SIF176D Prominence-to-Preeminence (P2PE) STEM Targeted Initiatives Fund

Immunology and Informatics for Precision ImmunoMedicine (iPRIME) in Cardiovascular Disease

Project Manager: Coleen McNamara

Approved: November 2021

Project Dates: 3/01/2022 – 2/28/2027

Total Funding: $5,500,000

Executive Summary

In collaboration with the Schools of Medicine, Engineering and Applied Science, Nursing, and Data Science, the goal of implement Precision ImmunoMedicine (iPRIME) is to designate UVA as the premier location for targeting the immune-system for research, diagnosis, prognosis and treatment of cardiovascular disease (CVD) using cutting edge technology, advanced clinical imaging, and innovative, sophisticated artificial intelligence. The team has collected substantial data from patient subjects and has the systems in place to recruit and obtain high dimensional immune system and imaging data and clinical outcomes on another 1000 CVD subjects over the next five years. The team has successfully used bioinformatics and machine learning in cohorts to develop algorithms to assist clinical decision making as a proof of concept. Melding all of these data and topics together will lead to fully realizing the potential preeminence for UVA in precision immunomedicine in CVD.

Progress:

The immunology, imaging, and informatics for precision immunomedicine for cardiovascular disease (CVD) (iPRIME) initiative met its first-year goals. The iPRIME team has been recruited and is working in the renovated space within the Carter Immunology Center. They recruited 274 (157 CAVA Cohort,117 CTA cohort) subjects and developed an end-to-end workflow that gathers consented patient blood samples, imaging and clinical data. A portion of the samples are processed for mass cytometry analysis which generates immune cell profiles. The remaining samples are biobanked for further studies. We established a process for investigators to apply for access to samples. The mass cytometry data is generated, assessed for quality and noise filtered by our specialists. They provide data to our bioinformatics team which has developed a mass cytometry integrative analysis pipeline. The team is analyzing and generating results for five EARLY WIN projects. Dr. Bekiranov and Dr. Aidong Zhang from Computer Science have developed an explainable machine learning/AI approach that classifies CVD patients according to risk using single cell immune data which will be adapted and incorporated into the iPRIME bioinformatics workflow. We are working with Joanna Loomba (Director of Informatics for iTHRIV) to generate iPRIME project sites and deposit data within the iTHRIV Research Data Commons. We started this at the pilot level. We awarded four teams with $100,000 and will showcase their work. These teams are performing innovative experiments and developing algorithms to address the role of the immune system in CVD and represent many divisions.  We launched our iPRIME Fellowship Award program to link graduate students in biomedical sciences to students in data science or computer science to foster collaborative work. We launched a website which advertises iPRIME, highlights achievements and is a portal for collaboration and information about how to apply for iPRIME faculty and student grants. Our EARLY WIN collaborations have led to successful funding of three grants (NIH, Leducq and CHRB), submission of another (NSF) and others that are being written for submission this year. We have published and submitted papers based on EARLY WIN projects. A number of postdoctoral researchers, graduate and undergraduate students working in the iPRIME PI, Faculty Seed Program PI and other iPRIME collaborator PI labs are now engaged in iPRIME research. We have rescheduled (due to the events of 11/13/2022) a symposium for April 18, 2023, that will showcase the work in this area across grounds, and introduce faculty and students to iPRIME.