Cambridge Healthtech Institute’s Third Annual
Clinical NGS Assays: Applications and Interpretation
Enhancing Next Generation Sequencing with New Trends in Analysis and Utilization
August 16-17, 2017 | Grand Hyatt Washington | Washington, DC
Precision medicine, as stated by the NIH, is an approach for disease treatment and prevention that takes into account individual variability in environment, lifestyle and genes for each person. This can be made possible through next-generation sequencing, by probing genomes in greater depth, leading to an improved knowledge of which variants cause diseases and phenotypes. In the past decade, genomic sequencing has advanced from spending billions to complete the Human Genome Project to analyzing a whole genome for under $1,000. While the raw cost of sequencing a genome has dropped dramatically in the past decade, other costs associated have not dropped as quickly, namely interpretation and annotation of the sequencing results. Other problems such as reimbursement issues, regulatory concerns and awareness of the next-generation sequencing for patients and clinicians alike hinder the clinical implementation of NGS. At the 3rd annual Clinical NGS Assays: Applications and Interpretation, we are here to provide scientists a forum to discuss best strategies to determine clinical significance and the challenges that surround NGS applications and analysis.
Final Agenda
Recommended Short Course(s)*
SC7: NGS Assay Development and Validation
SC11: Practical Considerations for NGS Data Analysis and Interpretation
*Separate registration required
WEDNESDAY, AUGUST 16
10:30 am Registration
1:05 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:35 Ice Cream and Cookie Break in the Exhibit Hall with Poster Viewing
2:05 Chairperson’s Opening Remarks
Robert Daber, Ph.D., Founder and CEO, Gnosity Consults
2:10 Broad Population Based NGS testing - Are we there yet?
Robert Daber, Ph.D., Founder and CEO, Gnosity Consults
Over the last few years, Next Generation Sequencing (NGS) has emerged as a technology of choice for both R&D discovery efforts as well as clinical testing. In the Clinical setting, testing has been most successful when leveraged to understand or diagnose disease in very specific applications. For example, panel based NGS testing is now routine at many cancer centers for the management of cancer patients. Despite its numerous applications, broad NGS testing or screening efforts whereby every patient with a specific clinical indication are tested is still lacking. Here we explore areas such as newborn screening to determine if the technology has matured to a point where large scale testing should become standard of care.
2:40 Geisinger’s Case Study: Integration of NGS into the EHR—eMERGE and Beyond
Marc S. Williams, M.D., FAAP, FACMG, FACMI, Director, Genomic Medicine Institute, Geisinger Health System
The volume of data needed for clinical decision-making is increasing exponentially and the addition of genomic sequence data will further add to the data overload. Human cognitive capacity is static necessitating the use of computers and informatics to synthesize information to aid in clinical decision-making. This talk will present strategies employed by Geisinger Health System to effectively use genomic information in clinical care.
3:10 Global Bacterial Surveillance via Whole Genome Sequencing
David E. Tabor, Ph.D., Senior Scientist, Applied Immunology and Microbiology, MedImmune
The presentation will discuss global bacterial surveillance studies that employed whole genome sequencing in an effort to understand the genetic diversity within specific bacterial species. This is analogous to investigating the diversity of bacterial species in microbiome studies, but drilling down a layer to investigate the genomic diversity within given species of bacteria. The use of next-generation sequencing to replace traditional methods will be highlighted.
3:40 Talk Title to be Announced
Andrew Barry, New England Bio Labs
4:10 Refreshment Break in the Exhibit Hall with Poster Viewing
5:00 Incidental Germline Mutations in Cancer Predisposition Genes during Routine Tumor Sequencing
Jennifer J.D. Morrissette, Ph.D., FACMG, Scientific Director, Clinical Cancer Cytogenetics, Clinical Director, Center for Personalized Diagnostics, Division of Precision and Computational Diagnostics, Department of Pathology, University of Pennsylvania
Recent studies have shown that 3-5% of cancer patients have germline mutations in cancer predisposition genes, and many oncology providers under-recognize this possibility. This talk will provide a review of somatic NGS tumor testing, allele frequency, nuances of result interpretation and strategies available to responsibly hypothesize whether a variant is suggestive of a germline mutation versus a somatic mutation alone, and discuss the collaborative development of a novel algorithm that could be used by ordering providers in considering when to refer a patient for germline genetic testing.
