Cambridge Healthtech Institute’s Inaugural

NGS Advances and Multimodality Assays

NGS Technology Trends and New Applications

August 26 - 27, 2020 ALL TIMES EDT

Next-generation sequencing (NGS) has become an integral part of molecular diagnostics, with applications ranging from inherited disorders and oncology, to infectious disease, to prenatal diagnostics. NGS-based assays are getting more sophisticated as they are combined in cohesive assays with other detection technologies and modalities. CHI's Inaugural NGS Advances and Multimodality Assays conference will focus on the latest NGS developments, including whole genome sequencing as a diagnostics platform, as well as on multiomics and multimodality assays.

Wednesday, August 26

PLENARY KEYNOTE SESSION

11:10 am

Organizer's Opening Remarks

Christina Lingham, Executive Director, Conferences and Fellow, Cambridge Healthtech Institute
11:15 am

Ultrasensitive SARS-CoV-2 Protein Assays for Precision Clinical Decisions

 

David Walt, PhD, HHMI Professor; Hansjörg Wyss Professor of Biologically Inspired Engineering, Harvard Medical School; Professor of Pathology, Department of Pathology-Brigham and Women’s Hospital; Core Faculty, Wyss Institute for Bioinspired Engineering, Harvard University

We have developed ultrasensitive single molecule assays for multiple relevant SAR-CoV-2 proteins that can detect both active virus and prior infection. The assays have been tested in thousands of individuals, including patients and healthcare workers and exhibit exceptional sensitivity and specificity. Additionally, we have followed these protein concentrations over time during the course of disease in many patients and can predict outcomes based on the dynamics of the protein responses.

 

11:40 am PANEL DISCUSSION :

Lessons Learned for Diagnostic Testing During the COVID-19 Pandemic

Panel Moderator:
Susan Hsiao, MD, PhD, Assistant Professor, Pathology and Cell Biology, Columbia University Medical Center
  • Supply chain challenges
  • Navigating and validating multiple platforms
  • Reimbursement
  • Value of distributed testing
  • Value of tests available: PCR vs. antigen vs. serology
  • Developing sustainable testing protocols
Panelists:
Alex Greninger, MD, PhD, MS, MPhil, Assistant Professor, Laboratory Medicine, University of Washington
Jordan S. Laser, MD, Medical Director, Department of Pathology and Laboratory Medicine; LIJMC; Associate Medical Director, Core Laboratories; Director, Division of Near Patient Testing, Northwell Health; Associate Professor, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell
David Walt, PhD, HHMI Professor; Hansjörg Wyss Professor of Biologically Inspired Engineering, Harvard Medical School; Professor of Pathology, Department of Pathology-Brigham and Women’s Hospital; Core Faculty, Wyss Institute for Bioinspired Engineering, Harvard University
Charles Mathews, Principal, ClearView Healthcare Partners
12:30 pm Fireside Chat
Panel Moderator:
Charles Mathews, Principal, ClearView Healthcare Partners
Panelists:
Sara Brenner, MD, MPH, Associate Director for Medical Affairs; CMO, In Vitro Diagnostics, Office of In Vitro Diagnostics & Radiological Health (OIR), Office of Product Evaluation & Quality (OPEQ), Center for Devices & Radiological Health (CDRH), U.S. Food & Drug Administration
12:55 pm Lunch Break - View Our Virtual Exhibit Hall

BREAKTHROUGHS AND NOVEL APPLICATIONS

1:30 pm The Intersection of Knowledge Informatics and Clinical NGS Platforms
Carl Morrison, MD, DVM, Senior Vice President, Pathology, Roswell Park Cancer Institute

Next generation sequencing for clinical tumor profiling can be considered to have four levels of analysis beginning with the conversion of raw data into sequencing data (FASTQ), alignment and variant calling (BAM, vcf),  annotation (filtered vcf), and interpretation (clinical report). Over the past few years the path of the first three of these steps have been extensively discussed and published, while the latter of interpretation, or clinical reporting, remains much less so. There are likely many reasons for this discrepancy, including intellectual property, but foremost is the lack of involvement of clinicians in the actual clinical reporting process. At the root cause of this issue is the lack of established clinically oriented knowledge informatics databases at the variant level. This talk will provide a background on the use of one or more knowledge informatics databases at the variant level that allows for the involvement of clinicians in the actual clinical reporting process beyond the typical analytical phases of analysis.

