The Winter 2019 Release of the Human Gene Mutation Database (HGMD) Professional is available, expanding the world’s largest collection of human inherited disease mutations to over 275,000 entries–that’s 11,699 more than the previous release.
HGMD Professional is the de facto standard resource for comprehensive coverage of published germline mutations in nuclear genes that underlie, or are closely associated with, human inherited disease.
A subset of the HGMD gross deletions has now been mapped to both builds of the reference genome (NCBI38/hg38 and legacy NCBI37/hg19). Due to the absence of accurate breakpoint data for most of these lesions, 3,348 entries have been mapped in this release. HGVS nomenclature is also provided for this dataset.
In addition to the standardized HGVS descriptions provided by HGMD, users can now view predicted HGVS nucleotide-level descriptions based on non-canonical RefSeq and Ensembl transcripts.
Founded and maintained by the Institute of Medical Genetics at Cardiff University in 1996, HGMD Professional provides users with a unique resource that can be utilized not only to obtain evidence to support the pathological authenticity and/or novelty of detected gene lesions and to acquire an overview of the mutational spectra for specific genes, but also as a knowledge base for use in bioinformatics and whole-genome screening projects. Unlike other mutation databases, HGMD mutations are all backed by peer-reviewed publications where there is evidence of clinical impact.
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 next-generation sequencing (NGS) data.
View the complete HGMD Professional statistics here.
HGMD Professional helps clinical testing labs analyze and annotate next-generation sequencing (NGS) data with current and trusted information. Unlike other mutation databases, HGMD mutations are all backed by peer-reviewed publications where there is evidence of clinical impact.
To get the most out of your HGMD Professional subscription, visit our Resources webpage for case studies, technical notes, and video tutorials. Or hear from Peter Stenson, manager of HGMD, in an on-demand webinar on how HGMD has empowered a generation of geneticists for precision medicine here.
Or hear from Peter Stenson, manager of HGMD, in an on-demand webinar on how HGMD has empowered a generation of geneticists for precision medicine here.
New ANNOVAR databases are also available.
Learn more about how ANNOVAR can be used with HGMD for variant annotation. Watch a recorded webinar featuring ANNOVAR here.
The Genome Trax™ update will roll out at the end of January, 2020. Updated tracks have been released with HGMD 2019.4 content for all HGMD-related tracks.
For labs looking to generate clinician-grade reports for germline or somatic NGS testing, QIAGEN Clinical Insight (QCI) Interpret reproducibly translates highly complex NGS data into standardized reports using current clinical evidence from the QIAGEN Knowledge Base, which consists of over 40 public and proprietary databases, including HGMD Professional.
Click here for a free demonstration of QCI Interpret.
On April 22, Nature Medicine published the first results from the UK's TARGET (Tumor chARacterisation to Guide Experimental Targeted therapy) study. The letter, written by researchers funded by Cancer Research UK, The Christie Charity, AstraZeneca, and the NIHR Manchester Biomedical Research Centre (BRC), adds new evidence for the feasibility and potential utility of liquid biopsy to identify clinically actionable mutations and guide clinical trial enrollment for patients with advanced cancer.
Currently, enrollment to trials depends on a patient's type of cancer or genetic data obtained from an invasive tumor biopsy, which is often months or years old and may not represent a patient's current disease due to the tumor's evolutionary changes.
TARGET is a molecular profiling program with the primary aim to match patients with different types of advanced cancers to early phase clinical trials on the basis of analysis of both somatic mutations and copy number alterations across a 641 cancer-associated-gene panel in a single ctDNA assay. In the first of the two-part trial, the investigators were able to collect, process and analyze blood samples from 100 patients in the Manchester area.
The results show that a small volume of blood can contain up-to-date genetic information about a patient's cancer to inform treatment choices. In this feasibility study of the first 100 patients, 11 were molecularly matched and enrolled into an available therapy.
Investigators used QIAGEN Clinical Insight (QCI) to identify the clinically actionable variants and geographically available clinical trials, stating:
Functional annotation of somatic variants was performed using ANNOVAR, the resultant VCF file was analyzed through the QIAGEN Clinical Insight for Somatic Cancer platform and reports were generated for discussion in the TARGET Molecular Tumor Board. ‘Actionable’ was defined as a target of known pathogenic significance for which either a licensed or experimental agent or relevant clinical trial was available at the time of discussion.
The investigators go on to describe the importance of using clinical interpretation and reporting tools that are connected to comprehensive knowledge resources needed to minimize the number of variants of unknown significance (VUS) with evidence. As they explain, it is nearly impossible for tumor boards to have knowledge of every actionable variant:
A potential reason why large molecular screening programs have traditionally allocated only 10–15% of patients to studies may be in the interpretation of variants of unknown significance7,8,9. It is challenging for any MTB to have knowledge of all possible variants, and databases are in development for pooling relevance of variants of unknown significance23,24. We addressed this issue by accessing software packages to aid interpretation of the relevance of specific variants and to identify appropriate trials in different regions of the United Kingdom or Europe. The QIAGEN Clinical Interface software package was considered valuable in differentiating actionable mutations (and recommended matched therapies) from those of unlikely clinical relevance, and provided tiering following ACMG/AMP/CAP guidelines.
