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Tutorials

I. Architecture of HLAsupE
II. Definition of HLA supertypes
III. Usage of HLAsupE
    i. Search for HLA supertype-specific epitopes or peptides
    ii. Map HLA supertype-specific epitopes or peptides on an input protein sequence
    iii. Search for mutated analogues of an input peptide
    iv. Search for the promiscuous peptides presented by HLA molecules across supertypes
IV. Notes

Architecture of HLAsupE

Definition of HLA supertypes in HLAsupE

The HLA class I supertypes for the HLA-A and B loci used here were defined by Sidney et al (2008), and the supertypes used for the HLA-C loci were based on the classification presented by Doytchinova (2004). The HLA class II supertypes used were consistent with Doytchinova’s definition (2005). Due to the relatively low number of HLA-DPA and DPB alleles with available peptide data, all available HLA-DPA and DPB alleles were classified into one DP supertype. The available supertypes and corresponding alleles can be found on the download page of HLAsupE.
Ref:
Sidney J, Peters B, Frahm N, Brander C, Sette A. HLA class I supertypes: a revised and updated classification. BMC Immunol. 2008 Jan 22;9:1
Doytchinova, I.A., Guan, P., Flower, D.R. (2004) Identifiying human MHC supertypes using bioinformatic methods. J Immunol, 172, 4314-4323.
Doytchinova, I.A., Flower, D.R. (2005) In silico identification of supertypes for class II MHCs. J Immunol, 174, 7085-7095.


Usage of HLAsupE

Search for HLA suppertype specific epitopes or peptidese

peptide sequence”: amino acid sequence coding with uppercase letters. example : "FLPSDFFPSV"
"HLA supertype": 14 HLA-I and 10 HLA-II supertypes are available.
Once a supertype is selected, the corresponding alleles belonging to this supertype are given. Users can choose at most five alleles to define their query for peptides that can bind or not to these alleles. Users also can search for supertype-specific peptides from a specific species by "selecting the source species". Such as “Hepatitis B virus”, “Influenza B virus” et.al.
In the output page, P, N and C represent the positive, negative and contradictory record, respectively.


Map HLA supertype-specific epitopes or peptides on an input protein sequence

Search for the HLA supertype-specific epitopes or binding peptides by protein sequence, the protein name could give an arbitrary name. The protein sequence should be a plain sequence. Such as:
MDIDPYKEFGATVELLSFLPSDFFPSVRDLLDTASALYREALESPEHCSPHHTALRQAILCWGELMTLATWVGVNLED
PASRDLVVSYVNTNMGLKFRQLLWFHISCLTFGRETVIEYLVSFGVWIRTPPAYRPPNAPILSTLPETTVVRRRGRSP
RRRTPSPRRRRSQSPRRRRSQSRESQC
peptides with positive results in HLAsupE are mapped onto this protein sequence. The starting position, length, sequence and supertype-restriction of matched peptides will be listed in the results


Search for mutated analogues of an input peptide

Search for the mutated analogues of an input peptide, amino acid sequence coding with uppercase letters. example : "FLPSDFFPSV".
Options:
“substring”, peptides that including the input sequence
“mutated analogues”, the mutated analogues of input sequence, here the analogues were defined as peptide that had no more than two different amino acid from the input sequence.


Search for promiscuous peptides presented by HLA molecules across supertypes

Search for promiscuous peptides to alleles across HLA supertypes by the supertyps or source species,


NOTES

HLAsupE and HLAsupB

The query tools provided in the home page of HLAsupE aim to search for supertype-specific epitopes (T-cell activities), whereas the query tools for supertype-specific binding peptides (MHC-binding data) are provided in HLAsupB.


Epitopes with the restrictions of serological HLA molecules

The peptides presented by serological proteins were difficult to integrate into the supertype-specific dataset with an exact allele restriction. These data were only maintained in the T-cell activity and HLA-peptide binding data blocks; as a result, these peptide data can be displayed when a user inspects the detailed activity of a specific peptide, but a direct query of these peptides is currently unavailable in HLAsupE


Frequency of alleles

The distribution of HLA genes in the human population varies with ethnicity and region. The frequency of alleles in a specific population should be taken into account. At present, Allele Frequency Net Database (AFND) and Population Coverage tool have been built to address this issue.
Allele Frequency Net Database (AFND): http://www.allelefrequencies.net/
Population Coverage tool: http://tools.iedb.org/tools/population/iedb_input


Update

We will continue to update our database by extracting and curating HLA-restricted peptide data from all available epitope databases and published literature. We also encourage researchers to submit their own data to our database via email to wangshufeng81@hotmail.com.



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contact: wangshufeng81@hotmail.com