1:50 pm Cell-by-Cell: Building High-Resolution Tumor Atlases
Asaf Rotem, PhD, Associate Director, Center for Cancer Precision Medicine, Dana Farber Cancer Institute

After years of improved cancer therapy, we still struggle to understand malignancies. A major obstacle is our lack of understanding of cancer complexity and its microenvironment. In the last years, we and others developed tools to uncover the transcriptomes of patient-derived single cells. This cutting-edge approach, complimented with other technologies, is central in understanding tumors by creating detailed atlases.

Robert Schlaberg, MD, PhD, MPH, Co-Founder, Chief Medical Officer, Medical & Scientific Affairs, IDbyDNA

Infectious disease detection is of critical importance in today’s pandemic-stricken world. Clinical metagenomics with next generation sequencing uniquely addresses the challenges of pathogen detection and surveillance using breakthrough technologies such as the Explify® Platform from IDbyDNA. Explify converts sequencing data to insight by applying robust bioinformatics and machine learning, and can be applied to unbiased shotgun sequencing, focused amplicon sequencing, or syndrome-based target enrichment to identify various pathogen types within a single sample.

2:35 pm PANEL DISCUSSION:

LIVE Q&A and Session Wrap Up

Panel Moderator:
Carl Morrison, MD, DVM, Senior Vice President, Pathology, Roswell Park Cancer Institute
Panelists:
Asaf Rotem, PhD, Associate Director, Center for Cancer Precision Medicine, Dana Farber Cancer Institute
Robert Schlaberg, MD, PhD, MPH, Co-Founder, Chief Medical Officer, Medical & Scientific Affairs, IDbyDNA
2:45 pm Refresh Break - View Our Virtual Exhibit Hall

FEATURED SESSION: NUCLEIC ACID DETECTION

3:35 pm Engineering Biology for Diagnostic Solutions
William Blake, PhD, CTO, Sherlock Biosciences

SHERLOCK is a method for single molecule detection of nucleic acid targets and stands for Specific High Sensitivity Enzymatic Reporter unLOCKing. It works by amplifying genetic sequences and programming a CRISPR molecule to detect the presence of a specific genetic signature in a sample, which can also be quantified. When it finds those signatures, the CRISPR enzyme is activated and releases a robust signal. This signal can be adapted to work on a simple paper strip test, in laboratory equipment, or to provide an electrochemical readout that can be read with a mobile phone.

3:55 pm Instrument-Free Paper-Based POC Pathogen Diagnostics for the Clinic and the Home
Paul Yager, PhD, Professor, Department of Bioengineering, University of Washington

Instruments ranging from the venerable GeneXpert to ones just coming on the market allow fairly rapid NAAT pathogen detection, but they are based on disposable cartridges and a permanent (and relatively expensive) instrument. Our lab has been developing instrument-free disposable NAAT devices that retain the advantages of the instrumented systems, but free the user from the need for purchasing a permanent instrument (and the upfront cost that incurs).

4:15 pm LIVE Q&A:

Session Wrap-Up

Panel Moderator:
Shawn Mulvaney, PhD, Section Head, Surface Nanoscience and Sensor Technology Section, Chemistry, U.S. Naval Research Laboratory
Panelists:
William Blake, PhD, CTO, Sherlock Biosciences
Paul Yager, PhD, Professor, Department of Bioengineering, University of Washington
4:25 pm Happy Hour - View Our Virtual Exhibit Hall
5:00 pm Close of Day

Thursday, August 27

MULTIPLEX PANELS

9:00 am

Chairperson's Remarks

Esther Babady, PhD, D(ABMM), FIDSA, Section Head, Clinical Microbiology Service, Memorial Sloan Kettering Cancer Center
9:05 am

Comparison: Nanopore Sequencing and Microarray Resequencing for Multiplex Pathogen Identification

Robert Duncan, PhD, Principal Investigator, Office of Blood Research and Review, Center for Biologics Evaluation and Research (CBER), FDA

GeneChip Resequencing microarrays have been advanced for infectious disease agent detection and identification from Ebola to Zika. Next-generation sequencing with the highly mobile and cost-effective nanopore sequencing device is challenging the supremacy of the microarray in rapid point-of-need pathogen detection. This talk will present results of side-by-side application of these two platforms for detection in pathogen-spiked blood samples and compare their performance.

