UCLA Precision Health and Genomic Medicine Changing the Future of Healthcare Dan Geschwind, MD, PhD 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

UCLA IPH Signature Initiatives Clara Lajonchere, PhD

SNP Genotyping (Illumina GSA) High Performance Computing 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 (recruitment) Central Biobanking (sample collection/storage) SNP Genotyping (Illumina GSA) High Performance Computing (clinical & genetic data integration) ATLAS 150k

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 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 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 Clinical Lab Draw Station (BURL) Burbank Santa Clarita

DEMOGRAPHICS ATLAS patients appear to be sicker than the average Count on 5/6/19  Total number of unique patient records in Epic                      5,234,304 Total number of unique active patients                      2,512,552 Number of annual Inpatient visits                           56,284 Number of annual Ambulatory visits                      3,132,514 Number of annual Emergency visits                         104,423 Number of Patients with a diabetes DX (E10, E11, 250)                         116,722 Number of Patients with a heart failure DX (I50, 428)                           44,462   Total number of ATLAS Patients (opt-in)                           26,867                           10,055                         376,897                             7,707                             4,747                             2,278 ATLAS patients appear to be sicker than the average “healthy” patient

ATLAS Genomic Data Resources V1 4/26/19 (CTD)

Parallel Genomic Data Repositories PLINK Very compact compression Designed for genetic association applications Access: Linux command line; Jupyter notebook (Python) I2B2 Repository of clinical data from CareConnect 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 Retrieve Genotype Data from (x) Samples at (y) Genomic Locations (J. Wang) Zeppelin paragraphs with Scala code Cut/paste sample IDs & SNP IDs into boxes Query Map SNPs to genomic coordinates Get genotype data

Genomics DB: I2b2 Variant View Plug-In If we wanted to get the reference and alternate allele counts at rs16942 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.

Is this result normal for someone like me? 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 PhD

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).