Ingenuity http://www.ingenuity.com Intuitive web-based applications for quickly analyzing and accurately interpreting the biological meaning in your genomics data Mon, 11 May 2015 13:15:16 +0000 en-US hourly 1 http://wordpress.org/?v=4.0.5 Conference Presentation: A Systems Biology Approach to Viral Research (West Nile Virus Case Study)http://www.ingenuity.com/blog/webinar/conference-presentation-systems-biology-approach-viral-research-west-nile-virus-case-study http://www.ingenuity.com/blog/webinar/conference-presentation-systems-biology-approach-viral-research-west-nile-virus-case-study#comments Tue, 28 Apr 2015 16:13:16 +0000 http://www.ingenuity.com/?p=5935 QIAGEN scientists, Jean-Noel Billaud, Ph.D. and Stuart Tugendreich, Ph.D., recently completed a demonstration project on how Biomedical Genomics Workbench and Ingenuity Pathway Analysis (IPA) can be used together to create a systems biology approach to exploring host response in West … Read More

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West Nile Virus Poster FINAL

Understanding West Nile Virus Infection: The QIAGEN Bioinformatics Solution: Biomedical Genomics Workbench + Ingenuity Pathway Analysis (IPA).

QIAGEN scientists, Jean-Noel Billaud, Ph.D. and Stuart Tugendreich, Ph.D., recently completed a demonstration project on how Biomedical Genomics Workbench and Ingenuity Pathway Analysis (IPA) can be used together to create a systems biology approach to exploring host response in West Nile Virus infection. Their findings were presented by Dr. Billaud at the 2015 Molecular Med Tri-Con meeting during the Genome and Transcriptome Analysis track.

West Nile Virus is a neurotropic virus that is transmitted via mosquito bite. Infection is a worldwide health issue and the most common cause of epidemic viral encephalitis in North America. Despite the potentially devastating health impacts of infection, its viral pathogenesis is still incompletely understood and there are no approved therapies for use in humans.

Utilizing RNA-Seq data generated by researchers at Yale University,[1] Billaud and Tugendreich evaluated gene pathways and cellular response to explore the difference in immune response between susceptible and resistant individuals.

One of the exciting hypotheses they generated was around the role that the CLEC7A gene plays in the progression of life-threatening encephalitis. This gene has been described as a host susceptibility factor required by West Nile Virus, but there are still questions about its larger role. Using the Molecule Activity Predictor (MAP) tool within IPA, for example, they were able to interrogate sub-networks and canonical pathways associated with CLEC7A and generate scenarios by selecting a molecule of interest, indicating up or down regulation, and simulating directional consequences of downstream molecules and the inferred activity upstream in the network or pathway.

“One of the things we were able to demonstrate was that if you can inhibit CLEC7A you could potentially reduce the risk of West Nile Virus-associated encephalitis. There is much more testing and validation that has to be done, but it’s the kind of finding that would be compelling enough to warrant further investigation of this gene as a therapeutic target,” said Tugendreich.

Watch a recording from recent webinar for more information on this study: IPA Webinar West Nile Virus – Leveraging IPA and RNA-seq Data For Infectious Disease Research.


 

[1] Qian F, et al. Identification of Genes Critical for Resistance to Infection by West Nile Virus Using RNA-Seq Analysis. Viruses. 2013 Jul; 5(7): 1664–1681. Published online 2013 Jul 8. doi:  10.3390/v5071664. Accessed at: http://www.mdpi.com/1999-4915/5/7/1664 .

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TGF-β3 Protein Structure Demonstrates Variant-to-3D Structure Functionhttp://www.ingenuity.com/blog/customer-stories/tgf-%ce%b23-protein-structure-demonstrates-variant-3d-structure-function http://www.ingenuity.com/blog/customer-stories/tgf-%ce%b23-protein-structure-demonstrates-variant-3d-structure-function#comments Tue, 28 Apr 2015 05:26:32 +0000 http://www.ingenuity.com/?p=6008 A new functionality in QIAGEN® Biomedical Genomics Workbench can be used in conjunction with Ingenuity® Variant Analysis™ to identify causal variants, which disrupt protein/drug binding or have an impact on the protein 3D structure.  The user gains an insight not … Read More

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A new functionality in QIAGEN® Biomedical Genomics Workbench can be used in conjunction with Ingenuity® Variant Analysis to identify causal variants, which disrupt protein/drug binding or have an impact on the protein 3D structure.  The user gains an insight not only if a variant is probably causal, but also why.

