DTU Health Tech
Department of Health Technology
This link is for the general contact of the DTU Health Tech institute.
If you need help with the bioinformatics programs, see the "Getting Help" section below the program.
The NetMHCpan-4.1 server predicts binding of peptides to any MHC molecule of known sequence using artificial neural networks (ANNs). The method is trained on a combination of more than 850,000 quantitative Binding Affinity (BA) and Mass-Spectrometry Eluted Ligands (EL) peptides. The BA data covers 170 MHC molecules from human (HLA-A, B, C, E), mouse (H-2), cattle (BoLA), primates (Patr, Mamu, Gogo), swine (SLA) and equine (Eqca). The EL data covers 177 MHC molecules from human (HLA-A, B, C, E), mouse (H-2), cattle (BoLA), primates (Patr, Mamu, Gogo), swine (SLA), equine (Eqca) and dog (DLA). Furthermore, the user can obtain predictions to any custom MHC class I molecule by uploading a full length MHC protein sequence. Predictions can be made for peptides of any length.
Note, as of 28/7/2020 the server has been updated (retrained on data resolving a curation error in the IEDB for a single allele (SA) eluted ligand H2-Db/H2-Kb data set. This recuration only affected ~2000 H2 data points, but has minor impacts on predictions for all MHC's.
To access the earlier version of NetMHCpan-4.1 click here version 4.1a
Note also, if you have installed the earlier version of NetMHCpan-4.1, click her e to download the updated data file data.tar.gz, and a file with the update test directory test.tar.gz.
The server returns as default the likelihood of a peptide being a natural ligand of the selected MHC(s). If selected, also the predicted binding affinity is rseported.
New in this version: together with Binding Affinity (BA) data, the method has now been trained on EL data from Single Allele (SA, peptides annotated to a single MHC) and Multi Allele (MA, peptides annotated to multiple MHCs) sources. The use of EL MA data is possible due to an upgrade af NNAlign (the core algorithm of NetMHCpan) called NNALign_MA (PMID: 31578220), which enables pseudo-labelling.
View the version history of this server. All previous versions are available online, for comparison and reference.
The project is a collaboration between CBS, and LIAI.
For publication of results, please cite:
Data resources used to develop this server was obtained from
Would you prefer to run NetMHCpan at your own site? NetMHCpan v. 4.1 is available as a stand-alone software package, with the same functionality as the service above. Ready-to-ship packages exist for the most common UNIX platforms. There is a download tap for academic users; other users are requested to contact CBS Software Package Manager at health-software@dtu.dk.
# NetMHCpan version 4.1 # Tmpdir made /usr/opt/www/webface/tmp/server/netmhcpan/5E4EEA2C000053D26D7D1DEF/netMHCpanYdWfgb # Input is in FSA format # Peptide length 8,9,10,11,12 # Make Eluted ligand likelihood predictions HLA-A03:01 : Distance to training data 0.000 (using nearest neighbor HLA-A03:01) # Rank Threshold for Strong binding peptides 0.500 # Rank Threshold for Weak binding peptides 2.000 ------------------------------------------------------------------------------------------------------------ Pos HLA Peptide Core Of Gp Gl Ip Il Icore Identity Score_EL Rnk_EL BindLevel ------------------------------------------------------------------------------------------------------------ 15 HLA-A*03:01 HQAAMQMLK HQAAMQMLK 0 0 0 0 0 HQAAMQMLK Gag_180_209 0.6594640 0.259 <= SB 14 HLA-A*03:01 GHQAAMQMLK GQAAMQMLK 0 1 1 0 0 GHQAAMQMLK Gag_180_209 0.2451190 1.084 <= WB 13 HLA-A*03:01 GGHQAAMQMLK GQAAMQMLK 0 1 2 0 0 GGHQAAMQMLK Gag_180_209 0.1045310 1.977 <= WB 12 HLA-A*03:01 VGGHQAAMQMLK VQAAMQMLK 0 1 3 0 0 VGGHQAAMQMLK Gag_180_209 0.0245250 4.089 7 HLA-A*03:01 TMLNTVGGH TMLNTVGGH 0 0 0 0 0 TMLNTVGGH Gag_180_209 0.0194210 4.545 15 HLA-A*03:01 HQAAMQMLKE HQAAMQMLK 0 0 0 0 0 HQAAMQMLK Gag_180_209 0.0083750 6.588 16 HLA-A*03:01 QAAMQMLK QAA-MQMLK 0 0 0 3 1 QAAMQMLK Gag_180_209 0.0042090 8.777 8 HLA-A*03:01 MLNTVGGHQ MLNTVGGHQ 0 0 0 0 0 MLNTVGGHQ Gag_180_209 0.0029890 10.119 21 HLA-A*03:01 MLKETINEE MLKETINEE 0 0 0 0 0 MLKETINEE Gag_180_209 0.0015830 13.034 11 HLA-A*03:01 TVGGHQAAM TVGGHQAAM 0 0 0 0 0 TVGGHQAAM Gag_180_209 0.0013180 14.043
The prediction output for each molecule consists of the following columns:
Three amino acid sequences are reported for each row of predictions:
The Peptide is the complete amino acid sequence evaluated by NetMHCpan. Peptides are the
full sequences submitted as a peptide list, or the result of digestion of source proteins (Fasta submission)
The iCore is a substring of Peptide, encompassing
all residues between P1 and P-omega of the MHC. For all intents and purposes, this is the minimal candidate
ligand/epitope that should be considered for further validation.
