Ingenuity http://www.ingenuity.com Intuitive web-based applications for quickly analyzing and accurately interpreting the biological meaning in your genomics data Tue, 28 Jul 2015 16:10:57 +0000 en-US hourly 1 http://wordpress.org/?v=4.0.6 Publication Roundup: Ingenuity Variant Analysis in the Literaturehttp://www.ingenuity.com/blog/customer-stories/publication-roundup-ingenuity-variant-analysis-literature http://www.ingenuity.com/blog/customer-stories/publication-roundup-ingenuity-variant-analysis-literature#comments Tue, 28 Jul 2015 16:10:57 +0000 http://www.ingenuity.com/?p=6297 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 … Read More

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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.  Today, 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!

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In Dublin, ISMB Celebrates Bioinformaticianshttp://www.ingenuity.com/blog/events/dublin-ismb-celebrates-bioinformaticians http://www.ingenuity.com/blog/events/dublin-ismb-celebrates-bioinformaticians#comments Thu, 23 Jul 2015 15:40:10 +0000 http://www.ingenuity.com/?p=6292 When it comes to bioinformatics — the kind of equation-rich, in-the-weeds technical detail that makes many a molecular biologist want to run the other way — there’s no event quite as geek-chic as ISMB. (It also has a unique family … Read More

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When it comes to bioinformatics — the kind of equation-rich, in-the-weeds technical detail that makes many a molecular biologist want to run the other way — there’s no event quite as geek-chic as ISMB. (It also has a unique family atmosphere.) This year, the 23rd annual International Conference on Intelligent Systems for Molecular Biology was held in conjunction with the 14th European Conference on Computational Biology in Dublin.

It was a privilege for QIAGEN Bioinformatics to serve as a sponsor of this event, and a treat for our team to attend and exhibit. After all, we’re still a bunch of computational folks who feel most at home hashing over the code of an algorithm to get it just right. So we fit right in with the other 1,500 attendees vying for the best view of the presentations and poster sessions!

Keynote presentations this year came from scientists including Stanford’s Michael Levitt, Eileen Furlong from EMBL, Kenneth Wolfe from the University College Dublin, and Amos Bairoch at the Swiss Institute of Bioinformatics. Stellar award presentations honored the Broad Institute’s Curtis Huttenhower and Cyrus Chothia of the MRC Laboratory of Molecular Biology; it was inspiring to hear about their experiences and advice for the field.

It was clear that genomics has entered the world of big data, as several speakers focused on data compression and methods for quickly discarding data that isn’t needed for future analysis. This will continue to be a major challenge in this field as databases grow. After all, biologists are trained to save every bit of data, but long-term storage won’t make sense for many applications. We’ll need to find clever approaches like the ones that have worked so well in astronomy and other fields facing an overwhelming volume of data.

Alex Kaplun, PhD, one of our team members from Global Informatics Solutions & Support also enjoyed giving a talk about a comparison of predicted promoters in two different builds of the human reference genome. In addition to the data, he shared insights that were gained about how regulatory features, such as transcription factor binding sites, are distributed.

We’re already looking forward to next year’s ISMB! In the meantime, we’re going back to the office and giving our brains a quick break before we start to think of exciting new ways to take advantage of everything we learned in Dublin.

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IPA Summer Release 2015http://www.ingenuity.com/blog/news/ipa-summer-release-2015 http://www.ingenuity.com/blog/news/ipa-summer-release-2015#comments Tue, 14 Jul 2015 18:22:06 +0000 http://www.ingenuity.com/?p=6254   We are very pleased to announce the annual summer release of IPA.  Since IPA was launched in 2003 (Beta in 2002), we have released new updates to the product every spring, summer, fall, and winter. Today, IPA has been broadly … Read More

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IPA Summer Release email banner 600x200

We are very pleased to announce the annual summer release of IPA.  Since IPA was launched in 2003 (Beta in 2002), we have released new updates to the product every spring, summer, fall, and winter. Today, IPA has been broadly adopted by the life science research community and is cited in more than 139,00 peer-reviewed journal articles.

One significant benefit of IPA is the ability to reveal potential causal associations hidden in your datasets of differentially expressed genes. A major new feature in this summer’s release is a new gene-level heatmap tool that provides greater clarity into which genes are up- or down-regulated in a particular pathway, upstream regulator, or downstream disease or function across conditions.

For example, if you were to perform two different analyses using different experimental conditions, IPA might predict that a particular upstream regulator is increasing in activity but these may not involve exactly the same set of genes across different datasets or analyses. The new gene heat maps found via IPA’s Comparison Analysis functionality can help you quickly examine and identify significant expression differences across those conditions.

