Leveraging Electronic Medical Records and Machine Learning Approaches to Study Endometriosis in Diverse Populations

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ABSTRACT - OVERALL (PARENT GRANT) Endometriosis is a chronic, debilitating estrogen-dependent disease wherein tissue similar to the uterine lining (endometrium) is found mainly on pelvic tissues and organs where it causes an inflammatory response, scarring, pelvic pain, and infertility. It affects millions of reproductive age women and severely impacts quality of life and professional life, and has a huge health economic impact of about $69B annually in the U.S. While its etiology is uncertain, profound dysfunction of the innate and adaptive immune systems is associated with inefficient lesion clearance and pelvic and systemic inflammation. The heterogeneity of endometriosis lesions and disease phenotypes is reflected in variable pain symptom presentations, unpredictable fertility potential, uncertain disease pathophysiology, and unpredictable responses to medical therapies, symptom and disease recurrence after surgical resection, and risks for co-morbidities. Clinical classifications of endometriosis are maladapted to the heterogeneity of disease expression, and thus efficient treatments for associated pain symptoms are lacking. Herein, our UCSF Stanford Endometriosis Center for Discovery, Innovation, Training and Community Engagement (“ENACT”) proposes a comprehensive systems biology and precision medicine approach to endometriosis. We propose to study endometriosis unmet needs and challenges through transdisciplinary collaboration and scientific and technologic innovations, integrating multi-omics data to dissect endometriosis disease mechanisms, identify phenotypic and environmental disease signatures, develop accurate disease stratification and diagnosis, and identify novel and repurposed drug classes to ameliorate pain symptoms. To achieve these goals, our Center is comprised of 3 independent and interactive projects and 2 Cores, focused on the central theme of Endometriosis Precision Medicine. Project 1 will focus on underlying immunological mechanisms in endometriosis pathogenesis and pathophysiology. Project 2 will address developing a multi- omic disease classification that will inform diagnostic strategies, and Project 3 will leverage existing and newly generated large-scale omic data to identify and validate new therapeutic interventions. Our long-standing Human Endometrial Tissue and DNA Bank and REDCap database and ongoing accruals with our collaborating network of surgeons will be a major resource for this Center's project. The Center will have an Administrative Core and an Education and Community Outreach Core that will engage students from the Bay Area in our research programs and empower women in our community and address health disparities associated with endometriosis. To achieve these goals, we have assembled a multi-disciplinary team of investigators at UCSF and Stanford University, many of whom are new to endometriosis research, as well as educators, trainees, and community representatives who are all committed to improve the lives of women and teen girls with endometriosis. Integrating multiple disciplines, fostering collaborations among those who are new to endometriosis, training the next generation and partnering with our community are key to the outcomes and impact of our Endometriosis Center.