Advances in molecular diagnostics technologies have sparked innovation, expanded research capabilities, and enhanced clinical diagnostics. Cambridge Healthtech Institute’s Fifth Annual PCR and NGS-Based Diagnostics puts an emphasis
on the technologies that drive personalized medicine, from PCR and NGS to microarrays, and showcases how they are being used to alter clinical outcomes. This event will provide a comprehensive look at integrating molecular diagnostics solutions for
biomarker discovery and development, point-of-care, companion diagnostics, and infectious disease. Molecular technologies will be compared and evaluated and case studies on getting regulatory approval will be shared. Overall, this event provides insight
into advanced techniques and tools for effective disease diagnosis.
Monday, February 12
10:30 am Conference Program Registration Open
11:50 Chairperson’s Opening Remarks
Apostolia-Maria Tsimberidou, M.D., Ph.D., Professor, Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center
12:00 pm Optimization of Precision Medicine in the Era of Immunotherapy
Apostolia-Maria Tsimberidou, M.D., Ph.D., Professor, Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center
The availability of novel immunotherapeutic agents and targeted therapy holds the promise of expediting the availability of precision medicine in the treatment of cancer. Development of clinically meaningful biomarkers and optimization of clinical trials
will improve the clinical outcomes of patients with advanced cancer. Objectives: 1) optimization of use of targeted therapy, 2) immunotherapy as targeted therapy: biomarker development, 3) completed and ongoing clinical trials to expedite the implementation
of precision medicine.
12:30 Different Whole Genome Sequencing Strategies for the Clinical Management of Patients with Oropharyngeal Squamous Cell Carcinoma
David I. Smith, Ph.D., Professor, Department of Laboratory Medicine and Pathology, Chairman of the Technology Assessment Group, Center for Individualized Medicine, Mayo Clinic
1:00 Session Break
1:10
Luncheon Presentation I: An Engineered DNA Ligase for Efficient Conversion of Input DNA during NGS Library Preparation
John Nicols President & CEO Codexis, Inc.
Molecular diagnostics NGS assays are critically dependent on efficient conversion of low-concentration DNA samples to sequencing-capable fragments via adapter ligation. An engineered DNA ligase was developed to achieve exceptional conversion of low-concentration
input DNA, with improved reaction kinetics relative to T4 ligase, while maintaining low adapter dimerization activity. The Codexis Performance DNA Ligase is ideally suited for NGS IVD applications, where it will improve assay sensitivity and increase
workflow flexibility and robustness.
1:40 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 Panel Discussion
Moderator: Apostolia-Maria Tsimberidou, M.D., Ph.D., Professor, Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center
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.
4:10Validation 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)
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
Weian Zhao, Ph.D., Assistant Professor, Department of Pharmaceutical Sciences, Sue and Bill Gross Stem Cell Research Center, Chao Family Comprehensive Cancer Center, Edwards Lifesciences Center for Advanced Cardiovascular Technology, Department
of Biomedical Engineering, University of California–Irvine
10:15 One-Step, Rapid Detection of Antibiotic Resistant Bacteria in Blood Stream Infections Using High Volume Droplet Blood PCR
Weian Zhao, Ph.D., Assistant Professor, Department of Pharmaceutical Sciences, Sue and Bill Gross Stem Cell Research Center, Chao Family Comprehensive Cancer Center, Edwards Lifesciences Center for Advanced Cardiovascular Technology, Department
of Biomedical Engineering, University of California, Irvine
Antibiotic resistance represents a major global health threat. Lack of rapid diagnostics in the current paradigm of clinical microbiology, especially for bloodstream infections (BSIs), has resulted in use of inappropriate or unnecessarily
broad-spectrum antibiotics, which are associated with significantly increased morbidity, mortality and healthcare cost as well as having the potential to select for resistant strains. In this presentation, we will discuss a new high
throughput blood droplet PCR technology for rapid bacterial detection directly in blood samples without culture and sample processing.
10:45 Rapid Phenotypic Antibiotic Susceptibility Testing Directly from Clinical Samples Using Single-Molecule Counting
Rustem Ismagilov, Ph.D., Professor, Chemistry & Chemical Engineering, California Institute of Technology
Rapid antibiotic susceptibility testing (AST) is critical for delivering care and enabling antibiotic stewardship. Phenotypic AST is the gold standard, but is unacceptably slow, requiring pre-culture steps. Genotypic AST has not been sufficiently
general to replace the gold standard (especially in Gram-negative organisms). We use SlipChip for digital single-molecule counting of pathogen-specific RNA and DNA to perform phenotypic AST directly from clinical samples in as fast
as 30 minutes.
