METHOD TO MATCH ORGAN DONORS TO RECIPIENTS FOR TRANSPLANTATION

摘要

This invention describes an allogenomics mismatch scoring method that estimates the genomic incompatibility between potential organ donors and a transplant recipient. The allogenomics method addresses immunological concerns and compares genotype information from matched, or potential, donors and recipients. The allogenomics method uses genomic data available before transplantation and predicts kidney graft function for greater than three years after transplantation. The strength of the inverse correlation between pre-transplantation genomic mismatches and transplant organ function increases with the time after transplantation: a low allogenomics mismatch score correlates with better acceptance and function of a donor transplant over time.

主权项

1. A method for identifying at least one match among multiple potential organ donors for at least one recipient in need of a transplanted organ, where the method comprises:
(a) assaying to determine amino acid mismatches encoded by the donor genomes that at least one selected recipient immune system could recognize as non-self; (b) separately summing the number of amino acid mismatches for each donor compared to at least one selected recipient where the mismatches can be recognized as non-self by the selected recipient(s); (c) determining an allogenomics mismatch score Δ(r,d) for each selected recipient r and each donor d, which is a sum of mismatches as shown in Equation 1:Δ(r,d)=∑p∈Pδp[Grp=genotype(r,p),Gdp=genotype(d,p)]Equation1 where:
δp is defined in Equation 2;P is a set of all genomic positions of interest;p is a polymorphic site in a set P:Grp is the genotype of the recipient r at genomic site/position p;Gdp is the genotype of the donor d at site p;δp(Grp,Gdp)=∑a∈Gdp{0ifa∈Gr,p1otherwiseEquation2 where
a is an allele; and (d) identifying a match among the multiple potential organ donors for at least one recipient in need of a transplanted organ by identifying one or more donor with an allogenomics mismatch score that is below a threshold value, or by identifying the donor with the lowest allogenomics score for a selected recipient.