In order to provide the best software and product support for our customers, QIAGEN must periodically retire older versions of our software. This enables us to dedicate all our resources in delivering the latest features, enhancements and support to our current versions and latest solutions.
At this time, we would like to announce the pending end of life of QIAGEN Ingenuity Variant Analysis (IVA). On December 31, 2020, Adobe will end support of Flash Player, the web-based technology that powers IVA.
“Adobe is planning to end-of-life Flash. Specifically, we will stop updating and distributing the Flash Player at the end of 2020 and encourage content creators to migrate any existing Flash content to these new open formats.”
QIAGEN Digital Insights has evolved from the collection of world-class bioinformatics and scientific and clinical content properties, such as Ingenuity, CLC bio, Biobase, OmicSoft, and N-of-One. As such, there has been an effort to streamline the QIAGEN Digital Insights portfolio.
We have taken the opportunity to deprecate the Flash version of IVA while merging its functionality into QIAGEN Clinical Insights (QCI). This way we can streamline the QIAGEN Digital Insights portfolio while preserving the IVA workflows in an HTML5 compliant platform.
During the 2020 transition period, IVA users will have full access to the classic, Flash-based IVA platform. By mid-2020, an updated version of QCI will contain elements supporting many of the existing IVA workflows. Once this version of QCI becomes available, all IVA users will automatically have access to QCI as part of their IVA subscription within 2020. With access to both IVA and QCI, users will be able to learn how to perform IVA workflows within QCI and provide feedback to the development team.
After December 31, 2020, all IVA users must use the QCI platform, as the classic IVA Flash platform will be terminated after that date.
If you have any questions, please contact us at bioinformaticssales@qiagen.com.
Our recent Variant Analysis update includes several key features, most notably, improved data export (now completed offline to improve performance) and better handling of uploaded VCF files. The Allele Frequency Community (AFC) now features CentoMD data, with details about 155,000 sequenced individuals whose genotypes offer a more comprehensive view of population genomics. We also updated the statistics available in AFC, which contains summary statistics from public, private and users from QIAGEN’s community. These statistics are now based on more than 750,000 samples that were analyzed through our platforms—including more than 38,000 whole genomes, and more than 358,000 exome samples. The new Variant Analysis release inspired us to look at how our customers are putting it to use it in their workflows. Read on for more details—and possibly some inspiration!
Oligogenic genetic variation of neurodegenerative disease genes in 980 postmortem human brains
First author: Michael J. Keogh
The Journal of Neurology, Neurosurgery and Psychiatry recently published a study developed by an UK-based team that analyzed genetic variants of three neurodegenerative diseases in 980 postmortem human brains. They used Variant Analysis to study 49 genes known to be associated with three neurodegenerative disorders: Alzheimer’s disease (AD), Parkinson’s disease-dementia with Lewy bodies (PD-DLB), and frontotemporal dementia-amyotrophic lateral sclerosis (FTD-ALS), and investigated whether synergistic interaction between two or more functional genetic variants contributed to increased likelihood of early onset. They determined that the presence of oligogenic variants did not influence the age of onset or disease severity, which they noted is an important a priori bias to guard against in future research.
Mutational landscape of radiation-associated angiosarcoma of the breast
First author: Bryan J. Thibodeau
A team of scientists from Michigan, California, and Alberta, Canada recently investigated genomic variation in biospecimens from radiation-associated breast angiosarcomas—a rare complication of radiation therapy for breast carcinoma. In their report, which was published in Oncotarget, the team mentioned using Variant Analysis to characterize variants and to investigate signaling pathways preferentially affected in radiation-association angiosarcomas. Due to the relative rarity of this type of tumor, the team recommended further investigation, using whole genome or exome sequencing, to further the discovery and confirmation of potential drug targets and to identify potential radiation-associated signatures.
