As the cost of an individual genome becomes more attainable, laboratories in North America and Europe are experimenting with offering clinical exome and genome sequencing for oncology.
In the second installment of our Advancing Clinical NGS series, Dr. Sheryl Elkin, Chief Scientific Officer at QIAGEN Digital Insights, discusses the clinical utility, cost-effectiveness, and patient impact of implementing genome sequencing as a routine part of precision oncology care
The first human genome, sequenced through the Human Genome Project, took 13 years and cost 3 billion dollars, and its completion was announced in 2003 (1). This version of the human genome was not even complete: a draft version of the human genome was published in 2000, and the genome was filled in to 92% “completion” in April 2003. The true completion of the genome, from “telomere to telomere” was not achieved until nearly twenty years later, in 2022.
The sequencing of the human genome represents an enormous step in the understanding of human biology, both in terms of normal function and disease. However, at the time that the human genome project concluded, the idea that individuals could have their genomes sequenced for routine diagnostics, in a therapeutic timeframe, was nearly inconceivable.
In 2007, the cost to sequence a single human genome was still hovering around $10,000,000, with the cost decreasing on a slope comparable to Moore’s law. However, the commercial transition from Sanger (dideoxy chain termination) DNA sequencing to next generation sequencing (NGS) technology led to a substantial reduction in the cost of DNA sequencing, and by 2015, the first “$1000 genome” was achieved. In effect, though, the true and complete cost of genome sequencing was not reflected in the $1000, which does not include any of the costs of downstream analysis. The amount of data generated by the sequencing of a genome created enormous and costly analytic challenges.
"The value of the genome sequencing in oncology depends on the ability to translate generated data into clinical applicability."
Sheryl Elkin, Ph.D.CSO, QIAGEN Digital Insights
Currently, genome sequencing as a diagnotistic tool in oncology is out of reach for the vast majority of patients. Yet, as the economics of genome sequencing continues to evolve, the technology further develops, for both the sequencing chemistry and the data analytics required to make sense of the information. As a result, laboratories in North America and Europe are starting to experiment with offering clinical exome and genome sequencing for oncology.
In a new white paper, Dr. Sheryl Elkin, CSO of QIAGEN Digital Insights, examines the opportunities and challenges of implementing exome and genome sequencing for oncology. Click the button below to read the full paper.
The fall 2023 release of the Human Gene Mutation Database (HGMD) Professional is now available, adding 12,617 new entries to the world's largest collection of human inherited disease mutations. In total, HGMD Pro 2023.3 now contains 456,702 expert-curated mutations.
Four times a year, the Institute of Medical Genetics at Cardiff University releases new updates to its market-leading database, ensuring that clinical geneticists always have access to the most current and comprehensive collection of expert-curated germline mutations. This, in turn, safeguards patients from misinterpretations and misdiagnoses.
In our most recent white paper, we share a real-life story that underscores the critical importance of precision and accuracy in clinical diagnostics. The case revolves around a 2-year-old experiencing seizures and muscle twitches whose family experienced deep emotional turbulence after her diagnostic Whole Exome Sequencing (WES) test was misinterpreted. If you'd like to explore the case further and understand how HGMD Professional could have could have played a pivotal role, we invite you to read the complete white paper here.
HGMD Professional is powered by a team of expert curators at Cardiff University. Data are collected weekly by a combination of manual and computerized search procedures. In excess of 250 journals are scanned for articles describing germline mutations causing human genetic disease. The required data are extracted from the original articles and augmented with the necessary supporting data.
The number of disease-associated germline mutations published per year has more than doubled in the past decade (Figure 1). As rare and novel genetic mutations continue to be uncovered, having access to the latest scientific evidence is critical for timely interpretations of NGS data.
Figure 1. Mutation entries in HGMD Professional 2023.3. The number of inherited disease-associated germline mutations published per year has more than doubled since 2010 (within 10 years).
View the complete HGMD Professional 2023.3 statistics, below.
Unlike new machine learning or artificial intelligence platforms that rapidly index millions of journal articles for mutations, HGMD Professional leverages human judgement and expertise—every catalogued mutation has been “touched” by a trained scientist to ensure accuracy, relevance, and context.
Learn more about the industry-leading database here, where you can explore features, watch videos, and request a complimentary 5-day trial.
It’s exciting that advancements in high-throughput sequencing techniques and analysis enable us to generate whole genome (WGS) and whole exome (WES) data in bulk for many species, including humans. With new machines and chemistries, the cost of sequencing has decreased significantly. However, the total cost of ownership associated with bioinformatic analysis of the resulting files remains a bottleneck (1).