5:30 Mining Therapeutic Targets in Germline DNA in Cancer: Integrated Germline and Somatic Interpretation Is Valuable for Cancer Therapeutic
Arezou Ghazani, Ph.D., Medical Geneticist/Scientist, Medical Oncology, Dana-Farber Cancer Institute
Germline genome sequencing results have traditionally been considered valuable information for inherited cancer risk assessment, but not for identification of therapeutic targets.
6:00 FDA Perspective: NGS Assays
You Li, Ph.D., Scientific Reviewer, Division of Molecular Genetics and Pathology, OIR/CDRH, FDA
Next-generation sequencing (NGS) is increasingly employed for use in the clinical setting. Analyzing big data generated by NGS is challenging, such as data format standardization, bioinformatics pipeline validation standards, methodologies, and reference material availability.
6:30 Close of Day
6:30 Dinner Short Course Registration
6:45 - 9:15 pm Recommended Dinner Short Course(s)*
SC13: Regulatory and Reimbursement Issues with Advanced Diagnostics and Circulating Biomarkers
*Separate registration required
THURSDAY, AUGUST 17
7:30 am Problem-Solving Breakout Discussions with Continental Breakfast
miRNA as a Biomarker
Moderator: Shanrong Zhao, Ph.D., Director, Precision Medicine, Pfizer
- The relationship between miRNAs and diseases
- The importance of microRNA isoforms
- The challenges of cell-free microRNA sequencing
Interpretation Challenges
Moderator: Lora H. Bean, Ph.D., Assistant Professor, Human Genetics, Emory University
- Choosing analysis tools – How to pick the right one?
- Standards for interpretation – When will clinical labs agree on classifications most of the time?
- Future challenges – When will reimbursement for interpretation happen?
8:25 Chairperson’s Opening Remarks
Annerose Berndt, Ph.D., Vice President, Clinical Genomics, UPMC
8:30 Using Exome Aggregation (ExAC) Dataset for the Interpretation of Rare Variants in Mendelian Diseases
Monkol Lek, Ph.D., Research Fellow, Massachusetts General Hospital
Large-scale reference data sets of human genetic variation are critical for the medical and functional interpretation of DNA sequence changes. The ExAC data set contains variants from over 120,000 individuals aggregated from a variety of large-scale sequencing projects. In this presentation, we will provide a general overview of the production of the ExAC data set, recent updates, and also discuss examples of how the data set has been used for the interpretation of rare variants and development of methods available to the community.
9:00 Discovery of miRNA as Biomarkers Using microRNA Sequencing
Shanrong Zhao, Ph.D., Director, Precision Medicine, Pfizer
Genome-wide miRNA expression data can be used to study miRNA dysregulation comprehensively. We designed and implemented a pipeline called QuickMIRSeq (https://sourceforge.net/projects/QuickMIRSeq/) for quick and accurate quantification of known miRNAs and miRNA isoforms (isomiRs) from large-scale sequencing experiments. QuickMIRSeq considers the unique nature of miRNAs and combines many important features into its implementation for the sake of computational efficiency and quantification accuracy
9:30 A Developers Platform to Support NGS Test Commercializations
Annerose Berndt, Ph.D., Vice President, Clinical Genomics, UPMC
Patients’ variability in genes, environment, lifestyle, and behavior determines the course of disease. To adjust treatment options to the individual, new applications are needed that analyze, gather, manage, and explore actionable information from multiple high-throughput data sources. Developing and commercializing those novel applications requires an integrated platform for analysts, developers, and engineers to freely exchange ideas. In this presentation, we will discuss the advantages and challenges of such a platform within a large-scale integrated delivery and finance healthcare system.
10:00 Coffee Break in the Exhibit Hall with Poster Viewing
11:00 Big Data in Cancer Care: Hopes, Dreams and Hard Realities
Wendy Rubinstein, M.D., Ph.D., Division Director, Clinical Data Management and Curation, CancerLinQ, LLC, American Society of Clinical Oncology
The cancer community has an unprecedented opportunity to improve cancer care with real-world evidence, and a wide variety of stakeholders are joining an effort underway to make it happen. Learn how data in ASCO’s CancerLinQ®, a HIT platform that connects and analyzes real-world evidence from almost any electronic record source, is structured and curated, and how CancerLinQ is convening the oncology community to help big data achieve its full potential.
