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.
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
The AACR Annual Meeting 2016 will be held in New Orleans, Louisiana, on April 16-20.
The theme this year is "Delivering Cures Through Cancer Science" and we're very much looking forward to presenting our solutions for data analysis and interpretation.
During the conference you can find us at booth #741 and on April 19, we'll host a presentation on transcriptome analysis of pancreatic cancer exomes.
Presentation
Transcriptome analysis of Kupffer cells after uptake of pancreatic cancer exosomes reveal pathways and biological processes involved in metastatic progression
Speaker: Jean-Noel Billaud, Ph.D., Principal Scientist, QIAGEN
Date and time: Tuesday, April 19 at 3:00 PM – 4:00 PM
Location: Spotlight Theater B – Hall J (enter through Lobby I)
There will be a video shoot at the presentation
Posters
Gene expression signatures in circulating tumor cells are prognostic for metastatic lesions in breast cancer patients and correlate with response to therapy
Presentation time: Sunday, April 17 at 1:00 PM - 5:00 PM
Location: Section 23, poster board #19
Our solutions have been used for this research and there will be a video shoot at the presentation
The presence and persistence of ERCC1 positive circulating tumor cells predicts worse prognosis in primary ovarian cancer patients
Presentation time: Sunday, April 17 at 1:00 PM - 5:00 PM
Location: Section 21, poster board #24
Our solutions have been used for this research
Development of a quantitative targeted RNA-Seq methodology for use in differential gene expression analysis
We have developed a new digital targeted RNA-Seq technology for differential gene expression analysis - grab a copy of our poster at poster board.
Presentation time: Monday, April 18 at 1:00 PM - 5:00 PM
Location: Section 3, poster board #13
Identification of potential immune targets in controlling endometrioid endometrial carcinoma metastatic progression
Presentation time: Wednesday, April 20 at 8:00 AM -12:00 PM
Location: Section 22, poster board #23
We're looking forward to seeing you in New Orleans!
You can get additional updates on the Biomarker Insights blog
Get more information about AACR
In the past several months there have been lots of noteworthy new papers citing the use of Ingenuity® Variant Analysis™ for interpretation and filtering. We round up just a few of them here to offer a sense of the types of studies for which Ingenuity Variant Analysis makes a difference.
A Case of HDR syndrome and Ichthyosis: Dual diagnosis by whole genome sequencing of novel mutations in GATA3 and STS genes
First author: Gregory Goodwin
In this paper, published in January 2016 in The Journal of Clinical Endocrinology & Metabolism, scientists from the Children’s Hospital of Boston report the genomic diagnosis of a young boy whose symptoms could not be understood through existing tests. They used Ingenuity Variant Analysis to filter and interpret the whole-genome data generated by Illumina sequencing, identifying 31 variants potentially associated with the child’s syndrome.
A novel missense mutation of TNNI2 in a Chinese family cause distal arthrogryposis type 1
First author: Bo Wang
Scientists from the Shanghai Jiao Tong University School of Medicine published in the American Journal of Medical Genetics results of their study of a three-generation Chinese family with several members who have distal arthrogryposis syndromes. The team performed exome sequencing of two affected and one unaffected family members, and evaluated SNPs and indels with Ingenuity Variant Analysis. They identified a novel pathogenic mutation in a gene that encodes some of the troponin complex, which is important for muscle contraction.
Application of whole genome and RNA sequencing to investigate the genomic landscape of common variable immunodeficiency disorders
First authors: Pauline van Schouwenburg and Emma Davenport
In this Clinical Immunology article, scientists from the UK and US collaborated to study patients with common variable immunodeficiency disorders. They sequenced the full genomes of 34 patients and incorporated transcriptome analysis, using Ingenuity Variant Analysis to identify variants (both known and novel) associated with these disorders.
Exome Sequencing Identifies Pathogenic and Modifier Mutations in a Child With Sporadic Dilated Cardiomyopathy
First author: Pamela Long
In the Journal of the American Heart Association, scientists from the Mayo Clinic and University of Arizona Medical Center describe a whole-exome sequencing study of a family trio with a child diagnosed with idiopathic dilated cardiomyopathy. The scientists used Ingenuity Variant Analysis to analyze variants called from the exomes. They found a novel missense mutation in TNNT2 and other mutations in XIRP2, genes related to heart physiology.
Whole-Exome Sequencing in the Differential Diagnosis of Primary Adrenal Insufficiency in Children
First author: Li Chan
Scientists from Queen Mary University of London published this Frontiers in Endocrinology paper about using exome analysis to determine the genetic basis for disease among 43 patients diagnosed with familial glucocorticoid deficiency. For 40% of patients, exome sequencing alone provided a near-immediate genetic diagnosis. Ingenuity Variant Analysis was used to screen for causal variants.
Learn more about Ingenuity Variant Analysis.
Did we miss your paper? Please contact us; we would love to feature you!
The Fall release of Ingenuity® Variant Analysis™ enriches the analysis functionality, adding speed and power, and offers new tools for the organization and management of sample analysis. We are committed to providing the most comprehensive solutions to our customers, and we’re delighted to share the highlights with you.
Analyze More Data with Greater Efficiency
Performance is important to our customers. When they pre-filter their whole genome data to exonic-only regions, they have previously been limited to data from 200 whole genome samples. We have increased that limit by 50%, so now customers can analyze up to 300 whole genome samples before the pre-filtering feature becomes mandatory. Users who are analyzing more than 300 whole genomes can either pre-filter, or bypass the pre-filter function altogether by contacting Customer Support for assistance with creating a work-around.
