SeraCare’s clinical genomics technologies are developed to address challenges faced across the spectrum of NGS assays. From early development of assays – either IVD assay manufacturers or clinical labs building their own LDTs - there is a scarcity of characterized, complex, difficult variants to ensure the assay can robustly detect all the critical genomic variants in a patient sample. Using our highly characterized, reproducible, and GMP-grade NGS standards, laboratories have a wide range of analytical and clinical validation tools to deeply characterize assay performance such as LOD, linearity, specificity, sensitivity, and reproducibility.   

On April 4^th, 2018, a new outbreak of Ebola Virus Disease (EVD) occurred in Equateur Province in the Democratic Republic of the Congo. As of June 10^th, there have been a total of 55 EVD cases and 28 deaths with a case fatality rate of 50.9%. Although the outbreak remains active, public health authorities have expressed cautious optimism because there have been no new cases in two of the three affected areas (Bikoro and Wangata zones) since May 17^th, 2018 and the rate of new cases in the third affected zone (Iboko) has slowed.¹

Next-generation sequencing (NGS) allows deeper insights than ever before into the human genome and a host of diseases and conditions. So it makes sense that there is a worldwide movement to employ NGS in a growing number of applications. But as the saying goes, with great power comes great responsibility.

Simply described, copy number variations (CNVs) are DNA segments present at a variable copy number in comparison to a normal genome. It was originally thought that a CNV consisted of a region of greater than 1 kilobases, however advances in technology have allowed for identification of CNVs as small as 50 basepairs¹.

The ability to rapidly and effectively evaluate the performance of customized next-generation sequencing (NGS) panels is critical to provide high-quality sequencing solutions to customers. New England Biolabs^®, together with Directed Genomics^®, is developing a new offering, NEBNext Direct^® Custom Ready Panels, which will allow researchers to select from a large library of genes for which baits have been developed and optimized, thus enabling rapid deployment of customized target-enrichment panels. Directed Genomics has been collaborating with SeraCare Life Sciences in order to streamline the optimization and characterization of NEBNext Direct target enrichment panels. 

Clinical labs must constantly evolve their test offerings in order to support the most recent advances in clinical care. For next-generation sequencing (NGS) tumor profiling assays, there are often multiple commercially available kits with similar claims for gene content and sensitivity, as well as customized solutions. How can you quickly perform an effective evaluation of available assay systems to make a data-driven choice?

On November 14, 2017, AMP hosted a forum to discuss genetic testing reference material availability and needs. The forum attracted attendees including EQA providers, developers in industry and government, as well as scientists from clinical laboratories. Topics for discussion included reference material use and needs for assay validation, quality control, and proficiency testing. Throughout the talks, a few themes emerged and were discussed by multiple speakers.

Myeloid cancers are “liquid” tumors that arise from the blood and bone marrow.  These diseases have undergone greater study and characterization than perhaps any other type of cancer, largely due to the ease of accessing these cancer cells via a blood draw rather than a tissue biopsy, as for solid tumors.  There are many different types and subtypes of these malignancies that are known to be caused by mutations in genes that encode proteins involved in cell signaling, transcription, epigenetic regulation, and splicing¹. 

Before next-generation sequencing became available in the hematology/oncology clinic, high-resolution genetic analysis of myeloid cancers relied primarily upon site-specific methods such as Fluorescence in Situ Hybridization (FISH) and PCR-based assays.  And, while other methods such as karyotyping and array comparative genomic hybridization are indeed able to survey large genomic rearrangements and copy number changes across the entire genome, these methods lack the resolution required for detection of many mutations that are important for myeloid cancers.

Despite the absence of clear guidelines or firmly established best practices, next-generation sequencing (NGS) assays are becoming the method of choice for gene fusion detection.

This is significant because, although some of the cancers that contain fusion RNAs are rare, they’re now treatable thanks to new targeted therapies. If your assay can detect fusion RNAs, it can help profile tumors for important diagnostic, prognostic, and therapeutic targets, which can lead to improved patient outcomes.

The old FISH method limited you to one type of fusion variant at a time; it was effective, but also slow and cumbersome. With the latest NGS techniques, detecting fusion RNAs is more efficient than ever. It’s more sensitive and can detect multiple fusions in the same assay.

Nevertheless, it’s still challenging because of the complex workflows and the need to rigorously ensure performance across all fusion variants. From extraction, to library prep, to sequencing, to the bioinformatics pipeline, there are countless points where something could go wrong.

At the 2017 Next Generation Dx Summit in Washington, DC, our CSO, Russell Garlick, PhD, presented a workshop on accelerating liquid biopsy assay development. He has worked closely with a variety of groups in the liquid biopsy space that are developing and validating circulating tumor DNA (ctDNA) assays. He highlighted some common challenges facing the field, and explained how SeraCare has been using these collaborations to develop QC tools specifically for ensuring the robustness of these cutting-edge tests.