April 2019

Rady Children’s Institute for Genomic Medicine Uses Artificial Intelligence to Diagnose Genetic Diseases

April 24, 2019–Researchers at Rady Children’s Institute for Genomic Medicine (RCIGM) have utilized automated machine-learning and clinical natural language processing (CNLP) to diagnose rare genetic diseases in record time. This new method is speeding answers to physicians caring for infants in intensive care and opening the door to increased use of genome sequencing as a first-line diagnostic test for babies with cryptic conditions.

“Some people call this artificial intelligence, we call it augmented intelligence,” said Stephen Kingsmore, MD, DSc, President and CEO of RCIGM. “Patient care will always begin and end with the doctor. By harnessing the power of technology, we can quickly and accurately determine the root cause of genetic diseases. We rapidly provide this critical information to intensive care physicians so they can focus on personalizing care for babies who are struggling to survive.”

A new study documenting the process was published today in the journal Science Translational Medicine. The workflow and research were led by the RCIGM team in collaboration with leading technology and data-science developers —Alexion, Clinithink, Diploid, Fabric Genomics and Illumina.

Dr. Kingsmore’s team has pioneered a rapid Whole Genome Sequencing process to deliver genetic test results to neonatal and pediatric intensive care (NICU/PICU) physicians to guide medical intervention. RCIGM is the research arm of Rady Children’s Hospital-San Diego.

By reducing the need for labor-intensive manual analysis of genomic data, the supervised automated pipeline provided significant time-savings. In February 2018, the same team achieved the Guinness World Record™ for fastest diagnosis through whole genome sequencing. Of the automated runs, the fastest times – averaging 19 hours – were achieved using augmented intelligence.

“This is truly pioneering work by the RCIGM team—saving the lives of very sick newborn babies by using AI to rapidly and accurately analyze their whole genome sequence “ says Eric Topol, MD, Professor of Molecular Medicine at Scripps Research and author of the new book Deep Medicine.

RCIGM has optimized and integrated several time-saving technologies into a rapid Whole Genome Sequencing (rWGS) process to screen a child’s entire genetic makeup for thousands of genetic anomalies from a blood sample.

Key components in the rWGS pipeline come from Illumina, the global leader in DNA sequencing, including Nextera DNA Flex library preparation, whole genome sequencing via the NovaSeq 6000 and the S1 flow cell format. Speed and accuracy are enhanced by Illumina’s DRAGEN (Dynamic Read Analysis for GENomics) Bio-IT Platform.

Other pipeline elements include Clinithink’s clinical natural language processing platform CliX ENRICH that quickly combs through a patient’s electronic medical record to automatically extract comprehensive patient phenotype information.

Another core element of the machine learning system is MOON by Diploid. The platform automates genome interpretation using AI to automatically filter and rank likely pathogenic variants. Deep phenotype integration, based on natural language processing of the medical literature, is one of the key features driving this automated interpretation. MOON takes five minutes to suggest the causal mutation out of the 4.5 million variants in a whole genome.

In addition, Alexion’s rare disease and data science expertise enabled the translation of clinical information into a computable format for guided variant interpretation.

As part of this study, the genetic sequencing data was fed into automated computational platforms under the supervision of researchers. For comparison and verification, clinical medical geneticists on the team used Fabric Genomics’ AI-based clinical decision support software, OPAL (now called Fabric Enterprise)—to confirm the output of the automated pipeline. Fabric software is part of RCIGM’s standard analysis and interpretation workflow.
The study titled “Diagnosis of genetic diseases in seriously ill children by rapid whole-genome sequencing and automated phenotyping and interpretation,” found that automated, retrospective diagnoses concurred with expert manual interpretation (97 percent recall, 99 percent precision in 95 children with 97 genetic diseases).

Researchers concluded that genome sequencing with automated phenotyping and interpretation—in a median 20:10 hours—may spur use in intensive care units, thereby enabling timely and precise medical care.
“Using machine-learning platforms doesn’t replace human experts. Instead it augments their capabilities,” said Michelle Clark, PhD, statistical scientist at RCIGM and the first author of the study. “By informing timely targeted treatments, rapid genome sequencing can improve the outcomes of seriously ill children with genetic diseases.”

An estimated four percent of newborns in North America are affected by genetic diseases, which are the leading cause of death in infants. Rare genetic diseases also account for approximately 15 percent of admissions to children’s hospitals.

The RCIGM workflow is engineered to speed and scale up genomic data interpretation to reduce the time and cost of whole genome sequencing. The team’s goal is to make rWGS accessible and available to any child who needs it.

Increased automation of the process removes a barrier to scaling up clinical use of WGS by reducing the need for time-consuming manual analysis and interpretation of the data by scarce certified clinical medical geneticists. There were fewer than 1,600 of these experts nationwide in 2017, according to the American Board of Medical Genetics and Genomics.

