With more clinical labs consistently turning to next-generation sequencing (NGS) assays, there is an overwhelming need to understand the fundamentals of running, designing, analyzing and validating NGS tests. The Second Annual Clinical NGS Assays will provide attendees with a comprehensive view of the technical considerations for implementing NGS assays as well as showcase best practices. Regulatory issues specific to NGS such as CLIA accreditation and FDA clearance will also be addressed from both the academic lab and commercial lab perspective. Finally, the clinical potential for NGS technologies will be explored by both physicians and research scientists, providing future directions for successful implementation.
TUESDAY, AUGUST 18
7:30 am Main Conference Registration & Morning Coffee
8:30 Chairperson’s Opening Remarks
Jimmy Lin, M.D., Ph.D., MHS, Director, Clinical Genomics, Genetics Branch, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH)
8:40 NCI Clinomics Program: Clinical Cancer Panel and Exome Sequencing and Beyond
Jimmy Lin, M.D., Ph.D., MHS, Director, Clinical Genomics, Genetics Branch, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH)
At the NCI Center for Cancer Research, the ClinOmics Program has been established to perform systematic molecular, genomic, transcriptomic, proteomic, metabolomics and other high throughput (³Omics²) profiling on tumor and normal tissues on enrolled patients treated at the CCR and other NCI divisions for the identification of biomarkers and targets for therapy. I will highlight the technical considerations for our validation and design rationale for our assays.
9:10 Considerations for Optimizing Results with Ion Proton Sequencing
Todd E. Arnold, Ph.D., Managing Director, Mount Sinai Genetic Testing Laboratory; Genetics and Genomic Sciences, Icahn Institute for Genomics and Multiscale Biology
The presentation will discuss important elements for sequencing assays run on the Ion Proton Platform. Topics will include assay design parameters, sample preparation, quality metrics, and multiplexing.
9:40 Rapid Turnaround Inherited Disease Panel in the NICU
Rong Mao, M.D., FACMG, Associate Professor, Pathology, University of Utah School of Medicine; Medical Director, Molecular Genetics and Genomics, ARUP Laboratories
Within the 4000 known single gene disorders, a significant fraction manifests symptoms during the newborn period. A rapid diagnosis of newborn diseases could make the difference between life and death and reduce length of stay in the neonatal intensive care unit (NICU). A targeted 4200 known disease causing gene panel has been developed with a short turnaround and a focused interpretation combining genetics etiology with phenotype will provide a comprehensive clinical understanding of disease in NICU.
10:10 Coffee Break in the Exhibit Hall with Poster Viewing
10:55 Chairperson’s Remarks
Justin Zook, Ph.D., Researcher, National Institute of Standards and Technology (NIST)
11:00 Genome in a Bottle: You May Have Sequenced, but How Well Did You Do?
Justin Zook, Ph.D., Researcher, National Institute of Standards and Technology (NIST)
Clinical laboratories, research laboratories and technology developers all need DNA samples with reliably known genotypes in order to help validate and improve their methods. The Genome in a Bottle Consortium (www.genomeinabottle.org) has been developing reference DNA standards with high-accuracy whole genome sequences to help support these efforts internationally.
11:30 From Gene Panels to Exome Sequencing - Validation and Implementation of NGS Assays in the Clinic
Matthew Lebo, Ph.D., FACMG, Director, Bioinformatics; Assistant Laboratory Director, Personalized Medicine Laboratory for Molecular Medicine, Partners Healthcare; Instructor, Pathology, Brigham and Women’s Hospital, Harvard Medical School
This presentation will give an overview of state of the art clinical NGS and discuss validation, clinical implementation and the migration from gene panels to exome sequencing for inherited disorders with clinical and genetic heterogeneity.
12:00 pm Strategies for the Validation of Next-Generation Sequencing-Based Multi-Gene Panels in Cancer Diagnostics including Copy Number Analysis
Martin P. Powers, M.D., Molecular Genetic Pathologist, Lab Director, Cancer Specialist, InVitae
When validating a multi-gene panel including copy number analysis, certain challenges may present themselves especially with regard to accuracy, precision, sample choice and verification of results. Strategies and proposed solutions to said problems will be presented in the framework of validating a multi-gene hereditary cancer panel.
