Ingenuity http://www.ingenuity.com Intuitive web-based applications for quickly analyzing and accurately interpreting the biological meaning in your genomics data Thu, 30 Oct 2014 19:07:03 +0000 en-US hourly 1 http://wordpress.org/?v=4.0 Product Update: QIAGEN’s IPA and Variant Analysis 2014 Fall Releaseshttp://www.ingenuity.com/blog/news/product-update-qiagens-ipa-variant-analysis-2014-fall-releases http://www.ingenuity.com/blog/news/product-update-qiagens-ipa-variant-analysis-2014-fall-releases#comments Thu, 30 Oct 2014 19:07:03 +0000 http://www.ingenuity.com/?p=5288 We’ve had a busy fall here at QIAGEN Bioinformatics, culminating in significant product updates for both the IPA and Ingenuity Variant Analysis applications. These updates are part of our ongoing commitment to innovation in data interpretation and keeping pace with … Read More

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We’ve had a busy fall here at QIAGEN Bioinformatics, culminating in significant product updates for both the IPA and Ingenuity Variant Analysis applications. These updates are part of our ongoing commitment to innovation in data interpretation and keeping pace with the rapid advances happening in biomedical research.

Here are some of the highlights: 

Ingenuity Variant Analysis:Ingenuity Variant Analysis 2014 Fall Release

One of the powerful new capabilities for Variant Analysis released this fall is the ability to pre-filter data during the pre-analysis step. This convenient feature allows you to speed loading and optimize system resources by focusing on exonic regions, high-quality variants or likely causal variants typically absent in a “normal” population. You can also filter on Copy Number Variants which are specified as a range of bases along with corresponding copy number in VCFS files.

The Ingenuity Variant Analysis Fall Release also includes:

  • Splice site prediction for calculating the effects of single nucleotide variations (SNVs) on splicing events
  • Tighter integration with HGMD which now includes HGMD findings directly within Ingenuity Variant Analysis, no need for a separate HGMD Pro subscription
  • Search for only variants that are also listed in HGMD Pro
  • Pre-filtering to speed up the analysis of vary large cohort studies

Watch the features highlight in Variant Analysis Fall Release video.

Ingenuity Pathway Analysis:

New to IPA is the ability to predict the activity of Canonical Pathways. Now IPA calculates whether Canonical Pathway activity is likely increased or decreased based on differentially expressed genes or proteins in your dataset.

The IPA Fall Release also includes:FallRelease_300x250_101414

  • PathTracer: A quick way to highlight relationships and nodes of interest within networks and pathways
  • BioProfiler: A new way to explore the detailed relationships between molecules and their associated diseases, functions, or phenotypes
  • Relationship Export: Export the structural information contained within IPA networks or pathways

Watch the features highlight in IPA Fall Release video.

 

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Getting Ready for ASHG: Variants, Variants Everywherehttp://www.ingenuity.com/blog/events/getting-ready-ashg-variants-variants-everywhere http://www.ingenuity.com/blog/events/getting-ready-ashg-variants-variants-everywhere#comments Fri, 17 Oct 2014 22:20:46 +0000 http://www.ingenuity.com/?p=5242 The QIAGEN Bioinformatics crew is eager for the upcoming annual meeting of the American Society of Human Genetics, taking place this year in San Diego from October 18-22. ASHG is something like the Super Bowl of genetics research, and each … Read More

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ashg2014logo
The QIAGEN Bioinformatics crew is eager for the upcoming annual meeting of the American Society of Human Genetics, taking place this year in San Diego from October 18-22. ASHG is something like the Super Bowl of genetics research, and each year we attend to see the terrific science being presented and catch up with thousands of our colleagues.

The 2014 conference continues a trend we’ve seen in the past several years at ASHG, and that’s the rapid uptake of NGS data throughout the genetics community. The program is packed with population studies, cancer studies, and other massive-scale hunts for causal variants driving biological change. That means even small genetics labs are now dealing with big data — and the analytical problems associated with it.