Better Sample Analysis and Management with New Private Control Libraries
The introduction of Private Control Libraries (PCL) delivers powerful new computation capabilities. PCLs enable users to compute and filter variant frequency from a select sample set, then compare case samples with all samples housed within the PCL. In addition, the PCL can accommodate larger volumes - up to 2000 whole genomes - when analyzing control samples, and can compare cases v. control samples using the Genetic Analysis and Statistical Analysis filters.
We have added two new tabs to PCL, which features a drag-and-drop interface to make management a snap. The first is called “My Control Libraries,” enabling you to store and easily access your PCLs. With the second tab, you can build a new library by clicking on the “New Library” tab in the “My Samples” view.
Additional Improvements
When considering other improvements that could really benefit our users, we recognized the intrinsic value of the Allele Frequency Community (AFC). We took this release as an opportunity to update the build of the AFC, which is now comprised of more than 120,000 consented exomes and genomes (about 12,000 of which are whole genomes). We have also improved integration between Ingenuity Variant Analysis and Ingenuity Pathway Analysis (the integration is in beta, with limited support), which enables Variant Analysis to export the list of gene IDs, the ACMG assessments, and the gain/loss of function information when you click on the “Export to IPA” button.
Learn more about Ingenuity Variant Analysis
Over the years, scientists around the world have been using our bioinformatics solutions in their research. We feel privileged that our applications have been assisting scientists in uncovering greater insights, landmark discoveries, and helping further the research that has a direct impact on humanity.
We are starting a new blog series to showcase some of these research papers from QIAGEN Bioinformatics customers. Here, we recap a handful of recent publications that used Ingenuity® Variant Analysis™ to help make sense of complex or hereditary disease phenotypes.
The use of whole-exome sequencing to disentangle complex phenotypes
First author: Hywel J Williams
This paper in the European Journal of Human Genetics comes from University College London’s GOSgene group, including lead author Hywel Williams, one of our featured researchers. Published in June, “The use of whole-exome sequencing to disentangle complex phenotypes” reports the identification of a causative mutation in two children with a previously uncharacterized disease marked by abnormal bronchial widening and peripheral neuropathy. The team used Ingenuity Variant Analysis to study exome sequence data, extracting the variants most likely to be causative. For more information on this paper, click here.
Alternating Hemiplegia of Childhood: Retrospective Genetic Study and Genotype-Phenotype Correlations in 187 Subjects from the US AHCF Registry (PLoS One)
First author: Louis Viollet
In May, a large team of scientists from institutions around the world report an ambitious effort to stratify patients with AHC, a neurological disorder associated with repeated bouts of temporary paralysis. The researchers analyzed mutations and genotype-phenotype correlations in nearly 200 patients, then used Ingenuity Variant Analysis to evaluate mutations detected in sequence data. In addition to finding novel mutations associated with the disorder, the team also determined that one known variant was linked to earlier onset and more severe symptoms, potentially offering a more accurate prognostic indicator (biomarker?) for newly diagnosed patients. You can read more about this work here.
A nonsense mutation of human XRCC4 is associated with adult‐onset progressive encephalocardiomyopathy
First author: Leonardo Bee
In the April issue of EMBO Molecular Medicine, scientists from Italy, the UK, and the US used exome sequencing to study twins with a progressive neurological syndrome; symptoms included cognitive impairment and depression, and both twins also had dilating cardiomyopathy. The publication reports the discovery of a homozygous nucleotide change affecting a protein associated with DNA repair. Ingenuity Variant Analysis was used to zero in on variants in the XRCC4 gene known to be involved in DNA repair. Using Ingenuity Variant Analysis’ Path to Phenotype™ investigators were able to link impairment of the XRCC4 gene to the subject’s observed developmental disorders. To learn more, click here.
Exome sequencing of case-unaffected-parents trios reveals recessive and de novo genetic variants in sporadic ALS
First author: Karyn Meltz Steinberg
In March, scientists from Washington University in St. Louis and the University of Sydney published this paper in Nature Scientific Reports. In it, they describe exome sequencing of 44 trios of patients with ALS and their unaffected parents. Using Ingenuity Variant Analysis as well as other analysis tools, they found a number of homozygous recessive and de novo variants that may be implicated in the disease. “This trio study indicates that rare private recessive variants could be a mechanism underlying some case of sporadic ALS, and that de novo mutations are also likely to play a part in the disease,” the authors report. Learn more about this work here.
Impaired Telomere Maintenance and Decreased Canonical WNT Signaling but Normal Ribosome Biogenesis in Induced Pluripotent Stem Cells from X-Linked Dyskeratosis Congenita Patients
First Author: Bai-Wei Gu
Finally, this May PLoS One publication from researchers at the Children’s Hospital of Philadelphia reports the use of induced pluripotent stem cells from patients with dyskeratosis congenita, a rare syndrome affecting bone marrow. By comparing these cell lines to ones with knocked-in wild type genes correcting the dysfunction, the scientists could analyze changes in telomere activity associated with the syndrome. The team used both Ingenuity Variant Analysis and Ingenuity Pathway Analysis (IPA) to look at mutations and gene expression data, finding decreased WNT signaling in mutant cells. Research paper is available here.
Did we miss your paper? Please contact us; we would love to feature you!
