Clinical NGS Diagnostics

Monday, February 12

10:30 am Conference Program Registration Open


11:50 Chairperson’s Opening Remarks

Maria E. Arcila, M.D., Pathologist and Director, Diagnostic Molecular Pathology Laboratory, Memorial Sloan Kettering Cancer Center (AMP Member)

12:00 pm Role of Practice Guidelines in NGS Oncology Testing

Maria E. Arcila, M.D., Pathologist and Director, Diagnostic Molecular Pathology Laboratory, Memorial Sloan Kettering Cancer Center (AMP Member)

Providing clinically relevant test results using next-generation sequencing methodologies is a complex process, requiring both analytical rigor and the expertise of molecular medical professionals. The Association for Molecular Pathology has convened and led a series of multidisciplinary subject matter expert working groups in collaboration with ACMG, AMIA, ASCO, and CAP to provide evidence-based NGS best practice guidelines. This trio of peer-reviewed publications provides a foundation for NGS testing procedures that spans the length of the process – from sample acceptance to production of a standardized report. By establishing guidance for laboratories and clinicians, professional organization driven practice guidelines work to improve patient care.

12:15 Best Practices for Validation of Clinical Next-Generation Sequencing Bioinformatics Pipelines

Somak Roy, M.D., Assistant Professor, University of Pittsburgh Medical Center (AMP Informatics Subdivision Representative to the AMP 2018 Program Committee; Member)

Bioinformatics pipelines are an integral component of next-generation sequencing (NGS) assay. However, there is significant variability in how bioinformatics pipelines are validated in the global molecular genetics and pathology community in the absence of published guidelines. To address this, the Association of Molecular Pathology (AMP) with liaison representation from the College of American Pathologists (CAP) and the American Medical Informatics Association (AMIA) have developed a set of best practice consensus recommendations for the validation of clinical NGS bioinformatics pipelines.

12:30 Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer

Marina N. Nikiforova, M.D., FCAP, Professor, Pathology; Director, Molecular & Genomic Pathology Laboratory, Pathology, University of Pittsburgh Medical Center (AMP Member)

Sequence variants detected by NGS are used to assist with diagnosis, prognostication and treatment of patients with cancer. The Association for Molecular Pathology, with liaison representation from the American Society of Clinical Oncology, and College of American Pathologists, and American College of Medical Genetics and Genomics (ACMG) have created consensus guidelines for annotation, interpretation, and reporting of somatic variants in cancer. The guideline describes a system for evidence-based variant categorization and the process of variant annotation, classification, and reporting.

12:45 PANEL DISCUSSION: New Clinical Practice Guideline Publications to be Discussed

  • Guidelines for Validation of Next-Generation Sequencing-Based Oncology Panels. A Joint Consensus Recommendation of the Association for Molecular Pathology and College of American Pathologists. Published in the May 2017 Issue of the Journal of Molecular Diagnostics.
  • Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer: A Joint Consensus Recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists. Published in the January 2017 issue of The Journal of Molecular Diagnostics.
  • AMP Bioinformatics Pipeline Validation Guidelines Working Group Manuscript (submitted for publication)

1:00 Session Break

DNA Software 1:10 Luncheon Presentation I:Large Scale Multiplex PCR Panel Design with >95% Success in Hours, Not Months

John SantaLucia, Ph.D., co-founder and CEO, DNA Software

We aim to solve the problem of multiplex PCR design by a three-pronged approach: 1. improved understanding of the mechanism of PCR and the causes of artifacts, 2. improved algorithms for predicting 2 structure and mis-hybridization, and 3. implementation of cloud to address large sequence databases. These approaches vastly improve the success of fully automated multiplex PCR design with larger plex sizes. This enables applications such as targeted enrichment for NGS and infectious disease molecular diagnostics.

1:40 Luncheon Presentation II (Sponsorship Opportunity Available)

2:10 Session Break


2:30 Chairperson’s Remarks

Apostolia-Maria Tsimberidou, M.D., Ph.D., Professor, Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center

2:40 Utility of Implementing Clinical NGS Assays as Standard of Care in Oncology

Andrea Ferreira-Gonzalez, Ph.D., Professor & Chair, Pathology, Virginia Commonwealth University

3:10 Clinical and Informatic Approaches to Genomic Screening of Ostensibly Healthy Individuals

Matthew Lebo, Ph.D., Director, Bioinformatics; Assistant Professor, Pathology, Brigham and Woman’s Hospital, Harvard Medical School

This talk will focus on approaches to implement a genomic screening program for unselected cohorts. Specific considerations will be placed on the clinical informatics components required to scale variant annotation, filtration, review, and reporting. Results from several studies will highlight key considerations and outcomes when utilizing different approaches.

