Cambridge Healthtech Institute’s Fourth Annual 

Genomic Sample Prep, Biomarker Assay Development and Validation

Technologies to Enable High Sensitivity Molecular Applications

February 20-22, 2017 | Moscone North Convention Center | San Francisco, CA
Part of the 24th International Molecular Medicine Tri-Conference

 

Developing a high sensitive, reproducible and robust molecular assay may be a challenge regardless of whether it is an IVD or an LDT assay. Sample preparation serves as the pivotal foundation for any advanced molecular assay development. Novel sample preparation technologies have the ability to significantly increase sensitivity and specificity of a test that is run on a heterogeneous sample or a sample that contains a low concentration of analyte. Cambridge Healthtech Institute’s Fourth Annual Genomic Sample Prep, Assay Development, and Validation conference is designed to bring together leading industry and academia experts in biospecimen science and molecular diagnostics to discuss major challenges and latest advances in sample preparation for advanced molecular diagnostics technologies as well as development and validation of NGS and other advanced diagnostics assays.



Monday, February 20

10:30 am Conference Program Registration Open

ASSAY DEVELOPMENT AND VALIDATION TO ADVANCE GENOMIC MEDICINE

11:50 Chairperson’s Opening Remarks

Lin Wu, Ph.D., Vice President, Development, Roche

12:00 pm KEYNOTE PRESENTATION: Analytical Validation of a Liquid Biopsy NGS Assay

Lin Wu, Ph.D., Vice President, Development, Roche Sequencing Solutions, Inc.

This presentation will focus on important issues of analytical validation of NGS assays. Both IVDs and LDTs strategies will the covered. In this talk we will share the Roche Sequencing Solutions best practices and approaches that allow to bring high sensitive and robust assays on the market. 

12:30 Eliminating Barriers to Precision Diagnostics: Cost, Content, Turn-Around Time and Sample Size

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

Next Generation Sequencing has tremendous potential for disrupting routine clinical practice in many areas of medicine. As many health care practices look to build precision medicine programs, access to clinical NGS testing for every patient is currently limited by several challenges. The key to successful broad adoption is building genomic programs that are cost effective, provide fast turnaround time, work with low levels of FFPE DNA input and are focused on content that reduces the incidence of unclear variants.

1:00 Session Break

1:10 Luncheon Presentation I: Optimization of a Magnetic-Bead Based Extraction Method Compared to a Silica-Based Method to Measure HSV-2 Viral Shedding Rapidly and Efficiently

David Yu, Ph.D., Group Leader, Molecular Core, Translational Medicine, Genocea Biosciences

 1:40 Session Break

UNCONVENTIONAL SPECIMENS AND BIOSPECIMEN SCIENCE ADVANCES

2:30 Chairperson’s Remarks

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

2:40 Saliva and Salivaomics

David T.W. Wong, D.M.D., DMSc, University of California Los Angeles, Felix & Mildred Yip Endowed Professor & Associate Dean of Research, School of Dentistry, Director, Center for Oral/Head & Neck Oncology Research

Advances in the science of salivary diagnostics have led to identification of disease signatures of candidate biomarkers and/or confirmation of genetic susceptibility for systemic conditions, particularly in molecular oncology. With the development of the salivary proteome, transcriptome, micro-RNA, metabolome and microbiome as diagnostics alphabets (salivaomics) fully enable saliva to be translated for personalized individual medicine applications. A recent development is the demonstration of saliva detection of oncogenic mutations in human cancers (e.g. EGFR mutations in NSCLC patients). Coupled with the development of point-of-care technologies and the emerging trend of chairside screening for medical conditions, the clinical impact of scientifically credentialed salivary biomarkers for molecular oncology application will include the improvement of access to care, reducing health disparities and impacting global health

3:10 Charting the Human Transcriptome: the Genotype Tissue Expression (GTEx) project.