The conference will kick off with a presidential address that really hits home for us: Cynthia Casson Morton from Brigham and Women’s Hospital and Harvard Medical School is slated to speak about challenges in variant interpretation and how best to deliver genetic information to patients. “We find ourselves engaged in frequent discourse about how to validate the function of variants and what results should be communicated to individuals,” she wrote in her abstract. As the developers of Ingenuity Variant Analysis, and our new web application Ingenuity Clinical Decision Support now in early customer access, we find ourselves participating in this dialogue on a daily basis. These are hard questions to answer. However, armed with the collective wisdom of peer-reviewed literature captured in a computable form using Ingenuity Knowledge Base, we know our customers are far better prepared to take on these difficult questions.

FEATURED RESEARCHER:

We’re pleased to report that Vivien Sheehan, an assistant professor of pediatrics at Texas Children’s Hospital and winner of a grant to use Ingenuity Variant Analysis in 2012, will be presenting some of her remarkable work at ASHG. Look for her on Tuesday, October 21, in the 4:30 pm–6:30 pm session entitled “From Association to Function in Complex Traits.”

POSTERS:

There will be several posters from customers featuring data analysis incorporating Ingenuity Variant Analysis or Ingenuity Pathway Analysis. Check out the poster sessions on Sunday, Monday, and Tuesday to see them (we recommend searching for “Ingenuity” or “QIAGEN” in ASHG’s abstract finder to locate them).

We also recommend checking out these posters from QIAGEN Bioinformatics:

  • Sunday, October 19, 5:00 pm – 6:00 pm
    Poster #1578S
    Comparing variant filters from transcriptome and exome sequencing data
  • Tuesday, October 21, 2:00 pm – 3:00 pm
    Poster #1391T
    Identification of differentially expressed genes and somatic mutations in esophageal adenocarinoma cancer patients

WORKSHOP:

In addition, QIAGEN will be hosting an educational workshop on Tuesday from 12:30 pm – 1:45 pm in room 11A of the convention center. The event, “Your Best Data: Teaming QIAGEN Chemistry & Informatics to Drive Samples to Insight,” will include customer data as well as information about the sample-to-insight workflow.

 DEMO & RAFFLE:

iPad raffle 1Finally, if you are at the conference, we hope to meet you! Please swing by booth #936 to get to know the QIAGEN Bioinformatics team and learn more about how our tools can accelerate your research and help you find your next hypothesis to test. We’ll be raffling off two iPad Air units on Monday evening; anyone who watches a demo at our booth will be entered to win.

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Baylor Scientist Uses Ingenuity Variant Analysis for Sickle Cell Discoveryhttp://www.ingenuity.com/blog/news/baylor-scientist-uses-ingenuity-variant-analysis-sickle-cell-discovery http://www.ingenuity.com/blog/news/baylor-scientist-uses-ingenuity-variant-analysis-sickle-cell-discovery#comments Thu, 16 Oct 2014 16:36:45 +0000 http://www.ingenuity.com/?p=5214 When Baylor’s Vivien Sheehan won a grant competition to use QIAGEN’s Ingenuity Variant Analysis, she found an exciting association in sickle cell anemia patients. It revealed a novel gene that can regulate fetal hemoglobin, and opens the door for a … Read More

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Sheehan, Vivien.

Vivien Sheehan, Assistant Professor of Pediatrics at Texas Children’s Hematology Center

When Baylor’s Vivien Sheehan won a grant competition to use QIAGEN’s Ingenuity Variant Analysis, she found an exciting association in sickle cell anemia patients. It revealed a novel gene that can regulate fetal hemoglobin, and opens the door for a possible new drug target.

Sheehan, an Assistant Professor of Pediatrics at Texas Children’s Hematology Center and Baylor College of Medicine, studied hydroxyurea-induced fetal hemoglobin levels in children with sickle cell disease. Unfortunately, not all individuals produce enough fetal hemoglobin in response to hydroxyurea to achieve clinical improvement. Sheehan’s goal was to use the genomics interpretation platform to mine exome sequence data for genetic variants related to endogenous fetal hemoglobin levels and drug response.

