Cambridge Healthtech Institute’s Seventh Annual

Personalized Diagnostics

Establishing Clinical Sequencing as a Routine Diagnostic Tool

March 7 – 9, 2016 | Moscone North Convention Center | San Francisco, CA
Part of the 23rd International Molecular Medicine Tri-Conference


This year, we will investigate subjects of controversy in the implementation of next-generation sequencing for routine clinical use. This includes deciphering driver mutations, determining when to sequence tumor DNA, using matched controls, evaluating and validating exome sequencing for routine diagnosis, profiling DNA to overcome tumor resistance and heterogeneity, weighing uses of tissue biopsy vs. cell-free DNA, and factoring in cost. The Personalized Diagnostics conference promises to be a dynamic interchange of ideas and advances impacting the field.

Scientific Advisory Board

German Pihan, M.D., Director, Hematopathology Lab, Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School

Victor Velculescu, M.D., Ph.D., Professor, Oncology; Co-Director, Cancer Biology, Johns Hopkins Sidney Kimmel Cancer Center; Co-Founder, Personal Genome Diagnostics

Karl V. Voelkerding, M.D., Professor, Pathology, University of Utah; Medical Director for Genomics and Bioinformatics, ARUP Laboratories

Monday, March 7

10:30 am Conference Program Registration Open


11:50 Chairperson’s Opening Remarks

Karl V. Voelkerding, M.D., Professor, Pathology, University of Utah; Medical Director, Genomics and Bioinformatics, ARUP Laboratories

12:00 pm “So You’ve Sequenced My Genome. How Well Did You Do?” - Resources for Validating Clinical Next-Gen Sequencing

Marc Salit, Ph.D., Leader, Genome-Scale Measurements Group, NIST Material Measurement Lab, NIST-JIMB; Consulting Professor, Bioengineering, Stanford University

The NIST-hosted Genome in a Bottle (GIAB) Consortium is one of those working to provide whole human genome reference samples with benchmark variant call sets that are developed in a rigorous, transparent, open, public manner from open, public data sets. The GIAB is also working with others to develop benchmark comparison tools and extend their methods so others can also develop benchmark call sets useful for analytical validation of targeted assays. This presentation will describe these efforts and present a snapshot of current best practices.

12:10 Regulatory Considerations for Next-Generation Sequencing

Xueying Sharon Liang, M.D., Ph.D., Regulatory Scientist, Division of Molecular Genetics and Pathology, OIR/CDRH, FDA

Next-generation sequencing (NGS) is increasingly employed for in vitro diagnostic use. As part of the Precision Medicine Initiative (PMI), FDA is actively engaged in discussions with a variety of stakeholders to develop a regulatory pathway to advance innovation in precision medicine and protect public health with sufficiently flexible standards to assess performance of NGS-based tests, including analytical standards, framework on bioinformatics pipeline validation and clinical validity of NGS tests.


1:00 Session Break

1:15 Luncheon Presentation I: Beyond the Cancer Genome - Computational Enablement of Holistic, Evidence-Driven Patient Care in Clinical Oncology

Gabriel Bien-Willner, M.D.,Ph.D., Medical Director, Medical, Molecular Health

In oncology,the molecular characterization of tumor genes as part of patient care is now synonymous with the concept of precision medicine. In this talk, I describe a computational platform that enables holistic clinical interpretation of multiple clinico-molecular parameters.

Abogen1:45 Luncheon Presentation II Spit Matters

Stephen Andrews, CSO, AboGen

Manasi Jain, Vice President, AboGen

Saliva is an underappreciated sample material that actually contains the same components found in blood. New technology developed by AboGen permits the collection, preservation, and isolation of all these components enabling noninvasive home based collection of blood components from saliva.

2:15 Session Break


2:30 Chairperson’s Remarks

Yaping Yang, Ph.D., Associate Professor, Molecular and Human Genetics, Baylor College of Medicine


2:40 Clinical Exome Sequencing: Utilities and Obstacles to Implementation in a Clinical Setting

Yaping Yang, Ph.D., Associate Professor, Molecular and Human Genetics, Baylor College of Medicine

Clinical exome sequencing has demonstrated its clinical utility in diagnosing rare genetic disorders. However, obstacles to the implementation of exome testing in a clinical setting exist due to the technical complexity and novelty of NGS, as well as challenges in return of results (ROR) and accessibility/medical insurance acceptances. Continuous efforts are needed to address the challenges to further establish the role of clinical exome sequencing in medical care.