11:30 Genomics in Healthy Individuals: Analyses and Results of Large-Scale Secondary Finding Projects
Matthew Lebo, Ph.D., FACMG, Director, Bioinformatics, Partners Personalized Medicine; Instructor, Pathology, Brigham and Women’s
With NGS testing, it is now feasible to do clinical genomics screening on otherwise ostensibly healthy individuals. Here, we discuss various approaches to this screening, with content ranging from ACMG Secondary Findings to the medically relevant regions of the genome. These studies include both randomized control studies and large Biobank cohorts. We will detail the bioinformatic and interpretation approaches, with insights into the clinical process behind returning these results.
12:00 pm Reporting Pharmacogenetic Variants from Clinical NGS Assays: Caveats and Opportunities
Yuan Ji, Ph.D., DABCP, DABMGG, FACMG, Medical Director, Department of Pathology, ARUP Laboratories
Despite the technical challenges, clinical laboratories have begun or are planning to report pharmacogenetic (PGx) variants through next-generation sequencing (NGS) testing such as clinical whole exome sequencing (WES) and whole genome sequencing (WGS); however, they have not universally provided useful PGx reports to guide therapy from the NGS data. We set up to compare clinical WES data with targeted genotyping approach for calling PGx variants and successfully identified several caveats that, if addressed, could greatly improve accuracy and yield of NGS-based PGx profiling.
12:30 Enjoy Lunch on Your Own
1:30 Session Break
2:00 Chairperson’s Opening Remarks
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
2:05 Harnessing the Power of New Data in Diagnosing Unsolved Cases: Considerations for Infrastructure Development
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 explosion of genomic information and novel gene discoveries, clinical laboratories are faced with critical challenges in data interpretation. Laboratories must develop strategies that can incorporate data in the interpretation of genetic variants and review that variant classification over time. In addition, for complex genetic tests such as exome sequencing in pediatric population, the clinical presentation of patient continues to evolve, therefore affecting the phenotype-driven analysis of genomic data. Using clinical cases as examples, this presentation will address these challenges and propose strategies that clinical laboratories can utilize for re-analysis of genomic data in exome sequencing.
2:35 Interpretation of Genome-Wide Sequencing Data in a Clinical Setting: Triumph and Challenges
Yaping Yang, Ph.D., Associate Professor, Molecular and Human Genetics, Baylor College of Medicine, Senior Laboratory Director, Whole Genome Laboratory, Baylor Genetics
The overall diagnostic rate for exome sequencing is about 30% for known genetic diseases; about 4-5% of the positive patients were diagnosed with two genetic disorders resulting in blended phenotypes. While exome sequencing primarily detects SNVs and some CNVs in protein coding regions, whole genome sequencing (WGS) covers all variant types in coding and non-coding regions and is the most comprehensive test in terms of the types of variants that can be reliably detected. However, further cost reduction for WGS and better software tools are needed to effectively translate WGS into the clinical setting.
3:05 What You Don’t See by Exome Sequencing: Pseudogene Interference in Next-Generation Sequencing
Lora H. Bean, Ph.D., Assistant Professor, Human Genetics, Emory University
Exome sequencing has become a powerful tool in genetic diagnostics; however, it is critical that we not lose sight of the remaining limitations of this technology. Many clinically relevant genes belong to highly homologous gene families or have highly homologous pseudogenes. Methods used to determine whether homologous regions exist and if data generated by next-generation sequencing can be used, as well as technical options when modified methods are needed, will be discussed.
3:35 NGS Test Results Interpretation in Clinical Setting
Pinar Bayrak-Toydemir, M.D., Ph.D., Medical Director, Molecular Genetics and Genomics, ARUP Laboratories
Next-generation sequencing (NGS) is becoming the main technology for molecular diagnosis in clinical laboratories. Establishing the wet lab is generally an easy task, however interpretation of the massive amount of data generated is a challenge. Interesting clinical multiple gene-panel and exome cases will be discussed with focus on relevant clinical features of cases, data interpretation, as well as quality assurance steps and necessity for Sanger sequencing confirmation.
4:05 Close of Conference
4:30 Symposia & Short Course Registration
5:00 – 7:30 pm Dinner Short Courses
Recommended Dinner Short Course(s)*
SC20: Bioinformatics Bootcamp: NGS for Forensic Scientists
*Separate registration required
RECOMMENDED CONFERENCE SYMPOSIA:
Digital PCR
Separate registration required
NGS for DNA Forensics
Separate registration required