3:40 Challenges of Validating NGS Assays: Using Hearing Loss Gene Panel as an Example

Rong Mao, M.D., FACMG, Medical Director, Molecular Genetics and Genomics, ARUP Laboratories; Assistant Professor, Pathology, University of Utah School of Medicine

With the advent of massively parallel sequencing methodologies, the number of genes implicated in human disease has increased substantially in the last decade. This has led to a surge in the number of clinical laboratory tests offered to detect genetic causes of inherited disorders. As more clinical laboratories tread the unfamiliar ground of NGS, they are faced with the challenges of establishing validation and quality control processes. Here I am using a hearing loss gene panel as an example to discuss validating the NGS assay, limitations of the assay, and CAP/FDA guidelines.

4:10 Validation of RNA Fusions for an NGS Based Clinical Assay 
Helen Fernandes, Ph.D., Co-Director, Genomic Oncology, Columbia University 
This presentation will focus on the design, development, and validation of an NGS assay to detect RNA fusions from FFPE tissue. The advantages of using highly multiplexed reference materials to achieve faster development time, lower validation costs, improved performance, and for submission to state regulatory agencies will be discussed.

4:25 Nuclease-Activated Probe (NucAP) Technology for Cancer Detection
Shambhavi Shubham, Ph.D., Postdoctoral fellow, Department of Internal Medicine, University of Iowa 

4:40 Refreshment Break and Transition to Plenary Session

5:00 Plenary Keynote Session (click here for more details)


Precision for Medicine

6:00 Grand Opening Reception in the Exhibit Hall with Poster Viewing

7:30 Close of Day

Tuesday, February 13

7:30 am Registration Open and Morning Coffee

8:00 Plenary Keynote Session (click here for more details)

9:00 Refreshment Break in the Exhibit Hall with Poster Viewing


10:05 Chairperson’s Remarks

Daniel H. Farkas, Ph.D., HCLD, Section Head, Molecular Pathology, Pathology and Laboratory Medicine Institute, Cleveland Clinic

10:15 NGS-Based vs. Immunologic Therapies: Current Status, Future Directions

Davendra P. S. Sohal, M.D., M.P.H., Assistant Professor, Medicine; Staff, Hematology & Medical Oncology; Director, Clinical Genomics Program, Taussig Cancer Institute, Cleveland Clinic

Next-generation sequencing platforms have made precision oncology possible, and applications continue to grow. Meanwhile, immunotherapies are transforming cancer treatment. The two areas intersect more closely than it might appear, however. The role of tumor mutation burden, microsatellite status, and response-altering mutations make it imperative that we continue to apply NGS platforms to understand disease biology and response selection and prediction even better.

10:30 Perceptions versus Reality Surrounding Targeted Therapy and Immunotherapy

Terence Rhodes, M.D., Ph.D., Director, Immuno Oncology, Intermountain Healthcare

Oncologists and patients have never had more options for systemic cancer treatments. Patient perceptions of their cancer’s biology, their body’s immune system, and communication from media outlets may influence patient’s decisions among possible equivalent systemic therapy choices. Review of published and ongoing studies of targeted therapy and cancer immunotherapy can provide oncologists with information to help patients make informed, evidence-based decisions regarding their treatment.

10:45 Immunotherapy versus NGS-Guided Targeted Therapy: Promise and Pitfalls of Both Approaches

Jordi Rodon, M.D., Ph.D., Associate Professor, Investigational Cancer Therapeutics, Cancer Medicine, U. T. M. D. Anderson Cancer Center

Next generation sequencing, improved selectivity in targeted therapies and a vast amount of tumor biology knowledge generated by large initiatives such as The Cancer Genome Atlas (TCGA) has enabled Precision Medicine. Recent successes in Immuno-oncology have drifted investment and drug development portfolios towards novel immunotherapies. In the innovation cycle, hype produces inflated expectations that obscure science and clinical research. Drug development strategies require learning from the emerging clinical and translational data and from errors in the past as well as defining new paradigms of drug development that fit the purpose of each drug class.