11:15 Developing Ultrasensitive Molecular Methods for Rapid Bacterial Identification and Antibiotic Resistance Profiling
Shana Kelley, Ph. D., Professor, Department of Pharmaceutical Sciences, University of Toronto
We are developing several different platforms for rapid bacterial analysis and the detection of antibiotic resistance. Devices that enable genetic analysis in heterogeneous samples will be described.
11:45 Enjoy Lunch on Your Own
1:25 Refreshment Break in the Exhibit Hall with Poster Viewing
2:00 Chairperson’s Remarks
Elaine Lyon, Ph.D., Medical Director, Molecular Genetics and Genomics, ARUP Laboratories; Professor, Pathology, University of Utah School of Medicine; Past President, Association for Molecular Pathology
2:10 Regulatory Innovation: Keeping Pace with NGS atop the Shifting Sands of Precision Medicine
Peggy Carter, Ph.D., Global Head, Regulatory Affairs, Oncology Precision Medicine, Novartis
Regulatory innovation may no longer be an oxymoron. The “one drug, one test” paradigm in precision medicine is not sustainable and we look to technologies such as NGS and new ways of regulatory thinking to move to the next
level. Recent examples of first-of-their kind approvals in the precision medicine space reveal the beginnings of a much-needed paradigm shift.
2:40 Setting Up a Framework to Facilitate Implementation of Performance and Design Standards for Clinical NGS
Birgit Funke, Ph.D., FACMG, Vice President, Clinical Affairs, Veritas Genetics; Associate Professor, Pathology, Harvard Medical School
Next-generation sequencing (NGS)-based testing has transitioned from a niche technology to widespread adoption in clinical testing. Numerous recommendations and guidelines provide high level education but detailed and practical implementation
support is lacking. This presentation describes an effort led by the College of American Pathologists (CAP) that provides systematic step-by-step education to guide clinical testing laboratories through all steps of the lifecycle
of a clinical NGS test.
3:10 Towards Design Control for LDTs: Establishing Performance Criteria for NIPT
Elaine Lyon, Ph.D., Medical Director, Molecular Genetics and Genomics, ARUP Laboratories; Professor, Pathology, University of Utah School of Medicine; Past President, Association for Molecular Pathology
CLIA requires that high complexity laboratories establish and verify performance characteristics before introducing a new testing procedure. Laboratory developed procedures (LDPs) may be validated under CLIA and CAP accreditation standards,
while ISO15189 accreditation and FDA clearance specifies that validation/verification must be performed under design control. This presentation will discuss establishing, validating and verifying performance characteristics under
design control for LDPs, using non-invasive prenatal testing (NIPT) as an example.
3:40 Using Genetics to Select Safer Targets and Drugs
Lucas D. Ward, Ph.D., Senior Scientist, Human Genetics and Functional Genomics, Comparative Biology and Safety Sciences, Amgen
Genetics is increasingly being used in two major ways: to discover new targets through variation in populations (studying diseases), and to stratify drug response clinically (studying patients; pharmacogenetics). Early-stage genetic
validation often focuses more on efficacy than safety. I will discuss how genetics can be used, even pre-clinically, to improve safety: anticipating target-mediated adverse events, which we have demonstrated are statistically linked
to target genetics; and constructing drug selectivity panels.
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, and 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 Medicine
Prasun Mishra, PhD, 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, PhD, 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
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
Gregory Storch, M.D., Ruth L. Siteman Professor, Pediatrics, Washington University School of Medicine
11:00 Relative Roles of PCR and NGS for Viral Diagnosis
Gregory Storch, M.D., Ruth L. Siteman Professor, Pediatrics, Washington University School of Medicine
Several important trends are occurring in diagnostic virology. Amplification-based testing is maturing, with increasing availability of FDA-approved and cleared assays. Some testing is moving towards centralized platforms in core laboratories
while other testing is moving centrifugally to near and at point-of-care locations. NGS offers very exciting potential for nonbiased detection. This talk will describe these trends and their interrelationships.
