PMID- 30171158
OWN - NLM
STAT- MEDLINE
DCOM- 20191030
LR  - 20221207
IS  - 1535-9484 (Electronic)
IS  - 1535-9476 (Print)
IS  - 1535-9476 (Linking)
VI  - 17
IP  - 12
DP  - 2018 Dec
TI  - Estimating the Contribution of Proteasomal Spliced Peptides to the HLA-I 
      Ligandome.
PG  - 2347-2357
LID - S1535-9476(20)31999-X [pii]
LID - 10.1074/mcp.RA118.000877 [doi]
AB  - Spliced peptides are short protein fragments spliced together in the proteasome 
      by peptide bond formation. True estimation of the contribution of 
      proteasome-spliced peptides (PSPs) to the global human leukocyte antigen (HLA) 
      ligandome is critical. A recent study suggested that PSPs contribute up to 30% of 
      the HLA ligandome. We performed a thorough reanalysis of the reported results 
      using multiple computational tools and various validation steps and concluded 
      that only a fraction of the proposed PSPs passes the quality filters. To better 
      estimate the actual number of PSPs, we present an alternative workflow. We 
      performed de novo sequencing of the HLA-peptide spectra and discarded all de novo 
      sequences found in the UniProt database. We checked whether the remaining de novo 
      sequences could match spliced peptides from human proteins. The spliced sequences 
      were appended to the UniProt fasta file, which was searched by two search tools 
      at a false discovery rate (FDR) of 1%. We find that 2-6% of the HLA ligandome 
      could be explained as spliced protein fragments. The majority of these potential 
      PSPs have good peptide-spectrum match properties and are predicted to bind the 
      respective HLA molecules. However, it remains to be shown how many of these 
      potential PSPs actually originate from proteasomal splicing events.
CI  - (c) 2018 Mylonas et al.
FAU - Mylonas, Roman
AU  - Mylonas R
AD  - Vital-IT, 1015 Lausanne, Switzerland; Swiss Institute of Bioinformatics, 1015 
      Lausanne, Switzerland.
FAU - Beer, Ilan
AU  - Beer I
AD  - Adicet Bio Israel, Ltd., Technion City, 32000, Haifa, Israel.
FAU - Iseli, Christian
AU  - Iseli C
AD  - Vital-IT, 1015 Lausanne, Switzerland; Swiss Institute of Bioinformatics, 1015 
      Lausanne, Switzerland.
FAU - Chong, Chloe
AU  - Chong C
AD  - Ludwig Cancer Research Center, University of Lausanne, 1066 Epalinges, 
      Switzerland; Department of Oncology, University Hospital of Lausanne, 1011 
      Lausanne, Switzerland.
FAU - Pak, Hui-Song
AU  - Pak HS
AD  - Ludwig Cancer Research Center, University of Lausanne, 1066 Epalinges, 
      Switzerland; Department of Oncology, University Hospital of Lausanne, 1011 
      Lausanne, Switzerland.
FAU - Gfeller, David
AU  - Gfeller D
AD  - Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland; Ludwig Cancer 
      Research Center, University of Lausanne, 1066 Epalinges, Switzerland.
FAU - Coukos, George
AU  - Coukos G
AD  - Ludwig Cancer Research Center, University of Lausanne, 1066 Epalinges, 
      Switzerland; Department of Oncology, University Hospital of Lausanne, 1011 
      Lausanne, Switzerland.
FAU - Xenarios, Ioannis
AU  - Xenarios I
AD  - Vital-IT, 1015 Lausanne, Switzerland; Swiss Institute of Bioinformatics, 1015 
      Lausanne, Switzerland.
FAU - Muller, Markus
AU  - Muller M
AD  - Vital-IT, 1015 Lausanne, Switzerland; Swiss Institute of Bioinformatics, 1015 
      Lausanne, Switzerland. Electronic address: Markus.Mueller@sib.swiss.
FAU - Bassani-Sternberg, Michal
AU  - Bassani-Sternberg M
AD  - Vital-IT, 1015 Lausanne, Switzerland; Swiss Institute of Bioinformatics, 1015 
      Lausanne, Switzerland. Electronic address: Michal.Bassani@chuv.ch.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180831
PL  - United States
TA  - Mol Cell Proteomics
JT  - Molecular & cellular proteomics : MCP
JID - 101125647
RN  - 0 (HLA Antigens)
RN  - 0 (Ligands)
RN  - 0 (Peptides)
RN  - 0 (Proteome)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Antigen Presentation/physiology
MH  - Cell Line, Tumor
MH  - Computational Biology/*methods
MH  - Exome
MH  - HLA Antigens/*metabolism
MH  - Humans
MH  - Ligands
MH  - Peptides/*genetics/*metabolism
MH  - Proteasome Endopeptidase Complex/*metabolism
MH  - Protein Binding
MH  - Protein Interaction Domains and Motifs
MH  - *Protein Splicing
MH  - Proteome
MH  - Signal Transduction
MH  - Tandem Mass Spectrometry
MH  - Exome Sequencing
PMC - PMC6283289
OTO - NOTNLM
OT  - Bioinformatics searching
OT  - De novo sequencing
OT  - Human Leukocyte Antigen
OT  - Immunology
OT  - Immunopeptidomics
OT  - Mass Spectrometry
OT  - Peptidomics
OT  - Proteasome-spliced peptides
COIS- Conflict of interest statement: I.B. is an employee of Adicet Bio Israel, Ltd. 
      All authors have no financial conflicts of interests.
EDAT- 2018/09/02 06:00
MHDA- 2019/10/31 06:00
PMCR- 2018/09/05
CRDT- 2018/09/02 06:00
PHST- 2018/05/22 00:00 [received]
PHST- 2018/08/27 00:00 [revised]
PHST- 2018/09/02 06:00 [pubmed]
PHST- 2019/10/31 06:00 [medline]
PHST- 2018/09/02 06:00 [entrez]
PHST- 2018/09/05 00:00 [pmc-release]
AID - S1535-9476(20)31999-X [pii]
AID - RA118.000877 [pii]
AID - 10.1074/mcp.RA118.000877 [doi]
PST - ppublish
SO  - Mol Cell Proteomics. 2018 Dec;17(12):2347-2357. doi: 10.1074/mcp.RA118.000877. 
      Epub 2018 Aug 31.