The researchers now hope the second part of TARGET, which is already underway, will show how often the blood test is successful at matching patients to early phase clinical trials and the impact this has on their overall survival. There is also an option of referring patients to other clinical trial sites, if suitable matched trials are available in other parts of the country--another great feature of QCI.
Reference: *Rothwell, et al. Utility of ctDNA to support patient selection for early phase clinical trials: The TARGET Study. Nature Medicine. (2019) DOI: https://doi.org/10.1038/s41591-019-0380-z
Read the full article here!
At the beginning of 2019, QIAGEN announced the acquisition of N-of-One, Inc., a molecular oncology decision support company that provides case-specific, expert-powered clinical NGS interpretation services and solutions.
We sat down with Sean Scott, QIAGEN’s Chief Business Officer and Vice President of Business Development for Clinical Genomics and Bioinformatics, to discuss QIAGEN’s plans for post-acquisition incorporation and what new value QIAGEN customers can expect.
How does the acquisition of N-of-One fit into QIAGEN’s clinical bioinformatics strategy?
Sean Scott: This acquisition represents a unique opportunity for QIAGEN and N-of-One to combine respective strengths to deliver the industry’s most robust portfolio of molecular oncology decision support solutions from one provider. N-of-One’s technology-enabled, yet human-driven, services and the proprietary MarkerMine™ database are planned to be integrated into QIAGEN Clinical Insight (QCI), our platform for NGS analysis and interpretation. We are opening the door to real-world evidence (RWE) and creating new opportunities for supporting healthcare providers and payers.
What does the acquisition mean from a pharmaceutical company’s perspective?
Sean Scott: The addition of N-of-One’s MarkerMine database and commercial data rights creates an attractive and expandable link into RWE insights. N-of-One’s Genomic Insights and analytics services can be commercialized to pharmaceutical industry partners—in particular to more than 25 companies with which QIAGEN has deep companion diagnostic co-development relationships—to support patient cohort analytics, patient stratification, trial protocol design, assay design and interpretation, trial accrual and market forecasting, patient-to-trial matching and other features.
How does N-of-One differ from other molecular decision support providers?
Sean Scott: N-of-One is one of the best-known brands in molecular oncology decision support. It is well-established with labs, pharma companies, and payers, and N-of-One has been the solution-of-choice for leading diagnostic companies, such as Foundation Medicine. Unlike other providers, N-of-One employs a team of over 30 PhD scientists and oncologists to research and analyze each patient case, and in the process, N-of-One has amassed one of the most comprehensive resources of oncology clinical and scientific evidence in the industry with more than 125,000 anonymized patient samples.
How could real-world evidence and patient data impact clinical development program design?
Sean Scott: Today, all stakeholders in the healthcare spectrum—pharmaceutical developers, payers, regulators, physicians and patients—are putting their money on the collection and analysis of many different types of RWE as a key enabling strategy, to close critical gaps in knowledge, give physicians and patients broader access to therapies, and help payers realize the actual value of those therapies in improving health and reducing costs. While still at an early stage, RWE is becoming increasingly used to complement traditional RCT data to inform important healthcare decisions. This suggests that RWE will have a significant impact on the healthcare industry in the years to come.
We are excited to announce our acquisition N-of-One, Inc., a privately-held U.S. molecular decision support company and pioneer in clinical interpretation services for complex genomic data.
The addition of N-of-One will enable QIAGEN to significantly expand its decision-support solutions while offering a broader range of software, content and service-based solutions. It will also enable QIAGEN to provide customers with greater access to valuable genomic data assets and service offerings.
N-of-One’s technology-enabled, yet human-driven, services and the proprietary MarkerMine™ database are planned to be integrated into QIAGEN Clinical Insight (QCI), enhancing this industry-leading clinical offering with medical interpretation and real-world evidence insights and offering robust decision support in oncology.
The proprietary database, services and processes of N-of-One produce case-specific reports based on data generated with molecular tests, including next-generation sequencing (NGS) technologies, and deliver clinical evidence for biomarkers and a list of therapeutic options for consideration. N-of-One also provides patient-specific clinical trial matching services and a somatic cancer database with more than 125,000 anonymized patient samples. This data will be added to the patient samples currently available in QCI, further increasing QIAGEN’s position in offering by far the largest genomics knowledge base.
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Day One kicked-off with numerous informational sessions, including talks on the role of AI in clinical decision-making, the importance of standardization for reimbursement, and the tremendous potential of genomic profiling in disease prevention, diagnosis, and treatment.
Dan Richards, Vice President of Biomedical Informatics at QIAGEN, spoke about the clinician's current challenge of curating all the evidence he or she needs to confidently sign-off on variant reports before they go to the prescribing physician. QIAGEN Clinical Insight (QCI) and N-of-One were featured as solutions providing options for either in-house curation with tailored workflows or on-demand curation services.
