This session is accredited.

Speakers:

Dr. Martin Somerville
Dr. Adam Shlien
Dr. Danny Miller

Application of Clinical Genomic Testing for Rare Disease Patients Speaker: Dr. Martin Somerville

This presentation will outline our experience with identifying a range of variant types obtained from a provincial clinical genome wide sequencing project. It will summarize our experience to-date after sequencing more than 1,000 patients with rare disease, and will include some recent examples of diagnoses that required analyses beyond single nucleotide variant calling. I will show that several variant types can identified by mining short-read sequence data, but full analysis may also require other methods such as long-read sequencing or RNA-Seq.

At the end of the session, participants will be able to:

  • Describe the clinical utility of genome wide sequencing methods.
  • Recognize the availability of different variant types within genome sequence data.

Target Audience: Geneticists, Trainees

CanMEDS Roles: Medical Expert (the integrating role), Collaborator, Health Advocate

Martin J. Somerville, PhD, FCCMG, FACMG, is Head of the Division of Genome Diagnostics in the Department of Paediatric Laboratory Medicine at the Hospital for Sick Children, and a Professor in the Department of Laboratory Medicine and Pathobiology at the University of Toronto. He obtained his BSc and MSc from the University of Western Ontario, his PhD from the University of Toronto, and did his CCMG fellowship training in molecular genetics at the Children’s Hospital of Eastern Ontario. His research activities have focused on identifying the causes of genetic disorders, with a more recent interest in the application of comprehensive genomic analysis. This has led to several discoveries of DNA changes associated with a wide range of conditions. He has also been actively involved in improving standards for clinical genetic testing through various provincial, national, and international policy initiatives.

New RNA platform with potential as universal diagnostic aid for cancer

The causes of pediatric cancers’ distinctiveness compared to adult-onset tumors of the same type are not completely clear and not fully explained by their genomes. I will present an optimized multilevel RNA clustering approach used to derive molecular definitions for most childhood cancers. Applying this method to 13,313 transcriptomes, we constructed a pediatric cancer atlas to explore age-associated changes. Tumor entities were sometimes unexpectedly grouped due to common lineages, drivers or stemness profiles. Some established entities were divided into subgroups that predicted outcome better than current diagnostic approaches. These definitions account for inter-tumoral and intra-tumoral heterogeneity and have the potential of enabling reproducible, quantifiable diagnostics. As a whole, childhood tumors had more transcriptional diversity than adult tumors, maintaining greater expression flexibility. To apply these insights, we designed an ensemble convolutional neural network classifier. We show that this tool was able to match or clarify the diagnosis for 85% of childhood tumors in a prospective cohort. If further validated, this framework could be extended to derive molecular definitions for all cancer types.

At the end of the session, participants will be able to:

  • Understand the utility of RNA-Seq in diagnosing cancer

Target Audience: Geneticists, Trainees

CanMEDS Roles: Leader, Scholar, Professional

Dr. Shlien is a Senior Scientist and Lab Director at the Hospital for Sick Children with over 20 years of experience in bioinformatics and genomics. He holds the Garron Family Chair in Childhood Cancer Research and was previously the Canada Research Chair in Childhood Cancer Genomics. He leads a computational oncology lab, which has used insights from research, to design, validate, and implement novel genomics tests that are in current use at his hospital. Dr. Shlien co-directs the KiCS precision medicine program. Dr. Shlien did his post-doctoral training at the Wellcome Trust Sanger Institute, supported by a H.L. Holmes Award. He designed some of the earliest integrative genomics studies, discovering the direct transcriptional consequences of somatic mutation. Dr. Shlien has made multiple discoveries into the mutational processes leading to childhood cancer, receiving additional awards including the St Baldrick’s Arceci award for “out of the box” research in pediatric cancer.

Streamlining clinical and research genetic testing: the promise of long-read sequencing Speaker: Dr. Danny Miller

A traditional laboratory genetic evaluation is diagnostic in less than 50% of individuals with a suspected genetic condition. I will discuss how new technologies, such as long-read sequencing could be used to streamline the genetic testing process, increase access to testing, and increase the diagnostic rate.

At the end of the session, participants will be able to:

  • Identify cases which may benefit from long-read sequencing.
  • Determine what type of testing could be streamlined into a single test, such as long-read sequencing.
  • Demonstrate understanding of how long-read sequencing works compared to prior genetic testing approaches.

Target Audience: Geneticists, Trainees

CanMEDS Roles: Scholar

Danny Miller is an Assistant Professor in the Department of Pediatrics, Division of Genetic Medicine, and the Department of Laboratory Medicine and Pathology at the University of Washington and Seattle Children’s Hospital in Seattle, Washington. His laboratory uses new technologies, such as long-read DNA and RNA sequencing, to identify missing disease-causing genetic variation and to better understand biological processes associated with human disease. His lab is working to develop long-read sequencing-based clinical genetic tests with a goal of increasing the rate of genetic diagnoses, reducing the amount of time required to make a genetic diagnosis, and lowering barriers to obtaining comprehensive clinical testing. Clinically, he cares for patients in both general genetics and skeletal dysplasia clinics. More information can be found on his lab website at www.millerlaboratory.com.

Declaration of Conflict of Interest: Has a relationship with Oxford Nanopore on the Scientific Advisory Board. Owns Stock Options of MyOme.

Event Timeslots (2)

Day 3
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Part 1 - Speakers: Dr. Martin Somerville and Dr. Adam Shlien - accredited

Day 3
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Part 2 - Speaker: Dr. Danny Miller - accredited