3:10 The Future Use of Exome Sequencing as the Genetic Test of Choice for Clinical Diagnostics

Wendy Chung, M.D., Associate Professor, Clinical Genetics Program, Columbia University

We will review the experience of using whole exome sequencing in clinical diagnostics for a wide range of genetic conditions including technical improvements of the test over time, the clinical yield of testing by indications, and the clinical utility in testing for patient care. We will also look forward to how the test is likely to be used in the future as a first line clinical test for all heritable conditions.

3:40 SNP-Catcher, a Database to Aid Mutation Detection and Discovery in Constitutional Disorders and Cancer

Peter L. Nagy, M.D., Ph.D., Assistant Professor, Pathology and Cell Biology; Director, Clinical Next-Generation Sequencing, Laboratory of Personalized Genomic Medicine

SNP-catcher is a web-based data system for the analysis and reporting of genomic variants for patients with constitutional disorders and cancer. It allows for the automated importing and processing of variant and coverage files and integration with data on frequency and pathogenicity from external databases. The web application allows for easy data mining based on patient and model organism phenotype and the molecular associations of the genes mutated.

4:10 An Integrated System for Targeted NGS that Enables
Simultaneous Analysis of DNA Mutations, Fusions and
RNA Expression

Brian Haynes, Ph.D., Senior Scientist, Computational Biology, Manager, Bioinformatics, Asuragen

We present QuantideX™ NGS, a comprehensive system for targeted clinical NGS that enables quantification of DNA and RNA through a streamlined workflow compatible with low-input, low quality total nucleic acid and a bioinformatics solution that incorporates pre-analytical QC data to improve accuracy of variant calling, fusion detection and RNA quantification.

4:40 Refreshment Break and Transition to Plenary Session

5:00 Plenary Keynote Session

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

7:30 Close of Day

Tuesday, March 8

7:00 am Registration Open and Morning Coffee

8:00 Plenary Keynote Session

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


10:05 Chairperson’s Remarks

David L. Rimm, M.D., Ph.D., Professor, Pathology, Yale University

10:15 Tissue-Based Assessment of PD-L1 and Other Tumor Microenvironmental Factors in Melanoma Specimens

Janis M. Taube, M.D., MSc, Director, Dermatopathology; Assistant Professor, Dermatology and Pathology, Johns Hopkins

Immunohistochemical detection of PD-L1 and other checkpoint molecules may serve as biomarkers for selecting immunotherapeutic regimens for patients with advanced melanoma. The evaluation of the utility of PD-L1 as a biomarker has been hampered by the different antibodies and assays used. We will discuss the current issues associated with immune checkpoint companion diagnostics and potential future applications for use of these assays in patients with melanoma.

10:45 Tissue-Based Analyses to Guide Immunotherapy for Lymphoma

Scott Rodig, M.D., Ph.D., Hematopathologist, Pathology, Brigham and Women’s Hospital

Targeted immunotherapy has achieved long-lasting clinical responses in a subset of patients with a variety of aggressive malignancies. I will discuss the cellular and molecular characteristics of classical Hodgkin lymphoma that render this tumor-type uniquely susceptible to PD-1 blockade and correlations between tissue-based biomarker analysis and clinical outcome with either conventional chemotherapy or immunotherapy, and extensions of these observations to additional lymphoma subtypes.

11:15 Immune Profiling of Lung Cancer Tissue Specimens

Ignacio I. Wistuba, M.D., Chair, Translational Molecular Pathology, Division of Pathology/Lab Medicine; Anderson Clinical Faculty Chair, Cancer Treatment and Research, The University of Texas MD Anderson Cancer Center

The anti-tumor benefit of blocking immune checkpoints in lung cancer, particularly PD-1 and PD-L1, has revolutionized the therapy of this disease. Because of variable responses to immunotherapy (IMT), there is an urgent need for predictive biomarkers to guide personalization of lung cancer treatment. A comprehensive approach to identify and validate IMT-related biomarkers in lung cancer tissue specimens, including digital pathology and genomic methodologies, will be described.

