Target enrichment offers several advantages over more comprehensive genomic profiling for a variety of scientific applications. The ability to selectively isolate specific genomic regions enables efficiencies in sequencing allowing greater depth of target coverage for higher sensitivity variant calling and inclusion of larger sample cohorts for improved power to drive scientific discovery. Drawbacks to target enrichment include complexities in sample processing through the variety of available approaches, high sample input requirements, and the inability to scale any technology across a broad range of target content.  During this webinar, we will explore these tradeoffs, and discuss novel approaches for selective enrichment of genomic targets.

Inappropriately prescribed antibacterials for viral respiratory illness contribute to increased healthcare costs, unnecessary drug-related adverse effects, and drive antimicrobial resistance. The inability to rapidly and reliably distinguish bacterial from viral or non-infectious etiologies is a major impediment to appropriate antibiotic use. Pathogen detection strategies can be helpful but are limited by poor sensitivity, long time-to-result, inability to distinguish infection from colonization, or restricted number of target pathogens. A complementary diagnostic strategy focuses on the host’s response to the infection. That response is itself encompasses a highly complex biology that can be detected in the transcriptome, proteome, and metabolome among other data types. Moreover, these markers can be single biomarkers such as procalcitonin or multi-analyte biomarker panels. This presentation will review strategies to discriminate viral from bacterial infection, discussing existing as well as emerging technologies.

I will update the current state of our candidate RM 8376 for mixed microbial DNA detection via NGS-based sequencing and metagenomics. After community engagement to understand the metrological needs in the metagenomics workspace, we have produced a candidate reference material to address some of the challenges facing the field; namely, characterizing some of the sequencing and informatics biases. Current efforts focus on characterizing the materials for concentration; homogeneity, identity, purity; and stability. In addition, we have begun examining possible experimental models that will enable metagenomic tool characterization of relative performance metrics (e.g. sensitivity, specificity). The early results of this show that “simple” mixtures can produce complex outputs that highlight strengths and weaknesses of each tool. We are also looking ahead to needs in other (viral) areas using sequencing and metagenomics, to identify potential materials and methods that will quickly address their challenges. 

In genomics, as in life, you need to be in the right place at the right time, and you need integrity, to be credible. Since the availability of the human genome sequence, there's been an explosion in genetic testing. And epigenetics is entering the clinic by measuring chemical modifications to DNA or proteins that influence gene expression. Tumor mutational burden and microsatellite instability assessments are used to try and better match patients to the right therapies. But basic cell biologists have known for years that the genome has a dynamic organization in the cell which influences its expression also. And with genomic instability as the hallmark of cancer, this nuclear organization too can become disrupted in disease. Our group has developed a platform that captures and evaluates the content and configuration of the genome in individual cells, and are bringing it to the clinic. By combining immunohistochemistry with telomere-FISH labelling, three-dimensional microscopy, and proprietary TeloView(TM) software analytics, distinct profiles are identified that can distinguish between disease severity, risk of disease progression, and likelihood of response to therapy. This technology establishes the dynamic organization of the genome as a novel universal biomarker paradigm. This session will cover some of the fundamental principles of this new approach, and its applications already in cancer and Alzheimer's disease.

Ready or not, direct-to-consumer (DTC) genetic testing is here and it is here to stay. As technologies continue to make genetic testing more affordable and accessible to the masses, more individuals are empowered to learn about their genetic information; with or without a physician’s help. Meanwhile, healthcare systems across the country and the world are recognizing how critical it is to integrate genomic testing into everyday patient care to improve outcomes and the overall patient experience. Great progress has been made in oncology and rare-disease diagnoses where genetic testing has become more mainstream. Although some clinical areas have caught up to using these resources, most providers are far behind offering their patients useful genetic testing options that can significantly improve their care. 
This presentation focuses on a healthcare system’s perspective of how genetic testing has been introduced within its organization, integrated into various service lines and how a shift to direct-to-consumer testing is challenging existing infrastructure. 

The Whiteson lab uses culture-independent metagenomics, metabolomics, and ecological statistics along with hypothesis driven, reductionist microbiology to answer questions about how bacteria and viruses affect human health. Several recent research projects will be presented from 1) healthy humans, 2) pre-mature infants from Children’s Hospital Orange County, and 3) Cystic Fibrosis patients.