12:30 Molecular Phenotyping Provides a Unique Insight into Health Assessment for Precision Medicine
Shaun Lonergan, Ph.D., Vice President, Precision Medicine, Metabolon
Metabolon has developed a platform technology capitalizing on advances in mass spectrometry, proprietary software and database analysis to provide unprecedented insight into biochemical pathways. This capability can help assess an individual’s health status. Along with information provided by whole genome or exome sequencing technologies, metabolite data provides ontology for determining genome wide associations. In precision medicine, this insight is critical to determining penetrance of a gene determinant of interest and relating it to health status.
1:00 Luncheon Presentation: Ashion Analytics: The Process of Moving from a Research to a Commercial Genomics Lab
Michael Demeure, M.D., Executive Vice President and General Manager, Ashion Analytics
Precision genomic profiling of tumors from patients with rare or refractory cancers offers prospects for improved survival and cost savings by directing patients toward more effective or less toxic chemotherapeutic regimens. Ashion Analytics has performed over 100 large panel (562 genes) somatic germline subtraction tests on Illumina platform with an average coverage of 400x tumor and 180x germline. Actionable targets associated with FDA approved drugs or clinical trials were seen in 88% of patients.
1:30 Refreshment Break in the Exhibit Hall with Poster Viewing
2:00 Chairperson’s Remarks
David I. Smith, Ph.D., Professor, Laboratory Medicine & Pathology, Mayo Clinic
2:05 Exploring Next-Generation Sequencing Data: Targeted vs. Genomic Approaches
Pinar Bayrak-Toydemir, M.D., Ph.D., Medical Director, Molecular Genetics and Genomics Laboratory, ARUP; Associate Professor, Pathology, University of Utah School of Medicine
2:35 Novel Targeted NGS Test for Retinal Dystrophy Empowers Precision Medicine
John Chiang, Ph.D., FACMG, Director, Casey Molecular Diagnostics Laboratory, Oregon Health and Science University
As molecular diagnosis becomes an integral component of clinical diagnosis of retinal dystrophy, the methods through which clinicians are granted insight into the molecular mechanisms underlying clinical presentation are rapidly evolving. The recent emergence of NGS offers an exciting new avenue for more comprehensive molecular diagnosis of complex inherited conditions like Retinal Dystrophy (RD). To this end we have developed a high quality and cost effective test for patients who present with RD. This clinical offering has been used to interrogate the underlying molecular mechanisms involved in the presentation of RD in over 700 patients up to date. Implementation of this Next Gen Dx has improved our understanding of the genes contributing to RD, is leading to improved patient care and offers certain patients the opportunities to be enrolled in clinical trials.
3:05 Next-Generation Sequencing Platforms: Where We Are and Where We’re Going
David I. Smith, Ph.D., Professor, Laboratory Medicine & Pathology, Mayo Clinic
I will briefly discuss the history of next generation sequencing and the various platforms that were developed using massively parallel sequencing. I will then discuss the current state of next generation sequencing and how these technologies are going to quickly transform clinical practice.
3:35 MyAML™ Next-Generation Sequencing (NGS) Assay Associates with Clinical Outcomes
Brad Patay, M.D., CMO, Genection
Demonstrate how Genection’s MyAML CLIA- and CAP-accredited next generation sequencing assay identifies clinically actionable pathogenic mutations in 194 acute myeloid leukemia (AML) genes. Give examples comparing conventional karyotyping and how a NGS assay outperforms standard cytogenetics by detecting novel fusion partners and cryptic translocations. Demonstrate actionability of MyAML assay showing links to clinical trials and druggable targets. Finally, the session will highlight compliance with secondary findings concepts from recent ACMG and AMP recommendations.
4:05 Refreshment Break in the Exhibit Hall with Poster Viewing
4:50 Using Genome Sequencing in the Clinical Setting
Jason Merker, M.D., Ph.D., Co-Director, Stanford Clinical Genomics Service; Assistant Professor, Pathology, Stanford University School of Medicine
Health care providers are more frequently using genome and exome sequencing to evaluate patients with unexplained heritable disease. I will describe our experience establishing a clinical genomics service at an academic medical center. I will then discuss our initial efforts to use genome sequencing to identify the molecular etiology in patients with unexplained pediatric syndromes, heritable cardiovascular disease, heritable cancer predisposition, and heritable drug reactions
5:20 The NGS Cost Equation in Cancer Care: Are We at the Tipping Point?
