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Cambridge Healthtech Institute’s Fourth Annual

Clinical NGS Assays: Interpretation and Clinical Utility

Establishing Next Generation Sequencing as the Standard of Care

August 20-21, 2018 | Grand Hyatt Washington | Washington, DC

Next generation sequencing has become an integral part of molecular diagnostics, with applications ranging from inherited disorders and oncology to infectious disease to prenatal diagnostics. To maximize the clinical utility of NGS, however, several challenges associated with downstream interpretation and implementation need to be addressed. The Fourth Annual Clinical NGS Assays: Interpretation and Clinical Utility conference will focus on data analysis, interpretation, and sharing; functional genomics; as well as challenges related to large gene variants of unknown clinical significance. In addition, we will examine the benefits and challenges related to gene panels, whole exome sequencing, whole genome sequencing, and the emerging role of diagnostic RNA sequencing. This conference will also focus on clinical readiness and case studies related to molecular oncology, infectious disease, and inherited disease diagnostics.

Final Agenda

Recommended Short Course*

SC5: NGS Diagnostics: Technology, Regulation and Reimbursement of ctDNA Pan Cancer Panels

Chris Karlovich, PhD, Associate Director (Contractor), Molecular Characterization Laboratory (MoCha), Leidos BioMedical Research, Inc., Frederick National Laboratory for Cancer Research

Soma Ghosh, PhD, Scientific Reviewer, Molecular Genetics & Pathology, Office of In Vitro Diagnostics and Radiological Health, FDA/CDRH

Charles Mathews, Principal, ClearView Healthcare Partners

Dana W.Y. Tsui, PhD, Assistant Attending Geneticist; Member, Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center

*Separate registration required


12:00 pm Main Conference Registration (Independence Foyer)

Constitution A

1:30 Chairperson’s Opening Remarks

Monkol Lek, PhD, Assistant Professor, Genetics, Yale School of Medicine

1:40 NGS Data Analysis for Inherited Disease

Monkol_LekMonkol Lek, PhD, Assistant Professor, Genetics, Yale School of Medicine

Population reference panels such as the Exome Aggregation Consortium (ExAC) data set have aided in the classification of rare variants; however, many of these variants are still classified as variants of unknown significance. A critical challenge is our inability to interpret clinical consequences of these rare missense variants in patients. This talk will discuss computational and functional genomics approaches in interpreting variants of unknown significance in inherited muscle diseases.

2:10 Enhanced Clinical Decision Support Enabled by High-Throughput Genomic Profiling in Oncology

Michael_BergerMichael Berger, PhD, Associate Director, Marie Josee & Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center

At Memorial Sloan Kettering Cancer Center, we have performed comprehensive genomic profiling of tumor and matched normal DNA in more than 20,000 active cancer patients to guide diagnosis and treatment selection. I will describe informatics systems and algorithmic tools we have developed to harness these data for improved clinical decision making and the discovery of prognostic and predictive biomarkers.

2:40 Whole Genome Sequencing Interpretation in the Cloud

Mentch SamanthaNEW: Samantha J. Mentch, PhD, Bioinformatic Analyst, UPMC Genome Center

We will show how UPMC has stood up its own in-house industrial scale and clinical-grade genome center, which is integrated with a cloud-only data infrastructure that allows for processing and securing genomic data for clinical processing. We will discuss strategies on processing and interpreting whole genome germline and somatic sequencing data, and we will highlight benefits and caveats of using whole genome sequencing interpretation in clinical settings.

Bluebee3:10 Optimizing Precision Medicine NGS Data Workflows for Scalability, Global-Compliance, and Clinical Data-to-Knowledge Value

Thomson_NaomiNaomi Thomson, MBA, Director, Business Development, Bluebee

Case examples will illustrate genomics data-to-report and knowledge management workflows to optimize for value. Bluebee is a highly secure and scalable cloud-based data solution. This talk will share how global assay manufacturers, biopharma and clinical genomics service providers are putting Bluebee in action through multiple phases of growth and demand.

3:40 Networking Coffee Break (Independence Foyer)

Constitution A&B

4:15 pm Chairperson’s Remarks

Charles Mathews, Principal, ClearView Healthcare Partners

4:25 - 5:45 pm Global Dx Insights: Policy and Prediction for Diagnostics

Moderator: Cecilia Schott, PhD, Former Vice President, Precision Medicine, AstraZeneca

  • Will value-based medicine replace fee-for-service?
  • PAMA impact on reimbursement
  • Changes in LDT oversight policy
  • Changing landscape of IVD regulation in U.K. and Europe after Brexit
  • What is the future of molecular diagnostics in medical care?
  • How will these policy changes affect the patient?


