microrna Associations and Signatures: An Approach to Map the Space en bloc

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1 GENReports: Market & Tech Analysis microrna Associations and Signatures: An Approach to Map the Space en bloc > Enal Razvi, Ph.D. Biotechnology Analyst, Managing Director SELECTBIO US > Gary Oosta, Ph.D. Biotechnology Analyst, SELECTBIO US

2 Topic Introduction and Scope The focus of this GEN Market & Tech Analysis Report is to present some of our recent industry tracking of the microrna publications ensemble as a means to describe hotspots of microrna association with biological phenotypes both spatially and temporally We ve harvested the entire set of publications where micrornas are mentioned in the title and/or abstract and this served as the starting material for algorithms to sort them based on their association into specific space Not only did we generate the hotspot map but also we examined the following The Evolution of the Hotspot Map over a 2 year Period Temporal Picture, ie., How the Associations Rolled Out Over Time This Analysis Provides a Means for Segmenting Associations of micrornas with Specific Physiological/Pathological States and also Allows us to Examine the Research Trends Associated with a Given Set of micrornas

3 30,000 25,000 Latest Version is v20.0, released in June 2013 with 24,521 entries 20,000 15,000 The Growth of Content in the mir base Database has been a Driver for the identification and Validation of microrna Signatures Associated with Disease 10,000 5,000 Dec 2002 Jan 2003 April 2003 May 2003 July 2003 July 2003 Sept 2003 Nov 2003 Jan 2004 April 2004 July 2004 Sept 2004 Dec 2004 April 2005 June 2005 Oct 2005 Feb 2006 May 2006 July 2006 Oct 2006 Feb 2007 May 2007 Aug 2007 Dec 2007 April 2008 Sept 2008 March 2009 Sept 2009 April 2010 Aug 2010 April 2011 Nov 2011 Aug 2012 June GENReports: Market & 9.0 Tech 9.1 Analysis, Produced by 13.0 Enal 14.0 Razvi, Ph.D

4 Expansion of the microrna Field 6000 Publication Activity in the MicroRNA Space Serves as a Metric to Assess the Expansion of the microrna Space EST. Drivers for Growth are Papers/Year Finite Content: Tight Associations with Physiological and Disease Processes Cancer is the Key Driver for microrna Research Currently Year

5

6 Segments into Which microrna Research Publications Segregate 450 Cancer is the Key Driver of the microrna Space: Bars in Blue Represent Large Numbers of Publications which Segregate Within the Various Cancer Spaces ADENOCARCINOMA B-CELL LYMPHOMA BLADDER CANCER BREAST CANCER BURKITT LYMPHOMA CERVICAL CANCER CHRONIC COLON CANCER COLORECTAL CANCER EM_TRANSITION HUMAN LYMPHOMA GASTRIC CANCER GLIOBLASTOMA HCC HEPATIC CANCER HEPATOCELLULAR HODGINS LYMPHOMA LEUKEMIA LUNG CANCER METASTASIS MYELODYSPLASTIC MYELOID LEUKEMIA NON-SMALL CELL LUNG OVARIAN CANCER PANCREATIC CANCER PROSTATE CANCER SQUAMOUS CELL THYROID CANCER ALZHEIMERS DISEASE ANGIOGENESIS DIABETES INFLAMMATION OBESITY SCHIZOPHRENIA CARDIOVASCULAR MYOCARDIAL DISEASE MYOCARDIAL NEURODEGENERATIVE NEUROLOGICAL DISEASE NEURONAL PARKINSONS DISEASE BONE MARROW HEMATOPOIESIS HEMATOPOIETIC HEPATITIS C VIRUS STEM CELLS TUMOR SUPPRESSOR Number of Publications

7 microrna Publications Hotspot Map. I: Intensity of the Hotspot in Each Cell is Proportional to the Numbers of Publications Focusing on the Given microrna and the Keyword Interrogated ADENOCARCINOMA B-CELL LYMPHOMA BLADDER CANCER BREAST CANCER BURKITT LYMPHOMA CERVICAL CANCER CHRONIC LYMPHOCYTIC LEUKEMIA COLON CANCER COLORECTAL CANCER EM_TRANSITION GASTRIC CANCER GLIOBLASTOMA HCC HEPATIC CANCER HEPATOCELLULAR CARCINOMA HODGINS LYMPHOMA HUMAN LYMPHOMA LEUKEMIA LUNG CANCER METASTASIS MYELODYSPLASTIC MYELOID LEUKEMIA MIR NAME LET MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR NON-SMALL CELL LUNG CANCER OVARIAN CANCER PANCREATIC CANCER PROSTATE CANCER SQUAMOUS CELL CARCINOMA THYROID CANCER CARDIOVASCULAR DISEASE MYOCARDIAL DISEASE MYOCARDIAL INFARCTION NEURODEGENERATIVE NEUROLOGICAL DISEASE NEURONAL PARKINSONS DISEASE ALZHEIMERS DISEASE ANGIOGENESIS DIABETES INFLAMMATION OBESITY SCHIZOPHRENIA BONE MARROW HEMATOPOIESIS HEMATOPOIETIC HEPATITIS C VIRUS STEM CELLS TUMOR SUPPRESSOR

