Tellen D. Bennett

Tiffany J. Callahan, Ignacio J. Tripodi, Adrianne L. Stefanski et al. · berkeley, harvard

Translational research requires data at multiple scales of biological organization. Advancements in sequencing and multi-omics technologies have increased the availability of these data, but researchers face significant integration challenges. Knowledge graphs (KGs) are used to model complex phenomena, and methods exist to construct them automatically. However, tackling complex biomedical integration problems requires flexibility in the way knowledge is modeled. Moreover, existing KG construction methods provide robust tooling at the cost of fixed or limited choices among knowledge representation models. PheKnowLator (Phenotype Knowledge Translator) is a semantic ecosystem for automating the FAIR (Findable, Accessible, Interoperable, and Reusable) construction of ontologically grounded KGs with fully customizable knowledge representation. The ecosystem includes KG construction resources (e.g., data preparation APIs), analysis tools (e.g., SPARQL endpoints and abstraction algorithms), and benchmarks (e.g., prebuilt KGs and embeddings). We evaluated the ecosystem by systematically comparing it to existing open-source KG construction methods and by analyzing its computational performance when used to construct 12 large-scale KGs. With flexible knowledge representation, PheKnowLator enables fully customizable KGs without compromising performance or usability.

Tiffany J. Callahan, Adrianne L. Stefanski, Jordan M. Wyrwa et al.

Background: Common data models solve many challenges of standardizing electronic health record (EHR) data, but are unable to semantically integrate all the resources needed for deep phenotyping. Open Biological and Biomedical Ontology (OBO) Foundry ontologies provide computable representations of biological knowledge and enable the integration of heterogeneous data. However, mapping EHR data to OBO ontologies requires significant manual curation and domain expertise. Objective: We introduce OMOP2OBO, an algorithm for mapping Observational Medical Outcomes Partnership (OMOP) vocabularies to OBO ontologies. Results: Using OMOP2OBO, we produced mappings for 92,367 conditions, 8611 drug ingredients, and 10,673 measurement results, which covered 68-99% of concepts used in clinical practice when examined across 24 hospitals. When used to phenotype rare disease patients, the mappings helped systematically identify undiagnosed patients who might benefit from genetic testing. Conclusions: By aligning OMOP vocabularies to OBO ontologies our algorithm presents new opportunities to advance EHR-based deep phenotyping.

David J. Albers, Tell D. Bennett, Jana de Wiljes et al.

Identifying the effects of mechanical ventilation strategies and protocols in critical care requires analyzing data from heterogeneous patient-ventilator systems within the context of the clinical decision-making environment. This research develops a framework to help understand the consequences of mechanical ventilation (MV) and adjunct care decisions on patient outcome from observations of critical care patients receiving MV. Developing an understanding of and improving critical care respiratory management requires the analysis of existing secondary-use clinical data to generate hypotheses about advantageous variations and adaptations of current care. This work introduces a perspective of the joint patient-ventilator-care systems (so-called J6) to develop a scalable method for analyzing data and trajectories of these complex systems. To that end, breath behaviors are analyzed using evolutionary game theory (EGT), which generates the necessary quantitative precursors for deeper analysis through probabilistic and stochastic machinery such as reinforcement learning. This result is one step along the pathway toward MV optimization and personalization. The EGT-based process is analytically validated on synthetic data to reveal potential caveats before proceeding to real-world ICU data applications that expose complexities of the data-generating process J6. The discussion includes potential developments toward a state transition model for the simulating effects of MV decision using empirical and game-theoretic elements.

Tellen Bennett, Seth Russell, James King et al.

Interest in an electronic health record-based computational model that can accurately predict a patient's risk of sepsis at a given point in time has grown rapidly in the last several years. Like other EHR vendors, the Epic Systems Corporation has developed a proprietary sepsis prediction model (ESPM). Epic developed the model using data from three health systems and penalized logistic regression. Demographic, comorbidity, vital sign, laboratory, medication, and procedural variables contribute to the model. The objective of this project was to compare the predictive performance of the ESPM with a regional health system's current Early Warning Score-based sepsis detection program.