TY - JOUR
T1 - InvitroSPI and a large database of proteasome-generated spliced and non-spliced peptides
AU - Roetschke, Hanna P.
AU - Rodriguez-Hernandez, Guillermo
AU - Cormican, John A.
AU - Yang, Xiaoping
AU - Lynham, Steven
AU - Mishto, Michele
AU - Liepe, Juliane
N1 - Funding Information:
We thank the CRUK-KHP Cancer Centre and the CEMS of KCL for the MS measurements, A. Mansurkhodzhaev and W.T. Soh (MPI-NAT) for PRIDE’s file uploading, W. Paes and P. Borrow (Oxford) to provide technical information related to their original paper. This work was financed in part by: (i) Cancer Research UK [C67500/A29686], National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s as well as St Thomas’ NHS Foundation Trust and King’s College London and/or the NIHR Clinical Research Facility, CRUK City of London Centre (CoL) Award and CRUK-CoL development fund [CTRQQR-2021/100004] to MM; (ii) ERC-StG 945528 IMAP to JL. HPR was funded by the Manfred Eigen-Förderstiftung (Principles of Cancer Research - Stipend for an exceptional, independently working young scientist), and by King’s College London as part of the “Neuro-Immune Interactions in Health & Disease Wellcome Trust PhD Programme”. JAC is supported by the International Max-Planck Research School (IMPRS) for Genome Science.
Funding Information:
We thank the CRUK-KHP Cancer Centre and the CEMS of KCL for the MS measurements, A. Mansurkhodzhaev and W.T. Soh (MPI-NAT) for PRIDE’s file uploading, W. Paes and P. Borrow (Oxford) to provide technical information related to their original paper. This work was financed in part by: (i) Cancer Research UK [C67500/A29686], National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s as well as St Thomas’ NHS Foundation Trust and King’s College London and/or the NIHR Clinical Research Facility, CRUK City of London Centre (CoL) Award and CRUK-CoL development fund [CTRQQR-2021/100004] to MM; (ii) ERC-StG 945528 IMAP to JL. HPR was funded by the Manfred Eigen-Förderstiftung (Principles of Cancer Research - Stipend for an exceptional, independently working young scientist), and by King’s College London as part of the “Neuro-Immune Interactions in Health & Disease Wellcome Trust PhD Programme”. JAC is supported by the International Max-Planck Research School (IMPRS) for Genome Science.
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12/10
Y1 - 2023/12/10
N2 - Noncanonical epitopes presented by Human Leucocyte Antigen class I (HLA-I) complexes to CD8+ T cells attracted the spotlight in the research of novel immunotherapies against cancer, infection and autoimmunity. Proteasomes, which are the main producers of HLA-I-bound antigenic peptides, can catalyze both peptide hydrolysis and peptide splicing. The prediction of proteasome-generated spliced peptides is an objective that still requires a reliable (and large) database of non-spliced and spliced peptides produced by these proteases. Here, we present an extended database of proteasome-generated spliced and non-spliced peptides, which was obtained by analyzing in vitro digestions of 80 unique synthetic polypeptide substrates, measured by different mass spectrometers. Peptides were identified through invitroSPI method, which was validated through in silico and in vitro strategies. The peptide product database contains 16,631 unique peptide products (5,493 non-spliced, 6,453 cis-spliced and 4,685 trans-spliced peptide products), and a substrate sequence variety that is a valuable source for predictors of proteasome-catalyzed peptide hydrolysis and splicing. Potential artefacts and skewed results due to different identification and analysis strategies are discussed.
AB - Noncanonical epitopes presented by Human Leucocyte Antigen class I (HLA-I) complexes to CD8+ T cells attracted the spotlight in the research of novel immunotherapies against cancer, infection and autoimmunity. Proteasomes, which are the main producers of HLA-I-bound antigenic peptides, can catalyze both peptide hydrolysis and peptide splicing. The prediction of proteasome-generated spliced peptides is an objective that still requires a reliable (and large) database of non-spliced and spliced peptides produced by these proteases. Here, we present an extended database of proteasome-generated spliced and non-spliced peptides, which was obtained by analyzing in vitro digestions of 80 unique synthetic polypeptide substrates, measured by different mass spectrometers. Peptides were identified through invitroSPI method, which was validated through in silico and in vitro strategies. The peptide product database contains 16,631 unique peptide products (5,493 non-spliced, 6,453 cis-spliced and 4,685 trans-spliced peptide products), and a substrate sequence variety that is a valuable source for predictors of proteasome-catalyzed peptide hydrolysis and splicing. Potential artefacts and skewed results due to different identification and analysis strategies are discussed.
UR - http://www.scopus.com/inward/record.url?scp=85146100628&partnerID=8YFLogxK
U2 - 10.1038/s41597-022-01890-6
DO - 10.1038/s41597-022-01890-6
M3 - Article
C2 - 36627305
AN - SCOPUS:85146100628
VL - 10
JO - Scientific Data
JF - Scientific Data
IS - 1
M1 - 18
ER -