NeoGenomics11:45 Next Generation Sequencing and Molecular Profiling in the Classification of Cancer
Maher Albitar, M.D.,  Senior Vice President, CMO, Director, Research and Development, NeoGenomics 
The role of NGS and molecular profiling in the classification of cancer will be discussed.  Various molecular approaches using NGS and how these approaches are currently used in cancer diagnosis, predicting prognosis and determining therapy will be discussed.  Clinical examples will be presented. 

12:00 pm  Sponsor Presentation (Opportunity Available)

12:15 Session Break

 ConversantBio 12:25 Luncheon Panel Presentation: Go Further. Faster: Cancer Diagnostics Need New Interdisciplinary Approaches to Improve Outcomes


Marshall Schreeder, CEO, Conversant Bio

Adel Mikhail, CEO, Folio


Dorothy French, DVM, Ph.D., DACVP, Director, Translational Pathology, Clinical Department, Abbvie Stemcentrix

Arnold Gelb, M.D., MS, FASCP, FCAP, Senior Director, Global Clinical Biomarkers and Companion Diagnostics, EMD Serono

Paul Van Hummelen, Ph.D., Senior Research Scientist, Division of Oncology, Department of Medicine Stanford University School of Medicine & Stanford Genome Technology Center

Beatrisa Boyadzhyan, Ph.D., Associate Director, Biomarker Discovery Group, Quest Diagnostics

Detecting cancer at actionable stages is the single best predictor of positive outcomes. Interdisciplinary efforts combining various technologies aim to detect cancer early and to personalize the diagnosis. Additional cross-disciplinary approaches are likely to improve survival.

1:25 Refreshment Break in the Exhibit Hall with Poster Viewing


2:00 Chairperson’s Remarks

Stephen F. Kingsmore, M.D., D.Sc., President and CEO, Rady Children’s Institute for Genomic Medicine

2:10 Rapid Precision Medicine in Neonatal and Pediatric Intensive Care Units

Stephen F. Kingsmore, M.D., D.Sc., President and CEO, Rady Children’s Institute for Genomic Medicine

Genetic disorders are a leading cause of morbidity and mortality in infants. Rapid Whole Genome Sequencing (rWGS) can rapidly diagnose genetic disorders enabling precision medicine interventions that can decrease morbidity and mortality in neonatal intensive care unit (NICU) infants. In the setting of case examples, I will review recent evidence that rWGS-based precision medicine improves outcomes and lowers healthcare utilization in inpatient infants.

2:30 A Clinical Utility Study of Exome Sequencing versus Conventional Genetic Testing in Pediatric Neurology

Joris A. Veltman, Ph.D., Professor, Human Genetics, Donders Centre for Neuroscience, Radboud University Medical Center

We studied the clinical utility of exome sequencing (WES) in 150 patients with complex pediatric neurology in terms of diagnostic yield and costs. All patients received both the standard diagnostic workup and WES simultaneously. This allowed direct comparison of diagnostic yield of both trajectories and provided insight into the economic implications of implementing WES. WES identified significantly more conclusive diagnoses (29.3%) than the standard care pathway (7.3%) without incurring higher costs.

2:50 Cost-Effectiveness Analysis of Genome Sequencing

Nancy J. Mendelsohn, M.D., Chief Specialty Pediatrics, Genomics Medicine Program Clinician, Children’s Minnesota

Medically complex children account for the majority of the total heath cost of pediatric care. We hypothesized that more timely and efficient genome sequencing would lower the cost of care and modeled the impact of performing rapid WES/WGS as a first-tier test in newborns. Analysis included cost per diagnosis and impact on cost of care from a payer and health care system perspective related to changes in clinical management.


  • Does it work as a diagnostic tool?
  • Does it change patient management?
  • Modeling cost effectiveness

3:40 Designing and Implementing Testing Strategies for Non-Oncology Applications

Joseph V. Ferrara, President, Boston Healthcare Associates

This session will provide an overview of the similarities and differences of non-oncology and oncology indications and describe key issues associated with both, e.g. testing large patient populations to locate small numbers of responders. Using case studies (e.g., obesity, ADHD, rare disease), we will examine best practice for creating and working with laboratories to implement successful diagnostic testing programs and explore how to build a cost effective testing program that facilitates patient identification.