11:45 Beyond PD-L1: Other Potential Companion Diagnostic Tests for Immune Checkpoint Therapy

David L. Rimm, M.D., Ph.D., Professor, Pathology, Yale University

The current companion diagnostic tests and nearly all publications related to immune checkpoint therapies are based on assessment of PD-L1. Some assess PD-L1 in the epithelial component while others emphasize stromal expression. However, there may be other methods for assessment of response to these therapies based on the presence of subsets of T-cells or assessment of the activation of these T-cells. It is also possible that assessment of other co-stimulators or competitive receptors may influence prediction of response to therapy. These non-Pd-L1 methods will be reviewed in this lecture.

12:15 pm Session Break

12:25 Luncheon Presentation I: Shared Accountability:
How Genomics & Informatics Will Engage Consumers,
Providers and Payers toward True Personalized Medicine

Satnam Alag, Ph.D., Vice President, Software Development, Enterprise Informatics

Genomics data is a big deal when context and meaning is attached to it. Smart data - the right data at the right time to the right person - can help Consumers, Providers and Payers enhance and inform care decisions. That's the prize but how do you get your hands on it? We will focus on Genomics & Informatics and how companies like Illumina are working to provide solutions.

Philips12:55 Luncheon Presentation II: Integrated Oncology Diagnostics Enabled by Digital Pathology

Reinhold Wimberger-Friedl, Ph.D., Principal Scientist, Philips Research Europe, Philips

At Philips we develop an integrated approach of staining-based and molecular characterization of the tumor and its micro-environment. Digital pathology with WSI analytics enables a comprehensive quantification of cellular composition of the tumor. A proprietary model determines the tumor-driving signaling pathways from mRNA expression profiles.

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

Balancing Costs with Results and Regulatory Requirements

2:00 Chairperson’s Remarks

Karl V. Voelkerding, M.D., Professor, Pathology, University of Utah; Medical Director, Genomics and Bioinformatics, ARUP Laboratories

2:10 The Utility of Exome Sequencing in Providing Deep Coverage of Disease-Relevant Targets

Avni B. Santani, Ph.D., Assistant Professor, Clinical Pathology and Laboratory Medicine, The Children’s Hospital of Philadelphia

To date, disease-targeted gene panels have generated a lot of interest but exome sequencing (ES) is increasingly gaining acceptance for inherited and somatic diseases with locus and allelic heterogeneity. In this talk, we cover our group’s effort in creating a technically enhanced ES assay that provides adequate coverage of all currently known disease-relevant genes, thereby facilitating high quality exome interpretation as well as exome “slices” for disease panels. Key considerations for test optimization including cost, specimen pooling, data quality and compliance will be discussed.

2:40 Diagnostic Gene Panels in the Exome Era – Using Exome Sequencing as a Universal Assay to Streamline Assay Development and Laboratory Operations

Birgit H. Funke, Ph.D., FACMG, Associate Professor, Pathology, MGH/Harvard Medical School; Director, Clinical Research and Development, Laboratory for Molecular Medicine, Partners HealthCare

The accelerating pace of disease gene discovery is presenting an increasing challenge for diagnostic laboratories as updating targeted gene panels is costly. Improved exome sequencing assays achieve near equal quality and decreasing costs open the door to replacing gene panel assays with virtual panels. This presentation summarizes our experience moving from targeted gene panels to exome-based virtual panels using inherited renal disorders as an example.

3:10 Laboratory Accreditation and Proficiency Testing for Next-Generation Sequencing Diagnostics: An Update on College of American Pathologists Programs

Karl V. Voelkerding, M.D., Professor, Pathology, University of Utah; Medical Director for Genomics and Bioinformatics, ARUP Laboratories

By late 2015, nearly 200 laboratories accredited by the College of American Pathologists indicated that they offered next-generation sequencing-based diagnostics. This number is expected to grow. This presentation will provide an update on accreditation requirements developed by the College specific to laboratories performing NGS based diagnostics. 2015 also marked the launch of the College’s first methods-based proficiency testing program for NGS-based detection of germline variants, for which summary results will be discussed.

