3.916667
#27
A STRUCTURED LANGUAGE FOR HLA TYPING IN BONE-MARROW TRANSPLANTATION.
Pedro Cano M.D. 1. 1 Laboratory Medicine, M.D. Anderson Cancer Center, Houston, TX, USA .
Project 2 (P2) is an attempt to create a structured language to manipulate HLA typing data in the context of bone-marrow transplantation (BMT). The complexity of HLA genetic typing comes from 1) the polymorphic variety of HLA genes, 2) the dynamic active changes of genetic material, and 3) the diploid presentation of genes in pairs. Tools in the form of both algorithms and data structures are required to manage this complexity. P2 is designed to meet this need. The interpretation of HLA typing consists in the comparison of a given haplotype to the distribution of all haplotypes in a given reference population. This comparison is the key to perform donor searches and to plan bone-marrow transplants. P2 provides functions to make, present and use these descriptions of HLA haplotypes in terms of where in the distribution of haplotypes in a reference population they fall. The difficulty of BMT is the difficulty of selecting a donor when no HLA-match is available. It can be shown that relative comparisons between donors leads to non-transitive ambiguities and suboptimal donor selections. To solve these ambiguities P2 provides a matching score function based on a geometric approach to HLA matching. In HLA typing, like in other high-complexity labs, steep curves representing the relationships of turn-around time and error rate to sample volume are characteristic. It is therefore essential for high-volume labs to build exact operations control into the design of testing procedures. P2 provides a rigorous cellular automata model to do so. We have reduced both the error rate and the turn-around-time significantly, and have identified three key elements in HLA typing automation: 1) formalisation of lab procedures, 2) operations control, and 3) waste reduction, that is, reduction in the use of unnecessary resources.