8 Change in microrna Publication Hotspots from : Temporal Increase in Publications Focused on Some micrornas ADENOCARCINOMA B-CELL LYMPHOMA BLADDER CANCER BREAST CANCER BURKITT LYMPHOMA CERVICAL CANCER CHRONIC LYMPHOCYTIC LEUKEMIA COLON CANCER COLORECTAL CANCER EM_TRANSITION GASTRIC CANCER GLIOBLASTOMA microrna Name LET MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR MIR Increases in Nr. MIR MIR of 0 Publications MIR MIR HCC HEPATIC CANCER HEPATOCELLULAR CARCINOMA HODGINS LYMPHOMA HUMAN LYMPHOMA LEUKEMIA LUNG CANCER METASTASIS MYELODYSPLASTIC MYELOID LEUKEMIA NON-SMALL CELL LUNG CANCER OVARIAN CANCER PANCREATIC CANCER PROSTATE CANCER SQUAMOUS CELL CARCINOMA THYROID CANCER CARDIOVASCULAR DISEASE MYOCARDIAL DISEASE MYOCARDIAL INFARCTION NEURODEGENERATIVE NEUROLOGICAL DISEASE NEURONAL PARKINSONS DISEASE ALZHEIMERS DISEASE ANGIOGENESIS DIABETES INFLAMMATION OBESITY SCHIZOPHRENIA BONE MARROW HEMATOPOIESIS HEMATOPOIETIC HEPATITIS C VIRUS STEM CELLS TUMOR SUPPRESSOR

9 Temporal Analysis of microrna Associations The Previous Slides Presented a Subset of the Publications Association Data we have Collected wherein Specific micrornas Mentioned in the Literature were Associated with Specific Disease Areas The Next Set of Slides Map the Timeline for this Trajectory ie., The Associated MicroRNAs and the Timelines for Publications Focusing on them This Allows us the Opportunity to View the Evolution of these Associations in Time [ie., How Recent are these Associations]

10 Interpreting our Temporal Charts The temporal chart shows the pattern of publishing activity for a class of cancer and related micrornas On the charts, each diamond is a PubMed document and is positioned by the document publication date Each line is a specific microrna. In this case, a line may contain papers from more than one institution, but each paper will mention the microrna from that line The microrna at the top has the most documents in the group. All other participants are rank ordered by the number of documents The colored boxes highlight key patterns: The blue box generally highlights microrna s that are strongly correlated with the disease based on publication numbers. The yellow box generally highlights microrna s that have been mentioned most recently. The white box highlights those microrna s that are no longer being mentioned in publications as connected to the class of cancer being studied. The picture allows an analyst to see at a glance how an area is developing and which microrna s are most important to developments in that class of cancer

11 Breast Cancer Time Axis

12 Glioblastoma Time Axis

13 Colon Cancer Time Axis

14 Tumor Suppressor Time Axis

15 Metastasis Time Axis

16 In Summary The Ability to Map the Publications Landscape of micrornas en bloc Affords us the Opportunity to Not Only View the Real Estate of micrornas which is Occupied with Associations but also Virgin Territory This Helps Focus Research Activities on Areas/Associations where Precedent Exists [in terms of the publications record] This Also Helps to Identify Areas where No Association[s] have been Published Thus Far We ve Extended past Analyses to View the Patent Landscape Which mirs/associations are the Subject of Disclosures All these Analyses are Designed to Discover and Document Associations of mir Signatures which May in the Future be Important as Circulating Biomarkers

17 About the Authors Enal Razvi, Ph.D., conducted his doctoral work on viral immunology and subsequent to receiving his Ph.D. went on to the Rockefeller University in New York to serve as Aaron Diamond Postdoctoral fellow under Professor Ralph Steinman [Nobel Prize Winner in 2011 for his discovery of dendritic cells in the early 70s with Zanvil Cohn]. Subsequently, Dr. Razvi completed his research fellowship at Harvard Medical School. For the last two decades Dr. Razvi has worked with small and large companies and consulted for more than 100 clients worldwide. He currently serves as Biotechnology Analyst and Managing Director of SelectBio U.S. He can be reached at Gary M. Oosta, Ph.D conducted doctoral work in Biophysics from Massachusetts Institute of Technology and a B.A. in Chemistry from E. Mich. Univ. He has 25 years of industrial research experience in various technology areas including medical diagnostics, thin layer coating, bioeffects of electromagnetic radiation, and blood coagulation. Dr. Oosta has authored 20 technical publications and is an inventor on 77 patents worldwide. In addition, he has managed research groups that were responsible for many other patented innovations. Dr. Oosta has a long standing interest in using patents and publications as strategic technology indicators for future technology selection and new product development.

18 All the Stakeholders in Circulating Biomarkers Come Together in Boston in March 2014 SELECTBIO Conference Brings Together all the Stakeholders in this Broad Space Composed of Exosomes, CTCs, micrornas, Epigenetics, and Circulating DNA: Circulating Biomarkers 2014, March 24 25, Boston Conference Website:

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