Fig 1

 

Make it easier to launch by installing the IPA client on your computer

This installer will enable you to access IPA like other desktop applications on your computer (though still requiring an internet connection). You will no longer need to launch IPA through a browser and no longer need to install Java.

You can try this new functionality by downloading the IPA Client installer from this link:

https://analysis.ingenuity.com/pa/installer/select and following the instructions.

 

 

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At Oxford, Scientists Use Ingenuity ® Variant Analysis ™ to Uncover Rare Neurological Mutationshttp://www.ingenuity.com/blog/customer-stories/oxford-scientists-use-ingenuity-variant-analysis-uncover-rare-neurological-mutations http://www.ingenuity.com/blog/customer-stories/oxford-scientists-use-ingenuity-variant-analysis-uncover-rare-neurological-mutations#comments Wed, 08 Jul 2015 16:05:58 +0000 http://www.ingenuity.com/?p=6236 At the Oxford Biomedical Research Center (BRC), scientists used Ingenuity Variant Analysis from QIAGEN Bioinformatics in a family study to pinpoint unknown mutations causing abnormal brain development. Now, a family with a history of conceiving babies with severe brain malformations … Read More

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Alistair Pagnamenta

Alistair Pagnamenta, Post Doc at Oxford Biomedical Research Center (BRC

At the Oxford Biomedical Research Center (BRC), scientists used Ingenuity Variant Analysis from QIAGEN Bioinformatics in a family study to pinpoint unknown mutations causing abnormal brain development. Now, a family with a history of conceiving babies with severe brain malformations has a new path toward having a healthy child. And the program that helped them could make a difference for many other families in similar situations as well.

Alistair Pagnamenta, a postdoc who has focused on neurological disorders since joining the center in 2010, was the lead author on a recent paper in Human Molecular Genetics reporting results for this family. They had had three pregnancies terminated due to the detection of abnormalities including polymicrogyria, a brain anomaly where poor organization of neurons results in an increased number of small folds in the cortex, instead of a smaller number of large folds to maximize the brain’s surface area. The condition can lead to intellectual disability, muscle weakness or paralysis, seizures, and more.

One challenge Pagnamenta and his colleagues faced early on was limited access to DNA samples from the three fetuses. With those precious samples as well as DNA from the parents, the team performed exome sequencing on all five individuals. Using Ingenuity Variant Analysis, they generated a list of genes already known to be associated with polymicrogyria and quickly determined that in this family, none of them was faulty. They would have to search for a novel gene.

But whole exome data from five people is a lot of DNA to comb through, so the team focused the search for a causal variant on genomic regions where all three fetuses had inherited the same chromosome segments from each parent. Targeting these identical-by-descent regions allowed the scientists to narrow their search to just 8.6 percent of the genome. “Then we searched within those regions and looked at all the variants present — how many of them were rare, how many were predicted deleterious,” Pagnamenta says. Within that subset of variants, they scanned for homozygous and compound heterozygous mutations.

The inheritance pattern for the variant of interest was unknown going into the project, Pagnamenta notes. “We thought it was most likely to be a recessive condition because there were multiple affected fetuses and the parents were unaffected,” he says. “But we couldn’t be absolutely sure. It could also have been germline mosaicism — a de novo mutation that was present in all three fetuses but not in DNA from the parents’ blood.”

Testing both modes of inheritance was another way that Ingenuity Variant Analysis proved to be a handy tool. “Having this software was quite useful because you can change the order that all the filtering is performed, and you can very quickly switch from the recessive mechanism to this de novo parental mosaicism model,” Pagnamenta says.

The team’s analysis turned up one very strong candidate that matched the expected autosomal recessive inheritance mode — compound heterozygous mutations in PI4KA on chromosome 22, one causing a premature stop and the other a missense substitution at a conserved location. The variants affect “an enzyme that’s part of a well-known signaling pathway,” Pagnamenta says. “Mutations in other components of this pathway were known to cause related brain malformations.”

To learn more about this study and BRC’s exome sequencing efforts, check out our full case study of Alistair Pagnamenta’s work.

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RNA-Seq Summit: Unlocking the transcriptome in Bostonhttp://www.ingenuity.com/blog/events/rna-seq-summit-unlocking-transcriptome-boston http://www.ingenuity.com/blog/events/rna-seq-summit-unlocking-transcriptome-boston#comments Tue, 23 Jun 2015 16:36:34 +0000 http://www.ingenuity.com/?p=6176 As we ease into summer, we are looking forward to getting together with the RNA-Seq research community at the 3rd annual Hanson Wade RNA-Seq Summit 2015 in Boston this week (June 23-25) . We are proud sponsors of this relatively new meeting which … Read More

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webinar_invite_600x290

As we ease into summer, we are looking forward to getting together with the RNA-Seq research community at the 3rd annual Hanson Wade RNA-Seq Summit 2015 in Boston this week (June 23-25) . We are proud sponsors of this relatively new meeting which brings together researchers from around the world to share their experience and the latest science in the analysis and application of RNA-Seq in basic research, drug discovery and development.

