Molecular Diagnostics 2019

Rapid, inexpensive, and sensitive nucleic acid detection may aid point-of-care pathogen detection, genotyping, and disease monitoring. We combine the RNA- targeting CRISPR effector Cas13 with isothermal amplification to establish a CRISPR-based diagnostic (CRISPR-Dx), providing rapid DNA or RNA detection with attomolar sensitivity and single-base mismatch specificity.  We use this Cas13a-based molecular detection platform, termed SHERLOCK, to detect specific strains of Zika and Dengue virus, distinguish pathogenic bacteria, genotype human DNA, and identify cell-free tumor DNA mutations. By leveraging CRISPR enzymology and lateral flow devices, we demonstrate further improvements on SHERLOCK, including multiplexing and instrument-free readout. CRISPR-Dx forms the basis for multiplexable, portable, rapid, and quantitative detection of nucleic acids.

Learning Objectives: 

1. At this seminar, attendees will gain and understanding of CRISPR enzyme diversity and the distinguish characteristics of Cas12 and Cas13 enzymes.
2. After attending this seminar, attendees will be able to describe the development of CRISPR tools for diagnostics in the field and the clinic

The BRCA1 and BRCA2 genes epitomize the modern understanding of cancer molecular genetics. Today, identifying germline and somatic mutations in BRCA1/2 has become routine practice, especially for hereditary cancer studies. However, the highly-fragmented nature of traditional sample to insight workflows can make the identification and classification of all pathogenic and actionable variants in BRCA1/2 particularly challenging. In this webinar, we explore these challenges and present solutions for streamlined, standardized, and accurate detection, interpretation, and reporting of challenging BRCA mutations, such as exon-level copy number variants (CNVs), splicing variants, and variants in homopolymer regions. 

In the first half of the webinar, we will introduce a fully-integrated Sample to Insight NGS clinical research workflow for the detection of BRCA1/2 mutations.  Designed as an integrated part of the GeneReader NGS System, the QIAact BRCA1/2 and the BRCA Advanced Panel leverages unique molecular index (UMI) technology to detect single nucleotide variants (SNVs), exon-level CNVs, even those at low-frequency, ensuring consideration of all variants within the sample. 

In the second half of the webinar, we will present a concordance study demonstrating the accuracy of QIAGEN Clinical Insight (QCI®), QIAGEN’s clinical decision support software for the interpretation and reporting of NGS data. The study compares QCI’s automated variant classification of over 6,000 BRCA1/2 variants to the human-derived variant classifications from expert panels (the ENIGMA consortium and ClinGen). QCI achieves extremely high concordance (99.6%) and provides automated tiered classifications according to all 28 ACMG guidelines with full transparency to the underlying evidence.  


Learning Objectives: 

1. QIAGEN’s GeneReader workflows are pre-optimized sample to insight solutions able to overcome the challenges of a fragmented NGS workflow
2. The BRCA ½ and the BRCA Advanced Panels coupled with the GeneReader enable comprehensive profiling of mutations within BRCA, including challenging mutations such as large Indels and exon-level CNVs, and with UMI technology, even those of low allele frequency
3. QCI Interpret as part of the GeneReader solution automates variant classification using all 28 ACMG criteria, while transparently providing the supporting evidence for variant assessment
4. In compelling concordance study, QCI-Interpret used to automatically classify >6000 BRCA1 and BRCA2 variants, demonstrating the extremely high concordance (99.6%) between automated tiered classification with this clinical decision support platform and classifications by a panel of experts. 

QIAGEN helps your team focus on the opportunities, not the obstacles, with an end-to-end clinical testing solution. During this talk, we will present our clinical decision support solutions, QIAGEN Clinical Insight and N-of-One, that allow you to optimize and scale your pipeline for clinical interpretation of genetic variants—from sequence data to report sign-off—without sacrificing accuracy. With the automated implementation of expert guidelines for pathogenicity and actionability based on an expansive knowledgebase derived from >20 years of manual curation, and now with N-of-One bringing in report-ready text tailored to the assay, supporting the clinical options with the most relevant evidence from the literature, QIAGEN provides a platform that provides the best-in-class evidence enabling clarity and confidence in reporting.