Whether you run a genome center, testing facility, core lab or provide sequencing services, you’ve got to deliver variant call files (VCFs) at an unbeatable price and with consistent quality and turnaround time, even at peak demand. Your customers, as well as your business, depend on it. Many high-speed NGS analysis solutions require purchasing expensive, highly specialized hardware, massive computers or large cloud computing contracts. The requirement for fast and consistent turnaround times, also at peak demand, can quickly translate into a need for more personnel, more processing power—and more investment. How do you keep costs down yet deliver quality results with quick turnaround in a world of shrinking budgets?
More investment in your bioinformatics infrastructure? Nope—now you don’t have to
What if there were a scalable, point-and-click solution that could handle all your WGS, WES and large panel data analysis needs without having to purchase vast amounts of specialized infrastructure? A software that could run with a GUI and be used by anyone with minimal training? What if you didn’t have to compromise between speed and quality?
Introducing a better, faster, cheaper and more flexible tool for WGS and WES analyses
Our all-in-one NGS bioinformatics software QIAGEN CLC Genomics Workbench Premium now offers you a faster, more accurate, more flexible and more affordable way to process WGS and WES files in bulk. This is made possible via QIAGEN CLC LightSpeed Module, which enables an ultra-fast and accurate FASTQ to VCF pipeline for hereditary germline mutation analysis.
What’s more, you’ll enjoy full flexibility. Our QIAGEN CLC Genomics Workbench Premium can process data from any sample, any panel and any species and run your analyses on a laptop, desktop, server or the cloud without depending on any new or specialized hardware.
Reduce cost with speed: Accelerate WGS secondary analysis down to just 25 mins
For certain licenses, you only pay an annual fee for software access, allowing you to run (and re-run) as many samples as you need. And because of our ultra-fast FASTQ to VCF pipeline, you can get more analyses done in less time. This translates into lower analysis costs, both for on-premise and cloud deployment.
In our recent benchmark study, we showed that using our ultra-fast QIAGEN CLC LightSpeed technology our FASTQ to VCF hereditary workflow analyzes 34x human WGS samples in just 25 minutes, whereas a QIAseq Exome v3 50x sample takes just 90 seconds. When run in Amazon Web Services (AWS), the incurred computing costs were about $1 per WGS and a few cents per WES. There is no other technology that can process WGS or WES this fast—or as cost-efficient.
With demonstrated high accuracy and reproducibility, and built on a scalable bioinformatics analysis platform, QIAGEN CLC LightSpeed technology will revolutionize your ability to perform high-volume whole genome sequencing.
A software that’s ‘cheaper than free’
QIAGEN CLC Genomics Workbench Premium is an NGS analysis software your core lab can’t do without. It enables you to deliver ultra-fast sequencing analysis results while controlling your costs. It does this by saving your lab time, processing capacity and energy, so you can provide affordable services. You’ll also enjoy a variety of specialized tools for all your sequencing needs. The CLC platform software QIAGEN CLC Genomics Server and QIAGEN CLC Genomics Cloud Module help you to build the scalable bioinformatics analysis architecture you need to offer a high-throughput genomics analysis service at affordable prices. In addition, our QIAGEN CLC Genomics platform is fully supported with tutorials and documentation, an excellent team of customer support professionals and dedicated trainers to ensure you have the support you need to perform your analyses. These advantages result in reduced total cost of ownership and are far cheaper than maintaining your current setup. Therefore transitioning to QIAGEN CLC Genomics Workbench Premium is a switch you’ll quickly discover is ‘cheaper than free’.
Get in touch
Learn more about the newest features of QIAGEN CLC in our latest release, check out our upcoming webinar and request a consultation from one of our experts. Ready to try it out for yourself? Request a trial of QIAGEN CLC Genomics Workbench Premium to see how this software will make it faster, easier and cheaper for you to analyze your NGS data.
Share your CLC LightSpeed results and win
Got killer runtime results using QIAGEN CLC LightSpeed? Share them with us on social media using #CLCLightSpeed. When you do, you'll enter for a chance to win one of three one-year licenses to QIAGEN CLC Genomics Workbench Premium. You may alternatively enter for a chance to win by submitting the online entry form available here. Terms and conditions apply.