This presentation illustrates the features of QIAGEN sample to insight approach, and how it combines a powerful chemistry based on unique molecular indexes (UMIs) and a UMI-aware bioinformatics workflow in the Biomedical Genomics Workbench with QIAseq Panel Analysis Plugin. This approach reaches impressive performances in detecting low allele-fraction variants, and the integration with other QIAGEN solutions such as Ingenuity Variant Analysis (IVA) and QCI Interpret allows to further explore the results for their biological and pathological relevance.

The use of DNA panels is a cost-effective approach to reach the high coverage needed for research  applications like liquid biopsy. In such scenarios, the capability to distinguish between sequencing or amplification errors and real findings is crucial, in order to detect clinically relevant mutations at low allele-fraction levels. UMIs address this challenge, if combined with bioinformatics capable of exploiting their added value. 

Liquid biopsy is emerging as a new and non-invasive approach to characterize cancer mutation profiles. However, some tumours like urothelial cancer are particularly challenging, due to their location and biology. In this work we explore the performance of our workflow and its insights on bladder cancer. 

We compared the results from tissue and plasma libraries extracted with QIAGEN QIAamp MinElute ccfDNA and QIAamp Circulating Nucleic Acid kits from individuals with bladder cancer, and show that the recovery of variants (i.e. variants identified in the tissue also called in the plasma) ranges above 70% for SNVs. A very good achievement, in the biological context of urothelial cancer. We further explore the results from a pathological perspective, and show the success in capturing biologically relevant mutations, classified by their pathogenicity and actionability according to existing guidelines.

Prostate cancer is one of the most common cancers in men and a major health issue in the US and Worldwide.  Until recently, prostate cancer was not felt to be a hereditary disease.  However, up to 13% of men who present with de novo metastatic disease have a hereditary gene defect and men with a family history are also at risk for hereditary disease.  The most common genes linked to hereditary prostate cancer include BRCA2, BRCA2, ATM, and CHEK2. In addition to hereditary genes, somatic mutations are common in advanced and castrate resistant disease and assessment in tumor and metastatic tissue is beginning to dictate novel therapeutics.  Measurement of tumor derived messenger RNA expression panels is the basis of a number of commercially available molecular biomarker tests including Prolaris, Oncotype GPS, and Decipher. This presentation will highlight hereditary and somatic tumor testing and current practical considerations for clinical practice.

Polypharmacy, the simultaneous use of multiple medications, is growing at an alarming rate with reports documenting a range of 12 to 22 prescriptions being used on average by individuals >50 years of age.  Before we can tackle the problem we must recognize it and its root causes. The healthcare consequences of polypharmacy range from drug-drug interactions, adverse drug events, prescribing cascades, chronic dependence and hospitalizations, all of which have significant health and economic consequences.  Recent attention on precision medicine and personalized therapeutics, along with advanced health informatics technology, provides a focus needed to manage this condition and avoid its multiple complications. We will discuss the continuum of problems associated with polypharmacy, its basis, and the role pharmacogenomics plays in providing solutions. The important role of clinical laboratories as major enablers of precision, personalized medicine will be discussed. Laboratory medicine as a discipline has the potential to deliver a much needed precision approach to pharmaco-therapeutics.

The availability of CLIA-waived point-of-care tests and the accessibility and training of community pharmacists creates an opportunity for the development of collaborative disease management programs.  This session will discuss the opportunities and barriers to implementing a sustainable point-of-care testing program in a community pharmacy setting.   

Screening for Down syndrome began with the question "How old will you be when you deliver?".  If the pregnant woman answered 35 years of age or older, she was offered amniocentesis and a karyotype (diagnostic testing). Since then, serum markers in the second trimester have been used to form the Quadruple test.  While in the first trimester the ultrasound  and serum markers are identified as the Combined test.  When results from both trimester are used, this is termed the integrated test.  The integrated test has about a 90% detection rate for a 2% false positive rate and was the highest performing test until 2011.  It is important to note that these are phenotypic-based tests.  The finding in 1997 that cfDNA from the feto-placenta unit was in the maternal circulation in a relatively high percentage, allowed for the eventual development of a screening test, once next generation sequencing was available.  It is now clear that cfDNA can detect about 99% of Down syndrome with a false positive rate of 1 or 2 per thousand.  Importantly, this is a genotypic-based test.  Since 2013, cfDNA screening has been routinely used as a secondary screening test in 'high risk' pregnancies.  High detection means that  most of these women will have a negative result and would likely avoid invasive testing.  The low false positive rate means the predictive value will be high.  Current cfDNA screening tests tend to focus on common autosomal aneuploidies, with some expanding coverage to the sex chromosomes.  Recently, laboratories have extending testing to other chromosomes as well as to a limited number of microdeletion syndromes.  However reduced costs and less complexity are needed to allow cfDNA screening to be offered as a first line prenatal test to the entire pregnancy population.  Some tests are now emerging that aim at reducing costs and complexity.  In addition, there are competing methodologies that can identify a broader array of disorders.

