News – Genomics Research: Infection Identification: Metagenomic Next-generation Sequencing vs PCR

News – Genomics Research: Infection Identification: Metagenomic Next-generation Sequencing vs PCR

Infection Identification: Metagenomic Next-generation Sequencing vs PCR

Nov 21, 2019
By Molly Campbell, Science Writer, Technology Networks

Molly Campbell
Science Writer
 @mollyrcampbell

In the U.S., the number of transplants is growing by approximately 4% each year. Of the 57,000 transplants that take place, roughly 30% of patients will suffer from a viral infection.

The current standard of care approach for identifying infections in post-transplant patients is quantitative PCR (qPCR). However, a new study, a joint publication of Arc Bio and Stanford University School of Medicine, demonstrates that a novel metagenomic next-generation sequencing (mNGS) platform shows comparable power in identifying the 10 most common infections in post-transplant patients when compared to qPCR.

We recently spoke with Meredith Carpenter, Director of Assay Research and Development for Arc Bio, to learn more about the capabilities of the platform.

Molly Campbell (MC) Why is it important to have a highly sensitive method for identifying infections in post-transplant patients?

Meredith Carpenter (MCa):
 Transplant patients are uniquely challenging to diagnose and manage with respect to infections because they are undergoing immunosuppressive therapy to reduce their risk of transplant rejection. However, the immunosuppressive drugs also increase their risk of infections and co-infections, while also suppressing many of the typical clinical signs and symptoms used to diagnose an infection. This means it’s crucial to have not only sensitive diagnostic tools but also ones that are highly multiplexed so you can simultaneously detect multiple potential pathogens, in this case from a single blood draw. This also allows the monitoring of viral loads, which qPCR has established as standard of care in this patient population, with the goal of customizing dosing and titration of immunosuppressive therapies and/or antivirals for each patient to maximize benefits while limiting toxicity of these drugs.

MC: Quantitative PCR is the current standard of care approach for identifying pathogens post-transplant patients. Why has it been difficult to adopt metagenomic next-generation sequencing (mNGS) in this space?

MCa:
 Adoption of mNGS within infectious diseases has been slower than in human genetics due to barriers related to the cost and complexity of developing and deploying these methods, as well as the small proportion of microbial genomes in a patient sample compared to the host genome, and a lack of clinical utility and outcome studies to show the value of such novel diagnostics in this setting. From a wet lab perspective, it requires that the user have expertise in preparing samples for sequencing, which can be complex. There is also a “dry lab” component, which requires a bioinformatician to analyse and interpret the sequencing data. In many cases this will need the user to build a bioinformatics pipeline in-house, which requires highly specialized expertise or the use of publicly available software; much of which is not very user friendly. Finally, the ability to quantify results requires the use of specially designed controls. Taken together, these cost and resource barriers have prevented many labs from adopting mNGS for routine use.

MC: Please can you tell us about the novel metagenomic next-generation sequencing (mNGS) test, and how it overcomes these issues?

MCa:
 Currently, the Galileo™ platform is for research use only and is intended to be used by researchers who are interested in the detection and quantification of DNA viruses that commonly cause infection (or reactivation of latent infections) in the transplant setting. The platform can overcome some of the barriers to deploying mNGS by including reagents and controls for sample preparation, as well as access to the Galileo™ Analytics software, which performs analysis and interpretation of the sequencing data. User-friendly reports are generated by the software that provide detection and quantification of 397 strains of 10 key DNA viruses (CMV, EBV, HHV-6A, HHV-6B, HSV-1, HSV-2, BKV, JCV, ADV, and VZV) as well as semi-quantitative detection of B19 and TTV strains. By providing a turnkey workflow, the Galileo™ platform can eliminate much of the learning curve for mNGS. This allows researchers to instead focus their time and resources on designing and conducting studies to generate the most impactful publications.

MC: What were your main findings in this study? What information can the mNGS test provide in this context that qPCR cannot?