Now, Sheehan has crunched data from nearly 180 exomes generated by Baylor’s Human Genome Sequencing Center. As part of her analysis, she looked for variants associated with endogenous fetal hemoglobin levels. “We didn’t find anything with linear association,” she says. But Ingenuity Variant Analysis lets users perform burden analysis, and “in doing that we found that there were variants in a gene called FOXO3 that were associated with a lower baseline fetal hemoglobin,” she adds.

The gene hadn’t come up in previous genome-wide association studies of the disease; it was the deep dive in Sheehan’s study that allowed her to find the link. “You can’t do a burden analysis unless you have the detail of whole exome or whole genome sequencing,” she says.

Data interpretation with Ingenuity Variant Analysis was able to direct Sheehan to a gene called FOXO3 that appears to be linked to the amount of fetal hemoglobin a sickle cell patient produces naturally. In addition, the analysis tool helped steer Sheehan away from a number of red herrings, saving valuable time and focusing her attention on the findings most likely to matter. She followed up with extensive functional studies and confirmed the biological effect of the FOXO3 mutations.

The FOXO3 research continues, particularly because the gene is already targeted by therapeutics on the market. “FOXO3 potentially could be a drug target,” Sheehan says. “There are some quite benign medications that have been shown to upregulate FOXO3, such as resveratrol and more potent antioxidants.” While still years away from potential clinical use, the finding offers a new path that might one day help ease symptoms for sickle cell patients.

To learn more about Sheehan’s project, as well as how she used Ingenuity Variant Analysis, check out her case study.

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QIAGEN Bioinformatics Tapped by Genomics England for UK100K Genomes Projecthttp://www.ingenuity.com/blog/news/qiagen-bioinformatics-tapped-genomics-england-uk100k-genomes-project http://www.ingenuity.com/blog/news/qiagen-bioinformatics-tapped-genomics-england-uk100k-genomes-project#comments Wed, 15 Oct 2014 19:54:00 +0000 http://www.ingenuity.com/?p=5258   Even with the lightning-quick pace of the genomics field, it’s still amazing to veterans like us to see efforts on the scale of Genomics England’s 100,000 Genomes Project. This project, and others like it, truly fulfill the promise of … Read More

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Even with the lightning-quick pace of the genomics field, it’s still amazing to veterans like us to see efforts on the scale of Genomics England’s 100,000 Genomes Project. This project, and others like it, truly fulfill the promise of next-generation sequencing that was set out more than a decade ago — but they also highlight the importance of analysis and interpretation for genomic data.

We’re excited to report that Ingenuity® Variant Analysis™ has been chosen for continued assessment to be an integral part of what’s known as the UK100K project. Scientists will have access to our powerful variant interpretation platform to rapidly identify and prioritize disease-causing genetic variants using advanced analytics.

Genomics England was set up by the UK Department of Health in 2013 to sequence 100,000 whole genomes by 2017. Funded with £300 million, the institution went on the hunt for technology partners to help it achieve this bold vision. Last year, Genomics England invited nearly 30 genomics companies like ours to submit information about their tools and services; this week, the group announced the 10 companies it will move forward with for further evaluation.

The project will focus on patients with cancer, rare diseases, and infectious diseases, which together affect a sizable fraction of the UK population. The primary goals are to help patients and establish clear consent guidelines while building a foundation for medical insights and a broader genomics industry in the UK.

In a public statement, Laura Furmanski, our Senior Vice President and Head of the Bioinformatics Business Area, said: “The UK100K project is a shining example of what is possible when many great institutions and technology innovators combine forces to advance the vision of personalized medicine.”

We look forward to working with the Genomics England team on critical analysis and interpretation steps to maximize its significant genome sequencing investment in the coming years.