Pediatric dilated cardiomyopathy‐associated LRRC10 (Leucine‐Rich Repeat–Containing 10) variant reveals LRRC10 as an auxiliary subunit of cardiac L‐type Ca2+ channels
First Author: Marites T. Woon
A group of researchers from Madison, Wisc., and Rochester, Minn. sought to further understand the genetic causes of dilated cardiomyopathy (DCM). Their report, published in the Journal of the American Heart Association, details their work and includes mention of Variant Analysis to analyze variant call format files. The team found a rare, homozygous variant in a cardiac‐specific protein, which provides evidence that variants in LRRC10 can serve as a genetic cause of DCM. This research deepens our burgeoning understanding of the condition and provides a potential link to its pathophysiology.
ARL6IP1 mutation causes congenital insensitivity to pain, acromutilation and spastic paraplegia
First Author: M. Nizon
A team from Nantes, France, reported in Clinical Genetics about their research on the role of ARL6IP1 in the pathophysiology of insensitivity to pain and spastic paraplegia, which are symptoms of hereditary sensory and autonomic neuropathies (HSAN) type II. They used Variant Analysis to generate variant annotation and interpretation analyses, enabling them to identify a homozygous variant in ARL6IP1, which they determined as a key factor in hereditary spastic paraplegia and sensorimotor neuropathy.
We’re not only honored to understand how our solutions are helping a range of researchers learn more about their fields, we’re also keen to learn more. If you’d like your work to be featured in one of our blog posts, we’d love to hear from you. To test out Variant Analysis for yourself, simply request it here.
An estimated 300 million people worldwide live with some form of rare disease. In the US, a disease is considered rare if it affects fewer than 200,000 people, while in the European Union, rare disease affects fewer than 1 in 2,000 people. Advances are being made in ongoing research and in initiatives and communities that support patients, and QIAGEN is pleased to once again support Rare Disease Day 2018 — the theme of which is research.
Research conquers scientific frontiers and translates genomic insights into new medicines in the rare disease community. At QIAGEN, we offer a suite of solutions that contribute to these efforts, including Biomedical Genomics Workbench, Biomedical Genomics Server, and Ingenuity Variant Analysis. We are proud that our tools are helping scientists contribute to efforts to unravel these challenging diseases.
Our tools have recently been cited by researchers in their efforts to better understand rare disease. To learn more about rare inherited cardiac disorders—the primary cause of sudden cardiac death for those below the age of 35—Anders Krogh Broendberg and his team cited CLC Genomics Workbench as one of the bioinformatics tools used to call variants in their study. At the University of Paris, Lydie Da Costa used CLC Biomedical Workbench to analyze ribosomal protein genes inherent in Diamond-Blackfan anemia, a rare congenital bone marrow failure syndrome.
QIAGEN is proud to advocate for further research to help those with rare diseases, and we stand with scientists who strive to solve these complex genetic conundrums.
Here at QIAGEN, we frequently fine-tune our solutions to better serve and support our customers in the international research and clinical communities, so they can continue to advance science and patient care. Changes range from minor tweaks — like bug fixes — to entirely new capabilities, like new templates or plugins. If you missed any of our recent updates about new features and capabilities of our line of bioinformatics solutions, here’s a brief roundup of some of the highlights you might want to know about.
This fall, we announced that our CLC Genomics Workbench 11 can be used as a genome browser to share, view and explore NGS analysis results, with no license required. This release also includes faster speeds, improved trimming and updated executables. We also released Biomedical Genomics Workbench 5, which debuted the QIAseq Targeted Panel Analysis plugin. This plugin enables accurate identification of genetic variants with ease, offers a user-friendly interface to simplify QIAseq data analysis, and introduces unique molecular indices and advanced algorithms to improve the accuracy of variant calling. The fall release of Ingenuity Variant Analysis included improvements to the Phenotype Driven Ranking feature by offering further sub-ranks for variants with identical scores. For QCI Interpret for Hereditary Cancer and QCI Interpret for Somatic Cancer, we introduced four new changes, including alignment of AMP/ASCO/CAP interpretation and reporting guidelines, increased flexibility, improved reporting templates and the ability for lab managers to set up groups. We also released updates that comprise the genome interpretation sector of our end-to-end sequencing solution: CLC Main Workbench, CLC Genomics Server 10, CLC Command Line Tools 5 and CLC Sequence Viewer 8.