Rady Children’s Institute began performing genomic sequencing in July 2016. As of the end of March 2019, the team had completed testing and interpretation of the genomes of more than 750 children. One-third of those children have received a genetic diagnosis with 25 percent of those benefitting from an immediate change in clinical care based on their diagnosis.

Rady Children’s Institute for Genomic Medicine Appoints Six New Members to Board of Directors

The Rady Children’s Institute for Genomic Medicine (RCIGM) is pleased to announce the appointment of six new members to the Institute’s Board of Directors.

“Each of these dynamic innovators brings extensive experience in providing strategic leadership and oversight to highly successful organizations,” said Dr. Stephen Kingsmore, president and CEO of the Institute. “Their guidance will help us prepare for future success as the Institute continues to grow and develop.”

David F. Hale, chairman of the Institute’s Board of Directors, likewise applauded the addition of the new trustees. “It’s our good fortune to welcome these accomplished individuals to the Board of the Institute,” he said. “Their commitment to excellence will help propel us toward our goal of transforming pediatric medicine.”

RCIGM is the research arm of Rady Children’s Hospital-San Diego. The Institute was founded with the mission of enabling the diagnosis, treatment and targeted clinical care for newborns and children with rare, life-threatening diseases. The Institute is focused on delivering molecular diagnoses through rapid Whole Genome Sequencing (rWGS) to facilitate fast, precise medical care of the most fragile young patients.

The Institute has continued to expand their impact on the world of advanced pediatric genomic medicine, and there is growing recognition for the groundbreaking work, from speed records, to legislative proclamations, to grant awards and scientific distinctions. The Institute is also dedicated to shaping the future of rapid precision medicine by providing educational expertise through ongoing training and mentoring opportunities, annual conferences and educational series.

The Board of Directors has been established to provide strategic oversight and guidance to the Institute. Each new member of the Board will serve a three-year term and bring the board roster to 18 members. The six newly appointed members are as follows:

1. Joe Beery
Senior Vice President and Chief Information Officer
Thermo Fisher Scientific
He is an instrumental leader who cultivates unified culture, and has focused on improving operational reliability and innovative strategies. He was named Senior Vice President of Information Technology and Chief Information Officer following his role as leader of global Information Technology infrastructure. He has spearheaded the merger of multiple organizations through the development and operation of I.T. systems and e-commerce platforms. He holds a B.A. in Business Administration and Business Computer Systems from the University of New Mexico.

2. Scott D. Kahn, PhD
Chief Information Officer
Luna PBC
He is an expert in informatics and data science strategy. Prior to his current role, he was Illumina’s first Chief Information Officer, and was an executive leader in Illumina’s Enterprise Informatics Unit. He holds a PhD in Theoretical Organic Chemistry from UC Irvine and was a Fellow Commoner of Churchill College at the University of Cambridge in England.

3. Donald B. Kearns, MD, MMM
President Emeritus
Rady Children’s Hospital and Health Center
He is a pediatric otolaryngologist who recently retired as CEO of Rady Children’s Hospital and Health Center. He had previously served Rady in various leadership positions including Chairman of the Department of Surgery, Surgeon-in-Chief and Chief Medical Officer. Dr. Kearns earned his medical degree from Louisiana State University School of Medicine and was awarded a Master of Medical Management degree from the Marshall School of Business at the University of Southern California.

4. Frederic B. Luddy
Founder and Chairman of the Board of Directors
He is an innovative entrepreneur with expertise in the growth and development of organizations. He founded ServiceNow in 2004, an enterprise software company that was ranked No. 1 on the 2018 Forbes Most Innovative Companies list. He stepped down as CEO in 2011 to focus on product development and now serves in an advisory capacity.

5. Trindl Reeves, CIC, AAI
Marsh & McLennan Insurance Agency
She has over 30 years of experience providing leadership and expertise in risk management and health and welfare consulting, and has held numerous leadership positions. She is responsible for leading the firm’s company wide sales effort and has played a key role in the company’s rapid growth. In 2011, she was named one of San Diego Business Journal’s Women Who Mean Business. She earned a B.A. in psychology from the University of California, Irvine, and holds the professional designations of Certified Insurance Counselor (CIC) and Accredited Advisor in Insurance (AAI).

6. Jon Soderstrom, PhD
Managing Director, Office of Cooperative Research
Yale University
He is responsible for defining and executing commercialization strategies including negotiation of licenses and corporate-sponsored research agreements, initiating strategic corporate partnerships, and development and marketing of new spin-off companies to the venture investment community. Since joining the Office in 1996, he has helped form 30 new ventures. Dr. Soderstrom was honored as the 87th “Point of Light” by President George H. W. Bush in March, 1990 for volunteer work with low-income families in East Tennessee to build and rehabilitate housing and provide other essential services. He received his Ph.D. from Northwestern University in 1980 and his B.A. from Hope College in 1976.