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Mount Sinai Scientists Find Novel Ovarian Cancer Biomarker with IPAhttp://www.ingenuity.com/blog/news/mount-sinai-scientists-find-novel-ovarian-cancer-biomarker-ipa http://www.ingenuity.com/blog/news/mount-sinai-scientists-find-novel-ovarian-cancer-biomarker-ipa#comments Wed, 08 Oct 2014 21:45:19 +0000 http://www.ingenuity.com/?p=5194 Treatment options for ovarian cancer haven’t changed much in three decades — but a powerful new biomarker identified by scientists at Mount Sinai has shed light on why some patients respond well to the gold-standard chemotherapy regimen while others do … Read More

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John Martignetti

John Martignetti, Associate Professor at the Icahn School of Medicine at Mount Sinai

Treatment options for ovarian cancer haven’t changed much in three decades — but a powerful new biomarker identified by scientists at Mount Sinai has shed light on why some patients respond well to the gold-standard chemotherapy regimen while others do not. They discovered IRF1 in just seven samples with Ingenuity Pathway Analysis (IPA) from QIAGEN.

In this study, scientists led by John Martignetti, Associate Professor at the Icahn School of Medicine at Mount Sinai, relied on a unique ovarian cancer biorepository he established seven years ago with Director of Gynecologic Oncology Peter Dottino. The biobank includes a longitudinal collection of blood and tissue specimens, creation of cell lines for all tumors, and the development of animal models for some patients as part of the personalized cancer therapy program at the Icahn Institute for Genomics and Multiscale Biology.

With this remarkable resource, the team identified a novel prognostic biomarker indicating whether a patient will respond well or poorly to the standard chemotherapy used for this aggressive type of cancer. In a project detailed in a recent publication in the journal Gynecologic Oncology, Martignetti and his colleagues dug into their biorepository to figure out why some patients with ovarian cancer respond to chemo while others become resistant. They chose just a few samples: four from people who eventually became resistant to platinum treatment, and three from patients who remained sensitive to the treatment over time.

Martignetti’s team performed a complete transcriptome analysis of the samples to determine whether gene expression levels in the tumors would have revealed each patient’s outcome. “That’s when we turned to IPA,” he says. Martignetti collaborated with QIAGEN scientists Jean-Noel Billaud and Richard Halpert for intensive analysis of the transcriptome data. “Using IPA and the Upstream Regulator Analysis module, with just seven cases, we found two really strong predictors for differences between the platinum-sensitive and the platinum-resistant patients,” he says. These two biomarker candidates, IRF1 and IRF7, were both linked to immune response — and conveniently, the former activated the latter, so the scientists focused their studies on IRF1.

Of course, identifying IRF1 from so few samples made it a candidate — but one that needed to be validated. Results from a second study of 31 samples, as well as an online resource that allowed them to look at IRF1 expression levels across more than 1,200 high-grade serous ovarian cancer samples, were consistent: “If you have high IRF1 levels, you have better progression-free survival and better overall survival rates,” Martignetti says.

He says that IPA was an instrumental analysis tool in this project. “The Upstream Regulator Analysis was important in pulling together all the disparate pathways that were being activated and upregulated to find the commonality of the IRF1 pathway,” Martignetti says. “That’s not something we could have done manually. We would not have seen that relationship without IPA.”

For more on this study,  follow-up research on the biomarker, and Mount Sinai’s ovarian cancer biorepository, please read the case study.

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A Quick review of the Annual Meeting of CAP 2014http://www.ingenuity.com/blog/news/quick-review-of-cap-2014 http://www.ingenuity.com/blog/news/quick-review-of-cap-2014#comments Thu, 18 Sep 2014 15:55:28 +0000 http://www.ingenuity.com/?p=5134 Last week, hundreds of pathologists gathered in Chicago for the annual meeting of the College of American Pathologists (CAP 2014). From the exhibition floor, our QIAGEN colleagues had the privilege of speaking to pathologists from around the world about the … Read More

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CAP 2014, ChicagoLast week, hundreds of pathologists gathered in Chicago for the annual meeting of the College of American Pathologists (CAP 2014). From the exhibition floor, our QIAGEN colleagues had the privilege of speaking to pathologists from around the world about the company’s complete offerings of tests, instrumentation and technologies for personalized healthcare.

