Building a knowledgebase that integrates multiple data repositories requires the concepts, relationships, and data schemas/formats to be harmonized across those repositories. One technique is designing a common data model (CDM) that encompasses all concepts and relationships, transforming the data into the CDM, and utilizing ontologies to provide shared semantics.
The Adaptive Immune Receptor Repertoire Knowledge Commons (AKC) is a publicly accessible repository that integrates data and knowledge about 1) adaptive immune receptors (AIRs) and AIR repertoires from the AIRR Data Commons, 2) AIR germline allele, genotype, haplotype, and population genetic data from the OGRDB and VDJbase, and 3) AIR specificity data from the IEDB and IRAD. We designed a CDM for the AKC based upon the Ontology for Biomedical Investigations, a community standard for scientific data integration, and we used the LinkML data modeling language for implementation.
The AKC provides a consistent CDM for study, subject, and sample information; immune exposures and other study events; sample collection; assays and processing; and data processing and analysis workflows. The CDM also provides adaptive immunity domain knowledge for chains, receptors, antigens, epitopes, and MHC/HLA. LinkML’s flexible data modeling language allows for existing data standards, such as the AIRR Standards, and ontologies from the OBO Foundry to be directly incorporated.
The foundation of the AKC is data integrated from these community-supported repositories and harmonized around a CDM based on widely adopted ontologies and data standards. The AKC assembles the critical mass of data required to develop highly accurate predictive algorithms for long-standing questions of critical importance (e.g., predicting AIR specificity, determining the contribution of AIR germline polymorphisms to disease propensity) and to ask questions across a large and diverse set of subjects with a variety of health and disease phenotypes.
The research described is supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award number U24AI177622.
Computational and Systems Immunology (COMP)
Scott Christley, Felix Breden, Kevin A. Burns et al.· Journal of Immunology· 0 citations
Communication between immune cells through direct contact is a critical feature of immune responses. Our previous work has highlighted that a significant fraction of immune cell doublets detected in non-imaging flow cytometry are not technical artifacts, and instead hold biological relevance. In particular, using non-imaging FACS (fluorescence-activated cell sorting), we have recently shown that circulating T cell-monocyte complexes during infection hold transcriptomic signatures of active immune interactions. However, conventional non-imaging FACS lacks the spatial resolution necessary to characterize doublets accurately.
In this study, we employed the recently commercialized FACSDiscoverTM S8 spectral imaging cell sorter to characterize different phenotypes of circulating T cell-monocyte complexes in a cohort of patients with tuberculosis. Using various combinations of imaging parameters, we found that T cell-monocyte doublets can be classified as either synaptic or coincidental. Synaptic doublets were defined by high spatial overlap between the two cells forming complexes, representing true biological conjugates. In contrast, coincidental doublets were non-interacting cells but in close proximity during acquisition, thus representing technical artifacts rather than biological interactions. For each patient, synaptic and coincidental T cell-monocyte doublets were sorted, resulting in physical separation of the two cells forming the doublet, and processed for single-cell droplet sequencing.
Sorting and single-cell sequencing analysis confirmed that synaptic doublets carried unique biological gene signatures associated with high metabolic activity and immune activation, while coincidental doublets resembled singlet T cells and monocytes.
Thus, image-based cell sorting provides unprecedented granularity in the study of immune doublets and enrichment for biological doublets over technical artifacts.
The Tullie and Rickey Families SPARK Awards for Innovations in Immunology, National Institute of Allergy and Infectious Diseases, Human Immunology Project Consortium, The Conrad Prebys Foundation
Immune Response Regulation: Cellular Mechanisms (IRC)
Ning-Xin Kang, Cheryl Kim, Thomas J. Scriba et al.· Journal of Immunology· 0 citations
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