Genomic considerations for FHIR®; eMERGE implementation lessons.

Structured representation of clinical genetic results is necessary for advancing precision medicine. The Electronic Medical Records and Genomics (eMERGE) Network's Phase III program initially used a commercially developed XML message format for standardized and structured representation of genetic results for electronic health record (EHR) integration. In a desire to move towards a standard representation, the network created a new standardized format based upon Health Level Seven Fast Healthcare Interoperability Resources (HL7® FHIR®), to represent clinical genomics results. These new standards improve the utility of HL7® FHIR® as an international healthcare interoperability standard for management of genetic data from patients. This work advances the establishment of standards that are being designed for broad adoption in the current health information technology landscape.

Data-driven discovery of a novel sepsis pre-shock state predicts impending septic shock in the ICU.

Septic shock is a life-threatening condition in which timely treatment substantially reduces mortality. Reliable identification of patients with sepsis who are at elevated risk of developing septic shock therefore has the potential to save lives by opening an early window of intervention. We hypothesize the existence of a novel clinical state of sepsis referred to as the "pre-shock" state, and that patients with sepsis who enter this state are highly likely to develop septic shock at some future time. We apply three different machine learning techniques to the electronic health record data of 15,930 patients in the MIMIC-III database to test this hypothesis. This novel paradigm yields improved performance in identifying patients with sepsis who will progress to septic shock, as defined by Sepsis- 3 criteria, with the best method achieving a 0.93 area under the receiver operating curve, 88% sensitivity, 84% specificity, and median early warning time of 7 hours. Additionally, we introduce the notion of patient-specific positive predictive value, assigning confidence to individual predictions, and achieving values as high as 91%. This study demonstrates that early prediction of impending septic shock, and thus early intervention, is possible many hours in advance.

Metadata-driven Clinical Data Loading into i2b2 for Clinical and Translational Science Institutes.

Clinical and Translational Science Award (CTSA) recipients have a need to create research data marts from their clinical data warehouses, through research data networks and the use of i2b2 and SHRINE technologies. These data marts may have different data requirements and representations, thus necessitating separate extract, transform and load (ETL) processes for populating each mart. Maintaining duplicative procedural logic for each ETL process is onerous. We have created an entirely metadata-driven ETL process that can be customized for different data marts through separate configurations, each stored in an extension of i2b2 's ontology database schema. We extended our previously reported and open source Eureka! Clinical Analytics software with this capability. The same software has created i2b2 data marts for several projects, the largest being the nascent Accrual for Clinical Trials (ACT) network, for which it has loaded over 147 million facts about 1.2 million patients.

Computing network-based features from physiological time series: application to sepsis detection.

Sepsis is a systemic deleterious host response to infection. It is a major healthcare problem that affects millions of patients every year in the intensive care units (ICUs) worldwide. Despite the fact that ICU patients are heavily instrumented with physiological sensors, early sepsis detection remains challenging, perhaps because clinicians identify sepsis by using static scores derived from bed-side measurements individually, i.e., without systematically accounting for potential interactions between these signals and their dynamics. In this study, we apply network-based data analysis to take into account interactions between bed-side physiological time series (PTS) data collected in ICU patients, and we investigate features to distinguish between sepsis and non-sepsis conditions. We treated each PTS source as a node on a graph and we retrieved the graph connectivity matrix over time by tracking the correlation between each pair of sources' signals over consecutive time windows. Then, for each connectivity matrix, we computed the eigenvalue decomposition. We found that, even though raw PTS measurements may have indistinguishable distributions in non-sepsis and early sepsis states, the median /I of the eigenvalues computed from the same data is statistically different (p <; 0.001) in the two states and the evolution of /I may reflect the disease progression. Although preliminary, these findings suggest that network-based features computed from continuous PTS data may be useful for early sepsis detection.

MASCOT HTML and XML parser: an implementation of a novel object model for protein identification data.

Protein identification using MS is an important technique in proteomics as well as a major generator of proteomics data. We have designed the protein identification data object model (PDOM) and developed a parser based on this model to facilitate the analysis and storage of these data. The parser works with HTML or XML files saved or exported from MASCOT MS/MS ions search in peptide summary report or MASCOT PMF search in protein summary report. The program creates PDOM objects, eliminates redundancy in the input file, and has the capability to output any PDOM object to a relational database. This program facilitates additional analysis of MASCOT search results and aids the storage of protein identification information. The implementation is extensible and can serve as a template to develop parsers for other search engines. The parser can be used as a stand-alone application or can be driven by other Java programs. It is currently being used as the front end for a system that loads HTML and XML result files of MASCOT searches into a relational database. The source code is freely available at http://www.ccbm.jhu.edu and the program uses only free and open-source Java libraries.