Learning Objectives: 

1. Struggling to keep pace with the latest clinical findings? Learn how you can remain up-to-date on the increasing number of publications, biomarker data, and remain informed of changing clinical trial availability and treatment options with the combined QIAGEN Knowledge Base and N-of-One’s MarkerMine, now the world’s largest clinical evidence database providing the most relevant and timely information needed in your clinical decision making. 
2. Looking for an automated NGS variant interpretation and reporting solution? Discover how to automate, scale and standardize your NGS variant interpretation and reporting according to the latest professional guidelines (ACMG/AMP, AMP/ASCO/CAP, etc.)
3. Learn about the flexible options for standardized and consistent clinical NGS reporting that suits your needs

Personalized medicine driven by genomic-based treatments continues to increase in importance. Representatives from two distinct healthcare entities – a regional reference lab and community based cancer medical center – provided their perspectives on how they approach the challenge of addressing this need. The speakers will present on the reasons why they chose to internalize NGS testing, the value it brings to their healthcare system/network and what was involved to actualize their programs. Digital analytics and analysis employed by LTS Health was incorporated to provide feedback on the impact to laboratory operations and forecasting for future growth.  

Learning Objectives: 

1. Recognize the biomarkers that prompt the need for a multi-gene panel to maximize testing results from a single tissue biopsy. 
2. List the attributes of a Comprehensive Genomics Panel that would be used to drive personalized medicine testing using NGS (next-generation sequencing). 
3. Describe the Molecular Tumor Board considerations when doing case reviews. 
4. Identify the components of a Quality Management System for NGS (next-generation sequencing) workflows. 

Myeloid leukemias encompass a group of different diseases that include myeloproliferative neoplasms (MPN), myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). These diseases are driven by somatic mutations acquired in 20-30 key genes. Given the genetic complexity of these heterogeneous disorders, there is an increasing need for molecular identification of key mutations across all of these genes. 

In this webinar we will introduce two solutions for the detection and interpretation of mutations associated with myeloid leukemias.

In the first half we introduce an integrated Sample to Insight NGS clinical research workflow for detection of myeloid leukemia mutations.  The QIAact Myeloid DNA UMI Panel in combination with the QIAGEN GeneReader™ NGS System provides a complete solution that can simultaneously test for around 9000 variants in 25 genes with reported relevance to clonal myeloid malignancy. The incorporation of unique molecular index (UMI) technology enables detection of even low-frequency variants, including JAK2 and KIT variants below the 1% variant allele frequency (VAF) and the KIT D816V mutation at 0.4% VAF. Accurate reporting of usually challenging-to-detect mutations such as the large CALR Type 1 (52 bp deletion), FLT3 ITDs (with identified insertion site), and GC-rich sequences such as in the CEBPA gene, are also possible due to the pairing of this digital sequencing approach with optimized bioinformatics. We will present clinical research data to show the successful detection and reporting low-frequency variants and challenging alterations with this complete assay.

In the second half we present a bioinformatics solution for the clinical interpretation of somatic myeloid leukemia mutations. Cancer laboratories need rapid and reliable interpretation of identified genomic alterations. One of the challenges they face is producing standardized, reproducible interpretation and reporting of the most current and actionable information. QIAGEN Clinical Insight (QCI™) Interpret allows labs to deliver evidence-based, actionable insights. We will discuss the methodology and benefits of automating guidelines (AMP/ASCO/CAP and ACMG/AMP) for vetting somatic cancer alterations for actionability and pathogenicity in the same workflow while providing full transparency to the underlying evidence.

Learning Objectives: 

1. Understand the value of a tailored integrated Sample to Insight NGS workflow for the detection of complex mutations in myeloid leukemia
2. Understand the value of standardized and consistent interpretation, especially for complex diseases like myeloid malignancies

Dr. Marlowe's presentation will cover: Integration of technology is influencing practice in the clinical laboratory and treatment of patients in the clinical practice arena. As laboratories begin to move from a volume to value model, the mining of big data and its ability to guide clinical decisions through artificial intelligence and machine learning will continue to alter the value assigned to laboratory medicine. These changes and the challenges they pose will be address to investigate the skill set that will be required from this and the next generation of laboratory leaders to successfully leverage the role of the laboratory in a post-technology world.

Ms. Sickler's presentation will cover: The evidence required to achieve regulatory approval is increasingly not enough to justify adoption of new and often more expensive technologies.  How a test could change clinical care if theoretically utilized in a certain way is no longer compelling to support value.   Clinical evidence must demonstrate in the real world how diagnostic results are integrated into a clinical care continuum and utilized to guide patient care to support value.  

Learning Objectives: 

1. Recognize the changing model of laboratory medicine
2. Define value based care
3. Discuss the challenges to leveraging laboratory data
4. Understand the skillset for the next generation laboratorian
5. Define the different types of diagnostic evidence and common endpoints
6. Understand the drivers of the shifting evidence landscape