The new tool, Link Variant to 3D Protein Structure, together with the new protein 3D viewer, offers a quick method for investigating the likely impact of a putative causal variant on the protein 3D structure. For each variant, the Biomedical Genomics Workbench combs through known protein structure information in the PDB database to predict the effect on structure, even for novel mutations. The tool also allows users to generate hypotheses for the effect of a mutation based on what part of the protein it changes. By eliminating the need to query a publicly available protein structure database for each mutation and then build a homology model, this tool dramatically accelerates a user’s ability to find the likely structural effect of DNA and RNA changes.

To show its effectiveness on a rare disease case, we went back to one of our favorite Ingenuity Variant Analysis data sets, the TGF-β3 data set generated by Dr. Hugh Rienhoff in his analysis of his daughter’s DNA. We loaded the causative mutation into Biomedical Genomics Workbench and used the new functionality to find out why the mutation in TGF- β3 is likely the disease causing one. In less than two minutes, we got the protein structure, which clearly illustrates how the mutation induces an amino acid change that breaks a disulfide bond and clashes with the surrounding protein structure. This suggests that this protein, which is probably non-functional, is damaged in a region required in the assembly of the larger protein complex.

These findings were experimentally validated by Dr. Rienhoff.

Picture from 3D Viewer in BxGWB

Pictures from the 3D viewer in the workbench. The protein chain affected by the mutation is shown in blue ribbon representation.

The leftmost picture shows the protein reference structure. Three disulfide bridges establishing a highly structured part of the protein are shown in sticks, and the cysteine being mutated is labeled (Cys409).

The rightmost picture shows the mutated amino acid (Tyr409) in space-filling, to illustrate how the increased size of the side chain will not fit inside the rigid structure. The amino acid is colored to show clashing atoms in red.

Picture2 from 3D Viewer in BxGWB

Picture from the 3D viewer in the workbench.

The protein chain affected by the mutation is shown in ribbon representation and the amino acid (Tyr409) resulting from the mutation is shown in ball-n-sticks and colored to show clashing atoms in red. Other protein chains from the larger protein complex are shown as molecular surfaces (blue and yellow). The mutation will disrupt an otherwise very stable part of the protein, forming an interface to the protein chain shown in blue surface.

You can read more about Dr. Rienhoff’s case study in our Featured Researcher section.

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Time to celebrate the Double Helix – DNA Day!http://www.ingenuity.com/blog/science/time-celebrate-double-helix-dna-day http://www.ingenuity.com/blog/science/time-celebrate-double-helix-dna-day#comments Wed, 22 Apr 2015 16:15:57 +0000 http://www.ingenuity.com/?p=5990 This year’s DNA Day celebration is happening a day early, on April 24th, presumably because this is one of the few holidays best celebrated with colleagues. Here at QIAGEN Bioinformatics, we’ll be raising a glass to the team that determined … Read More

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dnaday2015

This year’s DNA Day celebration is happening a day early, on April 24th, presumably because this is one of the few holidays best celebrated with colleagues. Here at QIAGEN Bioinformatics, we’ll be raising a glass to the team that determined the structure of DNA 62 years ago as well as to the massive global collaboration of scientists responsible for completing the first draft of the human genome a dozen years ago.

We’re thrilled that the National Human Genome Research Institute has continued annual celebrations for DNA Day, which was first designated in the U.S. as a one-time holiday back in 2003. This year, NHGRI highlighted a national Pinterest challenge to engage K-12 students in learning about DNA. Meanwhile, the American Society of Human Genetics is hosting its tenth annual essay contest for DNA Day, open to students in grades 9-12.

In the corridors of QIAGEN Bioinformatics, we like to think we celebrate DNA every day. Our applications and platforms are geared toward helping scientists glean more information from each genome they study, from filtering and interpreting genetic variants to predicting how those DNA changes might affect protein structure. As DNA data becomes increasingly important for patient care, we strive to provide extra layer of knowledge  to help scientists and clinicians find meaningful answers more quickly. You can read some of our customer case studies in our Featured Researcher section. Considering that the first snippets of DNA were sequenced with the most rudimentary tools only 40 years ago, it’s quite remarkable how much the community is achieving with DNA studies today. From accurately linking disease risk to genetic variants to understanding elements like epigenetics, advances and knowledge are developing at a breakneck pace. Recent innovations in gene and genome editing have been downright extraordinary. Truly, we’re witnessing one of the most fascinating revolutions humans have ever experienced.