Overall, we’re delighted to be ending 2017 with our solutions primed to take on even tougher bioinformatics challenges! If you’d like to learn more about one of these solutions or updates, please contact us here.
There are few meetings as important to the bioinformatics community as Intelligent Systems for Molecular Biology (ISMB), which is celebrating its 25th year at the upcoming event in Prague to be held July 21-25. Organized by the International Society for Computational Biology, ISMB is known for its wide range of presentations, from big-picture keynotes to its targeted “birds of a feather” discussions and much more. We love attending this conference as a way to connect with other bioinformatics geeks and hash out (bad pun fully intended) best practices for computational biology.
This year’s ISMB will be held in conjunction with the European Conference on Computational Biology. Organizers announced 14 communities of special interest (COSIs) that will be running themes throughout the event; examples include structural bioinformatics, visualization of biological data, and bioinformatics education.
Another COSI focuses on methods for understanding the impacts of genetic variation. In the VARI-COSI workshop taking place all day July 24, experts will offer a number of presentations and discussions on relevant topics. Our own Anika Joecker, Director of Clinical Partnering Bioinformatics, will give a talk entitled “The importance of using a most comprehensive knowledgebase for the identification of pathogenic variants in cancer and inherited diseases.” She’ll speak about HGMD as well as the QIAGEN Knowledge Base, which contains hundreds of thousands of manually curated pathogenic variants associated with oncology and inherited disease. The session will include real-world examples showing how scientists have used QIAGEN Clinical Insight Interpret and Ingenuity Variant Analysis to improve diagnosis and treatment for patients.
If you’re attending ISMB this year, enjoy!
How a leading academic hospital is analyzing complex clinical data and uncovering new medical insights with powerful precision medicine solution, QIAGEN Clinical Insight.
Next-generation sequencing (NGS) creates transformative opportunities to expand our understanding of biomedicine, reshape clinical care, and improve human health. NGS also opens broad vistas for innovation and technology.
At the University of Copenhagen, under Finn Cilius Nielsen, M.D., the Center for Genomic Medicine, Rigshospitalet, is implementing the QIAGEN Clinical Insight™ (QCI) platform QIAGEN’s Ingenuity Variant Analysis™ (IVA) platform to match patients with metastatic or refractory cancers with targeted therapies and clinical trials based on their molecular profiles. In a recent study of these QIAGEN technologies, in over 60% of cases of patients that were non-responders to first-line therapy, IVA rapidly identified a clinically-actionable oncodriver mutation that enabled these patients to enroll in clinical trials and targeted therapies based on their unique genetic profile.
What all of these mutations have in common is that they have been the subjects of several scientific publications, or are documented to be related to the outcome of specific therapies. They have been selected utilizing QIAGEN’s Ingenuity Knowledge Base, a unique large-scale information resource for interpretation and selection of molecular content containing more than 13 million facts and findings about disease genetics. One example is a mutation on the ERBB2 gene, which can occur in lung, breast, ovary, and bladder cancer, suggesting a similar mechanistic role in cancers across traditional organ-based classifications. At the end of 2015, this variant was the topic of at least 27 scientific articles, including clinical case reports that document if and when cancer patients with this variant had a positive response to a targeted treatment. QIAGEN’s Ingenuity Knowledge Base comprehensively collects such facts, as well as details on where the gene variant may be relevant in professional treatment guidelines or tied to enrollment criterial for Phase III clinical trials.
While IVA is built on QIAGEN’s Ingenuity Knowledge Base, so is QCI Interpret, an advanced software platform that provides clinical labs with easy-to-use, automated workflows to rapidly process patient tests and deliver clear, evidence-based clinical reports to physicians and their patients. With QCI’s clinical decision support capabilities, a patient’s NGS test results can be interpreted and reported with confidence and accuracy to deliver the clinical benefits of precision medicine. Combining the industry’s highest level of expertise and innovation, QCI saves time by zeroing in on the most clinically-relevant knowledge, and interprets it automatically by applying AI techniques to lab-selected reporting policies and clinical standards, such as the ACMG and AMP genetic interpretation guidelines. This automation dramatically reducing the time it takes to interpret a patient’s test result from hours to days to less than 15 minutes.