German Pihan, M.D., Staff Pathologist & Director, Hematopathology Lab, Pathology, Beth Israel Deaconess Medical Center
The cost-effectiveness of exome sequencing (WES) in the diagnosis, risk assessment and, particularly, therapy of cancer remains undetermined. This talk will address this very important issue and propose guidelines for the development of data-driven algorithms predicting cost-effective implementation of WES.
5:50 Wine & Cheese Pairing Welcome Reception in the Exhibit Hall with Poster Viewing
6:50 Close of Day
WEDNESDAY, AUGUST 19
7:15 am Registration
7:30 – 8:25 Problem-Solving Breakout Discussions with Continental Breakfast
These interactive discussion groups are open to all attendees, speakers, sponsors, & exhibitors. Participants choose a specific breakout discussion group to join. Each group has a moderator to ensure focused discussions around key issues within the topic. This format allows participants to meet potential collaborators, share examples from their work, vet ideas with peers, and be part of a group problem-solving endeavor. The discussions provide an informal exchange of ideas and are not meant to be a corporate or specific product discussion.
Is Sanger Confirmation Always Needed for Clinically-Relevant NGS Results?
Moderator: Justin Zook, Ph.D., Researcher, National Institute of Standards and Technology (NIST)
- Could variants be categorized into “almost certainly true so validation isn’t needed” vs. “questionable”, based on type of variant, genome context, coverage, or other known characteristics of the variant and sequencing method?
- What are the strengths/weaknesses of alternative confirmation methods besides Sanger (e.g., other NGS technology, same NGS technology at higher coverage, manual inspection of reads)?
Next Generation Sequencing Technology Platforms
Moderator: David I. Smith, Ph.D., Professor, Laboratory Medicine & Pathology, Mayo Clinic
- Living in an Illumina NGS world
- The CGI alternative
- Current state of the art of single molecule sequences
- New technologies on the horizon
8:25 Chairperson’s Opening Remarks
Robert D. Daber, Ph.D., Director, Research and Development and Sequencing Operations, Bio-Reference Laboratories
8:30 Utility of Implementing Clinical NGS Assays as Standard of Care in Oncology
Helen Fernandes, Ph.D., Director, Molecular Pathology, Pathology & Laboratory Medicine, Weill Cornell Medical College
The presentation will address the practical processes that need to be adopted for a NGS-based assay to be run in a routine clinical laboratory. The topics will address specific challenges encountered from the preanalytical to the analytical and postanalytical phases of the process. Details on achieving libraries with optimal quality from various types of specimens will be discussed. Factors that affect the implementation of the analytical process and the variability encountered in the interpretation of variants will be highlighted. Strategies for recognizing and dealing with the barriers will be included.
9:00 Development and Implementation of Clinical NGS Testing: Assay Development and Informatic Challenges
Robert D. Daber, Ph.D., Director, R&D and Sequencing Operations, Bio-Reference Laboratories
As genomic technologies continue to advance and new bio-markers emerge, rapid NGS assay development becomes critical in the age of Precision Diagnostics. Here we will discuss emerging methods to capture important biological markers and their associated informatic challenges during both the development and implementation phases.
9:30 Implementation of Clinical Exome Sequencing
Avni B. Santani, Ph.D., Assistant Professor, Clinical Pathology, University of Pennsylvania School of Medicine; Scientific Director, Molecular Genetics Laboratory, The Children’s Hospital of Philadelphia
With the advent of next generation sequencing (NGS), diagnostic laboratories are faced with unprecedented challenges in incorporating this technology in the clinical setting. This presentation will provide a comprehensive overview on the key considerations for implementation of clinical exome sequencing including resource allocation, assay development, compliance, bioinformatics, data management, analysis and interpretation of data.
10:00 Qualitative and Quantitative Tools for Performance Monitoring of NGS Tumor Profiling Assays
Russell Garlick, Ph.D., CSO, SeraCare Life Sciences
Biosynthetic mutation mixes for NGS assays are a powerful way to monitor the daily run performance--tracking both qualitative and quantitative measures. Unlike cell lines, biosynthetic mutation mixes offer a means to cover wide varieties of mutations and the ability to ‘tune’ them to specific allelic frequencies to evaluate the assay sensitivity and specificity. An overview of their development and use in a clinical setting will be discussed.
10:15 Sponsored Presentation (Opportunity Available)
10:30 Coffee Break in Exhibit Hall with Poster Viewing
1:10 Close of Clinical NGS Assays