On March 16, 2018, the Centers for Medicare and Medicaid Services (CMS) finalized a National Coverage Determination (NCD) for the use of Next Generation Sequencing (NGS) for tumor profiling in beneficiaries with cancer.  This national Medicare payment policy was formulated as part of a Food and Drug Administration (FDA) and CMS “Parallel Review Process” for Medical Devices, in response to a petition from Foundation Medicine, an NGS service provider.  Following FDA approval of Foundation’s FoundationOneCDx™ test in November 2017, CMS issued a proposed coverage determination that would have eliminated routine coverage of laboratory-developed NGS tests (LDTs).  In response to public comments, CMS issued a finalized NGS NCD that expanded the conditions of coverage for FDA-reviewed tests, while removing restrictions on payment for LDTs.  This webinar will discuss this NCD and explore its implications for payment of genomic profiling of tumors in Medicare patients with cancer.

Streptococcus pyogenes or Group A Streptococcus (GAS) is a pathogenic bacteria that causes both invasive and non-invasive infections resulting in mild to severe life-threatening disease.

Laboratory guidelines mandate that a more sensitive confirmatory test is performed on negative rapid antigen samples. However, routine culture detection of the organism can take an additional 24-48 hours. As an alternative, rapid molecular testing for Group A Strep can offer a faster and more efficient method for confirmation, contributing to the accelerated treatment of the patient.

During this presentation you will learn how our laboratory implemented a rapid, automated highthroughput method for molecular confirmation of rapid antigen negatives. The advantages of moving this assay from culture to molecular in terms of workflow and increased sensitivity will be discussed.

Genomic profiling in various cancers has become standard of care today.  Dr. Chandra will discuss the challenges and opportunities of precision oncology testing in community practice and will highlight key learning objectives through case studies.  

Advancements and innovation in in vitro diagnostic device (IVD) development are important for the success of personalized medicine. This is highlighted by the dramatic increase in the number of biomarker-targeted drug development programs since the first companion diagnostic and corresponding drug were approved in 1998. An overview of the current regulatory landscape for molecular diagnostics for oncology applications will be provided, with a focus on companion diagnostics and next generation sequencing (NGS)-based IVDs. Key issues and strategies impacting the regulatory framework for NGS assays for cancer indications will be discussed, and recent FDA clearances and approvals of diagnostic devices will serve as examples. 

Next-generation DNA sequencing began to enter the clinic a decade ago, a half decade after the draft human reference sequence was published.  The discovery of new genes, new variants of known genes, new genotype-phenotype correlations has produced a deluge of data, and it will take decades to figure out its clinical significance.  It will require sharing data of many kinds on many people over time, and correlation with clinical outcomes, environmental exposures, health habits, and other data.  The tasks are too large for any one institution, and yet the smooth flow of data will require cooperation and collective action: the formation of a commons.  Starting from a couple case scenarios that illustrate why data-sharing matters to clinical interpretation, we will turn to understanding the value of a commons, how it might form to enable scientific advance and better clinical care, using variants in BRCA1/2 as a case example.  We will finish with examples of policies that could make science work better and augment a learning health care system.

The exponential advents of advances in techniques and types of molecular diagnostic testing, and modifying strategies for these tests, are encouraging; but these evolutions simultaneously continue to introduce challenges in clinical evaluations and subsequent medical policy and reimbursement decisions related to these events. Robust critiques and standardized analyses are always recommended for coverage decisions, but flexibilities may need to be considered when appropriate. ACCE & PICOTS Models etc. must drive any assessments before financial/economic capacities come into play.