4:10 Valentine’s Day Celebration in the Exhibit Hall with Poster Viewing

5:00 Breakout Discussions in the Exhibit Hall

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.

    Next Generation Sequencing (NGS) in Precision Medicinev

    Prasun Mishra, Ph.D., Founder & CEO, Agility Pharmaceuticals

    • Whole Genome Sequencing (WGS) and Whole Exome Sequencing (WES)-based genome diagnostics
    • NGS-driven precision medicine approaches for hereditary cancers as an example
    • Utilizing cell-free DNA (cfDNA) for longitudinal patient monitoring
    • NGS applications in drug discovery and development

    Isothermal Molecular Diagnostics as Alternatives to PCR

    Robert Meagher, Ph.D., Research Scientist, Sandia National Laboratories

    • LAMP, NASBA, RPA, TMA, and more: sorting through the alphabet soup of techniques
    • Tradeoffs of sensitivity, specificity, and simplicity
    • Beyond resource-poor: designing assays and devices for use in awful conditions
    • Integrating assays with mobile technology
    • Intellectual property and licensing considerations

    The Challenge of Implementing Proteomics in Clinical Set Up

    Christoph Borchers, Ph.D., Professor, Director, University of Victoria Genome British Columbia Proteomics Centre

  • How to improve the training for clinical proteomics?
  • Is there demand for proteomics kits? If yes, for which application?
  • Is there a demand for ring studies in clinical proteomics? If yes, who could organize a study?
  • Lessons Learned: What I Wish I Had Known Before I Started Validation

    Jason N. Rosenbaum, M.D., Assistant Professor, Pathology and Laboratory Medicine, University of Pennsylvania

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

    Martin Siaw, Ph.D., MB(ASCP), Technical Consultant, Siaw Consulting

    • Selection of validation samples
    • Comparison to orthogonal assays
    • New CAP/AMP Guidelines
    • RNAseq in the clinical laboratory

    6:00 Close of Day

    Wednesday, February 14

    7:00 am Breakfast Presentation (Sponsorship Opportunity Available)  

    7:30 Registration Open and Morning Coffee

    8:00 Plenary Keynote Session (click here for more details)

    10:00 Refreshment Break and Poster Competition Winner Announced in the Exhibit Hall


    10:50 Chairperson’s Remarks

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

    11:00 Merging NGS Assays for Maximizing the Interrogation of Genomic Variants

    Helen Fernandes, Ph.D., Associate Professor, Personalized Genomics Laboratory, Department of Pathology & Cell Biology, Columbia University Medical Center

    Clinical laboratories use NGS assays for oncology that range from small to large targeted panels, to whole exome and transcriptome. Each assay has its advantages and limitations for the interrogation of relevant genomic variants. Concurrent sequencing of DNA based targeted NGS assays and RNA based assay for identification of fusions, are currently used in some laboratories. For the most part these integrated assays use the same chemistry with similar reagents. In this presentation, we will examine the merging of two assays with different chemistries for the concurrent identification of SNV’s, Indels and fusions from a single specimen. The validation, implementation and advantages of such applications will be discussed.

    11:30 Getting the Most Out of the Least: Validation and Mutation Detection in Small and Degraded Specimens

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

    Most next generation sequencing (NGS)-based clinical oncological testing has focused on sequencing all or most of the exons of clinically-relevant genes, which requires high DNA input and/or high quality DNA. Our academic laboratory receives tumor and specimen types for testing, some of which have insufficient amplifiable DNA for our larger 158 gene assay, either due to low quantity or poor quality. This talk will discuss the validation and clinical implementation of a two NGS panels for solid tumor specimens, with a large panel that covers over 150 genes and 750KB, and a small panel that captures hotspot amplicons and tumor suppressor exons, while requiring <1ng of input DNA. We have found that by providing a large panel for all tumor types, while offering an extremely targeted panel for specimens insufficient to run on larger panels, has expanded the application for NGS testing to include reflex testing of FFPE specimens with low DNA quantity or quality that fail QC for larger panels, small cytology specimens and other limited specimens.

