GRIMM: GRaph IMputation and matching for HLA genotypes.

Motivation: For over 10 years allele-level HLA matching for bone marrow registries has been performed in a probabilistic context. HLA typing technologies provide ambiguous results in that they could not distinguish among all known HLA alleles equences; therefore registries have implemented matching algorithms that provide lists of donor and cord blood units ordered in terms of the likelihood of allele-level matching at specific HLA loci. With the growth of registry sizes, current match algorithm implementations are unable to provide match results in real time.

Chromosome Y-encoded antigens associate with acute graft-versus-host disease in sex-mismatched stem cell transplant.

Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a curative option for blood cancers, but the coupled effects of graft-versus-tumor and graft-versus-host disease (GVHD) limit its broader application. Outcomes improve with matching at HLAs, but other factors are required to explain residual risk of GVHD. In an effort to identify genetic associations outside the major histocompatibility complex, we conducted a genome-wide clinical outcomes study on 205 acute myeloid leukemia patients and their fully HLA-A-, HLA-B-, HLA-C-, HLA-DRB1-, and HLA-DQB1-matched (10/10) unrelated donors.