Dennis J. Dietzen, PhD, DABCC, FAACC, President, AACC; Professor of Pathology & Immunology and Pediatrics, Washington University School of Medicine; Medical Director of Laboratory Services, St. Louis Children’s Hospital

John Leite, PhD, Vice President, Strategic Partnerships, Corporate and Business Development, Illumina

J. Leonard Lichtenfeld, MD, MACP, Deputy CMO, American Cancer Society, Inc.

Victoria M. Pratt, PhD, FACMG, Director, Pharmacogenomics and Molecular Genetics Laboratories, Department of Medical and Molecular Genetics, Indiana University School of Medicine (AMP President-Elect)

Susan Van Meter, Executive Director, AdvaMedDx

Ian S. Young, MD, PhD, Chief Scientific Advisor, Department of Health (Northern Ireland) and President, Association for Clinical Biochemistry and Laboratory Medicine (ACB), UK

5:45 Wine & Cheese Pairing Welcome Reception in the Exhibit Hall with Poster Viewing (Independence Ballroom)

7:00 Close of Day


7:15 am Registration (Independence Foyer)

7:30 Problem Solving Breakout Sessions with Continental Breakfast (Independence F-I)


How Can We Develop Reference Materials for Clinical NGS Tests?

Lisa Kalman, PhD, Senior Advisor for Repository Science, Division of Laboratory Systems, Centers for Disease Control and Prevention


  • How do laboratories validate the ability of their tests to detect a variety of variant types throughout the genome?
  • What reference materials are available for these validation activities? What materials are needed?
  • How can needed reference materials be developed?

NGS Tests In Clinical Settings; Challenges and Future Directions

Arezou Ghazani, PhD, FACMG; Senior Scientist and Medical Geneticist; Dana Farber Cancer Institute & Harvard Medical School


  • Moving from panel to whole genome; what are current clinical and diagnostic challenges
  • Overcoming clinical inertia; how to address and improve health professional preparedness for different genetic tests and incidental findings
  • Usefulness of genetics data; what are innovative methods to mine for clinically actionable targets in the genome

Constitution A

8:30 Chairperson’s Remarks

Jennifer J.D. Morrissette, PhD, FACMG, Scientific Director, Clinical Cancer Cytogenetics; Clinical Director, Center for Personalized Diagnostics, Department of Pathology, University of Pennsylvania

8:35 Bioinformatics and Interpretation Challenges with NGS

Avni_SantaniAvni Santani, PhD, FACMG, Director - Clinical Laboratories, Strategic Partnerships and Innovation, Center for Applied Genomics, Children’s Hospital of Philadelphia; Assistant Professor of Clinical Pathology, Perelman School of Medicine, University of Pennsylvania

Over the last decade, next-generation sequencing (NGS) has transformed the field of clinical genetic testing. Interpretation of genetic variants in a constantly evolving technology environment continues to be increasingly complex given the dramatic increase in the size of datasets. This requires clinical laboratories to be increasingly vigilant about the adoption of technology and informatics algorithms used in the application of interpretation. Using case studies as examples, this lecture provides specific challenges related to variant interpretation in the context of NGS derived data. We will discuss potential solutions to address these complexities as well as best practices during development and validation of these techniques.

9:05 Global Data Sharing in Rare Disease: Scientific, Clinical, and Regulatory Lessons from the GENESIS Platform

Stephan_ZuchnerStephan Zuchner, MD, PhD, Professor, Human Genetics, University of Miami

Rare disease gene and allele discovery is at a high pace, but only continued data aggregation and sharing will provide the power to identify the remaining 30-50% of genetic effects. Over the past 7 years we have provided the GENESIS data analysis and sharing platform in different iterations; allowing for hundreds of genetic matchmaking events and the discovery of over 60 novel disease genes. This presentation will share our experiences on different levels and the increasing importance of this resource for clinical trials.

9:35 Mutational Profiles in AML: Correlations With Cytogenetics and Mutational Shift

Jennifer_MorrissetteJennifer J.D. Morrissette, PhD, FACMG, Scientific Director, Clinical Cancer Cytogenetics; Clinical Director, Center for Personalized Diagnostics, Department of Pathology, University of Pennsylvania

Often NGS testing is only performed at diagnosis, with patients being monitored by single site testing of a known mutation present at diagnosis. The first part of the talk will discuss the utility of monitoring AML by NGS. By comparing mutations based on functional categorization the diagnostic profile can be suggestive of whether the patient is likely to relapse or go into remission. The mutational shift of critical disease genes can be important for assessing appropriate therapy, and can reveal tumor heterogeneity and allow for tracking of response to targeted and traditional chemotherapy. The second part of the talk will cover the correlation of mutational profiles with cytogenetic categories at diagnosis. Cytogenetic categorization of AML is part of the diagnostic workup and important for prognosis, and I will discuss different mutational profiles of AML patients based on the cytogenetic risk category. Co-authored by Priya Velu and Robyn Sussman, University of Pennsylvania

