Nicholas Be | 17-ERD-031
More informative diagnostic approaches are needed to guide treatment approaches for severe, survivable wounds from battlefield injuries, particularly when infection is indicated. Prognostic tools could personalize treatment; however, substantial gaps exist in our ability to assess the course of wound infection. We applied predictive analyses to microbial metagenomic data to fill this knowledge gap and identify variables and approaches for future diagnostics. Wounds from a cohort of combat-injured U.S. service members were subjected to microbial metagenomic sequencing, and researchers conducted clustering, correlation, and association analyses to evaluate microbial wound populations for composition and diversity. A range of genomic signatures for antimicrobial resistance were identified and associated with detection of pathogen sequence. Finally, machine learning classifiers were applied to identify wound and microbial variables associated with healing outcome and to assess the relative benefits of each statistical modeling treatment. Models demonstrated different balances of performance metrics for sensitivity, specificity, and precision toward predicting wound outcome, showing important proof-of-concept for use of microbial metagenomic data in predictive platforms. This study describes a systematic, multidimensional analysis of the microbial determinants representing bioburden in combat wounds. Further development will facilitate future tools that guide clinical decisions for combat wound infections.
This project directly supported priorities of the Lawrence Livermore National Laboratory chemical and biological countermeasures investment strategy by developing knowledge and tools that protect the warfighter and provide clinical care data that will benefit general civilian medicine. These efforts built on prior strengths while developing and experimentally validating novel concepts through application of computation to these unique datasets. This project substantially strengthened a robust and productive relationship with the faculty and leadership at the Uniformed Services University and Walter Reed National Military Medical Center.
Our results have expanded the breadth of scientific understanding of the environment of wound infection. By combining this knowledge with Livermore capabilities, we will be able to meet the mission needs of several government agencies, such as Department of Defense programs related to the field of combat wound diagnostics. Other mission-relevant applications of our work include projects aimed at protecting the warfighter, including the Congressionally Directed Medical Research Program (CDMRP) and Defense Threat Reduction Agency (DTRA).
Publications, Presentations, and Patents
Be, N. A., et al. 2018a. "Interrogation of combat wound infection through integrative metagenomic analyses of the wound microenvironment and corresponding clinical outcomes." Military Health System Research Symposium. LLNL-ABS-747447
——— 2018b. "Leveraging genomics for microbial detection in combat injuries." Biodefense World Summit. LLNL-ABS-744750
——— 2019a. "Composition, function, and relevance of the microbial microenvironment in wounds from combat injuries." Military Health System Research Symposium. LLNL-ABS-769143
——— 2019b. "Metagenomic interrogation of the microbial microenvironment in combat wounds." Multi-omics for Microbiomes. LLNL-ABS-776682
——— 2019c. "Targeted sequencing and network modeling for analysis of infection." Biodefense World Summit. LLNL-ABS-766643