Presentations on new biomarker research and molecular-based interventions were many and reconfirmed the accelerating pace at which genomic data is moving towards the clinic and the community’s excitement about the medical and economic benefits of targeted therapies.

Interestingly, the meeting’s kick-off panel was a discussion on covering the costs of high-value molecular-based medicine. As panelist Dr. Debra Leonard, a pathologist from the University of Vermont, agreed, genomic medicine is already showing evidence of improving individual outcomes, as well as population health outcomes, especially for cancer patients. These early successes have led to skyrocketing growth in the molecular medicine market, which according to CAP, represents 2 percent —an estimated $30 billion annually—of total health care spending in the U.S. But the elephant in the room remains who will pay for these high-value services and what is their true value to patients and society.

“What exactly are we getting with these tests?” posed Dr. Berger to the panel. “Is this just a cost driver or can it be a cost saver?”

At QIAGEN Silicon Valley we are working diligently on intuitive data interpretation software that helps researchers decrease the time and costs associated with interpreting genomic data. We are also heavily invested in creating the world’s most comprehensive resource of biological information. Simplifying the process of translational research not only leads to the development of new medicines and diagnostic tests, but has the potential to bring down the overall costs associated with integrating genomic data into routine healthcare.

Pathologists are critical members of the healthcare community and bring a scientist’s understanding of what laboratory evidence suggests and a specialty physician’s knowledge of medicine to help patients and their care givers make correct diagnoses.  We look forward to continuing our close collaboration with the pathology community and helping them through the development of data interpretation tools that enable them to provide vital molecular-based insights.

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RNA-Seq with iReport and InSilico DBhttp://www.ingenuity.com/blog/news/rna-seq-ireport-insilico-db http://www.ingenuity.com/blog/news/rna-seq-ireport-insilico-db#comments Tue, 09 Sep 2014 16:32:36 +0000 http://www.ingenuity.com/?p=5118   RNA-Seq, or transcriptome sequencing, continues to be an exciting way to explore gene expression using next-generation sequencing (NGS). But for many researchers, the interpretation of RNA-Seq data remains a daunting task because they are using spreadsheets to read transcript … Read More

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InSilico to iReport

RNA-Seq, or transcriptome sequencing, continues to be an exciting way to explore gene expression using next-generation sequencing (NGS). But for many researchers, the interpretation of RNA-Seq data remains a daunting task because they are using spreadsheets to read transcript names and expression values.

QIAGEN® Ingenuity iReport™ offers an easy-to-use alternative that provides researchers an interactive web-based report optimized for gene expression experiments from RNA-Seq, microarray, and real-time PCR platforms.  The iReport Data Analysis Pipeline incorporates best practices in statistical, quality, and differential expression analysis of gene expression data, providing the fastest way to understand the biological meaning of your expression data.

For users of InSilico DB, our colleagues at InSilico Genomics recently posted to their blog a simple two-step tutorial on how to visualize and interpret RNA-Seq differential gene expression and pathway analysis results with iReport. Last spring, we also posted on how to use the new integration of QIAGEN’s Ingenuity applications with the InSilico DB open data management platform.

InSilico DB contains a large number of microarray and NGS datasets originating from public repositories, NCBI Gene Expression Omnibus (GEO), Short Read Archive (SRA), The Cancer Genome Atlas project (TCGA) and the Broad Institute, among others. Currently, InSilico DB supports Affymetrix and Illumina gene expression microarray and Illumina NGS platforms.

Want to give it a try? Create your own free InSilico DB account, and get started.