The Core is always 9 amino acids long,
and is a construction used for sequence aligment and identification of binding anchors.
MAIN REFERENCE
NetMHCpan-4.1 and NetMHCIIpan-4.0: Improved predictions of MHC antigen presentation by concurrent motif deconvolution and integration of MS MHC eluted ligand data
Birkir Reynisson 1*, Bruno Alvarez 2*, and Morten Nielsen1,3
Accepted for publication, NAR webserver issue 2020
Major Histocompatibility Complex (MHC) molecules are expressed on the cell
surface, where they present peptides to T cells, which gives them a key
role in the development of T cell immune responses. MHC molecules come in
two main variants: MHC Class I (MHC-I) and MHC Class II (MHC-II). MHC-I
predominantly present peptides derived from intracellular proteins,
whereas MHC-II predominantly presents peptides from extracellular
proteins. In both cases, the binding between MHC and antigenic peptides
is the most selective step in the antigen presentation pathway. Therefore,
the prediction of peptide binding to MHC is a powerful utility to predict
the possible specificity of a T cell immune response. Commonly MHC binding
prediction tools are trained on binding affinity or mass spectrometry
eluted ligands. Recent studies have however demonstrated how the
integration of both data types can boost predictive performances. Inspired
by this, we here present NetMHCpan-4.1 and NetMHCIIpan-4.0, two
web-servers created to predict binding between peptides and MHC-I and
MHC-II, respectively. Both methods exploit tailored machine learning
strategies to integrate different training data types, resulting in
state-of-the-art performance and outperforming their competitors. The
servers are available at http://www.cbs.dtu.dk/services/NetMHCpan-4.1/
and http://www.cbs.dtu.dk/services/NetMHCIIpan-4.0/.
Vanessa Jurtz 1, Sinu Paul 2, Massimo Andreatta 3, Paolo Marcatili 1, Bjoern Peters 2, and Morten Nielsen1,3
The Journal of Immunology (2017) ji1700893; DOI: 10.4049/jimmunol.1700893
Full text
[PDF]
1
Department of Bio and Health Informatics, Technical University of Denmark, DK-2800 Lyngby, Denmark
2
Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, CA92037 La Jolla, USA
3
Instituto de Investigaciones Biotecnologicas, Universidad Nacional de San Martin, Buenos Aires, Argentina
Cytotoxic T cells are of central importance in the immune system’s response to disease.
They recognize defective cells by binding to peptides presented on the cell surface by MHC class I molecules.
Peptide binding to MHC molecules is the single most selective step in the Ag-presentation pathway.
Therefore, in the quest for T cell epitopes, the prediction of peptide binding to MHC molecules has attracted widespread attention.
In the past, predictors of peptide–MHC interactions have primarily been trained on binding affinity data.
Recently, an increasing number of MHC-presented peptides identified by mass spectrometry have been reported containing information about
peptide-processing steps in the presentation pathway and the length distribution of naturally presented peptides.
In this article, we present NetMHCpan-4.0, a method trained on binding affinity and eluted ligand data
leveraging the information from both data types. Large-scale benchmarking of the method demonstrates an
increase in predictive performance compared with state-of-the-art methods when it comes to identification of
naturally processed ligands, cancer neoantigens, and T cell epitopes.
NetMHCpan-3.0; improved prediction of binding to MHC class I molecules integrating information from multiple receptor and peptide length data sets
Morten Nielsen1,2 and Massimo Andreatta1
Genome Medicine (2016): 8:33
1Instituto de Investigaciones Biotecnologicas, Universidad Nacional de San Martin, Buenos Aires, Argentina
2Center for Biological Sequence Analysis,
Technical University of Denmark,
DK-2800 Lyngby, Denmark
Binding of peptides to MHC class I molecules (MHC-I) is essential for antigen presentation to cytotoxic T-cells. Here, we demonstrate how a simple alignment step allowing insertions and deletions in a pan-specific MHC-I binding machine-learning model enables combining information across both multiple MHC molecules and peptide lengths. This pan-allele/pan-length algorithm significantly outperforms state-of-the-art methods, and captures differences in the length profile of binders to different MHC molecules leading to increased accuracy for ligand identification. Using this model, we demonstrate that percentile ranks in contrast to affinity-based thresholds are optimal for ligand identification due to uniform sampling of the MHC space.
