IPA^®

The last two releases of IPA (IPA 8 in December and IPA 8.5 in February) were complimentary releases that hit on many of the same themes.  In case you missed it, here’s what’s new in IPA since our last newsletter:

• Reports: We've added interactive, dynamic reports that summarize the broader biological and therapeutic relevance of a particular pathway, gene list (including your own), or analysis.  You can PDF these reports and easily share insights with colleagues through a simple email.
• Weekly Content Updates: Content updates now occur weekly. In addition to our manually curated Ingenuity^® Expert Findings, we’ve also added automatically extracted, manually reviewed Ingenuity^® ExpertAssist Findings, which contains information published as recently as the prior week.
• Clinical Biomarkers: We have added over 1200 gene, transcript, protein, and metabolite biomarkers that are used in the clinical setting. They are relevant to over 190 diseases and can be identified by specific application (disease diagnosis, disease progression, markers of drug efficacy, etc.).
• Pathway Generation/Exploration Tools: You can now build larger molecular networks, consolidating key molecular events. Use the new date range filters to highlight recent discoveries and update pathways with new Findings (see Feature Highlight and Quick Tip).
• HMDB support: Upload lists with HMDB identifiers, and search on HMDB identifiers to view more comprehensive information on metabolites, such as expression and localization Findings.
• Collaboration Workspace: Easily create shared workspaces for a large group of collaborators within a single research institute or company, or between collaborating institutes.
• New Content: Twenty-seven new pathways, new protein-protein interaction content from INTACT, BIOGRID, MINT, and DIP, and more.

» Learn more about features and content in the IPA 8.0 release
» Learn more about features and content in the IPA 8.5 release

Ingenuity^® Answers

Updates
Ingenuity Answers released new functionality in December, making it even easier to get quick, accurate answer to biological questions. These improvements included the ability to ask new questions around clinical trials, biomarkers, and toxicity events. New filters were added to let you drill down around mutation and modification types, clinical phase, therapeutic type of chemical, and more.  Lastly, performance was enhanced for faster searches on complex queries.

Ingenuity Answers Alpha
We have also just launched our Ingenuity Answers Alpha program.  For a limited time, we are offering current IPA customers free access to Ingenuity Answers Alpha.  Because it is a free alpha version, some of the functionality is limited.

Try it and let us know what you think! 

Log in with your IPA user name and password. Comments or thoughts?  - email us at answers@ingenuity.com.

See what your colleagues have said:

• "Quick answers that would be difficult to find otherwise."
• "Getting to very specific within-context findings quickly was quite powerful."
• "I see Answers as a very useful tool which is complementary to IPA. Most time I had both applications open at the same time, switching from one to the other."
• "A very intuitive and quick way to generate lists of items of interest."

» Learn more about Ingenuity Answers

IPA has been broadly adopted in the life sciences community as an essential tool for basic research as well as early drug discovery and development.  But how is IPA helping in the efforts to translate those discoveries into positive outcomes for patients?  In this issue of the Ingenuity Insider we are highlighting recent publications from our IPA community that highlight workflows and methods being applied with the aim of fulfilling the promise of translational medicine.  Five years ago, when the field of molecular profiling and gene expression were arguably still settling down, generating an interesting and statistically significant gene signature was of sufficient interest for most peer-reviewed journals.  The stakes are a little higher in today’s world of molecular profiling.  Translational medicine researchers need to understand those signatures in a complete, dynamic biological context, articulate the pathway and functional relevance of those signatures, and validate them with in vivo models in order to translate those signatures into tools that can be used in the clinic to improve diagnosis and treatment of disease.

Below we have highlighted some of the more recent IPA publications in the area of translational and clinical medicine.  This collection of publications touch on therapeutic areas such as oncology, cardiovascular disease, arthritis, and metabolic syndrome and highlight research goals as diverse as building in vivo models to understand drug resistance, identifying predictive markers to restrict therapy to responders, stratifying patients  by molecular phenotype,  and clinical validation of pharmacodynamic markers.  For a complete list of Translational and Clinical Medicine publications citing IPA, please go to http://www.ingenuity.com/library/search-pub.html and search the entire bibliography using keywords such as "translational" or "clinic."

• Identification of Therapeutic Targets for Quiescent, Chemotherapy-Resistant Human Leukemia Stem Cells. Science Translational Medicine, Feb 2010; 2: 17ra9. Yoriko Saito, Hiroshi Kitamura, Atsushi Hijikata, Mariko Tomizawa-Murasawa, Satoshi Tanaka, Shinsuke Takagi, Naoyuki Uchida, Nahoko Suzuki, Akiko Sone, Yuho Najima, Hidetoshi Ozawa, Atsushi Wake, Shuichi Taniguchi, Leonard D. Shultz, Osamu Ohara, and Fumihiko Ishikawa.
  
  
• Anti-viral state segregates two molecular phenotypes of pancreatic adenocarcinoma: potential relevance for adenoviral gene therapy. J Transl Med. 2010 Jan 29;8(1):10. [Epub ahead of print] Monsurro V, Beghelli S, Wang R, Barbi S, Coin S, Di Pasquale G, Bersani S, Castellucci M, Sorio C, Eleuteri S, Worschech A, Chiorini JA, Pederzoli P, Alter H, Marincola FM, Scarpa A.
  
  
• A Gene Expression Profile of the Myocardial Response to Clenbuterol. J Cardiovascular Translational Research Volume 2(2):191-197, June 2009. Enrique Lara-Pezzi, Cesare M. N. Terracciano, Gopal K. R. Soppa, Ryszard T. Smolenski, Leanne E. Felkin, Magdi H. Yacoub and Paul J. R. Barton.
  
  
• Identification of Biomarkers in Human Head and Neck Tumor Cell Lines That Predict For In Vitro Sensitivity to Gefitinib. Clinical and Translational Science. Published Online: 8 May 2009. D. Mark Hickinson, Ph.D., Gayle B. Marshall, B.Sc., Garry J. Beran, M.Sc., Marileila Varella-Garcia, Ph.D., Elizabeth A. Mills, M.Sc. 2 , Marie C. South, Ph.D. 2 , Andrew M. Cassidy, B.Sc., Kerry L Acheson, B.Sc., Gael McWalter, M.Sc., Rose M. McCormack, Ph.D., Paul A. Bunn, M.D., Tim French, Ph.D., Alex Graham, Ph.D., Brian R. Holloway Ph.D., Fred R. Hirsch, M.D., and Georgina Speake.  
  
  
• Preclinical biomarkers for a cyclin-dependent kinase inhibitor translate to candidate pharmacodynamic biomarkers in phase I patients. Mol Cancer Ther. 2009 Sep;8(9):2517-25. Epub 2009 Sep 15. Berkofsky-Fessler W, Nguyen TQ, Delmar P, Molnos J, Kanwal C, DePinto W, Rosinski J, McLoughlin P, Ritland S, DeMario M, Tobon K, Reidhaar-Olson JF, Rueger R, Hilton H.
  
  
• CD11c as a Transcriptional Biomarker to Predict Response to Anti-TNF Monotherapy With Adalimumab in Patients With Rheumatoid Arthritis. Clin Pharmacol Ther. 2009 Dec 23. [Epub ahead of print] Stuhlmüller B, Häupl T, Hernandez MM, Grützkau A, Kuban RJ, Tandon N, Voss JW, Salfeld J, Kinne RW, Burmester GR.
• Gene Expression Profiling of Paraffin-Embedded Primary Melanoma Using the DASL Assay Identifies Increased Osteopontin Expression as Predictive of Reduced Relapse-Free Survival. Clin Cancer Res. 2009 Nov 15;15(22):6939-46. Epub 2009 Nov 3. Conway C, Mitra A, Jewell R, Randerson-Moor J, Lobo S, Nsengimana J, Edward S, Sanders DS, Cook M, Powell B, Boon A, Elliott F, de Kort F, Knowles MA, Bishop DT, Newton-Bishop J.
  
  
• A saturated fatty acid–rich diet induces an obesity-linked proinflammatory gene expression profile in adipose tissue of subjects at risk of metabolic syndrome. Am J Clin Nutr. 2009 Oct 14. van Dijk SJ, Feskens EJ, Bos MB, Hoelen DW, Heijligenberg R, Bromhaar MG, de Groot LC, de Vries JH, Müller M, Afman LA.

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Over 100 IPA Certified Analysts

We are pleased to announce there are now over 100 IPA Certified Analysts! Why should you join their ranks? The IPA Certification program is a great way to learn IPA best practices, make your research more efficient, and distinguish your research expertise – and best of all, it’s free. See what Elena Nikonova, our featured IPA Certified Analyst, has to say about the program and how it’s helped her.

"The IPA certification program has been incredibly helpful to me. Its clear categorization of the available IPA features greatly improved my analyses. Importantly, the skills learned from the program stand strong years later, even with the constant upgrades the IPA has undergone. This program helped me become more versatile in multiple area molecular profiling studies, which I have been involved with. I highly recommend investing time and effort into this program." -Elena Nikonova, MD  Staff Scientist, The Wistar Institute, Systems Biology

Elena's publications with IPA are cited: Showe MK, Vachani A, Kossenkov AV, Yousef M, Nichols CE, Nikonova EV, Chang C, Tran B, Wakeam E, Yie TA, Speicher D, Rom WN, Albelda SM and Showe LC (2009) Gene Expression Profiles in Peripheral Blood Mononuclear Cells Can Distinguish Patients with Non-Small Cell Lung Cancer from Patients with Nonmalignant Lung Disease. Cancer Research 69 (24): 9202-10. Qin H, Chan MWY, Liyanarachchi S, Balch C, Potter D, Souriraj IJ, Cheng ASL, Agosto-Perez FJ, Nikonova EV, Yan PS, Lin H-J, Nephew KP, Saltz JH, Showe LC, Huang THM and Davuluri RV (2009). An Integrative ChIP-chip and Gene Expression Profiling to Model SMAD Regulatory Modules. BMC Syst Biol 3 (1): 73

You can read other testimonials from IPA Certified Analysts, and learn more about the IPA Certification program by going to: http://www.ingenuity.com/company/ipa_certification_program.html.

IPA user group on LinkedIn

Dr. Patrick De Boever, R&D Scientist at VITO, has started an IPA user group on LinkedIn. This group welcomes scientists who use IPA for analyzing ‘omics data and other purposes. Concepts of pathway analysis can be discussed and the group can be used to exchange tips and tricks related to the use of IPA. Dr. De Boever and VITO’s environmental risk and health group use gene expression analysis to identify biomarkers that predict health effects of chemicals and environmental pollutants. He says, "IPA is our valuable tool for discovery of the relevant biological process in minimum of time and it helps us to formulate hypothesis about the mechanisms of action."

You can join the group by clicking here, or search LinkedIn groups for "Ingenuity User Group."

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Report from CHI's Molecular Medicine Tri-Conference 2010

Missed Molecular Medicine? Dr. Megan Laurance, our Senior Scientist in Product Marketing, chaired the "Real Examples of Integrating Pathway Data" session at Molecular Medicine in San Francisco in February. Here’s what she took away from the session:

"I was really pleased with the way the session turned out (Real Examples of Integrating Pathway Data, Thursday, Feb 4th, part of the larger Cancer Profiling and Pathways track). We had great attendance, standing room only in the back of the room, and an enthusiastic set of speakers."

"Ken Buetow (Associate Director, bioinformatics and Information Technology, National Cancer Institute) really set the tone for the session with a big picture view of the opportunities and challenges that researchers at the NCI are encountering in their efforts to integrate and understand a tremendous amount of data from clinical tumor samples. When asked what he felt the biggest challenge was in turning all of this data and effort into better outcomes for patients (IT challenges, patient registry challenges, scientists sharing data and tissues, etc.), he was quick to acknowledge the big cultural hurdles associated with getting scientists who are essentially operating within silos of their specific discipline to share data, share tissue samples, use the same terminology etc …"

Finish reading the article at http://ingenuitysystems.blogspot.com/2010/02/comments-from-floor-at-mol-med-dr-megan.html

Ingenuity also presented a poster at Molecular Medicine. Co-authored by Antoaneta Vladimirova, Ph.D., Scientific Manager, Ingenuity Systems, and Gene Oligner, Ph.D., US Army Research Institute of Infectious Diseases (USAMRIID), it was titled: "In Silico Approaches Inform Drug Repurposing Strategies for the Treatment of Ebola Infection."  You can view the poster on our website at: http://www.ingenuity.com/library/pdf/poster_drug_repurposing_molecular_tri-conference.pdf

IPA Training Overview

With all the strain and pressure on both academic and industry to make discoveries faster, the best way to get more value and efficiency out of IPA is to attend an IPA training session. We offer a variety of training offerings – with many of them being short, free, and online.  

Thursday Trainings:
Every Thursday, Ingenuity offers a free, live, 1-hour training webinar on basic topics in IPA such as search, data analysis, toxicology, and biomarkers.  You can get more details and view dates on our website at http://www.ingenuity.com/products/training.html.

Getting Started Trainings:
Occurring twice a month on Wednesdays, these free, live, training webinars walk beginning users through the system configurations needed to launch IPA, and describes the key terms used in the application. You will also learn the basics of searching the wealth of literature in IPA and learn how to upload data and run a basic analysis to identify the functions, pathways, and networks relevant to your data. View dates on our website at http://www.ingenuity.com/products/training.html.

Scientific Seminars:
Every month, Ingenuity hosts a free, live scientific seminar that explores in detail how to use IPA to answer a specific scientific question.  To view recorded versions of past webinars, please navigate the Help section of IPA to IPA Learning Center/Videos/Scientific Seminar Videos.  You can view this month’s webinar at http://www.ingenuity.com/products/training.html. 

IPA Certification:
The IPA Certification Program is a free online course offered by Ingenuity Systems for customers who want an in-depth understanding of IPA. This structured curriculum provides comprehensive training in IPA and includes a certification exam. After successfully completing the course and exam, the student receives official certification as an IPA Certified Analyst. Learn more at http://www.ingenuity.com/company/ipa_certification_program.html.

Regional Training:

In 2009, Ingenuity launched a series of successful regional IPA trainings in Boston, San Francisco, and San Diego. Thanks to your enthusiastic response, we are expanding that program to more cities and more locations in 2010. See below for our current schedule for 2010, and click on the learn more button for more details.

Upcoming Events

Join us at one of our upcoming conferences:

ABRF
March 20-23, Sacramento, CA
Booth 510

New Mexico Bioinformatics Symposium
March 25-25, Santa Fe, NM
Ingenuity Presentation: Thursday, March 25, 4:30 pm

International Conference on Primate Genomics
April 13-16, Seattle, WA

American Association for Cancer Research (AACR)
April 18-21, Washington, DC
Booth 1606

Bio-IT World
April 20-22, Boston, MA
Booth 307

Ingenuity Showcase and Training Event
May 18-20, Edison, NJ

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The publication date range filter allows you to filter on molecular relationships where the evidence for that relationship comes from literature published within a specified date range. Publication dates can be entered for the month and year of publication. The "From" field incorporates all publications from the first day of the month. The "To" field incorporates all publications through the last day of the month.

The publication date range filter option is available for the following tools within IPA: Grow, Path Explorer, Connect, Trim, Keep, and Highlight. If using the Trim, Keep, or Highlight tools, the publication date range is limited to the population of relationships on the pathway, network, or neighborhood. You can see that it is not possible to remove or highlight relationships or molecules which are not already present on the pathway.

Some relationships within the Ingenuity^® Knowledge Base have an unspecified publication date. Most of these come from Ingenuity^® Supported Third-party Information (from third party databases). If all relationships within a pathway have the publication date unspecified, the pull-down menus on Trim, Keep, and Highlight will be grayed out, indicating that the relationships cannot be further filtered.

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How can I find out if there is any newly published information on the molecular interactions present in my Network or Pathway?

1. Open your Pathway or Network-of-interest. From the Build tools, select Connect.

2. In the Datasources filter, select all.

3. Select all the molecules and relationships on the Network and click "Apply"

4. The Connect menu will display the number of new relationships and corresponding findings that have been added to the Ingenuity Knowledge Base since the last time you saved the Network or Pathway.

5. Next, click the Overlay button and select the Highlight tool.

6. From the Publication Date Range filter, enter the dates you are interested in.

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