PROJECT SUMMARY Our objective is to develop a clinically-usable test that can diagnose gastrointestinal disease early in infants. Initially described nearly 200 years ago, necrotizing enterocolitis (NEC) is the most frequent gastrointestinal disorder in preterm infants. It affects 7-12% of preterm infants born with very low birth weight (< 1.5 kg). Thus, nearly 6,000 preterm infants per year suffer from this bowel disease and an average total in-hospital treatment is $500,000 per infant. NEC is a lethal disease, due to delayed diagnosis: nearly 30% of infants who contract NEC die and median time to death is 1 day after x-ray imaging of free air in the intestine. Since NEC is not diagnosed with high specificity or in a timely fashion, survivors of surgical intervention are faced with long-term complications, such as shortened gut, nutritional deficiency, and neurodevelopmental delays. In sum, infants afflicted with NEC incur $5 billion in US medical care annually. Our value proposition is that early and accurate diagnosis would decrease the number of infant deaths, prevent long-term health challenges of survivors, and lower the economic expense of the disease. Such a model has three requirements to fulfill its commercialization promise. First, early detection of disease is actionable. Second, as prematurity is a health inequity, the method of testing is universally accessible regardless of resources, easy to adopt, and can integrate in current medical workflows. Third, disease delineation in patients, who are asymptomatic or present confounding general symptoms, opens new opportunities for therapeutic development and personalizing treatment for each patient. To achieve this, the initial barrier is elucidation of molecular characteristics, or biomarkers, that intersect with dysbiosis, human metabolism, and inflammatory responses of NEC. Our maiden biomarker, NECDetect, provides direct readout of an individual human’s ability to modulate gut homeostasis. For this application, we address unique technical, logistic, and regulatory challenges for NECDetect. To do so, we have assembled a multidisciplinary team of discovery scientists, clinicians, biomarker assay developers, and regulatory consultants. Project aims encompass kit prototype development, sample collection, assay validation, and sample analysis for regulatory evaluation. End goals are predictive disease segmentation of infants using the NECDetect prototype and reference values in the neonatal population.