10:05 Coffee Break in the Exhibit Hall with Poster Viewing (Independence Ballroom)

Constitution A

11:00 Mining and Reporting Pharmacogenomic Variants from Clinical Whole Exome Sequencing: A Medication-Guided Approach

Yuan_JiYuan Ji, PhD, DABCP, DABMGG, FACMG, Assistant Professor of Clinical Pathology/Medical Director, Pathology, ARUP Laboratories/University of Utah School of Medicine

Reporting pharmacogenomic (PGx) variants from clinical whole exome sequencing (WES) or whole genomic sequencing (WGS) are being considered by many laboratories with the hope of further enhancing the clinical utility of WES/WGS, especially in patients with negative diagnostic yield of those expensive tests. We explored a novel process of reporting PGx variants through WES using a medication-guided approach. Specifically, we aim to identify and report PGx variants relevant to a patient’s current medication(s) and to test the feasibility of a personalized approach in reporting PGx variants from clinical WES.

11:30 Diagnostic Utility of Whole Genome Sequencing in Pediatric Medicine

Christian_MarshallChristian R. Marshall, PhD, FACMG, Molecular Laboratory Director, Genome Diagnostics, The Hospital for Sick Children

Whole-genome sequencing (WGS) provides a comprehensive testing platform that has the potential to streamline genetic assessments, but there are limited comparative data to guide its clinical use. In a prospective study, we show that WGS could feasibly be deployed as a single molecular test capable of providing superior diagnostic rate compared to targeted genetic testing used in current practices.

12:00 pm Standardize Clinical Workflows for Both WGS and WES with Covaris Adaptive Focused Acoustics®

Holly Tillson, Applications Specialist, Covaris

To improve efficiency and sample recovery for high-throughput library prep, Covaris developed a specially engineered polymer vessel designed for Focused-ultrasonicators utilizing AFA® technology. This novel oneTUBE configuration standardizes automated sample prep for WGS and WES applications producing highly accurate and reproducible fragment distributions ideal for low mass samples.

12:15 Advances in Precision Oncology: The Value of Germline Genome Beyond Cancer Risk Assessment

Arezou Ghazani, PhD, FACMG, Senior Scientist and Medical Geneticist, Dana Farber Cancer Institute & Harvard Medical School

The value of germline DNA in oncology has been traditionally centered around the assessment of patient cancer risk and familial implications. At Dana Farber Cancer Institute, we demonstrated that the assessment of patient’s germline DNA in pancreatic cancer can help identify targets to guide therapeutic decisions. This talk will discuss our approach for an integrated clinical interpretation system of somatic and germline DNA and will highlight the clinical findings in pancreatic cancer.

Integrated DNA Technologies (IDT)12:30 Luncheon Presentation: Choosing the Right Adapter for Your NGS Workflow

Mirna Jarosz, PhD, Director, NGS Business Development, Global Sales, Integrated DNA Technologies

While the original purpose of sequencing adapters was to enable samples to be attached to and read on a flowcell, they have evolved to play a broader role. The design and quality of the adapters used in an NGS workflow directly impact the quality and accuracy of the resulting data. In this presentation, we will review how adapters can be used to enable high levels of sample multiplexing and accurate detection of low frequency variants.

1:00 Refreshment and Cookie Break in the Exhibit Hall with Poster Viewing (Independence Ballroom)

Constitution A

1:30 Chairperson’s Remarks

Christian R. Marshall, PhD, FACMG, Molecular Laboratory Director, Genome Diagnostics, The Hospital for Sick Children

1:35 Reference Materials for Clinical Genetic Testing

Lisa_KalmanLisa Kalman, PhD, Senior Advisor for Repository Science, Division of Laboratory Systems, Centers for Disease Control and Prevention

Genetic tests are currently offered for over 10,000 human genetic disorders. However, there are no publicly available, characterized reference materials for the vast majority of these tests. To address this problem, the Genetic Testing Reference Materials Coordination Program (GeT-RM) was established at the CDC in partnership with the genetics community. Since 2004, the GeT-RM has characterized over 400 publicly available genomic DNA reference materials for many commonly tested genes.