3:40 Genome-Wide Prenatal Cell Free DNA Testing: Validation and Clinical Experience

Daniel Grosu, M.D., MBA, CMO, Sequenom, Inc.

A significant proportion of chromosomal and subchromosomal abnormalities in the prenatal setting are not detectable by conventional cfDNA testing. Sequenom seeks to bridge this informational gap through a genome-wide approach that reports on whole chromosome aneuoploidies and CNVs 7 Mb in size across the entire genome, in addition to select microdeletions <7 Mb in size. Validation and clinical experience data will be presented for the new approach.

4:10 St. Patrick’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. 

Integration of various laboratory data into genomic data analysis
Peter L. Nagy, M.D., Ph.D., Assistant Professor, Pathology and Cell Biology; Director, Clinical Next-Generation Sequencing, Laboratory of Personalized Genomic Medicine

  • Database architecture to maximize sensitivity and specificity for detection of previously reported pathogenic variants
  • How to identify novel pathogenic variants
  • How to follow up on novel potentially pathogenic variants

Recent FDA Feedback, Tips and Trends for IVDs

Gail Radcliffe, President, Consulting, Radcliffe Consulting, Inc.


  • RTA Checklist: tips for jumping over the first hurdle
  • Next-Gen Testing: regulation snafu
  • CLIA Waiver: simple and low risk of erroneous result
  • De Novo: providing rationale to support De Novo classification


Genome-Wide Prenatal Cell Free DNA Testing: Closing the Clinical Information Gap

Daniel S. Grosu, MD, MBA, Chief Medical Officer, Sequenom, Inc.


  • How much information is missed by “conventional” NIPT?
  • Clinical relevance of the additional information provided by a genome-wide approach
  • What other “gaps” need to be addressed by non-invasive prenatal testing?


6:00 Close of Day

Wednesday, March 9

7:00 am Registration Open

7:00 am Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee

8:00 Plenary Keynote Session Panel

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


10:50 Chairperson’s Remarks

Victor Velculescu, M.D., Ph.D., Professor, Oncology; Co-Director, Cancer Biology, Johns Hopkins Sidney Kimmel Cancer Center; Co-Founder, Personal Genome Diagnostics

11:00 Precision Medicine and Cancer Drug Discovery

Atul J. Butte, M.D., Ph.D., Director, Institute for Computational Health Sciences; Professor, Pediatrics, University of California, San Francisco

Dr. Butte, a bioinformatician and pediatric endocrinologist, will highlight his lab’s work on using publicly-available molecular measurements to find new uses for drugs including drug repositioning, discovering new durable targets in disease, the evaluation of patients and populations presenting with whole genomes sequenced, and new work on integrating and reusing the clinical and genomic data that result from clinical trials. Dr. Butte will especially cover big data in biomedicine as a platform for innovation and entrepreneurship.

11:30 Characterization of Driver Alterations in Tissue and Liquid Biopsies

Victor Velculescu, M.D., Ph.D., Professor, Oncology; Co-Director, Cancer Biology, Johns Hopkins Sidney Kimmel Cancer Center; Co-Founder, Personal Genome Diagnostics

Analyses of cancer genomes have revealed mechanisms underlying tumorigenesis and new avenues for therapeutic intervention.  In this presentation, I will discuss lessons learned through the characterization of cancer genome landscapes, challenges in translating these analyses to the clinic, and new technologies that have emerged to analyze molecular alterations in the circulation of cancer patients as cell-free tumor DNA.  These approaches have important implications for non-invasive detection and monitoring of human cancer, therapeutic stratification, and identification of mechanisms of resistance to targeted therapies.