On Tuesday morning, the conversation continued with a panel hosted by Sean Scott, Chief Business Officer of Clinical Genomics and Bioinformatics at QIAGEN, that discussed the emergence and application of real-world evidence in the clinical setting, especially in precision diagnostics and clinical trial protocol design.
The panel consisted of Raju K Pillai, MD, Hematopathologist and Molecular Pathologist at City of Hope National Medical Center, James Hadfield, Director and Principal Diagnostic Scientist at AstraZeneca, and Sheryl Krevsky Elkin, Chief Scientific Officer of N-of-One.
Also on Tuesday morning, Mary Napier, Associate Director of NGS Strategy at QIAGEN, gave a timely talk on how diagnostic labs and pharma companies can gain a comprehensive understanding of tumor mutational burden signature by implementing our new QIAseq Tumor Mutational Burden panel.
What does she mean by "comprehensive"?
Find out here!
Thank you to everyone who visited the QIAGEN booth, we truly enjoyed talking to all of you about the industry challenges, and changes you see happening now and in the future.
See you at our next event:
Advances in Genome Biology and Technology (AGBT) 2019 in Marco Island, Florida!
February 27th - March 2nd
Want to know more about our clinical solutions and real-world evidence?
Stop by booth #1557 at ASH to explore our complete Sample to Insight solution for interrogating 25 genes for variants with known significance to clonal myeloid malignancies.
Coupled with QIAGEN Clinical Insight (QCI) Analyze and Interpret, QIAGEN’s secondary and tertiary NGS analysis platform that provides seamless variant detection, interpretation and reporting based on actionability tiers from the 2017 AMP/ASCO/CAP guidelines, the streamlined solution enables sub-classification and prognostic assessment of hematological malignancies, including leukemia, Non-Hodgkin lymphoma, Hodgkin lymphoma and multiple myeloma.
QCI Interpret for myeloid malignancies offers a specialized workflow that guides prognostication and treatment decisions. With features that incorporate cytogenetic information, World Health Organization (WHO) somatic frequencies, and variant-level prognostic evidence from the QIAGEN Knowledge Base, QCI Interpret helps you assess actionability through multiple levels of information.
Meet and talk with our experts at ASH 18, booth #1557!
Featured Products and Solutions
Check out our Sample to Insight oncohematology solutions here.
See you in San Diego!
Your QIAGEN team
Though not technically summer, on May 25th, the EU passed the General Data Protection Regulation (GDPR) into law, creating a global ripple effect. The law impacts the world of clinical decision support software because it stipulates the “right to explanation,” around automated decision-making (i.e., algorithms) and the expected consequences of applying those decisions. This requirement for transparency does not bode well for the walled-off “black box” approach to clinical decision support. For another perspective, read this contributed piece in The Pathologist, written by our own Ramon Felciano, in which he positions QCI as an enabling tool to transition to precision medicine in a cost-effective, scalable, and transparent way.
Artificial intelligence (AI) was frequently in the news over the past few months. In particular, we saw quite a few stories about IBM’s Watson and its limitations in beating cancer. Though Watson has not yet lived up to its promise of generating insights and identifying new approaches to cancer treatment, there remains hope in the industry that AI will eventually revolutionize medicine—whether through data pattern recognition, its impact on pharmaceutical development, or—even someday—cancer. In the meantime, we at QIAGEN continue to focus on our clinical decision support tools (big data, informatics and augmented intelligence) to improve test interpretation and accuracy of results.
QIAGEN was in the news as well.
Our second consecutive win during AMP Europe’s Battle of the Bioinformatics Pipeline event was covered in GenomeWeb; we published our own recap of the results to provide additional detail and background around standardizing variant interpretation and reporting. Finally, we recently hosted three international OmicSoft User Group Meetings:
We hope you had a wonderful summer, and we look forward to the busier pace and renewed activity that fall brings.
Whether you’re using PCR or NGS, targeted panels or whole-genome sequencing, mono- or multiplex testing, we have a solution to empower your workflow. Stop by booth #607 to explore and demo some of our products, including QCI Interpret.
Sip, mingle, and connect while gearing up for an exciting weekend of events, which include three QIAGEN-sponsored Corporate Workshops and two QIAGEN Innovation Stage Spotlights.
In a not-to-be-missed talk, Dr. Fergus Couch of the Mayo Clinic will discuss the current challenges and opportunities of liquid biopsy in oncology research.
Meet us at the Innovation Stage on November 1st.
Learn about QIAGEN Clinical Insight (QCI), a flexible clinical decision support suite that is compatible with any NGS platform, running any assay, targeting any indication, including somatic, hereditary, hematological or childhood cancers. During this talk, Dan Richards, Vice President of Biomedical Informatics at QIAGEN and co-founder of Ingenuity Systems, will present a lung cancer case study to show how QCI allows you to optimize and scale your pipeline for the clinical interpretation of genetic variants—from sequence data to report sign-off—without sacrificing accuracy or utility.
We are days away from one of the largest gatherings of molecular pathologists and diagnostic professionals and we couldn’t be more excited to support your path to precision medicine.
Visit us at booth #607 to demo our solutions or chat with our experts.
Learn more at our AMP 2018 event page.
See you in San Antonio!