 

 

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Content Sources Powering the Ingenuity Knowledge Base Part I: Major NCBI Databaseshttp://www.ingenuity.com/blog/news/content-sources-powering-ingenuity-knowledge-base-part-major-ncbi-databases http://www.ingenuity.com/blog/news/content-sources-powering-ingenuity-knowledge-base-part-major-ncbi-databases#comments Tue, 02 Sep 2014 16:09:37 +0000 http://www.ingenuity.com/?p=5065     Snapshot: Major NCBI Databases The Ingenuity Knowledge Base that powers all of the QIAGEN Ingenuity web applications incorporates data from a large number of sources. We dedicate a lot of attention to the high-quality, manually curated content from … Read More

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Ingenuity Knowledge Base: Spot light on major NCBI Database

 

Snapshot: Major NCBI Databases

The Ingenuity Knowledge Base that powers all of the QIAGEN Ingenuity web applications incorporates data from a large number of sources. We dedicate a lot of attention to the high-quality, manually curated content from published literature. But our investments don’t stop there because scientific knowledge doesn’t stop there, either.  The Knowledge Base is a nexus for structuring, integrating, and making almost any type of biomedical content computable to help biomedical researchers and clinicians understand and interpret the biological meaning of their data.

In this blog series, we’ll take a look at how we go beyond manually curated content by integrating it with data from public and privately funded databases. Hopefully this will provide a better sense of the scope and utility of what’s inside the Knowledge Base.

As you may recall from this recent blog post, the way we structure and integrate all this content is QIAGEN’s Ingenuity Ontology. It’s a framework we use for organizing and describing biological evidence and is what allows us to integrate data from disparate sources, enabling users to ask questions across all of these data sources and get coherent answers and predictive hypotheses. While other scientific taxonomies tend to be isolated, our ontology offers a way to integrate all of the content with consistent terms and references. That careful structure lets us add new information and keep existing information up-to-date all the time without having to reclassify existing data. The idea was simple: there’s a lot of insight that can be extracted from a very large, horizontally and vertically integrated knowledge base, so that is what we built. Now let’s see how we feed it.

We begin with the major databases hosted by the National Center for Biotechnology Information, as these are often the first stop for scientists looking to put their experimental data in context. NCBI is one of the most trusted sources of information in genomics, and with good reason — their experts do a remarkable job of building, curating, and maintaining top-notch repositories.

Three of the NCBI databases we integrate directly into Knowledge Base are EntrezGene, RefSeq, and OMIM. As NCBI describes it, EntrezGene (sometimes just called Gene) “supplies gene-specific connections in the nexus of map, sequence, expression, structure, function, citation, and homology data.” Unique gene identifiers are used across NCBI databases to make cross-database use more efficient.

RefSeq — its official name is the Reference Sequence collection — includes annotated sequences related to DNA, RNA, and proteins. The NCBI Handbook describes it this way: “Similar to a review article, a RefSeq is a synthesis of information integrated across multiple sources at a given time. RefSeqs provide a foundation for uniting sequence data with genetic and functional information.”

OMIM, short for Online Mendelian Inheritance in Man, is frequently used when studying disease associations. Hosted by NCBI, it is built on a collection originally published by Victor McKusick at Johns Hopkins and is still curated by scientists at the college’s School of Medicine. It is frequently updated with genetic disorders and traits and aims to connect genetic variation with its correlated phenotype.

Scientists who only know Ingenuity applications for gene- and pathway-centric content might be surprised at the vast amount of genetic sequences, locus-specific details, and structural genetic information fully integrated through the ontology. This includes connections between genetic sequence variation, phenotypic, pathway, and network information that is unavailable as an integrated resource anywhere else — and it’s part of what makes the Knowledge Base unique.

Throughout this series, we’ll be looking at many types of databases, including clinical databases, FDA information, cancer-specific data, and more. For your reference, here is an index of data sources. For a handy graphical representation of Knowledge Base click here. Check back soon for our next database snapshot.

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