The QCI platform provides a simple, secure, and scalable platform, for both software and content, to deliver high-confidence NGS interpretation workflows that deliver actionable insights into a patient’s specific disease genetics and treatment options. QIAGEN’s IVA and QCI Interpret products leverage this shared technology platform to deliver powerful capabilities across translational and clinical testing applications. QCI Interpret provides a particularly complete solution for NGS testing labs who want fast, trusted interpretation and reporting of patient tests, and enables these labs to rapidly launch new NGS tests and scale up operations cost-effectively. QCI provides a crucial step for the acceleration of precision medicine capabilities—transparent evidence that can be distributed and retrieved in real-time for better decision-making.
As stated by Dr. Nielsen, “There is no doubt that we should do genomic tests as early as possible. When we come in very early, we know that we can actually change the course of disease for the patient.” The clinical use of precision medicine will benefit strongly from an agile interpretation and reporting solution that assures clinicians and patients of the reliability, safety, and validity of diagnostic tests results. Just as IVA has informed patient-specific variant discoveries, QCI too will drive the delivery of high-quality, evidence-based clinical genetics decision-making to the bedside to enhance patient care and outcomes.
By advancing the pace of NGS technologies and applications, QCI can enable any organization to harness the power of precision medicine to improve population health worldwide.
Learn more about QIAGEN Clinical Insight
It’s great to read about how our solutions are being used and the amazing work they support. We rounded up some recent peer-reviewed literature citing the use of Ingenuity Variant Analysis. We are thrilled to read about the many ways in which the tool and its integrated content help scientists to identify and prioritize variants from human sequencing data.
The most common cause of acquired heart disease for children, Kawasaki Disease (KD) is commonly attributed to complex genetic variants — only a small number of which have been validated, until now. This report, published in PLOS, includes the findings of a San Diego-based team that conducted whole genome sequencing (WGS) on an African American family of six with two affected children. The team used Ingenuity Variant Analysis to identify the CAG10 variants of Tier 1 genes and to perform tertiary analysis of variant call format files. Ultimately, this analysis enabled the team to associate genetic variation in TLR6 with susceptibility to KD.
When seeking the cause of early onset cerebellar ataxia, a Qatar-based group of researchers focused on a large consanguineous family in which members displayed autosomal recessively-inherited cerebellar ataxia, manifesting before age 2. The team used WGS rather than exome sequencing to reveal an associated point mutation in noncoding RNA RNU12, and published their findings in Annals of Neurology. The report included several mentions of Ingenuity Variant Analysis, including a detailed graphic identifying causal variants in the study. Ultimately, the team credited the benefit of conducting WGS in finding the causative mutation, and alluded to an improved understanding and potentially new therapeutic approaches to neurodegeneration.
Earlier in May, a group of researchers based in Germany and Turkey looked at which mutations might cause left-handedness — the most pronounced behavioral asymmetry in humans. They used whole exome sequencing on a Turkish family with a strong history of left handedness, then Ingenuity Variant Analysis to conduct quantitative trait analysis. Though this revealed rare variants on 49 loci on 26 genes, the biological significance for handedness remained unclear to the team. In their findings, published in the May issue of Symmetry, the team concluded that left-handedness was the result of complex polygenic and/or epigenetic factors, confirming the results of similar studies undertaken previously.
Kids with primary adrenal insufficiency (PAI) have reduced life expectancy; the condition can even be fatal. A team based in England and Argentina focused on an extended, consanguineous family with four PAI-affected people, two of whom also had steroid-resistant nephrotic syndrome. Scientists used exome sequencing to conduct their research, using Ingenuity Variant Analysis and assessing SNPs with threshold coverage of at least 10 reads. Ultimately, they identified four homozygous mutations, and reported their results in the Journal of Clinical Investigation.
