A recent study, published in the Journal of Molecular Diagnostics, describes a new, more sensitive Hepatitis B Virus (HBV) assay1. This study, led by Song-Mei Liu, MD, PhD, of the Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University in China, is particularly exciting because the new assay can be used to diagnose hepatocellular carcinoma (HCC) at an earlier stage and to manage antiviral HBV treatments more effectively. It also highlights the way innovative molecular diagnostics can play a synergistic role with the development of new pharmaceutical therapeutics.
Microsatellites are simple tandem repeats that are present at millions of sites in the human genome. Microsatellite Instability (MSI) is defined as a change of any length due to either insertion or deletion of repeating units in a microsatellite within a tumor compared with normal tissue.1 The molecular mechanism for the change in repeat length is slippage of nascent DNA strand with respect to the template strand during replication followed by failure to recognize the mismatch due to deficiency in mismatch repair genes.
On April 4th, 2018, a new outbreak of Ebola Virus Disease (EVD) occurred in Equateur Province in the Democratic Republic of the Congo. As of June 10th, 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 17th, 2018 and the rate of new cases in the third affected zone (Iboko) has slowed.1
Highly multiplexed reference materials are particularly valuable when developing and optimizing new NGS assays because they allow you to evaluate the performance of your assay across a large number of variants including different variant types (SNVs, indels, homopolymeric variants, etc.) and contexts. However, it can be frustrating when a variant in the reference material is not detected, or not detected at the expected variant allele frequency. Troubleshooting such issues can give new insight into the performance of the assay. Here we share some stories from Seraseq™ users where the lack of detection of one or more variants at the expected levels helped them improve their assay or set more appropriate QC thresholds.
Jennifer Doudna is not a cancer biologist and joked that she might deliver her entire lecture at the 2018 AACR Annual Meeting without ever mentioning the word “cancer.” However, when presenting the Irving Weinstein Foundation Distinguished Lecture, she told a fascinating story about how curiosity regarding an interesting sequence motif in bacteria led to gene-editing tools, and how investigation of the mechanisms behind those tools may lead to innovative diagnostics for the future.
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.
The Association for Molecular Pathology Meeting (AMP) was held this year in Salt Lake City, Utah on November 15-18. For me, one of the highlights of this year’s meeting was the lecture given by Dr. Andy Feinberg, who is a professor at Johns Hopkins University School of Medicine Center for Epigenetics and the winner of the AMP award for Excellence in Molecular Genetics.Dr. Feinberg spoke on “The Epigenetic Basis of Common Human Disease.” He defined epigenetic changes as stable, heritable, modifications of the genome that are not based on actual sequence changes. These epigenetic changes can be modifications of either the DNA, or the DNA associated factors that are maintained through cell division. Examples include DNA methylation, particularly at CpG islands, histone tail modifications, nucleosome remodeling and changes in higher order chromatin structure (such as compaction).
Stochasticity mosaic painting by Andy Feinberg, after a portrait of Conrad Waddington by Ruth Collet,
was featured on the cover of Nature Genetics May 2017 Volume 49 No 5.