François Aguet, Ph.D., Computational Biologist, GTEx LDACC, Broad Institute of Harvard and MIT

The GTEx project is an NIH funded project with an ambitious goal of collecting multiple human tissue samples from post-mortem donors and sequencing both the donor’s DNA, and tissue-derived RNA, to characterize the genetic basis of gene expression, gene regulation, and how these relate to health and disease. Over 25,000 histologically-characterized tissues have been collected from 960 donors and RNA-sequenced, creating the largest multi-tissue map of the human transcriptome.

3:40 How to Expedite Access to Large Biospecimen Collections Needed to Validate Liquid Biopsy Based Assays

Pascal Puchois, Ph.D., CEO, Trans-Hit Biomarkers

Access to large biospecimen collection (low-incidence-of-mutations, late-stage-cancers, matched-tissues-and-blood-material, relevant-associated-medical-data,..) is the major bottleneck for rapidly validating liquid biopsy based assays. A worldwide network of biobanks able to collect thousands of specimen (colorectal-cancer, lung-cancer,) under strict procedures is key for Industry,…

4:10 Total Nucleic Acid Profiling of FFPE Tumors

Jeffrey Conroy, Senior Vice President, Technology Development, OmniSeq Precision Medicine; Director, Genomic Technologies, Roswell Park Cancer Institute

Formalin-fixed, paraffin-embedded (FFPE) tissue samples provide a valuable source of nucleic acids. Extraction of DNA and RNA in tumor samples is a challenge, however, given the limited mass, method of preservation and downstream clinical test requirements. In this talk, we will discuss the aspects of tissue selection, pre-analytical processing, and total nucleic acid extraction from a single tissue specimen for downstream targeted NGS mutation detection and gene expression profiling.

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, February 21

7:30 am Registration Open and Morning Coffee

8:00 Plenary Keynote Session

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

NGS ASSAY DEVELOPMENT AND VALIDATION

10:05 Chairperson’s Remarks

Jamie Platt, Ph.D., Managing Director, BRIDGenomics, LLC

10:15 Whole Exome Sequencing as a Diagnostic Test: From Preanalytical Processing to Assay Validation

Madhuri Hegde, Ph.D., FACMG, Adjunct Professor, Emory University, Vice President and Chief Scientific Officer, Global Laboratory Services, Diagnostics, PerkinElmer, Inc.

Clinical exome sequencing has been fully integrated into clinical practice with most clinicians successfully ordering this test to end the diagnostic odyssey for many patients. The assay development starts determining the targets which can give a high coverage of >98% for 22,000 genes and a 100% coverage for > 5306 genes associated with disease. The preanalytical phase to complete assay design is a step by step process, which includes development of a bioinformatics pipeline.

10:45 Genomic Assays for Clinical Development: Identifying the Right Solution from a Wealth of Potential Approaches

Patrick Hurban, Ph.D., Senior Director and Global Head, Translational Genomics, Q Squared Solutions

Genomic analysis permeates clinical development, with demonstrated utility at all points along the continuum from discovery to diagnostics. Manifold sample types and testing requirements, as well as evolving needs, pose significant challenges. Developing the right solution requires a detailed understanding of pre-analytical variables and analytical performance across an array of potential technologies. Specific use cases will be presented to demonstrate how these challenges can be overcome, and why a diverse toolkit enhances the likelihood of success.

11:15 Automation of Sample Preparation for Clinical NGS: The Requirements and the Challenges Presented by the Various Clinical Sample Types

Martin Siaw, Ph.D., MB(ASCP), Vice President of Science and Innovation, BRIDGenomics.

Sample preparation is an important component of any molecular testing that is being done in clinical laboratories. With the increasing use of NGS for clinical testing comes the need to process increasingly larger numbers of patient samples. Automation of sample preparation should be considered to be critical to the workflow of diagnostic tests involving the use of NGS. My presentation will focus on the requirements for CLIA certified clinical laboratories, the various patient specimens to be tested (including those for liquid biopsies), the methods currently in use for nucleic acid extraction and the various commercial kits that are available in the market.

