CHI currently manages 26 active collaborations across 8 Institutes and the Clinical Center. These are divided into 3 stages: sample collection (8 studies), assay (9 studies), and write up (9 studies). An example is the CHAPLE study with Mike Lenardo, where a cohort of longitudinally sampled children with CD55 deficiency have been treated with eculizumab, a substitute complement inhibitor. CHI has performed SomaLogic analysis of peripheral blood serum, finding between cases and controls 96 proteins which differ significantly (FDR<0.05) prior to therapy, of which 36 proteins change significantly in cases within 1 week of therapy. Ongoing work will involve CyTOF phenotyping of PBL, in addition to stool microbiome analysis. This represents a study where high dimensional phenotyping can lead to better understanding of the patient pathology, may inform use of a nascent therapy, and give basic biology insight into, in this case, CD55 function and the mechanisms of complement inhibition. CHI also provides fee-for-service access to assays not otherwise accessible to NIH reseachers. The SomaLogic proteomic assay has been run for over 3000 samples, for 7 investigators, in the last year. To develop this capacity, a 35 marker mass cytometry immune phenotyping assay and analysis pipeline has been adapted for fee-for service deployment. To support CHIs mission we continue to develop infrastructure. For single cell sequencing technologies using the 10x plaform, we have developed CITE-Seq analysis and TCR sequencing. With mass cytometry, an assay has been established to quantify phosphorylation of 10 intracellular proteins, in addition to 20 cell phenotype markers, in response to 12 in vitro stimulation conditions. For flow cytometry, we have validated a 28 color cytometry panel on a new BD FACSymphony, and onboarded a spectral sorter. Throughout we are optimizing automation technologies, such as for cell staining (Tecan Fluent) and NGS library preparation (pipeline of QIAsymphony, Biomek FX, Agilent TapeStation and QIAgility). Going forward we are testing O-link as replacement for SomaLogic serum proteomic analysis, and exploring isolation and analysis of leukocytes from tissues.
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