For our part, we’ll keep pushing the boundaries of what’s possible with automated interpretation and analysis based on elegantly curated data and knowledge. Given how rapidly the field is moving, we can’t wait to see what’s new and exciting on DNA Day next year! Share in the comments, how you will be celebrating The DNA Day!

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AACR 2015: Looking Forward to Phillyhttp://www.ingenuity.com/blog/news/aacr-2015-looking-forward-philly http://www.ingenuity.com/blog/news/aacr-2015-looking-forward-philly#comments Thu, 16 Apr 2015 16:18:56 +0000 http://www.ingenuity.com/?p=5972 Later this week we’ll be heading to the annual meeting of the American Association for Cancer Research (AACR 2015), held this year April 18-22 at the massive Pennsylvania Convention Center in Philadelphia. AACR is a master class for the most … Read More

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Later this week we’ll be heading to the annual meeting of the American Association for Cancer Research (AACR 2015), held this year April 18-22 at the massive Pennsylvania Convention Center in Philadelphia. AACR is a master class for the most cutting-edge science related to understanding, diagnosing, and treating cancer. Attended by thousands of researchers and clinicians each year, the conference is the best cancer-focused meeting around.

The AACR meeting is notable for a number of reasons, but two of our favorites are its well-rounded program and its focus on career advice. A quick skim of this year’s agenda shows that a wide range of topics will be covered, including immunotherapy, stem cells, epigenetics, and noncoding RNA. For students (really, for scientists at any career stage), AACR is an unmatched source of career education and professional advancement information. We’re pleased to see a full series of career advice sessions sprinkled throughout the meeting to help shape the future paths of these promising young researchers.

There are several lectures and panel sessions that we’re particularly looking forward to this year. AACR always does an excellent job recognizing talent, and we’re eager to hear from Caltech’s David Baltimore, Bill Hahn of Dana-Farber, and current AACR president Carlos Arteaga at Vanderbilt during just a few of the great award presentations and distinguished lectures. There are also several sessions focused on using genomic data in the clinic, with great speakers such as FDA’s Zivana Tezak, MSKCC’s Ross Levine, and University of Michigan’s Arul Chinnaiyan, to name just a few.

We’re also eager to learn more about the latest from CSER, the Clinical Sequencing Exploratory Research Program, which has been helping to elucidate the utility of genetic variants found in tumors. The scientists and clinicians working on CSER are really making a difference in how the community understands variants as well as differences in how they’re interpreted across labs. This is important work, and we can’t wait to hear from several participants at this special AACR session.

Mark your calendar for our presentation:

  • Understanding West Nile Virus Infection: The QIAGEN Bioinformatics Solution: Biomedical Genomics Workbench + Ingenuity Pathway Analysis (IPA)
    Speaker: Jean-Noel Billaud, Ph.D., Principal Scientist
    Booth: #1925
    Day & Time: Sunday @ 1 pm
    Day & Time: Wednesday @ 9 am

Don’t miss our poster sessions:

  • Presenter: Bodil Oester
    Title: Comparison and interpretation of variants in RNA and DNA from sarcoma cancer sample
    Session Title: Systematic Analysis of Omic Data
    Abstract Number: 2178
    Session Category: Molecular and Cellular Biology
    Date and Time: Monday Apr 20, 2015 1:00 PM – 5:00 PM
    Location: Section 11
  • Presenter: Jean-Noel Billaud, PhD
    Title: Deconstructing protein and gene expression pathways to define the anticancer effects of XPO1 inhibition in ovarian cancer
    Session Title: Novel Agents and Mechanisms of Action
    Abstract Number: 1758
    Session Category: Experimental and Molecular Therapeutics
    Date and Time: Monday, Apr 20, 2015, 8:00 AM -12:00 PM
    Location: Section 32
  • Presenter: Anika Joecker
    Title: Streamlined analysis and interpretation of RNA editing variants from melanoma cancer samples
    Session Title: Biological Conclusions from Computational Approaches
    Abstract Number: 1925
    Session Category: Molecular and Cellular Biology
    Date and Time: Monday Apr 20, 2015 1:00 PM – 5:00 PM
    Location: Section 2
  • Presenter: Song Tian
    Title: lncRNA profiling and its potential usage as thyroid cancer biomarker
    Session Title: Diagnostic Biomarkers
    Abstract Number: 531
    Session Category: Clinical Research
    Date and Time: Sunday, April 19, 2015, 1:00 pm – 5:00 pm
    Location: Section 23
  • Presenter: Quan Peng
    Title: Reducing amplification artifacts in highly multiplex amplicon sequencing by using molecular barcodes
    Session Title: New Development in Sequencing
    Abstract Number: 4879
    Session Category: Molecular and Cellular Biology
    Date and Time: Wednesday, April 22, 2015, 8:00 am – 12:00 pm
    Location: Section 6

In addition, QIAGEN Bioinformatics will have a booth at the event (#2162), and we encourage AACR attendees to stop by. We’ll be showcasing Ingenuity Variant Analysis, CLC Biomedical Genomics Workbench, and BIOBASE PharmacoGenomic Mutation Database (PGMD) — and of course we’d be happy to answer questions about how any of our other products can help.

We hope to see you in Philly!

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Conference Preview: Big Data & Bioinformatics at Bio-IT World in Bostonhttp://www.ingenuity.com/blog/events/conference-preview-big-data-bioinformatics-bio-world-boston http://www.ingenuity.com/blog/events/conference-preview-big-data-bioinformatics-bio-world-boston#comments Thu, 16 Apr 2015 16:17:50 +0000 http://www.ingenuity.com/?p=5985   Later this month, we will head to Boston for the annual Bio-IT World Conference & Expo.  This year some 3,000 life sciences, pharma, clinical, healthcare, and IT professionals from more than 32 countries will gather to discuss new trends … Read More

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Bio-IT2015

 

Later this month, we will head to Boston for the annual Bio-IT World Conference & Expo.  This year some 3,000 life sciences, pharma, clinical, healthcare, and IT professionals from more than 32 countries will gather to discuss new trends in data generation, knowledge management, and information technology for the life sciences and drug development.

The QIAGEN Bioinformatics team will be based on the showroom floor (Booth #144). Please stop by, we’d enjoy the opportunity to learn more about your work and discuss how our portfolio of data interpretation solutions may be able to help you. We will also be presenting about the CLC Server in the Vendor Theater on Tuesday, April 21 at 5:50pm.

On Thursday morning at 8:25am, during the plenary session panel, QIAGEN Field Application Scientist, Katherine Wendelsdorf, Ph.D. will join PatientsLikeMe CEO Benjamin Heywood and Open Medicines Institute founder Andreas Kogelnik to discuss the evolving roles and opportunities for patients and patient data in the R&D process. One of the greatest challenges for every branch of medical science is rounding up patients for studies, trials, and endless measurements. They will discuss how they keep patients in the research loop, and how non-professionals can be a driving force behind the medical breakthroughs of the future.

For more information on our presentation at Bio-IT World Conference & Expo, please visit our events page. 

We look forward to seeing you in Boston.

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QIAGEN Supports New ACMG Guidelines with Integration into Data Interpretation Toolshttp://www.ingenuity.com/blog/news/qiagen-supports-new-acmg-guidelines-integration-data-interpretation-tools http://www.ingenuity.com/blog/news/qiagen-supports-new-acmg-guidelines-integration-data-interpretation-tools#comments Wed, 25 Mar 2015 18:15:26 +0000 http://www.ingenuity.com/?p=5906 The American College of Medical Genetics and Genomics (ACMG), in collaboration with the Association for Molecular Pathology (AMP), recently published new guidelines for the interpretation of sequence variants. These guidelines are significant in their inclusion of an evidence-based gene variant … Read More

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The American College of Medical Genetics and Genomics (ACMG), in collaboration with the Association for Molecular Pathology (AMP), recently published new guidelines for the interpretation of sequence variants. These guidelines are significant in their inclusion of an evidence-based gene variant classification system and accompanying standard terminology designed to assist genetic testing laboratories and clinical geneticists tasked with assessing the pathogenicity of  individual variants.