Has a QIAGEN Bioinformatics tool been helpful in your research? We’d love to hear about it! If you’d like to request a trial, just click here.
Research scientist Dr. Margarete Odenthal leads the translational molecular pathology group at University Hospital Cologne, putting new technologies through their paces to determine which ones best fit the needs and workflows of the diagnostics lab. Recently, she has worked closely with QIAGEN to assess sample extraction, target enrichment, and library preparation kits as well as data analysis and interpretation tools in a variety of cancer studies.
In one NGS-based study, she and her team analyzed BRCA1 and BRCA2 mutations in samples from severe ovarian cancer using QIAGEN products for library preparation, amplicon sequencing, and data analysis. Odenthal began with macrodissected FFPE ovarian cancer samples, which carried known germline point mutations or large deletions in the BRCA genes, using the GeneRead DNAseq Targeted Panels for human BRCA1 and BRCA2 exons for target enrichment. After sequencing, results were analyzed with Biomedical Genomics Workbench to identify somatic pathogenic mutations. “We used the copy number variation tool in order to see big deletions in the BRCA1 and BRCA2 genes,” Odenthal says. “Normally you don’t see these deletions very easily, so people have found this quite interesting.” By using the analysis tool to detect large deletions, her team is able to quickly evaluate pathogenic mutations likely to damage the protein.
In other work, she has been focused on new approaches to make sense of tumor activity that cannot be explained by DNA mutations alone. “In these cases, the tumor driving force might be less about mutations and more about different expression and splicing patterns,” Odenthal says. “There are some transcripts which are alternatively spliced and have a more oncogenic version of the protein.” Having this information can be relevant for decisions about which therapy to use, so Odenthal has been using a cohort of prostate cancer samples as the foundation for studies of DNA and RNA together. “QIAGEN has good chemistry to see the DNA mutations and in parallel to look at splicing variants and expression,” she notes.
In this pipeline, she combines DNA and cDNA in a single sequencing run. “You do the mutation and expression analysis in one workflow and you have everything together. I think modern pathology has to have everything in one pipeline,” Odenthal says. She believes that running separate FISH, NGS, and DNA promoter methylation analysis workflows will not be sustainable as diagnostic labs continue to ramp up their capacity. “It is much more efficient to have one workflow and get all this information,” she adds.
To learn more about how Dr. Odenthal has used QIAGEN Bioinformatics tools, read the full case study here.
Photo credit: Uniklinik Köln
Nearly 250 million people around the world are affected by rare diseases, which are typically genetic in nature. Their rarity means that these diseases are not well understood, and funding to research and cure them is often limited. Genome sequencing has contributed to a far better characterization of rare disease by allowing scientists to home in on causal variants. For researchers who work on rare diseases, time is often the enemy. Solutions that provide fast, easy, and profound insights can significantly improve patient care. Clinical genome and exome sequencing can be integrated more broadly into the routine practice of medicine for the betterment of public health.
We are therefore thrilled to share details here about our collaboration with the Rare Genomics Institute (RG). We’ve provided RG with access to our Hereditary Disease Solution for interpreting whole exome and genome data, so that their scientists can use the tool to better understand rare diseases by identifying potential causal mutations missed by other platforms and methods. This collaboration expands their access to our genomic data interpretation tool. According to RG analyst William Chiu, “Ingenuity has a very intuitive user interface, one can easily zoom in to a short-list of potential mutations of interests in a few clicks.”
Ingenuity Variant Analysis features robust algorithms and the deeply curated QIAGEN Knowledge Base, enabling quick identification of known or novel causal variants in disease genes and discovery of novel variants or genes by leveraging pathway and network analysis.
As a provider of bioinformatics tools designed to provide insight and accelerate scientific analysis and interpretation, we love to read about ways in which researchers are using our tools such as Ingenuity® Variant Analysis™. From rare disease mutation discovery to pharmacogenomics, this tool is deployed across many sectors of scientific discovery. Here’s a quick look at some of the most recent studies we’ve found.
