Cambridge Healthtech Institute’s Third Annual
Sample Prep and Target Enrichment in
Sample Quality and Sample Prep for NGS and Other Technologies
Part of the Precision Diagnostics Summit
June 16-17, 2014 | Hilton Boston Back Bay| Boston, MA
Pre-detection/pre-analytical processing is a pivotal part of molecular diagnostics in general and in nucleic acid testing in particular. Next Generation Sequencing that is making its way into clinical laboratory imposes especially high requirements of precision on sample quality and pre-analytical processing. As a rule, the modernization of pre-analytical processing should closely follow or even precede the emergence of new molecular diagnostics technologies. Target enrichment as part of pre-analytical processing has 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 Third Annual Sample Prep and Target Enrichment in Molecular Diagnostics is designed to demonstrate the latest advances in pre-analytical processing, sample preparation and target enrichment in molecular diagnostics, particularly in next generation sequencing and other nucleic testing technologies.
MONDAY, June 16, 2014
7:15 am Registration & Morning Coffee
7:45 Welcome Remarks from Marina Filshtinsky, M.D., Conference Director
7:55 Chairperson’s Opening Remarks
8:00 Biomarker Development for Precision Medicine: A Systems Approach Beginning with the Right Stuff
Carolyn Compton, M.D., Ph.D., Professor, School of Life Sciences, Arizona State University
The National Biomarker Development Alliance (NBDA) is a nonprofit organization of academic, industry and government partners which aims to create a standards-based, comprehensive end-to-end approach to the development of biomarkers of different categories within a given context of use, guided throughout the development pipeline by regulatory and clinical implementation requirements. At the starting end of the pipeline is the right fit-for-purpose biospecimen. The ever-rapid development of assay technologies dictates that standards that allow them to be applied successfully to biomarker development keep pace. This can only be accomplished through broad coordination of effort and consensus, which is the goal of the National Biomarker Development Alliance.
8:30 The Challenges of Developing and Implementing Biospecimen Evidence-Based Practices
Helen Moore, Ph.D., Program Director, Biorepositories & Biospecimen Research Branch, Cancer Diagnosis Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute
The U.S. National Cancer Institute has led progress in biobanking with the NCI Best Practices for Biospecimen Resources and the Biospecimen Research Network (BRN). Incorporating new scientific data into best practices is another challenge.
9:00 A Call to Standardize Preanalytic Data Elements for Biospecimens
James Robb, M.D., FCAP, Leidos Biomedical Research, Inc.
Biospecimens must have appropriate clinical annotation to ensure optimal quality for both patient care and research. A quantitative list of 170 clinical preanalytic variables (data fields), along with their relative importance, which can vary depending on downstream use, institutional needs, and information technology capabilities, have been developed and published by the College of American Pathologists. Notes, definitions, and negative impacts have been provided for each variable. This list can be used as a guide for site-specific implementation into patient care and/or research biorepository processes.
9:30 Ultracold vs. LN2 Cryopreservation for Biospecimens Destined for Genomically-Informed Precision Medicine
Mark Cosentino, D.P.M., Ph.D., Head, BioProcessing and DNA Extraction, Staging Laboratories, Biogen
The storage temperature of biospecimens of various material types tends to be selected based on historical antidotal information. What is needed is scientific-based research to define “Best Practices” that links the appropriate storage temperature of analytes to specific downstream testing applications. This is not a trivial matter. The presentation will discuss the possibility of storing biospecimens below the Glass Transition Temperature of Water (GTTW). An experimental approach and call for scientific collaboration will also be discussed.
10:00 Sponsored Presentations (Opportunities Available)
10:30 Coffee Break with Exhibit and Poster Viewing
11:00 Quantitative Measurement of Protein Degradation in FFPE Samples
Veronique Neumeister, M.D., Specialized Translational Services Laboratory, Department of Pathology, Yale University
Companion diagnostic tests are critically dependent on tissue quality. However, tissue handling and processing are not always tightly controlled and pre-analytical variables can significantly alter tissue quality. Cold ischemic time is amongst the most important variables. This presentation will discuss the effect of this variable in the diagnostic and research setting and show data on analytes that are particularly sensitive to this issue. Tools to control tissue quality will be discussed and the construction of an internally calibrated tissue quality index (TQI) as a way to monitor tissue quality for immunological assessments will be illustrated.
11:30 Practical Approaches to Expanding Biorepository Representation: Innovative Tissue Print Technologies for Collecting High Quality Snap-Frozen Specimens for Biomarker Research
Sandra M. Gaston, Ph.D., Director, Molecular Biomarkers Research Laboratory, Department of Pathology and Laboratory Medicine, Tufts Medical Center Assistant Professor of Pathology, Tufts University School of Medicine
Most human tissue samples obtained from clinical biopsy and surgical resections are only secondarily considered as research specimens, and any plan to collect tissue for research must put first priority on patient care. . Remnant tissues obtained from fresh surgical specimens are the mainstay for biorepositories that provide high quality snap-frozen samples for research, but many critical areas of a surgical resection and most diagnostic biopsies cannot be easily “divvied up” before the tissue is submitted for processing as a formalin-fixed paraffin embedded (FFPE) specimen. Our group has developed a set of tissue print micropeel technologies that offer an innovative and practical approach to obtaining high quality RNA and DNA from biopsies and other “high value” specimens without compromising pathology diagnosis. Application of these technologies for cancer biomarker discovery will be discussed.