TriMetis11:45 The Insider’s Guide to Collecting Quality Human Biosamples and Essential Questions All Researchers Should Be Asking

Jon Wetzel, COO, TriMetis Life Sciences

Asking the right questions can lead to accelerated research. Jon Wetzel, COO of TriMetis Life Sciences, has over 21 years of assessing and auditing multiple biorepositories, biobanks, SOP’s and collection procedures. With over 6 of those years as a bench researcher and 15 years acquiring, processing and shipping samples, Jon has experienced first-hand the mistakes companies have made in acquiring these highly-sought after samples. He has taken his experience and is letting researchers in on the essential questions they need to ask to make sure that the samples they are using are going to give them the best experimental results possible.

Rubicon Genomics 12:00 pm ThruPLEX® Tag-seq Kit: Unleash the Power of Unique Molecular Tags for Accurate Detection of Low-Frequency Variants

Anthony Popkie, Ph.D., Applications Scientist, Rubicon Genomics

Unique molecular tags differentiate between sequencing artifacts and true variants. Data will be shown that demonstrates libraries prepared with ThruPLEX® Tag-seq kit can detect < 0.5% allele frequency at 99% specificity with as little as 10 ng of cell-free DNA.

12:15 Enjoy Lunch on Your Own

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

NGS ASSAYS IN ONCOLOGY

2:00 Chairperson’s Remarks

Patrick Hurban, Ph.D., Senior Director and Global Head, Translational Genomics,
Q Squared Solutions

2:10 Choosing an Effective Validation Plan for NGS Assays in Oncology

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

The analytical validation of an NGS assay for the most part determines the reliability of results and therefore dictates the effectiveness of the assay for management of the cancer. As the number of laboratories offering NGS tests in oncology increases, the need for recommendations and guidelines that address the processes of assay validation are noteworthy. Several organizations and regulatory bodies have been working on developing documents to help and guide laboratories plan and execute the validation of NGS assays for oncology. In this presentation, we will discuss the validation prerequisites that are important and need to be addressed for implementing a reliable and useful NGS assay for oncology.

2:40 Towards Implementation of NGS as Clinical Assay: FFPE Pre-Analytical Optimization and Analytical Consideration in WES Commercial Lab Selection

Ping Qiu, Ph.D.,Principal Scientist, Translational Molecular Biomarkers (TMB), Genomics, Merck Research Laboratories

Higher non-synonymous mutational burden assessed by whole exome sequencing in tumors is associated with durable clinical benefit in immune checkpoint inhibitors treatment. Cancer genome WES poses a unique challenge due to limited tissue, tumor heterogeneity and sequencing artifacts introduced by FFPE tissue. Multiple genomics CROs were assessed on their NGS pre-analytics and the quality of WES data generated. Recommendations are made on FFPE WES pre-analytics and data interpretation.

3:10 Co-Presentation: Genotyping in an HTP Drug Development Pipeline: Tough Assays, High Sample Numbers, and Ever-Changing Goals

J. Colin Cox, Ph.D., Science Manager, Genentech

Deborah Siler, Ph.D., Senior Scientific Researcher, Mouse Genetics, Genetech

We use “acoustic droplet ejection” (ADE) to perform high-throughput genotyping in the context of an R&D biotherapeutics pipeline. Our lab processes roughly 350,000 samples a year in order to generate ~800,000 genotypes on very complex genetic models. Recently, we validated a no-downtime upgrade from traditional pipetting robots to ADE dispensers and investigated the effect on cross-contamination and return-on-investment.

SeraCare3:40 Real-World Examples of Validating a Cancer Sequencing Assay: Case Example, RNA Fusions

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

Laboratories have difficulties reconciling vague guidelines against sample scarcity and budget limits. How can labs validate and implement cancer assays? In this talk we will demonstrate the mixture of natural and synthetic materials to implement robust and reliable assays.