NetMHCpan - MHC class I binding prediction beyond humans
Hoof I1,
Peter B3,
Sidney J3,
Pedersen LE2
Lund O1,
Buus S2,
Nielsen M1
Immunogenetics. (2009) Jan;61(1):1-13.
1Center for Biological Sequence Analysis,
Technical University of Denmark,
DK-2800 Lyngby, Denmark
2Division of Experimental Immunology,
Institute of Medical Microbiology and Immunology,
University of Copenhagen, Denmark
3La Jolla Institute for Allergy and Immunology, San Diego, California, United States of America
Binding of peptides to major histocompatibility complex (MHC) molecules is the single most selective step in the recognition of pathogens by the cellular immune system. The human MHC genomic region (called HLA) is extremely polymorphic comprising several thousand alleles, each encoding a distinct MHC molecule. The potentially unique specificity of the majority of HLA alleles that have been identified to date remains uncharacterized. Likewise, only a limited number of chimpanzee and rhesus macaque MHC class I molecules have been characterized experimentally. Here, we present NetMHCpan-2.0, a method that generates quantitative predictions of the affinity of any peptide-MHC class I interaction. NetMHCpan-2.0 has been trained on the hitherto largest set of quantitative MHC binding data available, covering HLA-A and HLA-B, as well as chimpanzee, rhesus macaque, gorilla, and mouse MHC class I molecules. We show that the NetMHCpan-2.0 method can accurately predict binding to uncharacterized HLA molecules, including HLA-C and HLA-G. Moreover, NetMHCpan-2.0 is demonstrated to accurately predict peptide binding to chimpanzee and macaque MHC class I molecules. The power of NetMHCpan-2.0 to guide immunologists in interpreting cellular immune responses in large out-bred populations is demonstrated. Further, we used NetMHCpan-2.0 to predict potential binding peptides for the pig MHC class I molecule SLA-1*0401. Ninety-three percent of the predicted peptides were demonstrated to bind stronger than 500 nM. The high performance of NetMHCpan-2.0 for non-human primates documents the method's ability to provide broad allelic coverage also beyond human MHC molecules. The method is available at http://www.cbs.dtu.dk/services/NetMHCpan.
PMID: 19002680
Here, you will find the data set used for evaluation of NetMHCpan-4.1 and NetMHCIIpan-4.0 methods.
HLA-A02:02
HLA-A02:05
HLA-A02:06
HLA-A02:11
HLA-A11:01
HLA-A23:01
HLA-A25:01
HLA-A26:01
HLA-A30:01
HLA-A30:02
HLA-A32:01
HLA-A33:01
HLA-A66:01
HLA-A68:01
HLA-B07:02
HLA-B08:01
HLA-B14:02
HLA-B15:01
HLA-B15:02
HLA-B15:03
HLA-B15:17
HLA-B18:01
HLA-B35:03
HLA-B37:01
HLA-B38:01
HLA-B40:01
HLA-B40:02
HLA-B45:01
HLA-B46:01
HLA-B53:01
HLA-B58:01
HLA-C03:03
HLA-C05:01
HLA-C07:02
HLA-C08:02
HLA-C12:03
NetMHCpan-4.1 and NetMHCIIpan-4.0: Improved predictions of MHC antigen presentation by concurrent motif deconvolution and integration of MS MHC eluted ligand data
Submitted 2020.
Please click on the version number to activate the corresponding server (if available).
4.1 |
Online since 10 Dec 2019. New in this version:
Publication:
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4.0 |
Online since 5 Sep 2017. New in this version:
Publication:
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3.0 |
Online since 10 Feb 2016. New in this version:
Publication:
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2.8 |
Online since 26 Feb 2013. New in this version:
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2.4 |
Online since 18 Dec 2010. New in this version:
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2.3 |
Online since 08 Sept 2010. New in this version:
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2.2 |
Online since 01 Sept 2009. New in this version:
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2.1 |
Online since 06 April 2009. New in this version:
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2.0 |
Online since 24 June, 2008. New in this version:
Publication:
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1.1 |
Online from March 2007 until 24 of June, 2008. New in this version:
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1.0 |
Original version (online version until March 2007):
Publication:
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If you need help regarding technical issues (e.g. errors or missing results) contact Technical Support. Please include the name of the service and version (e.g. NetPhos-4.0) and the options you have selected. If the error occurs after the job has started running, please include the JOB ID (the long code that you see while the job is running).
If you have scientific questions (e.g. how the method works or how to interpret results), contact Correspondence.
Correspondence:
Technical Support: