The August IPA content release significantly expanded knowledge in key therapeutic areas, enabling you to better understand the molecular basis of disease, identify novel points of therapeutic intervention, and prioritize biomarkers from large sets of candidate genes and metabolites. Key highlights included:

• Metabolite content from the Human Metabolome Database (HMDB),with an emphasis on detection in biofluids, subcellular location, and tissue localization.
• New drug to disease knowledge from DrugBank and Clinicaltrials.gov, including drug to disease relationships, drug brand names, clinical trial status, and drug approval information.
• New content for key therapeutic areas including Alzheimer’s disease, Infectious Disease/Immune Response, and Oncology.
• Twenty-two new pathways.

For full details, please click here.

Stay tuned for more information about our next release of IPA, currently scheduled for November.

In 2007, Nature Biotechnology published a commentary entitled "Systems biology and the host response to viral infection" which outlined various systems approaches that were being applied to study virus-host interactions, and how those approaches could provide insights into novel targets for therapeutic intervention, host factors for biomarker discovery, and viral factors for diagnostics.  As mentioned in the article, one of the important components to successful application of these systems approaches was the use of data analysis and modeling tools such as IPA to identify key genes and pathways, generate testable hypotheses to be validated in in vitro experiments and eventually applied to more complex systems such as the host. 

Over the past few months we have seen those efforts, and the adoption of those approaches pay off in the form of identification of novel cellular targets against Ebola and Influenza virus, and advances in the understanding of cellular pathways key to progression from infection to lethal disease. 

Below we’ve highlighted a sample of some of the more recent IPA publications in the area of host response to various infectious agents including Ebola virus, influenza, SARS-CoV, Lyme disease spirochetes, anthrax, and SIV.  For a complete list of Infectious Disease publications citing IPA, please go to http://www.ingenuity.com/library/search-pub.html and select Infectious Disease from the Research Area/Field of Interest menu, or simply search the entire bibliography using keywords such as "virus" or "infection".

• Reduced levels of protein tyrosine phosphatase CD45 protect mice from the lethal effects of Ebola virus infection. 
  Cell Host Microbe. 2009 Aug 20;6(2):162-73. Panchal RG, Bradfute SB, Peyser BD, Warfield KL, Ruthel G, Lane D, Kenny TA, Anderson AO, Raschke WC, Bavari S.
• Identification of Novel Cellular Targets for Therapeutic Intervention Against Ebola Virus Infection by siRNA Screening.
  DRUG DEVELOPMENT RESEARCH 70 : 255–265 (2009) Andrey A. Kolokoltsov, Mohammad F. Saeed, Alexander N. Freiberg, Michael R. Holbrook, Robert A. Davey.
• P58IPK: A Novel "CIHD" Member of the Host Innate Defense Response against Pathogenic Virus Infection.
  PLoS Pathog. 2009 May; 5(5): e1000438. Published online 2009 May 22. Alan G. Goodman, Jamie L. Fornek, Guruprasad R. Medigeshi, Lucy A. Perrone, Xinxia Peng, Matthew D. Dyer, Sean C. Proll, Sue E. Knoblaugh, Victoria S. Carter, Marcus J. Korth, Jay A. Nelson, Terrence M. Tumpey, and Michael G. Katze.
• Early Upregulation of ARDS Associated Cytokines Promote Lethal Disease in an Aged Mouse Model of SARS-CoV Infection.
  J Virol. 2009 May 6. [Epub ahead of print] Rockx B, Baas T, Zornetzer GA, Haagmans B, Sheahan T, Frieman M, Dyer MD, Teal TH, Proll S, van den Brand J, Baric R, Katze MG.
• The Antibiotics Doxycycline and Minocycline Inhibit the Inflammatory Responses to the Lyme Disease Spirochete Borrelia burgdorferi.
  J Infect Dis. 2009 May 1;199(9):1379-88. Bernardino AL, Kaushal D, Philipp MT.
• Gene Expression Profiling of Human Alveolar Macrophages Infected by B. anthracis Spores Demonstrates TNF-α and NF-κB Are Key Components of the Innate Immune Response to the Pathogen.
  Am. J. Respir. Crit. Care Med., Apr 2009; 179: A3239. M Dozmorov, W Wu, K Chakrabarty, JL Booth, RE Hurst, KM Coggeshall, and JP Metcalf.
• Transcriptional Profiling in Pathogenic and Non-Pathogenic SIV Infections Reveals Significant Distinctions in Kinetics and Tissue Compartmentalization.
  PLoS Pathog. 2009 Feb;5(2):e1000296. Epub 2009 Feb 13. Lederer S, Favre D, Walters KA, Proll S, Kanwar B, Kasakow Z, Baskin CR, Palermo R, McCune JM, Katze MG.
• A genome-wide association study identifies novel and functionally related susceptibility Loci for Kawasaki disease.
  PLoS Genet. 2009 Jan;5(1):e1000319. Epub 2009 Jan 9. Burgner D, Davila S, Breunis WB, Ng SB, Li Y, Bonnard C, Ling L, Wright VJ, Thalamuthu A, Odam M, Shimizu C, Burns JC, Levin M, Kuijpers TW, Hibberd ML; International Kawasaki Disease Genetics Consortium.

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Ingenuity Launches New Product: Ingenuity® Answers

We’re happy to report the successful launch of Ingenuity Answers 1.0!  You may remember from our last newsletter that back in April, attendees at Bio-IT World got a sneak peek at Ingenuity Answers – a new advanced search tool that lets you quickly and reliably answer broad or complex biological questions by leveraging the highly structured information in the Ingenuity Knowledge Base. Now, its ability to ask highly specific questions across multiple levels of biology plus its easy-to-use interface are winning rave reviews from testers and users.  Here’s what they had to say:

• "Quick answers that would be difficult to find otherwise."
• "Getting to very specific within-context findings quickly was quite powerful."
• "This is a great tool that provides scientists immediate answers to simple as well as complex scientific queries, which can aid in developing a sound knowledge-based hypothesis."
• "Generally, a very intuitive and quick way to generate lists of items of interest."

Or, let’s take a specific example, such as epigenetics research. With implications in cancer and heritable diseases such as cystic fibrosis, the study of epigenetic mechanisms is becoming more popular, and incorporated into more research programs.  Research efforts including biomarker identification, potential drug target identification, and gaining a better understanding of factors that predispose individuals to disease all require a detailed understanding of DNA methylation and histone modifications such as acetylation and phosphorylation.

How can Ingenuity Answers help?  With Ingenuity Answers you can ask for specific information about a gene such as mutation details, sites of post-translational modification, whether it contains a particular domain, if it is expressed in a certain tissue or cell line, and whether it is associated with a particular disease or phenotype. With Ingenuity Answers, you can also ask for the list of biochemical modifications of key epigenetics regulators such as histones.  Not only do you get a list of the modifications and their location on the protein, you get information about the biological impact of those modifications and links to the references where they were originally published.

To learn more or to try it out, go to http://www.ingenuity.com/products/answers.html.

Ingenuity invited to participate in NIH-initiated workshop on biosecurity

Ramon Felciano, Ingenuity’s CTO and Vice President of Research, discussed systems biology and pathway modeling of pathogenesis and host response as the workshop panel explored the science and biology behind pathogenic virulence. The workshop examined the scientific challenges and potential of predicting pathogenicity from sequence, and how scientific advances may be applied to the oversight of select agents. The panel also reviewed and discussed current biosafety and biosecurity guidelines and the impact that emerging technologies, such as synthetic and systems biology, may have on oversight of select agents.

Learn more by clicking here.

BD Biosciences Launches Cell Pathways, Powered by Ingenuity

BD Biosciences launched BD Cell Pathways on their website – a user-friendly search application that enables customers to easily locate products most relevant to their research by leveraging the knowledge in the Ingenuity Knowledge Base.  You can search for genes, proteins, pathways, and more, and then explore related pathways and networks to easily identify products of interest.  You can also quickly understand alternative product and experimental design options by exploring gene pathways and molecular interaction networks - including a molecule's role in diseases, biological processes, functions, and tissues - all based on knowledge from the scientific literature. Learn more at http://www.ingenuity.com/news/html/pr_090811_bd.html, or try it at http://www.bdbiosciences.com/pathways/index.jsp.

JAMA article highlights application of IPA to clinical and translational research

Check out the Ingenuity blog post on the article. Written by Ingenuity Senior Scientist Megan Laurance, it summarizes the research and highlights how IPA helped integrate and analyze several lines of molecular data (gene dosage, genetic mutations, and gene expression) to generate a network model describing the cooperative nature of these alterations.  You can also link through to the original JAMA article.  Click here to read it.

Sigma's YFG Powered by Ingenuity launches "Your Favorite Gene" Facebook application

Do you want to tell the world about your gene?  What about your involvement in classifying part of a pathway?  "What's Your Favorite Gene?"(beta)  is a new Facebook application, which uses data from Your Favorite Gene powered by Ingenuity to help you:

• Pull publications into your Facebook profile directly from PubMed
  
• Connect to other scientists with similar research interests
  
• Post your genes and pathways to your profile
  
• Take the "What gene are you?" quiz

Try the Your Favorite Gene app now
Become a fan of IPA on Facebook

Upcoming Events

New - IPA training coming to a city near you!
Want to make sure you’re making the most of IPA? Want to learn IPA best practices? Interested in becoming IPA Certified, or get new members of your lab up to speed with IPA?  Ingenuity is launching a new regional training series this fall. Ingenuity scientists will be coming to locations in San Diego, San Francisco, and Boston to offer two days of hand-on IPA training. There are two different full-day classes being offered. The first, Fundamentals of IPA, teaches you basic steps and best practices around the most common IPA tasks. The second, IPA Certification, dives deeper in the application and gives you the necessary groundwork to complete the IPA Certification exam.

Trainings start October 28. Want to learn more, or register?  Click here.

Webinar with Ingenuity and Life Technologies – Transcriptome Analysis Workflow
Please join us for an upcoming joint webinar called "A Powerful Experimental Workflow for Transcriptome Analysis in Single Cells: Using Applied Biosystems SOLiD™ System, TaqMan® Assay Platforms, and IPA."  You’ll learn how to combine these systems with IPA to analyze and understand the functional impacts of large scale disruption of the transcriptome and to prioritize validation studies. Click on a time below to register.

October 29, 2009 – 7 am or 11 am PST
November 3, 2009 – 7 am or 11 am PST

Upcoming Conferences

American Society of Human Genetics (ASHG)
October 20-24, Honolulu, Hawaii
Booth 134

Bristol Meyers Squibb Scientific Symposium
November 9, Princeton, NJ
Booth 121

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Did you know that you can use the Merge and Keep tools in IPA to create a context-specific network from a larger network? 

For example, in this IPA analysis (Figure 1), there are several molecular interaction networks that are associated with immune response and infectious disease themes.  These can be easily merged together by clicking the box next to the Network ID, and clicking Merge Networks.

This very large resulting molecular interaction network of immune response/infectious disease genes (Figure 2) can be easily refocused to highlight all of the molecular interactions that were specifically measured in the context of immune cells by clicking the Build menu and selecting the Keep tool.

Refocus the network on all immune cell specific relationships by clicking the Tissues & Cell Lines menu, then selecting Immune cells and Immune cell lines, and selecting Stringent Filter (Figure 3).  Highlight all nodes in the network by dragging your mouse over them, and click Apply.

This combination of Merge & Keep enables you to generate large networks focused on common processes and functions (here, Immune Response and infectious disease), and then refocus that network on the molecular events measured in a specific cellular context (here, in immune cells). See Figure 4 below for final, refocused result.

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One of the key outputs of any IPA analysis is the identification of biological processes, cellular phenotypes, and diseases associated with a given set of genes, proteins, or metabolites. 

What makes this analysis particularly valuable is the ability to determine the net effect that your genes may have on a particular process or phenotype.  So, while it is useful to know, for example, that genes in your molecular profile play a role in cell invasion, it is particularly useful to identify the subset of those genes that increase or decrease cell invasion, because this enables you to infer the functional impact of gene expression changes in that particular process.

Let’s take a specific case where we analyze gene expression changes in metastatic prostate cancer tissue with the aim of understanding the functional implications of those genes being deregulated, relative to normal tissue.

Step 1 - Click on the Functions tab in your analysis results.  This will highlight the high level categories of biological processes, cellular events, and diseases most relevant to the metastatic prostate cancer genes.  (See Figure 1 below)

Step 2 -Click on the Show Categories button (see Figure 1) to show the specific processes associated with your genes.  This reveals that there are 54 genes (up and down regulated) from the metastatic prostate cancer profile that play a role in cell invasion.  (See Figure 2)

Step 3 - Click on the "invasion of cells" link to access the Effect on Function feature and understand which of the 54 genes promote or decrease cell invasion.  Here we see that 17 of the 54 genes decrease cell invasion, and 32 promote invasion.  You can also link to the original Finding. (See Figure 3)

Step 4 - Further visualize the potential impact of up/downregulation of these genes by clicking the check boxes next to each category and sending them to a pathway canvas in IPA. (See Figure 4)

Summary – The Effect on Function feature gives you the ability to group genes by the net effect they have on a particular cellular process - cell invasion.  This enables us to infer that the collective downregulation of genes that decrease cell invasion, and the relative upregulation of genes that promote invasion may contribute to tumor invasiveness.  This generates a testable hypothesis as to the molecular mechanisms that may contribute to prostate tumor metastasis.

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This month, we’re happy to offer you a few new PDF resources to highlight how IPA can help with various experimental approaches.