    12:00 pm Impact of Preanalytical Variables on Tissues by Studying Global Protein and Gene Expression: Implications for Use in Clinical Research

    Lokesh Agrawal, Ph.D., Program Director, Biorepositories and Biospecimen Research Branch (BBRB), Cancer Diagnosis Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute

    Clinically relevant protemic biomarkers obtained from tissues promise to revolutionize cancer diagnosis and therapy. Several preanalytical factors have been shown to influence qualification and validation of these biomarkers. The talk will focus on biospecimen science issues and their standardization for assessing clinical biomarkers including validating upcoming immunotherapy markers. The talk will discuss the need to understand and standardize collection, processing, and storage procedures and develop quality control tools in order to minimize variations observed in biospecimens when assessing these biomarkers. This may also inform the future development of biomarkers and assist in the development and validation of diagnostic tests.

    12:30 Session Break

    12:40 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

    1:10 Dessert Break in the Exhibit Hall and Last Chance for Poster Viewing


    1:50 Chairperson’s Remarks

    Kai Wang, Ph.D., Principal Scientist, Institute for Systems Biology

    2:00 Tissue Histopathology Investigations in Support of Clinical Trials for Novel Therapeutics: Considerations and Perspectives

    Keith Wharton, M.D., Ph.D., Senior Medical Director, Leica Biosystems

    Tissue histopathology investigations are central to discovery and preclinical development of novel therapeutics and for routine medical care, but their variable use in clinical trials represents a missed opportunity to improve our understanding of disease and the effects of various therapies on disease. I present major considerations and propose a question-based framework for implementation of tissue histopathology biomarker investigations in clinical trials, including several examples

    2:30 Development and Clinical Validation of Large-Scale NGS Oncology Panels for Detection of SNVs, Indels, Fusion Genes and CNVs

    Jeremy Segal, M.D., Ph.D., Director, Genomic and Molecular Pathology, Pathology, University of Chicago

    More than ever, oncology genomics laboratories are under pressure to deliver more results at less cost and in less time using smaller and smaller specimens. Careful laboratory planning and a high level of technical proficiency are necessary to successfully navigate this environment, with a strong emphasis on creating individual assays that can deliver comprehensive genetic information about specimens, including SNVs, indels, fusion genes, CNVs and more. This session will provide strategies, examples and lessons learned during the process of creating and validating a large-scale hybrid capture cancer profiling assay at University of Chicago.

    3:00 Turning Lead to Gold: Validating the Detection of Fusion Transcripts against an Imperfect Standard

    Jason N. Rosenbaum, M.D., Assistant Professor, Pathology and Laboratory Medicine, University of Pennsylvania

    Many therapeutic targets for cancer are fusion transcripts not easily multiplexed in traditional assays, such as fluorescent in situ hybridization (FISH). RNA-based next-generation sequencing (NGS) offers multiplexed detection and more detailed genomic information, offering significant advantages over FISH. Moreover, despite operating as a de facto “gold-standard,” FISH has a significant false-positive rate. We present our experience validating a clinical RNA-NGS assay against imperfect “gold-standards.”

    3:30 Session Break


    3:40 Chairperson’s Remarks

    Kimberly Hanson, M.D., MHS, Associate Professor, Medicine and Pathology, University of Utah

    3:45 Upcoming New Guidelines for Management of C. difficile

    Stuart Johnson, M.D., Professor, Infectious Disease, Loyola Medicine, Hines VA Hospital


    4:15 Diagnosing Infectious Disease in Transplant Patients: Rapid Molecular Tests

    Kimberly Hanson, M.D., MHS, Associate Professor, Medicine and Pathology, University of Utah

    This presentation will review recent developments in rapid diagnostics for opportunistic infections.

    4:45 Next-Generation Diagnostics for Meningitis and Encephalitis in Transplant Patients

    Michael Wilson, M.D., MAS, Assistant Professor, Neurology, UCSF School of Medicine

    Dr. Wilson’s talk will summarize the potential for metagenomic next-generation sequencing to transform how we identify infections in patients with neuroinflammatory diseases like meningitis and encephalitis and, in particular, how this could impact the care of transplant patients and screening of potential organ donors.

    5:15 Close of Conference Program

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