12:00 pm Sponsored Presentations (Opportunities Available)
12:30 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch On Your Own
1:55 Chairperson’s Remarks
2:00 Development, Validation and Implementation of Sample Prep Procedures for Clinical Whole Exome Sequencing at the Broad Institute
Niall J. Lennon, Ph.D., Director, Technology Development, Genomics Platform & Clinical Applications Development, Clinical Research Sequencing Platform, Broad Institute of MIT & Harvard
The development of the Whole Exome Sequencing assay offered by the Broad clinical lab will be discussed as an example of the need for, and application of, process design and quality management systems in molecular diagnostics. Though the documentation and validation requirements may differ between clinical and research processes there are a common set of challenges that must be tackled through the identification and elimination of process variability, rigorous supply chain control, enhanced tracking and troubleshooting, and automation of both lab and analytical pipeline functions.
2:30 Use of a Next-Generation Sequencing Assay to Compare Results Obtained from Matched Formalin-Fixed and Frozen Tissue Specimens
Patrick Hurban, Ph.D., Senior Director, Translational Research and Development, Global Head, Genomic Research and Development, Expression Analysis, The Quintiles Company
Formalin-fixed tissues present many sample preparation, extraction and method development challenges. It can also be challenging to understand whether certain findings stem from intrinsic genetic properties of the sample, or alternatively, are a product of how the sample was handled. Despite advancements in preservation methods, vast collections of FFPE material await analysis. Results will be presented comparing matched formalin-fixed and frozen tumor samples analyzed using a sensitive next generation sequencing assay.
3:00 Comparison of Various Preanalytical Strategies in Molecular Testing for Infectious Diseases
David R. Hillyard, M.D., Medical Director, Molecular Infectious Diseases, Arup Laboratories
3:30 Refreshment Break with Exhibit & Poster Viewing
4:00 Inferring Dynamic Signatures of Microbes in Complex Host Ecosystems
Lynn Bry, Ph.D., M.D., Associate Professor of Pathology, Brigham and Women’s Hospital
4:30 Panel Discussion: Matching Nucleic Acid Extraction Method with the Goals of an Assay
Moderator: Patrick Hurban, Ph.D., Senior Director, Translational Research and Development, Global Head, Genomic Research and Development, Expression Analysis, The Quintiles Company
Panelists: Monday Speakers
5:10 Welcome Reception with Exhibit & Poster Viewing
6:00 Short Course Registration
6:15-9:00pm Dinner Short Course: How to Launch a Laboratory Test: Everything You Wanted to Know but Were Afraid to Ask *
Instructors: Steven Gutman, M.D., Strategic Advisor, NA, Myraqa, Inc.
Tonya Dowd, Director, Reimbursement Policy, Quorum Consulting, Inc.
* Separate Registration Required
Tuesday, June 17
8:15 am Breakout Discussions with Continental Breakfast
9:10 Chairperson’s Remarks
9:15 Challenges and Prospects of Circulating RNA
Kai Wang, Ph.D., Principle Scientists, Institute of Systems Biology
Since extracellular microRNAs (miRNAs) were discovered, their impact on biomarker related applications has been a surprising and exciting field. The discovery of exogenous RNAs in circulation further expands the possibility of using circulating RNA to assess the interactions between host and microbiome. The fundamental requirement for biomarker development is a reliable and accurate measurement method, which is still lacking for miRNA and other short RNAs in circulation. Factors that are known to affect circulating RNA measurements include sample type, sample preparation, storage condition, measurement platform, and many others. While new measurement methods are needed, caution needs to be taken in interpreting circulating RNA based results.
9:45 Electronic Label-Free Biosensing Assays
Mark A. Reed, Harold Hodgkinson Professor of Electrical Engineering, Departments of Electrical Engineering and Applied Physics, Yale University
Nanoscale electronic devices have the potential to achieve exquisite sensitivity, selectivity, and portability as sensors for detection of protein biomarkers. Nanowire-FETs compatible with standard microelectronics technology enable a high yield and low-cost technology with simple system integration. This talk discusses the application of this technology to a wide range of label-free biochemical and macromolecule sensing at clinically important concentrations for biomarker assays.
10:15 Sponsored Presentation (Opportunity Available)
10:30 Coffee Break with Exhibit and Poster Viewing
11:00 MAD NAAT: Multiplexable Autonomous Disposable Nucleic Acid Amplification Test for Low-Resource Settings
Barry Lutz, Ph.D., Research Assistant Professor, Department of Bioengineering, University of Washington
We are developing tests for DNA and RNA that can be performed anywhere, including your home. All steps from sample preparation to visual readout are carried out automatically without an instrument. Data collection by a cell phone will allow transmission of results to a healthcare provider and medical record. Project goals include commercializable tests as well as broad platform capabilities for future tests.
11:30 A Microfluidic DNA Library Preparation Platform for Next-Generation Sequencing
Kamlesh Patel, Ph.D., Manager, Advance Systems Engineering and Deployment, Sandia National Labs
DNA sequencing is advancing at an unprecedented rate, but sample preparation methods rely on manual bench-top processes, which are labor-intensive. The introduction of fast, low-throughput sequencers warrant a need to automate these protocols. We report on our work to integrate novel digital microfluidic technology to automate DNA library preparation workflows for characterization of novel and emerging pathogens from clinical samples.
12:00 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:00 Chairperson’s Remarks
1:05 PLENARY KEYNOTE: Sample Preparation Considerations for Digital Technologies
N. Reginald Beer, Ph.D., Medical Diagnostics Initiative Leader, Center for Micro and Nanotechnologies, Lawrence Livermore National Laboratory
Digital PCR provides extremely accurate quantification as compared to traditional standard curve methods but pre-detection processing remains pivotal. Critical factors such as sample preparation, sample homogeneity, reaction volume measurements, thermal cycler uniformity, template GC content and methylation can all effect data quality. In this talk we will discuss the benefits of digital technologies as well as steps to ensure accurate measurement. Attention will be given to future trends driving the field and moving out of the lab and onto the bench.
2:05 Close of Sample Preparation Conference