In a statement, Heidi Rehm, Ph.D., Chief Laboratory Director at Partners Laboratory for Molecular Medicine said, “Navigating the complexity of genetic evidence and how to weigh the strength of that evidence is challenging for laboratories and this guidance will help provide a consistent framework for that process.”

QIAGEN is on the forefront of helping research scientists and clinicians interpret DNA sequence data and evaluate the disease-causing potential of genetic variation. We have been actively working with ACMG to compute classifications based on these new guidelines given how content-dependent, complex and time consuming it is for labs to manually score variants.

QIAGEN’s Ingenuity Variant Analysis, for example, implements the new ACMG guidelines computationally and leverages QIAGEN’s manually-curated clinical evidence from the literature to automatically provide ACMG classifications. Classifications are presented to users in a gene-relevant disease context for every variant in their datasets and there is visibility into which of the approximately 30 ACMG criteria have been applied to the computed classification.  Here is an example of how a BRCA missense variant appears in Ingenuity Variant Analysis when a user clicks on a classification finding deemed “Pathogenic:”

BRCA missense in IVA

The ACMG guidelines have also been incorporated into our soon-to-be-released platform for the interpretation of next-generation sequencing data in clinical settings. In this example, we are showing a BRCA2 variant (p.R3052W) in the disease context (HBOC = hereditary breast and/or ovarian cancer syndrome) that many clinical labs utilize to report these BRCA1/2 hereditary cancer variants.

Computational Classification explanation

QIAGEN is also supporting other community initiatives aimed at increasing the clinical utility of genomic information, including the recently announced Allele Frequency Community (AFC). The formation of the AFC addresses a key challenge in interpreting sequencing data for research and clinical applications: the lack of an extensive, high quality, ethnically-diverse collection of human genomes as a reference set. Scientists need diverse, large-scale data on allele frequencies to accurately identify potential disease-causing DNA changes in a population. Information on allele frequency also tells clinicians how common certain changes are within the population, helping to distinguish rare, disease-causing DNA changes from more common variations.

QIAGEN applauds the new guidelines and remains committed to working with organizations such as ACMG and our customers to develop technologies that help researchers and clinicians who are working to make genomic data more informative and actionable.

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Countdown to ACMG 2015!http://www.ingenuity.com/blog/news/countdown-acmg-2015 http://www.ingenuity.com/blog/news/countdown-acmg-2015#comments Thu, 19 Mar 2015 16:37:15 +0000 http://www.ingenuity.com/?p=5888 If you’ll be heading to Salt Lake City next week, we hope to see you there! The QIAGEN Bioinformatics team is gearing up for the ACMG Annual Clinical Genetics Meeting to be held March 24-28 at the Salt Palace Convention … Read More

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If you’ll be heading to Salt Lake City next week, we hope to see you there! The QIAGEN Bioinformatics team is gearing up for the ACMG Annual Clinical Genetics Meeting to be held March 24-28 at the Salt Palace Convention Center. This is one of the best clinical meetings we attend each year, and we can’t wait to see what’s in store this year.

The organization that hosts the event, the American College of Medical Genetics and Genomics, got attention recently with its revamped guidelines for reporting incidental findings. We’re grateful that a group as reputable as ACMG has waded into this area — as next-gen sequencing becomes more commonplace in the clinic, incidental findings are a growing challenge for physicians and clinical geneticists.

There are a number of sessions we’re particularly looking forward to at this event. The presidential plenary session will include a presentation from ACMG President Gail Herman as well as talks from Kevin Flanigan and Dan MacArthur, all focused on recent advances in clinical genomics. Another session will focus on genotype-phenotype correlations, with some speakers talking about the importance of understanding allele penetrance. The topic is really important to us as co-founders of the Allele Frequency Community, which aims to provide broader access to this kind of data. Two sessions on using NGS data for diagnostic purposes look really interesting: one hosted by Deanna Church, Heidi Rehm, and Robert Nussbaum on improving diagnostic yield with exome sequencing, and another focused on metabolic disease that includes a talk from NIH’s Bill Gahl about the Undiagnosed Disease Program. Finally, we’re delighted to see big data on the agenda this year, representing a critical trend as clinical labs learn new methods to interpret the huge amounts of data being generated by NGS technologies.

