Stockholm, Sweden.
authors.forename: Tina
authors.initials: T
authors.lastname: Holm
authors.affiliation: Science for Life Laboratory, School of Biotechnology, Royal Institute of Technology, 17121 Solna, Sweden.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Sigurgeirsson
authors.affiliation: Computational and Systems Biology, Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), 138672, Singapore.
authors.forename: Guangxi
authors.initials: G
authors.lastname: Wu
authors.affiliation: Molecular Mycology Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560 064, India.
authors.forename: Sundar Ram
authors.initials: SR
authors.lastname: Sankaranarayanan
authors.affiliation: The Institute of Mathematical Sciences/HBNI, Taramani, Chennai 600 113, India.
authors.forename: Rahul
authors.initials: R
authors.lastname: Siddharthan
authors.affiliation: Molecular Mycology Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560 064, India.
authors.forename: Kaustuv
authors.initials: K
authors.lastname: Sanyal
authors.affiliation: Science for Life Laboratory, School of Biotechnology, Royal Institute of Technology, 17121 Solna, Sweden.
authors.forename: Joakim
authors.initials: J
authors.lastname: Lundeberg
authors.affiliation: Science for Life Laboratory, Department of Cell and Molecular Biology, Uppsala University, 75123 Uppsala, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Nystedt
authors.affiliation: CBS-Fungal Biodiversity Centre, Utrecht, 3508, The Netherlands and Institute for Biodiversity and ecosystem Dynamics (IBED), University of Amsterdam, 1012 WX Amsterdam, The Netherlands.
authors.forename: Teun
authors.initials: T
authors.lastname: Boekhout
authors.affiliation: Institute of Medical Biology, Agency for Science, Technology and Research (A*STAR), 138648, Singapore.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Dawson
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Heitman
authors.affiliation: Science for Life Laboratory, Department of Clinical Science and Education, Karolinska Institutet, and Sachs' Children and Youth Hospital, Södersjukhuset, SE-118 83 Stockholm, Sweden.
authors.forename: Annika
authors.initials: A
authors.lastname: Scheynius
authors.affiliation: Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, 17121 Solna, Sweden.
authors.forename: Janne
authors.initials: J
authors.lastname: Lehtiö
mesh_terms: D005656:Fungal Proteins / Q000235:genetics*; D005800:Genes, Fungal; D016681:Genome, Fungal; D054629:Genome, Mitochondrial; D008290:Malassezia / Q000235:genetics*; D058977:Molecular Sequence Annotation / Q000379:methods*; D010455:Peptides / Q000235:genetics; D000072417:Protein Domains; D000071696:Proteogenomics / Q000379:methods*; D017423:Sequence Analysis, RNA
chemical_list: D005656:Fungal Proteins; D010455:Peptides