9:20 am Syndromic Testing for Meningitis/Encephalitis: Saga of the Love-Hate Relationship
Jennifer Dien Bard, PhD, D(ABMM), Director, Microbiology and Virology, Children’s Hospital Los Angeles; Associate Professor, Pathology and Laboratory Medicine, Keck School of Medicine, University of Southern California

As part of the Multiplex Panel session, this talk will focus on multiplex testing for the laboratory diagnosis of meningitis and encephalitis as compared to standard-of-care testing. The potential benefits and limitations of panel testing for meningitis and encephalitis compared to standard-of-care testing will be discussed. The potential approaches to maximize testing yield will also be discussed.

9:35 am The Biofire Pneumonia Panel: Does It Relate to Microbiological and Clinical Variables?
Kenneth Rand, MD, Medical Director, Clinical Microbiology Laboratory; Professor, Pathology and Medicine, University of Florida

The BioFire FilmArray Pneumonia Panel (PP) detects 15 common bacterial pathogens semi-quantitatively (copy # from 104 to 107), 3 atypical pneumonia bacteria, 8 viruses, and 7 antimicrobial resistance markers by multiplex PCR in about 1 hour in the laboratory. Results of our 396-patient study suggest PP detects more bacterial isolates than conventional microbiology, and the copy number correlates with outcome variables, such as ICU length of stay, temperature, and white cells in the BAL. Results reported in a 3-4 h timeframe after a BAL could potentially improve both antibiotic choice and de-escalation in critically ill intubated patients.

9:50 am PANEL DISCUSSION : Advancing Multiplex Panels for Clinical Diagnostics
Panel Moderator:
Esther Babady, PhD, D(ABMM), FIDSA, Section Head, Clinical Microbiology Service, Memorial Sloan Kettering Cancer Center
  • Comparison of multiplex platforms
  • Reimbursement considerations
  • Proving clinical utility of multiplex diagnostic tests
Panelists:
Robert Duncan, PhD, Principal Investigator, Office of Blood Research and Review, Center for Biologics Evaluation and Research (CBER), FDA
Jennifer Dien Bard, PhD, D(ABMM), Director, Microbiology and Virology, Children’s Hospital Los Angeles; Associate Professor, Pathology and Laboratory Medicine, Keck School of Medicine, University of Southern California
Kenneth Rand, MD, Medical Director, Clinical Microbiology Laboratory; Professor, Pathology and Medicine, University of Florida
10:05 am Coffee Break - View Our Virtual Exhibit Hall
10:15 am Problem Solving Discussions - View Our Virtual Exhibit Hall

BREAKOUT 13: Genomic Biomarkers in Oncology: Today and Tomorrow

Carl Morrison, MD, DVM, Senior Vice President, Pathology, Roswell Park Cancer Institute

OPPORTUNITIES AND CHALLENGES OF EARLY DIAGNOSIS OF DISEASE

10:45 am

Chairperson's Remarks

John Sninsky, PhD, Independent Consultant, Translational Medicine and Science
10:50 am Opportunity for Pre-Competitive Multi-Stakeholder Collaboration for NAFLD Detection and Intervention
Veronica Miller, PhD, Executive Director, Forum for Collaborative Research

Non-alcoholic fatty liver disease (NAFLD) affects approximately 25% of adults and 10% of children in the U.S. and is associated with obesity, type 2 diabetes mellitus, dyslipidemia and hypertension. Severe clinical outcomes include decompensated cirrhosis and hepatocellular carcinoma. The current diagnostic standard for non-alcoholic steatohepatitis (NASH), the more advanced form of NAFLD, is based on liver biopsies. Early diagnosis of the higher risk individuals is paramount. Representation and active engagement of scientific experts from all stakeholder groups in a non-competitive environment increases clarity and standardization while decreasing uncertainty. Lessons learned will be summarized.