References
Next-generation sequencing (NGS) techniques allow high-throughput detection of a vast amount of genetic variations in a cost-effective manner. However, there are still inconsistencies and debates about how to process and analyze this "big data". To accurately extract relevant information from genomics data, choosing appropriate tools, knowing how best to use them, and interpreting the results correctly is crucial.
In this article, we discuss an important step in the NGS data analysis workflow–variant filtering and prioritization–including how to overcome challenges, best practices, and how to determine which NGS variant analysis solution is right for you.
Variant filtering is a secondary NGS analysis step that consists of identifying highly confident variants and removing the ones that are falsely called. The variant filtering step used to be mostly left out from deeper testing, even though it can has been shown to significantly improve precision of variant calls.
Variant prioritization is a vital step in discovering causal variants in order to identify disease-causing mutations. This is because the results of NGS technologies and applications, such as whole-exome sequencing (WES) or whole-genome sequencing (WGS), will often consist of a list of several thousands of variants of unknown significance, many of which are proved to benign (even though any rare variant has the potential to be pathogenic).
On average, WES of human samples detects approximately 20,000–30,000 SNVs and indel calls (1).
Therefore, variant prioritization accelerates and simplifies variant interpretation because the results enable the interpretation of variants of unknown significance. It is a process that with filtering identifies which variants found via NGS testing are likely to affect the function of a gene.
1. Content and curation - During the variant filtering and prioritization processes, narrowing down tens of thousands of variants to a manageable list often entails a laborious process of seeking gene-phenotype relationships by consulting numerous separate databases. In addition, when testing for rare genetic diseases, public databases are widely used for the initial elimination of common variants [minor allele frequency (MAF) > 0.01]. However, some public databases may not have variants that are present within private databases, such as the Human Gene Mutation Database (HGMD) Professional.
If causative variants can be identified earlier due to a high rank from prioritization, it’s possible that the full filtered variant list can be short-circuited, reducing the total number of variants reviewed and therefore the time to analyze a case. Additionally, accurate prioritization is a step towards the ultimate goal of fully automating the analysis of the sequencing data for NGS testing.
3. Standardization - Variant filtering and prioritization must be consistent, reproducible, and standardized. However, many clinical research and translational labs use multiple software tools to perform different steps in the NGS secondary analysis workflow, including annotation, variant filtering, and prioritization. Using multiple software tools can introduce workflow complexities and inconsistencies. Now, the gold standard is for NGS labs to use one solution that automates and standardizes variant annotation, filtering and prioritization through a single, user-controlled workflow.
1. Automated curation - To help accelerate the variant filtering and prioritization process, select a NGS assessment software solution that eliminates manual curation by providing users accesses to multiple sources of pre-curated content to rapidly and comprehensively prioritize variants [including Single Nucleotide Variants (SNVs), indels, structural, and Copy Number Variants (CNVs)].
2. Powerful algorithms - With the exponential growth of biomedical data sets in NGS testing, it is increasingly important to combine large data sets with machine learning and powerful algorithms in order to quickly identify potential causal variants within minutes.
3. Transparency and full-user control - To enable consistent, reproducible, and standardized variant filtering and prioritization, select a software solution that dynamically computes assessments with full transparency and gives users total control over parameters, policies, and output.
QCI Interpret Translational is a NGS variant assessment software solution that enables rapid, evidence-powered variant annotation, filtering, and triage for human exome, genome, and large cohort sequencing data.
Leveraging the QIAGEN Knowledge Base, the industry’s largest collection of biological and clinical findings, QCI Interpret Translational improves research efficiency and accuracy by automating manual curation processes, dynamically and transparently assessing variants according to society guidelines with full user-control, and optimizing resource allocation, allowing users to focus on what matters most: transforming genomic data into publishable insights.
References
Wednesday, March 25, hear from Dr. Anthony M Magliocco, CEO and Founder of Protean BioDiagnostics, as he discusses the application of whole exome sequencing for guiding clinical trial enrollment for patients with cancer.
The remarkable advances in precision medicine are unfortunately not currently available to all patients, especially those being treated in community cancer settings. This growing “gap” is now challenging the health system to provide cost-effective, scalable, innovative solutions for underserved patients. Protean BioDiagnostics was founded to close this gap and accelerate access to precision oncology for all patients, regardless of where they live. To this end, Protean has created an adaptable and innovative framework for rapidly deploying the latest companion diagnostics. Protean’s simplification of universal access to complex diagnostics is poised to change the practice of precision oncology in the community and truly “close the gap.”
In this webinar, you will learn more about
Date: Wednesday, March 25, 2020
Time: 11 am EDT
