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Principal Investigator: JILL Allison HOLLENBACH
Organization: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
Fiscal Year: 2024
Award: $449,783
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY
The Human Leukocyte Antigen (HLA) region on human chromosome 6p21 is the most medically important region
of the human genome. Over 100 infectious, autoimmune and pharmacological disease phenotypes and cancers
are associated with genetic variation of HLA, and matching of HLA genotypes is required for bone marrow and
solid organ transplantation. HLA molecules have functional interactions with Killer cell Immunoglobulin-like
Receptor (KIR) molecules, also recognized to play critical roles in transplantation and disease. The genes
encoding these molecules are highly polymorphic and display extensive structural variation relative to other
genomic regions. Recognizing the need to consolidate complex data from a broad field, in the prior project
periods we developed a suite of tools and programs for the standardized analysis, collection, exchange and
storage (ACES) of all current and future immunogenomic data. These tools serve to fill gaps in genomic data-
management and analysis tools, which are primarily designed for use with single nucleotide polymorphism (SNP)
and whole-genome and whole-exome sequence (WG/ES) data, and do not support the highly polymorphic
genetic data characterized by the immunogenomic loci and other highly polymorphic genetic systems. Our
standards and tools have been widely adopted by the immunogenomics community, but there remains an urgent
and unmet need for integrated, easy-to use, clinical-grade tools that unify immunogenomic genotype, SNP and
WG/ES data, while anticipating future genomic data formats. In the previous project periods, we have made
substantial progress on the development of these tools and resources, which are designed to maximize the
ongoing utility of immunogenomic data for clinical and basic research science. In the proposed project period,
we will advance the development of these tools, expanding their scope and improving ease of use, centralizing
their availability and enabling interoperability with electronic medical record (EMR) systems, and making them
available adjacent to these highly complex datasets for application in translational medicine. We will expand the
utility of our tools and services to accommodate additional data types and analytical methods, as well as
integrating across methods. Building on our development of an infrastructure to support transmission of HLA
data using HL7 FHIR resources, we will work to incorporate these resources into our data management tools
and pipeline. Finally, we will build on an infrastructure developed to support aggregation and standardized
analysis of HLA data in the context of COVID-19 to support additional data types and disease phenotypes for
immunogenomic disease association studies. By integrating these resources, and other tools and services we
have developed, and empowering them to generate FHIR messages, the products of these immunogenomic
ACES resources can be made available and accessible to researchers and within health systems, improving our
understanding of immunogenomics in human health and facilitating application for translational medicine.
Terms: <6p21><Address><Adopted><Advanced Development><Amino Acid Motifs><Autoimmune><Basic Research><Basic Science><Big Data><BigData><Bone Marrow><Bone Marrow Reticuloendothelial System><CD94 Antigen><COVID-19><COVID-19 antigen><CV-19><Cancers><Chromosome 19><Chromosome 6><Clinical><Clinical Data><Clinical Research><Clinical Study><Code><Coding System><Collection><Communication><Communities><Complex><Computer software><Computerized Medical Record><Copy Number Polymorphism><Coronavirus Infectious Disease 2019><Data><Data Analyses><Data Analysis><Data Bases><Data Set><Databases><Development><Disease><Disorder><EMR system><Electronic Medical Record><FHIR><Fast Healthcare Interoperability Resources><Fostering><Future><Future Generations><Gene variant><Genes><Genetic><Genetic Diversity><Genetic Variation><Genomic Segment><Genotype><Goals><Grafting Procedure><HIPAA><HL-A Antigens><HLA Antigens><Health><Health Insurance Portability and Accountability Act><Health Status><Health system><Housing><Human><Human Chromosomes><Human Genome><Human Leukocyte Antigens><Immune><Immune Globulins><Immunes><Immunogenetics><Immunogenomics><Immunoglobulins><Informatics><Infrastructure><Integrated Health Care Systems><Investigators><K Cells><KLRD1 Protein><Kennedy Kassebaum Act><Killer Cell Lectin-Like Receptor Subfamily D, Member 1><Killer Cell Lectin-Like Receptor Subfamily D, Member 1 Isoforms 1, 2><Killer Cell Lectin-Like Receptor Subfamily D, Member 1 Protein><Killer Cells><Kp43 antigen><Leukocyte Antigens><Level of Health><Ligands><Malignant Neoplasms><Malignant Tumor><Medical><Metadata><Methods><Modern Man><Modernization><NK Cell Receptor><NK receptor><Natural Killer Cells Antigen CD94><Organ Transplantation><Organ Transplants><PL 104-191><PL104-191><Play><Protein Motifs><Public Law 104-191><Receptor Gene><Receptor Protein><Reporting><Research><Research Personnel><Research Resources><Researchers><Resources><Rest><Role><SARS-CoV-2 antigen><SNP genotyping><Science><Services><Single Base Polymorphism><Single Nucleotide Polymorphism><Software><Solid><Standardization><System><Transmission><Transplantation><United States Health Insurance Portability and Accountability Act><Variant><Variation><Work><allele variant><allelic variant><analytical method><bench bed side><bench bedside><bench to bed side><bench to bedside><bench to clinic><bench to clinical practice><clinical phenotype><complex data><copy number variant><copy number variation><coronavirus disease 2019><coronavirus disease 2019 antigen><coronavirus disease-19><coronavirus infectious disease-19><data base><data format><data interpretation><data management><design><designing><developmental><disease phenotype><electronic data><electronic medical record system><electronic medical system><empowerment><entire genome><exome><exomes><experience><full genome><genetic variant><genome segment><genomic data><genomic data-set><genomic dataset><genomic region><genomic variant><health care management><health level><health management><healthcare management><human data><human disease><human whole genome><improved><infrastructure development><integrated health system><integrated healthcare systems><integrated system of care><interoperability><malignancy><meta data><neoplasm/cancer><next generation><novel><open source><organ allograft><organ graft><organ xenograft><pharmacologic><precision medicine><precision-based medicine><programs><rare allele><rare mutation><rare variant><receptor><severe acute respiratory syndrome coronavirus 2 antigen><single nucleotide polymorphism genotyping><single nucleotide variant><social role><tool><tool development><translational applications><translational medicine><transmission process><transplant><whole genome>