RNA-Seq offers significant advantages over existing high throughput methods for gene expression analysis, including more precise measurement of transcript levels, the ability to distinguish different isoforms, and a broader dynamic range to quantify gene expression levels.  It is precisely these advantages, however, that make interpretation of RNA-Seq data a daunting task.

QIAGEN’s portfolio of bioinformatics solutions offers powerful tools to accurately interpret and distill large RNA-Seq data sets. QIAGEN’s Ingenuity Pathway Analysis (IPA), for example, enables you to quickly identify significant differentially expressed isoforms between condition and control samples, and interpret the impact of expression changes in the context of biological processes, disease and cellular phenotypes, and molecular interactions.

For those of you who will be at this year’s meeting, Senior QIAGEN Field Application Scientist Sean Prince will discuss these solutions at the RNA-Seq Summit in a presentation on Wednesday (June 24) and a RNA-Seq workshop on Thursday (June 25):

Wednesday, June 24

  • 2:10pm ET: Application of the QIAGEN Bioinformatics Complete RNA-Seq workflow in a West Nile Virus infection Case Study

Thursday June 25

  • 2:00pm ET: Maximize Your Biological Interpretations With QIAGEN Bioinformatics Complete RNA-Seq Workflow

You can register for the workshop by clicking below:

Register

Can’t make it to the RNA-Seq Summit this year? You can click on the link to download our West Nile Virus Case Study Poster.

Our blog and website also have a number of informative RNA-Seq-specific resources where you can learn more about our portfolio of products and how researchers are using them to investigate things like  West Nile Virus infection and breast cancer networks.

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At Stanford Discovery Walk, IPA for Posterityhttp://www.ingenuity.com/blog/news/stanford-discovery-walk-ipa-posterity http://www.ingenuity.com/blog/news/stanford-discovery-walk-ipa-posterity#comments Tue, 09 Jun 2015 16:14:31 +0000 http://www.ingenuity.com/?p=6118 Stanford University is renowned for its beautiful campus, but it wasn’t the lovely foliage or grand architecture that had us inspired the other day. On a recent visit to campus, we spotted odes to our very own application, images from … Read More

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Stanford Discovery Walk, IPA in Posterity!

Stanford University is renowned for its beautiful campus, but it wasn’t the lovely foliage or grand architecture that had us inspired the other day. On a recent visit to campus, we spotted odes to our very own application, images from Ingenuity Pathway Analysis (IPA), etched into granite!

A few years ago, Stanford unveiled the Discovery Walk, a series of artistic renderings that pay tribute to important biomedical advances from the past 150 years. These black granite panels cover a row of benches that make up a walkway about the size of a city block. Among the notable advances are an fMRI brain scan, a DNA double helix, and a leukemia cell seen through a microscope.

Stanford Discovery Walk, IPA in Posterity!

But the one we’re especially proud of is a depiction of an IPA network derived from gene expression effects from anti-CD3 therapy. Permanently preserved in stone! That’s really cool.

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And just around the corner, we found an etching from a different Stanford lab highlighting the role of MYC as a key transcription factor in a cellular network.

Stanford Discovery Walk, IPA in Posterity!

To help you locate the Discovery Walk at Stanford University, here is the map:

Discovery_Walk_map

Next time you happen to be at Stanford, we hope you stop to check it out, take a picture with you in the frame and share it with us! If you have to elbow some people out of the way to get a glimpse, don’t worry about it — it’s probably just the QIAGEN Bioinformatics team gawking at this great honor!

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New Product – QIAGEN® Clinical Insight Launched!http://www.ingenuity.com/blog/news/new-product-qiagen-clinical-insight-launched http://www.ingenuity.com/blog/news/new-product-qiagen-clinical-insight-launched#comments Thu, 04 Jun 2015 16:47:49 +0000 http://www.ingenuity.com/?p=6103 We are very pleased to announce the general availability of QIAGEN® Clinical Insight, the most comprehensive, scalable bioinformatics platform for clinical labs interpreting and reporting on genomic variants identified using next-generation sequencing. The first two supported applications are in oncology, … Read More

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We are very pleased to announce the general availability of QIAGEN® Clinical Insight, the most comprehensive, scalable bioinformatics platform for clinical labs interpreting and reporting on genomic variants identified using next-generation sequencing. The first two supported applications are in oncology, for somatic and hereditary cancer testing.

