TY - GEN
T1 - How do amino acid mismatches affect the outcome of hematopoietic cell transplants? A structural perspective
AU - Yanover, Chen
AU - Malkki, Mari
AU - Gooley, Ted
AU - Petersdorf, Effie W.
AU - Bradley, Philip
PY - 2010/10/25
Y1 - 2010/10/25
N2 - The success of hematopoietic cell transplantation from an unrelated donor depends in part on the degree of Human Histocompatibility Leukocyte Antigen (HLA) matching between donor and patient. We present a structure-based analysis of HLA mismatching, focusing on individual amino acid mismatches and their effect on peptide binding specificity. Using molecular modeling simulations of HLA-peptide interactions, we find evidence that amino acid mismatches predicted to perturb peptide binding specificity are associated with higher risk of mortality in a large and diverse dataset of patient-donor pairs assembled by the International Histocompatibility Working Group in Hematopoietic Cell Transplantation consortium. Although preliminary, this analysis may represent a first step toward sequence-based prediction of relative risk for HLA allele mismatches.
AB - The success of hematopoietic cell transplantation from an unrelated donor depends in part on the degree of Human Histocompatibility Leukocyte Antigen (HLA) matching between donor and patient. We present a structure-based analysis of HLA mismatching, focusing on individual amino acid mismatches and their effect on peptide binding specificity. Using molecular modeling simulations of HLA-peptide interactions, we find evidence that amino acid mismatches predicted to perturb peptide binding specificity are associated with higher risk of mortality in a large and diverse dataset of patient-donor pairs assembled by the International Histocompatibility Working Group in Hematopoietic Cell Transplantation consortium. Although preliminary, this analysis may represent a first step toward sequence-based prediction of relative risk for HLA allele mismatches.
UR - http://www.scopus.com/inward/record.url?scp=77958048431&partnerID=8YFLogxK
U2 - 10.1145/1854776.1854893
DO - 10.1145/1854776.1854893
M3 - Conference contribution
AN - SCOPUS:77958048431
SN - 9781450304382
T3 - 2010 ACM International Conference on Bioinformatics and Computational Biology, ACM-BCB 2010
SP - 627
EP - 633
BT - 2010 ACM International Conference on Bioinformatics and Computational Biology, ACM-BCB 2010
T2 - 2010 ACM International Conference on Bioinformatics and Computational Biology, ACM-BCB 2010
Y2 - 2 August 2010 through 4 August 2010
ER -