Web Tools
Computational Immunology

 

The Institute for Transfusion Medicine at Hanover Medical School is dedicated to providing web-based bioinformatic solutions to several of the current issues in immunology.

 

The HistoCheck webtool offers clinitians a way of investigating the structural differences between related HLA alleles, to help find the best donor/recipient match for hematopoietic stem cell transplation.

 

We are currently developing a tool for finding GvL-relevant peptides, called PeptideCheck. Allogeneic stem cell transplantations have the therapeutic effect of eliminating leukemia cells, with the danger of developing graft versus host disease. When donor and patient are HLA-identical, these effects are due to minor histocompatibility antigens, which are expressed from polymorphic genes. Identifing which genes and which peptides cause the GvL effect, without the development of GvHD is of great importance to immunotherapy, and is the goal of the PeptideCheck web tool.

 

HLA alleles are highly polymorphic, and there are thousands of known variants in the human population. Although this polymorphism can result from point mutations, it is mainly a product of recombination. To explore the relationships between different HLA alleles, we have developed a modular model of HLA. By breaking down the HLA binding groove into modules, we have been able to maximize the number of alleles for which peptide binding prediction is possible. The HLA Module Explorer (PeptideCheck) is a webtool, which allows one to investigate the relationships between HLA alleles on modular level.

 

Considering HLA allele and haplotype frequencies can be very useful when interpreting typing results and finding appropriate donors (HaploCheck). Simply knowing that a patient's haplotype is extremely rare can prevent futile registry searches. Considering allele frequency alone is insufficient, because a rare allele can be acceptable when it is found in its most common haplotype. Being aware of rare alleles and haplotypes is also an important factor in quality control. Furthermore, typing results in registries are often incomplete. In the case where there are two matching donors, but each donor typing is incomplete with respect to different alleles, then haplotype frequencies can help choose the donor who is most likely to be an exact match. Here we present HaploCheck, a web tool targeted at clarifying typing results based upon haplotype frequencies. The user enters the typing results for a patient, for which the cis/trans coupling is unknown. The result is a list of separated haplotypes, ordered by frequency. Very rare alleles and associations are highlighted to inform the user of potential problems when searching registries, or to identify potential typing errors. For the case that a single mismatch is unavoidable, the user is presented with a list of mismatch-containing haplotypes and their frequencies. This can not only prevent futile registry searches, but also enable the clinician to make decisions about mismatches permissively before initiating the registry search. Correct interpretation of HLA typing results in combination with known haplotype data is complicated, but effective and resource-efficient. The HaploCheck web tool drastically reduces the amount of additional research that a clinician must perform when conducting registry searches.