Precision Health refers to employing molecular and/or clinical biomarkers to effectively match biomarkers in patients to therapies to improve therapeutic efficacy and minimize toxicity. Hence, precision health covers the translational continuum from mathematical modeling through cellular and in vivo models, and culminates in clinical interventions and assessment of those interventions on patient outcomes. We describe below the areas of research in this domain.
Human Factors Engineering
Eye-tracking studies help identify the strengths and weaknesses in content and form of molecular diagnostic (MDX) test reports which in turn inform clinical decision-making. Our collaborators include MedStar National Center for Human Factors Engineering. The ICBI team gurus that work in this research domain are Dr Subha Madhavan, Dr. Simina Boca, Dr. Peter McGarvey, Dr. Kristen Miller and Dr. Raj Ratwani.
Data curation, Standardization and Integration
To share and effectively utilize biomedical data, it needs to be integrated with different data types and annotated with metadata using standard terminologies and methods. Similarly biological objects such as genes, proteins, pathways, drug interactions, and treatments need to be culled from the literature and organized by their functions and interactions, as well as clinical significance through expert curation and automated methods including natural language processing – even the best-automated methods need quality training sets. Only organized data informs! ICBI team members actively participate in and lead large international consortium and crowdsourcing efforts including the Clinical Genome (ClinGen) Resource Somatic Cancer Working Group, GA4GH – Variant Interpretation for Cancer Consortium (VICC), VICC – Virtual Molecular Tumor Board project, Clinical Interpretations of Variants in Cancer (CIViC), Clinical Proteomics Tumor Analysis Consortium (CPTAC) and UniProt. Our current projects in this area include, MACE2K and CDGnet. ICBI celebrities involved in this effort include Dr. Peter McGarvey, Dr. Simina Boca, Dr Subha Madhavan, Dr. Robert Beckman and Shruti Rao.
The Georgetown Database of Cancer (G-DOC)
G-DOC is our Flagship precision medicine platform that enables the integrative analysis of multiple data types to understand disease mechanisms. G-DOC was designed and engineered to be a unique multi-omics data analysis resource for translational cancer research. It currently integrates clinical, transcriptomic, metabolomic, and systems-level analysis into a single, user-friendly cloud based platform. This integration allows users to identify trends and patterns in complex datasets. Our collaborators include Lombardi Cancer Center Programs and Shared Resources. ICBI superheroes involved in this work include Dr Subha Madhavan, Dr. Yuriy Gusev, Krithika Bhuvaneshwar and Anas Belouali
Our research work includes mathematical modeling by Dr. Robert Beckman, molecular modeling by Dr. Matthew McCoy, statistical modeling by Dr. Simina Boca, and computational modeling by Dr. Yuriy Gusev.
Dr. Beckman creates mathematical models of the evolution of cancer, both in the initial formation of a tumor and also under the influence of therapy. His models have predicted a number of features of tumor evolution that have subsequently been validated by large genomic datasets, and more recently resulted in new approaches for understanding the kinetics of resistance development. Further, they have led to the development of an alternative approach to precision therapy of cancers, dynamic precision medicine, that explicitly considers intratumoral heterogeneity and the dynamics of tumor evolution. Computational simulation of these models suggests that dynamic precision medicine has the potential to double median survival throughout oncology. Collaborations aimed at experimental validation are underway.
Protein Structure Modeling
Missense variants can alter protein function by disrupting wildtype interactions and dynamics, and predicting the functional impact of a given mutation has enormous translational applications. For example, understanding how specific variants differentially disrupt interactions with a library of targeted inhibitors can lead to improved therapeutic strategies. Dr. Matthew McCoy had developed the molecular simulation workflow SNP2SIM to simulate the dynamics of protein variant structures and quantify changes to the interaction with small molecules. Current research is focused on using the SNP2SIM workflow to integrate simulation generated features with experimental data to build predictive models of variant induced changes to specific molecular functions.
Multi omics integration
At ICBI, we apply a wide range of statistical and computational approaches such as machine learning, regression and correlation analysis, systems biology methods and tools such as pathway enrichment and network analysis and advanced computational methodologies for immuno-oncology for integration of molecular data with clinical attributes, correlating the results from high-throughput molecular platforms, tumor microenvironment, patient characteristics, drug response and outcomes to improve public health. As such, we collaborate with numerous experts in basic and translational biomedical sciences, cancer research, health educators, and other data scientists. The ICBI faculty and staff in this domain include Dr. Yuriy Gusev, Dr. Simina Boca, Dr. Matthew McCoy, and Krithika Bhuvaneshwar.
Clinical Trial Design
Dr. Robert Beckman has been championing Complex Innovative Designs (CID) in the clinical trial space, particularly in the areas of oncology and rare diseases. The designs have the potential to increase the efficiency and lower the cost of drug development. Development of new drugs for rare diseases, very difficult by conventional designs, is greatly facilitated by the use of CID. Dr. Beckman also studies decision analysis to further optimize the efficiency of both conventional and complex designs. He leads a 200 person international group devoted to developing and advocating for clinical trial designs that improve development efficiency for the benefit of patients. He has partnered with the US Food and Drug Administration, the European Medicines Agency, and the International Committee on Harmonization in these efforts to enhance patient access to life altering therapies.