UCLA Precision Health and Genomic Medicine Changing the

UCLA Precision Health and Genomic Medicine Changing the Future of Healthcare Dan Geschwind, MD, Ph. D Director, Institute for Precision Health Senior Associate Dean and Associate Vice Chancellor, Precision Health David Geffen School of Medicine UCLA Data Day May 9, 2019 1

UCLA IPH Signature Initiatives Clara Lajonchere, Ph. D 3

UCLA ATLAS Project Vision: Create a powerful and robust cloud-based clinical and multi-omic data resource from a diverse sample of 150, 000 patients across the health system for cutting-edge translational research Universal Consent AT LA S 1 50 k (recruitment) Central Biobanking (sample collection/storage) SNP Genotyping (Illumina GSA) High Performance Computing (clinical & genetic data integration)

ATLAS IS CONSENTING PATIENTS ACROSS UCLA HEALTH (21 Locations) Westwood Locations Santa Monica • Ronald Reagan Medical Center - Surgical Procedures (PTU) • • • Ronald Regan Medical Center – Admissions • Cardiothoracic Surgery Inpatient Unit (Bedside) • Medicine and Surgery Inpatient Unit (Bedside) • Medical Procedure Unit (MPU) • Clinical Laboratories SM Hospital Admissions SM Hospital GI Clinic SM Pre-op Oncology Inpatient Unit Merle Norman (Medical/Surgical) Inpatient Unit • SM Medical Office Building – Surgery Center Admissions • Radiology • 100 Medical Plaza, Suite 245 • 200 Medical Plaza, Suite 145 • Cardiology Clinics • 100 Medical Plaza, Suite 630 West • 100 Medical Plaza, Suite 630 East • Center for Inflammatory Bowel Disease (GI Clinic) • Neurology Outpatient Clinic Burbank • Clinical Lab Draw Station (BURL) Santa Clarita • Radiology • Clinical Lab Draw Station (BURL) 5

DEMOGRAPHICS Count on 5/6/19 Total number of unique patient records in Epic Total number of unique active patients Number of annual Inpatient visits Number of annual Ambulatory visits Number of annual Emergency visits Number of Patients with a diabetes DX (E 10, E 11, 250) Number of Patients with a heart failure DX (I 50, 428) Total number of ATLAS Patients (opt-in) Number of annual Inpatient visits Number of annual Ambulatory visits Number of annual Emergency visits Number of Patients with a diabetes DX (E 10, E 11, 250) Number of Patients with a heart failure DX (I 50, 428) 5, 234, 304 2, 512, 552 56, 284 3, 132, 514 104, 423 116, 722 44, 462 26, 867 10, 055 376, 897 7, 707 4, 747 2, 278 ATLAS patients appear to be sicker than the average “healthy” patient 7

ATLAS Genomic Data Resources V 1 4/26/19 (CTD)

Parallel Genomic Data Repositories ATLAS Genotyped Samples: 16, 658 • PLINK • Very compact compression • Designed for genetic association applications • Access: Linux command line; Jupyter notebook (Python) • I 2 B 2 • Repository of clinical data from Care. Connect • Cohort finding based on clinical and genetic attributes • Access: Graphical User Interface • Genomics DB • . vcf files stored as sparse arrays • Comprehensive genomic data store • Access: Zeppelin notebook (Scala)

Retrieve Genotype Data from (x) Samples at (y) Genomic Locations (J. Wang) Zeppelin paragraphs with Scala code Query Cut/paste sample IDs & SNP IDs into boxes Map SNPs to genomic coordinates Get genotype data

Genomics DB: I 2 b 2 Variant View Plug -In • If we wanted to get the reference and alternate allele counts at rs 16942 for patients who consented to share their genetic data, and have been diagnosed with malignant neoplasms of the breast. The Total Allele Counts report will allow us to answer this query. 11

Insights from big data - Define new normal range for blood test based on personalized features Is this result normal for someone like me? GENOMICS eranhalperingenomics. com

Ancestry adjusted normal ranges Work by Noah Zaitlen’s group (UCLA, Neurology) African American patients are 3 times more likely to exceed upper threshold Eran Halperin

Performance of mortality prediction Eran Halperin Ph. D

Summary • ATLAS is running in many clinics and labs • We are working to expand under-represented minority populations • We will have about 30, 000 patients genotyped within 3 months and hope to attain 50, 000 people this year. • These clinical and genetic datasets are available and can be linked to the EHR (manually, via honest broker, we will automate later this year). 15