11:10 am Breast Cancer Overdiagnosis and the Precancer Problem
Alexander Borowsky, PhD, Associate Professor, Pathology and Laboratory Medicine, University of California, Davis

Breast cancer screening by mammography, which began in the U.S. about 40 years ago, has led to significant increases in the incidence of early-stage breast cancers, including ductal carcinoma in situ (DCIS), also called precancer or stage 0 disease. However, the expected reciprocal decrease in subsequent late-stage breast cancers was not found. It is now clear that some screen-detected breast “cancers” are indolent lesions without significant malignant potential.

11:30 am PANEL DISCUSSION:

Opportunities and Challenges of Early Diagnosis of Disease

Panel Moderator:
John Sninsky, PhD, Independent Consultant, Translational Medicine and Science
Panelists:
Alexander Borowsky, PhD, Associate Professor, Pathology and Laboratory Medicine, University of California, Davis
Veronica Miller, PhD, Executive Director, Forum for Collaborative Research
11:50 am Lunch Break - View our Virtual Exhibit Hall

NEXT-GENERATION AND CLINICAL METAGENOMIC SEQUENCING

12:15 pm

Chairperson's Remarks

Norman Moore, PhD, Director, Scientific Affairs, Abbott
12:40 pm Clinical Metagenomic Sequencing and Human Host Response: Changing the Diagnostic Paradigm?
Charles Chiu, MD, PhD, Professor, Laboratory Medicine and Medicine/Infectious Diseases, Director, UCSF-Abbott Viral Diagnostics and Discovery Center, Associate Director, UCSF Clinical Microbiology Laboratory, UCSF School of Medicine

Metagenomic next-generation sequencing (mNGS) is a transformative technology for infectious disease diagnosis as it enables detection of nearly all pathogens – viruses, bacteria, fungi, and parasites – in a single assay. Here we will discuss the integration of multiple approaches to enhance the clinical utility of body fluid mNGS, including nanopore sequencing, CRISPR-Cas12-based pathogen detection, complementary host response analyses, and simultaneous diagnosis of cancer.

12:20 pm FLASH: A Next-Generation CRISPR Diagnostic for Multiplexed Detection of Antimicrobial Resistance Sequences
Emily Crawford, PhD, Scientist II, Infectious Disease Initiative, Chan Zuckerberg Biohub
1:00 pm

Metagenomic Next-Generation Sequencing to Detect & Predict Antimicrobial Resistance

Patricia Simner, PhD, D(ABMM), Associate Professor, Pathology; Director, Bacteriology, Division of Medical Microbiology, The Johns Hopkins University School of Medicine

Initial efforts for applying metagenomic next-generation sequencing (mNGS) for infectious disease diagnostics have focused on pathogen detection. However, we can also gain information on antimicrobial resistance markers, virulence factors or even host biomarkers associated with different disease states. In this presentation, we will discuss the challenges of using mNGS for detection of antimicrobial resistance genes to predict phenotypes and discuss the current status of mNGS for detection of antimicrobial resistance.

1:20 pm LIVE Q&A:

Session Wrap-Up

Panel Moderator:
Norman Moore, PhD, Director, Scientific Affairs, Abbott
Panelists:
Emily Crawford, PhD, Scientist II, Infectious Disease Initiative, Chan Zuckerberg Biohub
Charles Chiu, MD, PhD, Professor, Laboratory Medicine and Medicine/Infectious Diseases, Director, UCSF-Abbott Viral Diagnostics and Discovery Center, Associate Director, UCSF Clinical Microbiology Laboratory, UCSF School of Medicine
Patricia Simner, PhD, D(ABMM), Associate Professor, Pathology; Director, Bacteriology, Division of Medical Microbiology, The Johns Hopkins University School of Medicine
Robert Schlaberg, MD, PhD, MPH, Co-Founder, Chief Medical Officer, Medical & Scientific Affairs, IDbyDNA
1:35 pm Close of Summit