Our team has a number of tools to help this audience make sense of their data. You can learn more about Ingenuity Variant Analysis, particularly handy for solving diagnostic odysseys, from our users: check out abstract 230 (Devaney et al.) and 570 (Wang et al.) to see how these teams implemented the application. We’ll also be in the exhibit hall — booth #614 — if you want to learn more about the Allele Frequency Community, HGMD, or our newest application, the Ingenuity Clinical Decision Support platform.

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CNV Expert Rajini Haraksingh Studies Human Variation at Stanford, Rare Genomics Institutehttp://www.ingenuity.com/blog/customer-stories/cnv-expert-rajini-haraksingh-studies-human-variation-stanford-rare-genomics-institute http://www.ingenuity.com/blog/customer-stories/cnv-expert-rajini-haraksingh-studies-human-variation-stanford-rare-genomics-institute#comments Wed, 18 Mar 2015 18:33:29 +0000 http://www.ingenuity.com/?p=5875 Rajini Haraksingh aims for a broad understanding of the complexities of human variation. Along the way, she has uncovered some key genetic causes of disease. She relies on QIAGEN’s Ingenuity Variant Analysis to ask better questions of her data with … Read More

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Rajini Haraksingh, Postdoctoral Fellow in Stanford School of Medicine

Rajini Haraksingh, Postdoctoral Fellow in Stanford School of Medicine

Rajini Haraksingh aims for a broad understanding of the complexities of human variation. Along the way, she has uncovered some key genetic causes of disease. She relies on QIAGEN’s Ingenuity Variant Analysis to ask better questions of her data with simplicity and speed.

During the course of her PhD, advances in genome sequencing and variant mapping technologies made it possible to study all of the genetic variants in large numbers of individuals and develop a deeper understanding of normal human genetic variation. Haraksingh gained a strong interest in learning everything she could about the interactions between genes and other DNA elements, and how they work together as a system to produce our phenotypically diverse species.

Now a postdoctoral fellow in Alexander Urban’s lab at Stanford School of Medicine, Haraksingh focuses on the functional implications of copy number variants (CNVs) and other structural variation. This expertise in the fundamental elements of the genome allows her to dive into any disease or condition and make important connections. “I try to understand the interplay between different levels of gene expression and gene regulation,” she says. “How does the entire set of genomic content work together to create a functioning cell, a functioning system, and ultimately a functioning being?”

Her postdoc work, which largely continues her PhD focus, included a study of samples from patients with sensorineural hereditary hearing loss. Earlier work by her colleagues had revealed that taste receptors and olfactory receptors were copy number variable, so Haraksingh theorized that hearing might be another sense affected by CNVs. “It was known that copy number variants were enriched in genes involved in sensory perception and interaction with the environment,” she says.

Using patient samples collected by Stanford pathology professor Iris Schrijver, Haraksingh and her team performed exome sequencing of families and isolated cases, and genome-wide CNV variant mapping on some 300 cases and controls to learn what they could about the complex process of hearing. Both technical approaches were important. Haraksingh says, “One of our most important conclusions was that in order to discover novel contributors to complex disease, we really need to use multiple complementary strategies.”

The project led to a publication in BMC Genomics in which lead author Haraksingh and her collaborators report a novel gene and a novel copy number variant linked to the phenotype. The experimental work yielded thousands of variants that under other circumstances would have required a Herculean effort to interpret using a number of external databases. “It’s extremely challenging to work with these databases. You’re constantly downloading and moving around large data sets,” she says. “It’s really messy and it takes a long time.”

Fortunately for Haraksingh, she was spared the endless hours that such a process would have required. “We came across Ingenuity Variant Analysis and it was a godsend,” she says, noting that the application is connected to those external databases and can easily query them in one fell swoop. “It turned what was an extremely frustrating experience into one that was actually really fun.”

Haraksingh also uses the web application in her nonprofit work with the Rare Genomics Institute, an organization that enables patients to take advantage of genomic solutions for diseases that defy diagnosis. “I’m not an expert in any particular disease,” she says. “I come at this from the angle of trying to understand the variation in the genome, and what that means for developing different diseases.”

To learn more about how Haraksingh used Ingenuity Variant Analysis to discover a novel gene and a novel copy number variation, visit our Featured Researcher section. You can also download the full case study.

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