The secure QCI web application rapidly classifies variants, identifies treatment options and performs geographical clinical trial matching. The platform’s interpretation tools are supported by a unique evidence-based approach, which evaluates genomic variants in the context of published biomedical literature, professional association guidelines, publicly available databases and annotations, drug labels and clinical trials. QCI also provides access to the Allele Frequency Community, the world’s largest repository of ancestral and ethnic diversity data.

In creating this platform, we gathered input from more than 100 clinical testing labs and worked with 50 of them to evaluate the QCI content and software in their workflows for laboratory-developed tests. One of the clinical collaborators that evaluated QCI was Dr. Madhuri Hegde, Professor of Human Genetics at the Emory University School of Medicine and Executive Director of the Emory Genetics Laboratory (EGL):

“Clinical labs developing and offering NGS-based clinical tests are confronted with two key challenges: the complexity of translating genetic information into actionable insights for ordering physicians and the time and effort it takes to interpret and report clinically relevant variants. Through its collaboration with EGL and other leading labs on the design and validation of its new QCI offering, QIAGEN has developed a deep understanding of these unmet needs. QCI supports both germline and somatic test indication which is important to labs offering diverse test indications. And it provides full platform and assay agnostic interpretation and reporting workflow support which enables clinical testing labs to reduce time and cost associated with NGS based testing.”

QCI is the latest addition to QIAGEN’s portfolio of bioinformatics solutions that are driving the growth of next-generation sequencing for clinical research and diagnostic labs. For more information on QCI visit our webpage.

Please sign up if you are interested in learning more about QIAGEN Clinical Insight:

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Dartmouth Bioinformatician Uses Dual Stressors, IPA for New Findings in Evolutionhttp://www.ingenuity.com/blog/customer-stories/dartmouth-bioinformatician-uses-dual-stressors-ipa-new-findings-evolution http://www.ingenuity.com/blog/customer-stories/dartmouth-bioinformatician-uses-dual-stressors-ipa-new-findings-evolution#comments Fri, 29 May 2015 15:30:38 +0000 http://www.ingenuity.com/?p=6083 New research from Thomas Hampton, a senior bioinformatics analyst at the Geisel School of Medicine at Dartmouth College, and collaborators used a dual-stressor system to discover important aspects of evolution in a fish with unique phenotypic plasticity. QIAGEN’s Ingenuity Pathway … Read More

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Thomas Hampton, Senior Bioinformatics Analyst, Geisel School of Medicine - Dartmouth College

Thomas Hampton, Senior Bioinformatics Analyst, Geisel School of Medicine – Dartmouth College

New research from Thomas Hampton, a senior bioinformatics analyst at the Geisel School of Medicine at Dartmouth College, and collaborators used a dual-stressor system to discover important aspects of evolution in a fish with unique phenotypic plasticity. QIAGEN’s Ingenuity Pathway Analysis (IPA) helped them make the connection.

In the study, the team collaborators used IPA to characterize genes underlying an important biological mechanism in Fundulus heteroclitus, a type of killifish. Their results were published in Molecular Biology and Evolution in a paper entitled “Natural Selection Canalizes Expression Variation of Environmentally Induced Plasticity-Enabling Genes.”

The paper sheds light on a poorly understood but critical trait in killifish, and would not have been possible without conducting a dual-stressor study, Hampton says. Such studies are rare in science because of concerns about confounding variability, but Hampton and his team were able to carefully craft their experiments and use IPA to determine the meaning of the gene expression data they generated. The result is a new look at the scale of evolution in killifish, which may contribute to a better appreciation of how evolution functions in other organisms too.

Hampton and his collaborators, including Joseph Shaw at Indiana University and John Colbourne at the University of Birmingham, chose to study killifish for a most unusual trait: the fish is equally happy in fresh water or in salt water, due to its ability to change the morphology and function of its gills as needed to adjust for salinity levels in the water. “This is really special. They can remodel their gills on a week-to-week basis,” Hampton says. “This would be like if anytime we needed to fly, we just sprouted a pair of wings.”

During the experiment, the team interrogated gene expression with custom arrays to reveal what was going on during gill remodeling. But in this case, expression analysis was not terribly insightful. “The kinds of genes engaged in this plasticity response were not that interesting, viewed from a distance,” Hampton says. “It looks like a bunch of different genes that are not related to anything that makes a tremendous amount of sense.”

Fortunately, the team used IPA to dig deeper, looking at the genes on a network level. “We found that the genes that facilitate phenotypic plasticity seem to be less connected to other genes, almost as if they’re in their own little world, ready to be activated in one direction or another to facilitate this process without a lot of cross-talk from other systems,” Hampton says. “That’s what Ingenuity helped us figure out. It’s an interesting result that suggests that evolution has acted not just on genes but on gene networks to make phenotypic plasticity happen.”

For more information on the study and on how Hampton uses IPA, check out the full case study here.

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