11:30 MPseq and Its Applications to the Clinical Setting
George Vasmatzis, Ph.D., Co-Director, Biomarker Discovery Program, Center for Individualized Medicine; Consultant, Department of Molecular Medicine; Associate Professor, Molecular Medicine, Mayo Clinic College of Medicine and Science,
Rochester, MN
We have developed MPseq, an accurate and inexpensive whole genome sequencing platform that has been used to detect structural variants. MPseq is a combination of a protocol and algorithms that can replace several cytogenetic tests
and provide comprehensive diagnostic value with high specificity, sensitivity and cost-effectiveness. Most importantly our process can provide a detailed description of all DNA rearrangements at a resolution that can show how individual
genes are disturbed thus providing necessary novel insight for correct clinical interpretation.
12:00 pm Molecular Detection of Emerging Pathogens in Low-Resource Settings
Robert Meagher, Ph.D., Research Scientist, Sandia National Laboratories
Emerging infectious diseases often occur in parts of the world that lack even the most basic infrastructure that underlies modern clinical diagnostics. We summarize developments in molecular assays, sample prep, and detection that
increasingly allow laboratory-quality diagnostic assays to be performed in low-resource settings, including our own work with smartphone-based detection of viral pathogens. We also discuss limitations of these techniques and open
areas of inquiry, including tradeoffs between simplicity and assay performance.
12:30 Session Break
12:40 Enjoy Lunch on Your Own
1:10 Dessert Break in the Exhibit Hall and Last Chance for Poster Viewing
1:50 Chairperson’s Remarks
Gregory Storch, M.D., Ruth L. Siteman Professor, Pediatrics, Washington University School of Medicine
2:00 GV9 – A New, Sensitive and Economic Method for Species-Level 16S Bacterial Characterization
Seth Crosby, M.D., Director, Partnerships & Alliances, Washington University School of Medicine
16S methods currently employed are, generally, limited to analysis of a single hypervariable region which makes taxonomic classification difficult beyond the genus level without a substantial false positive rate. To address this issue,
a novel method, named GV9, has been developed to enhance species level calls and abundance estimates through simultaneous analysis and dynamic selection of multiple hypervariable regions.
2:30 Multiplex Real-Time PCR Assays that Assess the Abundance of Rare Mutations Associated with Cancer
Fred Kramer, Ph.D., Professor, Microbiology, Biochemistry & Molecular Genetics, Public Health Research Institute, Rutgers University
“SuperSelective” PCR primers, due to their unique design, amplify rare mutant DNA fragments in liquid biopsy samples, while ignoring abundant related wild-type fragments. Multiplex PCR assays utilize SuperSelective primers
that contain unique 5’-tag sequences, enabling each different amplicon to be detected with a differently colored molecular beacon probe. As many as 35 different mutations can be assessed simultaneously. These assays are extraordinarily
sensitive, rapid, and inexpensive.
3:30 Session Break
3:40 Chairperson’s Remarks
Kai Wang, Ph.D., Principal Scientist, Institute for Systems Biology
3:45 The Prospect of PCR & NGS-Based Molecular Diagnostics
Kai Wang, Ph.D., Principal Scientist, Institute for Systems Biology
Circulating nucleic acids, especially cell-free DNA, has been the center of most NGS-based molecular diagnostics in recent years. Even though the circulating RNA isn’t as well developed as DNA in clinical application yet, it
has tremendous potential. Several factors may impact the analysis of circulating nucleic acids. We will address and discuss some of the possible issues.
4:15 A Non-Invasive Urinary Common Rejection Module (uCRM) QPCR Gene Expression Score for Kidney Transplant Injury
Tara Sigdel, Ph.D., Assistant Professor, Surgery, University of California, San Francisco
Urine offers an attractive source of biomarkers for urological and kidney related diseases. A qPCR assay for a gene panel as a biomarker for kidney transplant rejection and injury has been developed and optimized. The talk will summarize
the strategy for discovery and validation of this assay which is highly relevant in other diseases as well.
4:45 Comparison of Gene Expression Profiles on nanoString vs. Fluidigm qPCR Platforms on Human Renal Allograft Biopsies
Dejan Dobi, M.D., Postdoctoral Scholar, Pathology, University of California, San Francisco
We conducted a performance comparison study between nanoString’s nCounter platform (barcoded oligonucleotide-based technology for gene-expression analysis) and standard (Fluidigm) qPCR on matched FFPE and RNA later-preserved
human kidney allograft biopsies. In addition to demonstrating the feasibility of the nanoString platform on FFPE samples, we show various applications to address biologically relevant questions in the renal transplant setting.
5:15 Close of Conference Program