Webinar: Curating the Human Genome to Advance Early Identification of Rare Diseases

In this webinar, Mark Kiel, MD, PhD, and Brittnee Jones, PhD discuss how current approaches of interpreting variants one-by-one are impractical when it comes to screening newborns with whole genome sequencing – and how a unique combination of AI-driven technology and expert scientific review has emerged as the only viable way to curate all variants in the human genome.

You will learn:

• How a unique balance of AI and expert review creates a solid foundation of high-quality evidence to understand the genetic basis of a targeted disease
• How the integration of data from the scientific literature with commonly used variant databases like ClinVar streamline accurate and timely diagnoses for patients
• How this approach is being used to comprehensively access and classify every variant in the human genome, starting with newborn sequencing applications

00:00 Welcome, Tamara Tucker- Ibarisha, PhD
00:29 About the Mastermind Genomic Search Engine
02:00 Introductions
07:15 Genomenon's mission, Mark Kiel, MD, PhD
12:08 The challenge in the clinic
14:27 Challenge - Sensitivity, Proliferation of Information in Unstructured References
16:22 Solution - Sensitivity, Computational Intelligence is Necessary to Ensure Nothing is Missed
18:46 Our Computational Approach: Genomic Language Processing
20:31 Mastermind: The Most Comprehensive Source of Genomic Evidence
23:27 ClinVar in Mastermind - A Valuable Resource for Clinically Encountered Genetic Variants
28:01 Benefits of the ClinVar Integration in Mastermind
31:16 Challenge - Specificity, Accurately Interpreting Genetic Information Requires a Human
32:15 Solution - Specificity, Curation by Experts is Necessary to Ensure Calls are Correct
32:54 Disease-Specific Curated Content
33:44 Our Philosophy - Combination of Computation and Curation
34:18 ACMG/AMP framework
36:06 Challenge - Sensitivity/Specificity, Ensuring the Data is both Maximally Sensitive and Maximally Specific
36:22 The Power of Comprehensive Curated Evidence
40:39 Newborn Sequencing
45:00 Challenge - Newborn Sequencing, Newborn Sequencing Needs a Database of Every Actionable Variant Interpreted in Context of Screening Functioning as a Lookup Table
48:00 Mastermind Demos, Britt Jones, PhD
1:08:00 Q&A

This presentation is a part of the 2022 ASHG Genetics and Genomics Digital Forum.