12:00 pm Enterprise-Wide Clinical Sequencing to Match Patients to Personalized Cancer Therapies

Michael F. Berger, Ph.D., Associate Director, Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center

Massively parallel sequencing can empower oncologists to make treatment decisions informed by the molecular composition of their patients’ cancers. We have developed and implemented a robust molecular profiling platform for use in real-time patient management at a large academic cancer center. I will discuss the large-scale clinical deployment of our platform and its utility in matching patients to clinical trials to provide investigational therapies the greatest chance of success.

12:30 Session Break

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

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


1:50 Chairperson’s Remarks

German Pihan, M.D., Director, Hematopathology Lab, Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School

2:00 Novel Clinical Applications of Cancer Genomics

Luis A. Diaz, M.D., Associate Professor, Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Novel technologies to evaluate genomics-based tumor burden in tumor tissue and bodily fluids have opened the doors for several new clinical applications that will address unmet clinical needs in Oncology. This lecture will discuss these high-impact applications in the context of the most recent technologies.

2:30 What is a Cancer Mutation? Challenges in Detecting, Interpreting, and Targeting Somatic Variants

Joshua M. Stuart, Ph.D., Baskin Engineering Endowed Chair & Professor, Biomolecular Engineering,; Associate Director, Center for Biomolecular Science and Engineering, University of California, Santa Cruz

DNA sequencing provides an unprecedented potential to catalog all somatic alterations in tumor genomes. Yet the task of assembling raw reads into biologically-interpretable information is still a “Wild West” of algorithms. In the talk, I will discuss an open competition to identify the best mutation calling algorithms. After a year of collecting results from hundreds of methods, we learned some ingenious tricks from some, and pitfalls that tripped up most, competitors.

3:00 Noninvasive Monitoring of Lymphoma by Sequencing of Circulating Tumor DNA

Ash A. Alizadeh, Ph.D., Principal Investigator, Assistant Professor, Medicine, Divisions of Oncology & of Hematology; Attending Physician, Lymphoma Oncology Clinic, Stanford Cancer Center, Stanford University

Recent studies have shown limited utility of routine surveillance imaging for diffuse large B-cell lymphoma (DLBCL) patients achieving remission. Detection of molecular disease in peripheral blood provides an alternate strategy for surveillance. I will describe strategies for noninvasive monitoring of lymphoma by sequencing of circulating tumor DNA, including performance characteristics of various assays, their clinical applications, and their promise for future translations studies.

3:30 NGS-Based Diagnostics: Developing Assays and Monitoring Performance Using Novel Biosynthetic QC Tools

Russell Garlick, Ph.D., CSO, SeraCare Life Sciences

Results from an Inter-Laboratory Study Using Novel Biosynthetic QC Tools: There are currently no widely-accepted NGS QC standards for multi-analyte diagnostic assays which hampers the ability to compare the performance of different assays. Preliminary results will be presented from a study testing the SeraseqTM Solid Tumor Mix-I as a qualitative and quantitative QC indicator for tumor profiling.

4:00 Session Break

4:10 Chairperson’s Remarks

German Pihan, M.D., Staff Pathologist and Director, Diagnostic Hematopathology Service, Pathology, Beth Israel Deaconess Medical Center

4:15 Darwinian Cancer Genome Evolution: The Achilles Heel of Precision Cancer Medicine. Can It Be Overcome?

German Pihan, M.D., Staff Pathologist and Director, Diagnostic Hematopathology Service, Pathology, Beth Israel Deaconess Medical Center

The high rate of mutations in cancer is the single most important challenge to the success of precision medicine in cancer. Whole genome sequencing is beginning to elucidate the patterns, pathways and causes of the astonishingly dynamic high rate of somatic mutation in most cancers. Understanding these pathways will prove challenging but fundamentally important to succeed in the fight against cancer. This talk will define the nature of the Darwinian cancer genome evolution challenge and propose possible avenues to surmount it.

4:45 Who Should Regulate Cancer NGS Tests: FDA, CMS/CLIA, or Both?

Roger D. Klein, M.D., J.D., Chair, Professional Relations Committee, Association for Molecular Pathology (AMP); Medical Director, Molecular Oncology, Cleveland Clinic

This presentation will discuss current controversies and potential regulatory approaches for the oversight of next generation sequencing testing for oncology applications.


5:45 Close of Conference Program