MCa:
This study was a collaborative effort between Dr. Benjamin Pinsky at the Clinical Virology Laboratory at Stanford University School of Medicine and Arc Bio to validate the Galileo™ platform using both contrived and residual clinical samples as compared to the current gold standard methods (individual qPCR assays). We report comparable performance of the Galileo™ platform and singleplex qPCR assays across a range of analytical parameters, including sensitivity, limit of detection, and viral quantitation. In addition, because Galileo™ is highly multiplexed, it identified several cases of co-infections from a single sample. While singleplex PCR could have identified these additional pathogens, they were not requested by the clinical teams at the time of ordering. This highlights one advantage of highly multiplexed technologies such as mNGS, although the clinical relevance of these additional findings must be established. Overall, the ability to detect and quantify 397 viral strains simultaneously from a single specimen could mean significantly lower time and cost burdens for researchers evaluating viral infections and reactivations.

MC: In the future, do you envision mNGS replacing qPCR as the standard of care method for identifying infections in transplant patients?

MCa:
I believe many researchers and clinicians do envision mNGS eventually replacing PCR as the standard of care for diagnosing many types of complex infections, including transplant patients. However, we must begin with generating evidence of value and identifying the most cost-effective patient populations to apply this powerful technology. The Galileo™ platform is ideally positioned to help clinical researchers robustly evaluate the potential of mNGS and generate the necessary data for demonstrating value to clinicians, regulators and payers.

MC: What are your next steps in this space?

MCa: 
We are continuing to broaden the potential utility of the Galileo™ platform by adding key features and menu expansions aimed at extending the value of mNGS to other areas of infectious disease research.

Meredith Carpenter, Director of Assay Research and Development for Arc Bio, was speaking with Molly Campbell, Science Writer, Technology Networks.

Article Reposted From: Genomics Research from TECHNOLOGY NETWORKS

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News – FierceBioTech: Illumina scientist’s startup aims to rapidly detect drug resistance in bacterial DNA

News – FierceBioTech: Illumina scientist’s startup aims to rapidly detect drug resistance in bacterial DNA

FierceBiotech: Illumina scientist’s startup aims to rapidly detect drug resistance in bacterial DNA

Jul 27, 2018

One of the founding scientists of Illumina has come out with a new gene-sequencing software startup that aims to tackle antimicrobial resistance and rapid pathogen detection.

Arc Bio launched with its first cloud-based product, Galileo AMR, which promises to detect possible drug resistance and provide annotations for any gram-negative bacterial DNA sequence in under five minutes. Tracking certain genes can help researchers better understand how drug resistance spreads through different strains.

Based in Menlo Park, California, and Cambridge, Massachusetts, Arc Bio’s CEO, Todd Dickinson, is joined by scientific co-founders Carlos Bustamante and David Andrew Sinclair. Bustamante is a population geneticist and professor of biomedical data science, genetics and biology at Stanford University, while Sinclair is a professor of genetics at Harvard University.

“As the CDC reports, every year over 2 million people are infected by antibiotic-resistant bacteria, causing more than 23,000 deaths in the U.S.,” Dickinson said in a statement. “Rapid identification of various strains of antimicrobial resistance, and better understanding their transmission and evolution, is vital to protecting public health.”

Dickinson served as director of product development for Illumina’s DNA sequencing operations and spent more than 12 years with the company. He also served as VP of global commercial operations at BioNano Genomics.

Galileo AMR—formerly known as MARA and acquired from Spokade—draws from a digital archive of validated gram-negative AMR genes, cassettes, and other mobile elements.

“Our goal at Arc Bio is to revolutionize pathogen detection by developing a unique NGS lab workflow and software solution that allows for smarter and simple to use analysis,” Bustamante said. “Our current emphasis is on assisting those in public health and life science researchers who study antimicrobial resistance transmission and evolution of gram-negative bacteria.”

Arc Bio, which operates under Sinclair’s EdenRoc Sciences, aims to build a suite of next-generation sequencing products in bacterial and pathogen analysis.

 

Article reposted with permission from FierceBiotech

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