HIV molecular immunology database

 

Hepitope: HLA-Enriched Possible Epitope

 

The Hepitope tool searches for hopeful-epitopes or "Hepitopes". The tool tests for HLA alleles that are enriched in a set of individuals that react with a set of peptides. This can be used in conjunction with ELF (Epitope Location Finder) to scan the peptides for known epitopes in the database and anchor motifs to help identify epitopes within a larger peptide fragment. See below for details about the input and output of the program.

 

Input

List of patient HLA alleles

Sample Input is shown. Click "Submit" to see output.

List of reactive peptides

Options

Sort peptides alphabetically by name Yes No
Search only reactive patient HLAs Yes No
Run the Epitope Location Finder for each peptide   Yes No

 

 


 

Details

To look for HLA enrichment in reactive individuals, we just do a 2 by 2 contingency table. We present four columns of data:

a
The number of individuals that carry the HLA allele and react with the peptide
b
The number of individuals that do not carry the HLA allele and react with the peptide
c
The number of individuals that carry the HLA allele and do not react with the peptide
d
The number of individuals that do not carry the HLA allele and do not react with the peptide

We then calculate the a one-sided Fishers exact test to determine if the distribution of those that carry the HLA allele among the reactive individuals is enriched for the given HLA more than would be expected by chance alone, in a fifth column. This test is conducted for every unique HLA found in the set of people that react with the peptide. The ELF program then could be used to rapidly search the database for known epitopes embedded in the peptide, and for anchor motifs for the epitope of interest. Links to the alignment of known epitopes can be quickly obtained, as well as the database entries regarding the epitopes.

The input requires two files:

The output provides a recapitulation of the input files and the results for each peptide, including a list of the HLA's of each patient.

Peptide Sequence HLA Type  a   b   c   d   P 
Gag1 MGARASVLSGGELDRWEK
B*1701 1 0 0 3 0.25000000
B*5703 1 0 0 3 0.25000000
Cw*0705 1 0 0 3 0.25000000
A*0201 1 0 1 2 0.50000000
Cw*0701 1 0 2 1 0.75000000
Patient HLA
Patient1 A*0201 A*0201 B*1701 B*5703 Cw*0701 Cw*0705

The columns a, b, c, and d are the four elements of the contingency table described above, and P is one-sided Fisher's exact p-value.

And so on for each peptide entered.

Questions or comments? Contact us at immuno@lanl.gov
 
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