4:10 Hollywood Oscar Dessert Reception 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. Pre-registration to sign up for one of the topics will occur a week or two prior to the Event via the App.

NGS Assay Development and Validation

Martin Siaw, Ph.D., MB(ASCP), Vice President of Science and Innovation, BRIDGenomics.

Jamie Platt, Ph.D., Managing Director, BRIDGenomics, LLC.

  • Commercially available sample prep kits
  • Sample prep for liquid biopsy applications
  • The need for automation for sample prep

Liquid Biopsy Based Assay Development

Sid Scudder, M.D., Senior Director, Clinical Science, Genomics & Oncology, Roche Molecular Systems

  • ctDNA-based EGFR testing vs tissue based EGFR testing
  • Need for companion tests to guide EGFR inhibition therapy
  • Expanding past NSCLC

Lab-on-a-Chip Technologies

Joshua T. Smith, Ph.D., Research Staff Member, Translational Systems Biology and Nanobiotechnology, IBM T. J. Watson Research Center

  • Automated Sample Prep for Differential Isolation and Enrichment of Exosomes and Cell-Free Circulating Nucleic Acids
  • Electrical and Electrochemical Detection Enabling Technologies for IVD and POC
  • Translation of Lab-on-a-Chip Concepts: Successes, Failures, Prospects, and Opportunities

6:00 Close of Day

Wednesday, February 22

7:00 am Registration Open

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

8:00 Plenary Keynote Session

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

LIQUID BIOPSY-BASED ASSAYS

10:50 Chairperson’s Remarks

Raja Luthra, Ph.D., Professor, Hematopathology, The University of Texas MD Anderson Cancer Center

11:00 Liquid Biopsy for EGFR, the cobas® EGFR Mutation Test v2: The Long and Winding Road

Sid Scudder, M.D., Senior Director, Clinical Science, Genomics & Oncology, Roche Molecular Systems

Liquid biopsies for the detection of actionable mutations in cancer offer advantages to tissue biopsies in terms of safety, discomfort and sequential testing. Liquid biopsies can obviate the problems of insufficient tissue, tissue exhaustion, or inability to undergo a biopsy. The cobas® EGFR Mutation Test v2 detects 42 mutations in exons 18-21 of the EGFR gene, including T790M and test has been approved by the FDA as a co-diagnostic for Tarceva® and Tagrisso® (tissue). The development of the test as a liquid biopsy highlights the difficulty in developing companion diagnostics along with unexpected pitfalls. It also emphasizes the need for creativity, flexibility and the need for close communication with regulatory agencies to reach the final goal.

11:30 Co-Presentation: Mutation Screening of Liquid Biopsies: Promise, Clinical Utility and Technical Challenges

Raja Luthra, Ph.D., Professor, Hematopathology, The University of Texas MD Anderson Cancer Center

Rajesh Singh, Ph.D., Director, Clinical Next Generation Sequencing Assay Development, MD Anderson Cancer Center

Screening of genomic aberrations in circulating cell free DNA (ccfDNA) holds tremendous promise as a minimally invasive option for early detection, monitoring of disease progression and therapy response in solid tumors. However, its routine implementation in a diagnostic laboratory raises several logistic and technical challenges. This talk will discuss the potential, clinical utility and technical challenges associated with isolation and screening of ccfDNA in a clinical diagnostic laboratory setup.

12:00 pm Enjoy Lunch on Your Own

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

PORTABLE SEQUENCING AND LAB-ON-CHIP TECHNOLOGY

1:50 Chairperson’s Remarks

Joshua T. Smith, Ph.D., Research Staff Member, Translational Systems Biology and Nanobiotechnology, IBM T. J. Watson Research Center

2:00 Co-Presentation: PORTABLE SEQUENCING: Fundamentals in Sequencing Technology with Nanopores, Sample Preparation and Data Analysis

Harikrishnan Jayamohan, Ph.D.,Postdoctoral Appointee, Advance Systems Engineering and Deployment, Sandia National Laboratories

Raga Krishnakumar, Ph.D., Bioinformatics, Sandia National Laboratories

The Oxford Nanopore MinION is a portable real-time sequencing device which operates by sensing the change in current flow through a nanopore as DNA traverses through it. The relative small-size, portability, simple sample preparation, long-read lengths, and real-time informatics makes this commercially available technology a game-changer for DNA sequencing. In this short-course, we will present on the following topics from a users’ perspective.