2:05 Establishment of Reference Samples and Quality Metrics for the Detection of Somatic Variants in Cancer

Wenming_XiaoWenming Xiao, PhD, Principle Investigator, Division of Bioinformatics and Biostatistics, NCTR/FDA

The FDA is well aware of the crucial role that next-generation sequencing (NGS) plays in precision medicine, and this technology is already leveraged in regulatory decision-making. However, lack of well-characterized and community-validated reference samples and data benchmarks creates a potential challenge for development and review of NGS applications. To address this challenge, 60+ institutions and 160+ scientists have come together to form a somatic mutation working group within the FDA-led Sequencing Quality Control Phase II (SEQC2) consortium.

2:35 Best Practices for Using Genome in a Bottle Reference Materials to Benchmark Small and Large Germline Variant Calls

Justin_ZookJustin Zook, PhD, Research Scientist, Genome-Scale Measurements Group, National Institute of Standards and Technology (NIST)

The Genome in a Bottle (GIAB) Consortium has developed authoritatively characterized human genomes for benchmarking germline variant calls, and is actively integrating short, linked, and long reads to characterize increasingly difficult variants (e.g., large indels and structural variants) and regions (e.g., repetitive regions). The Global Alliance for Genomics and Health Benchmarking Team developed best practices and methods for comparing to GIAB and other benchmarks to obtain standardized performance metrics stratified by variant type and genome context.

3:05 Achieving Compliance with Next-Generation Quality Control for Next-Generation Sequencing

Russell Garlick, CSO, SeraCare Life Sciences

Gayatry Mohapatra, MD, Director, Laboratory of Genomic Medicine, Department of Pathology, University of Illinois at Chicago

To help labs achieve regulatory compliance and sustain best-in-class performance, SeraCare has developed a QC solution encompassing comprehensive reference materials with QC analysis software. Join us as we present key success factors for submissions and in production. Gayatry Mohapatra, PhD, Director, Laboratory of Genomic Medicine, Department of Pathology, University of Illinois at Chicago will discuss her recent experience launching an NGS based clinical oncology test. Assay design, validation and QC will be emphasized..

3:35 Refreshment Break in the Exhibit Hall with Poster Viewing (Independence Ballroom)

Constitution A

4:20 Chairperson’s Remarks

Carol Saunders, PhD, FACMG, Clinical Laboratory Director, Professor of Pediatric Pathology, Center for Pediatric Genomic Medicine, Children’s Mercy Kansas City

4:25 The Regulatory Landscape for Clinical NGS: Where Are We and Where Should We Be Going?

Gail_JavittGail Javitt, Member of the Firm, Health Care & Life Sciences, Epstein Becker & Green, P.C.

Clinical integration of NGS is quickly becoming a reality, but without a clear roadmap, or consensus on how best to achieve it. Thus far, federal regulatory bodies have played a limited role in regulating NGS-based assays, while the private sector has been experimenting with a variety of business models to facilitate the provision of NGS services. This session will describe various approaches to clinical integration of NGS assays currently being used, identify key challenges facing clinical laboratories, physicians and patients, and discuss the current and potential future roles of FDA and CMS in facilitating the delivery of clinically valid and useful NGS-based assays to patients.

4:55 FEATURED PRESENTATION: Variant Reinterpretation: Examining Clinical Practices of Returning Genetic Test Results
Constitution A

Carol_SaundersCarol Saunders, PhD, FACMG, Clinical Laboratory Director, Professor of Pediatric Pathology, Center for Pediatric Genomic Medicine, Children’s Mercy Kansas City

Emily_FarrowEmily Farrow, PhD, CGC, Associate Professor, UMKC School of Medicine, Director of Laboratory, Operations Center for Pediatric Genomic Medicine, Center for Pediatric Genomic Medicine, Children’s Mercy Hospitals and Clinics

Eric_RushEric Rush, MD, FAAP, FACMG, Clinical Geneticist, Associate Professor of Pediatrics, Pediatrics, Children’s Mercy Kansas City

The interpretation of genetic variants remains a challenging endeavor, and while guidelines have been published for clinical testing laboratories, there is no such guidance for clinicians tasked with integrating the results into patient care. In some cases, there is a discrepancy between the clinical laboratory result and the result returned to families. This session will examine variant interpretation from clinical laboratory, physician and genetic counseling perspectives and provide data from ongoing research examining factors clinicians use for variant reinterpretation as well as the frequency of reinterpretation.

5:55 End of Clinical NGS Assays: Interpretation and Clinical Utility

6:00 Dinner Short Course Registration (Independence Foyer)

6:45 - 9:15 pm Recommended Dinner Short Course*

SC7: Practical Considerations for NGS Data Analysis and Interpretation

Robert D. Daber, PhD, Founder and CEO, Gnosity Consults

Matthew Lebo, PhD, FACMG, Director, Bioinformatics, Partners Personalized Medicine; Instructor, Pathology, Brigham and Women’s and Harvard Medical School

*Separate registration required

Register by July 24 & SAVE $200! 

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