A Hypothesis for Using Pathway Genetic Load Analysis for Understanding Complex Outcomes in Bilirubin Encephalopathy
Sean M. Riordan, et al.
With neonatal jaundice affecting between 60-80% of newborns, healthcare professionals are careful to prevent the condition from escalating into chronic bilirubin encephalopathy (CBE) — a considerably rarer and more impactful condition when genetically based. In a recent report from Frontiers in Neuroscience, a team led by Sean M. Riordan of Children's Mercy Hospital in Kansas City, MO, used Ingenuity Variant Analysis and QIAGEN Knowledge Base to identify causal variants in their study of significantly-narrowed SNPs. This study has not only improved medicine’s understanding of the genetic causes of CBE; it may also impact how rare disease is studied despite the lack of available GWAS or large sample sizes.
Lethal Multiple Pterygium Syndrome, the Extreme End of the RYR1 Spectrum
Ariana Kariminejad, et al.
The BMC journal Musculoskeletal Disorders recently published a study by a Tehrani team that focused on determining the cause of Lethal Multiple Pterygium Syndrome (LMPS). By conducting a range of tests (including whole exome sequencing, DNA isolation, variant annotation/selection and Sanger sequencing) on two affected fetuses, the team was able to associate LMPS with allelic defects in the excitation-contraction coupling process, and to confirm that it is an extreme sector of the spectrum related to Ryanodine receptor 1 (RYRI1) neonatal myopathy. IVA was used as a filtering strategy directed to gene candidates and focused on exonic variants where the mutation produced a missense change, stop gain or stop loss.
Resequencing and Association Analysis of Six PSD-95-Related Genes as Possible Susceptibility Genes for Schizophrenia and Autism Spectrum Disorders
Jingrui Xing, et al.
Nature recently featured a study by researchers at Japan’s Nagoya University Graduate School of Medicine, which continued an existing focus on the association between genes that encode post-synaptic density (PSD) proteins and schizophrenia and autism spectrum disorders. As part of its resequencing and genetic association analysis, the team used Ingenuity Variant Analysis to identify 26 rare, non-synonymous variants specific to carriers of schizophrenia and autism spectrum disorders. They then completed an association analysis in a larger sample set for three of those variants. The resulting investigation suggested that rare PSD mutations may increase susceptibility to schizophrenia and autism spectrum disorders.
Genomic Architecture of Inflammatory Bowel Disease in Five Families with Multiple Affected Individuals
Anna B. Stittrich, et al.
NIH’s Human Genome Variation journal ran the results of a study on families with multiple inflammatory bowel disease (IBD)-affected individuals from a team led by scientists at Seattle’s Institute of Systems Biology. Moving beyond existing GWAS which indicate a strong genetic risk factor for IBD, the researchers used whole genome sequencing to look at 38 individuals from five families. They used Ingenuity Variant Analysis to identify variants, and QIAGEN Knowledge Base to filter the variants and identify commons factors, including rare risk variants that are shared among family members and substantially affect disease development. While ultimately their findings could not point to only rare variants as significant causal factors, they did uncover the possibility that very-early-onset IBD might be an entirely new disease entity, separate from classical IBD.
Next-generation sequencing of common osteogenesis imperfecta-related genes in clinical practice
Kristóf Árvai, et al.
Researchers from Budapest’s Semmelweis University used IVA for variant interpretation in their recent report published in the NIH’s Scientific Reports. Focused on Osteogenesis imperfecta (also known as brittle-bone disease) and led by Kristóf Árvai, the team used NGS to determine the most significant genetic variants of the disease. Their resulting data allowed them to assert that clinicians could indeed use NGS to supplement diagnostic process with molecular genetic data—particularly when a disease has complex genetic background and non-recurrent mutation hot spots.
Ingenuity Variant Analysis is providing significant scientific insight around the world. We’d love to hear how you’re using it – so send us an email if you’d like to share your research, or request a trial if you’re not yet using Ingenuity Variant
