Proteogenomics produces comprehensive and highly accurate protein-coding gene annotation in a complete genome assembly of Malassezia sympodialis.

Zhu Y, Engström PG, Tellgren-Roth C, Baudo CD, Kennell JC, Sun S, Billmyre RB, Schröder MS, Andersson A, Holm T, Sigurgeirsson B, Wu G, Sankaranarayanan SR, Siddharthan R, Sanyal K, Lundeberg J, Nystedt B, Boekhout T, Dawson TL, Heitman J, Scheynius A, Lehtiö J

Nucleic Acids Res. 45 (5) 2629-2643 [2017-03-17; online 2017-01-20]

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.

Bioinformatics Compute and Storage [Service]

Bioinformatics Long-term Support WABI [Collaborative]

Chemical Proteomics & Proteogenomics [Technology development]

Clinical Proteomics Mass spectrometry [Technology development]

NGI Uppsala (Uppsala Genome Center) [Collaborative]

QC bibliography QC xrefs

PubMed 28100699

DOI 10.1093/nar/gkx006

Crossref 10.1093/nar/gkx006

gkx006

pmc PMC5389616

E-MTAB-4589 [RNA-seq data]

PRJEB13283 [DNA sequence reads, genome assemblies and gene annotation]

PXD003773 [Proteomics data]