• Overview of the fundamentals in single molecule DNA sequencing technology with nanopores,

• Survey of the latest advancements in nanopore sequencing applications,

• Differentiating strengths compared to traditional sequencing methods,

• Hands-on experience and sample preparation for the nanopore sequencer,

• Emerging bioinformatics and real-time data analysis strategies for long-read sequencing

3:00 Sample Prep for Liquid Biopsies on a Chip: Exosomes, DNA and Beyond

Joshua T. Smith, Ph.D., Research Staff Member, Translational Systems Biology and Nanobiotechnology, IBM T. J. Watson Research Center

We recently used nanoscale deterministic lateral displacement (nanoDLD) technology for on-chip size separation of exosomes and DNA, and showed that its sensitivity is sufficient to interrogate individual exosomes and DNA molecules in samples with low concentrations of analyte. In this talk, we will show that the continuous flow nature of the technology allows us to isolate, enrich and purify analytes at preparative level volumes for downstream genomics analysis.

3:30 Session Break

NOVEL APPROACHES FOR ASSAY VALIDATION

3:40 Chairperson’s Remarks

Andrew Brooks, Ph.D., COO, RUCDR Infinite Biologics

3:45 Finding the Best Fit: Cancer Specimen Predicaments and How to Solve Them

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

With the wave of clinical genomic sequencing performed for cancer diagnosis and prognosis, the decision regarding the correct sample and appropriate breadth of testing has never been more important. This discussion will focus on specimen types, laboratory parameters and their relationship with library content. Tumor specimens can differ substantially, from fresh tissue to formalin fixed paraffin embedded tissue, and from biopsy specimens to fine needle aspirations. Decisions for sequencing and the ability to detect clinically useful mutations rely on the biology of these specimens, each with their own advantages and disadvantages. Due to the intrinsic variability in neoplastic tissue, the management of specimens entering into the laboratory for sequencing, the quantity and quality of the nucleic acid and appropriate tumor percentage is critical in the relationship to mutation detection. The diversity and availability of input DNA molecules governs the logistics of sequencing and the implications to detect low abundance mutations and tumor heterogeneity.

4:15 Capturing the Broad Spectrum of Pathogenic Mutations with NGS: Challenges in Assay Development and Validation

Stephen Lincoln, Scientific Affairs, Invitae

Technically challenging variants are a substantial fraction (10% or more) of findings in routine clinical testing. These can include CNVs affecting only a single exon, either large indels or complex variants, or alterations in low-complexity, highly conserved or extreme-GC regions. Novel biochemical and bioinformatics methods can help address many of these although supplementary assays are sometimes required. Published validation studies often omit these variants, and benign SNPs dominate most sensitivity calculations. In part this may be due to difficulty obtaining positive controls. We thus have developed and tested, in multiple laboratories, synthetic controls containing a diverse set of challenging mutations in commonly tested genes.

4:45 Panel Discussion: Assay Validation Tips and Tricks

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

Panelists:

Jamie Platt, Ph.D., Managing Director, BRIDGenomics, LLC.

 

  • Validation and Implementation of NGS Diagnostic Assays Bringing up NGS Assays in the CLIA Lab Selection 
  • Development and Analytical Validation of a Targeted NGS Assay for the Support of the NCI-MATCH Trial 
  • Validation and Implementation of NGS Assays within the Framework of CAP Accreditation and Proficiency Testing Requirements

 

5:15 Close of Conference Program


Stay on for these Tri-Conference Symposium, taking place at February 23-24, 2017 at Moscone South Convention Center


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