Opportunities at the NIH

1. Opportunities at the NIH 6th Georgia Tech / ORNL International Conference on Bioinformatics Peter Good, Ph.D. NHGRI November 17, 2007 Georgia Tech / ORNL Bioinformatics Conference

2. How is NIH funding? • I don’t know. • NIH is only funded one year at a time through congressional appropriations • Current bill requesting a 3% increase over last year (inflation) was vetoed by the president Georgia Tech / ORNL Bioinformatics Conference

3. How to get an NIH grant in computational biology/bioinformatics • Pick an important problem in biomedicine • Know the field • Develop a plan to improve on the state of the art • Include a plan to validate computational approach with experimental data • Spend time to write a good application Georgia Tech / ORNL Bioinformatics Conference

4. Biomedical Information Science and Technology Initiative (BISTI) • BISTI is aimed at making optimal use of computer science and technology • BISTI Consortium (BISTIC) program representatives from many NIH Institutes and Centers • Develop programs to encourage bioinformatics and computational biology • www.bisti.nih.gov Georgia Tech / ORNL Bioinformatics Conference

5. Funding opportunities through BISTI Innovations in Biomedical Computational Science and Technology PAR-07-344 Mechanism: R01 Exploratory Innovations in Biomed. Comp. Science and Technology PAR-06-411 Mechanism: R21 Continued Development and Maintenance of SoftwarePAR-08-010 Mechanism: R01 Predictive Multiscale Models of the Physiome in Health and Disease PAR-08-023 Mechanism: R01 Georgia Tech / ORNL Bioinformatics Conference

6. ….develop an ontology that will make it possible for software to understand how two or more existing data sets relate to each other. Title: Data Ontologies for Biomedical Research (R01) Program Announcement (PA) Number: PAR-07-425 Title: Sharing Data and Tools: Federation using the BIRN and caBIG Infrastructures (R01) Program Announcement (PA) Number: PAR-07-426 …make either data or tools more broadly available to the research community by making use of the BIRN and/or the caBIG™ infrastructure. Georgia Tech / ORNL Bioinformatics Conference

7. April, 1953 April, 2003 Georgia Tech / ORNL Bioinformatics Conference

8. Notes From the Front Lines of the Genomic Revolution • Comparative genomics is providing a wealth of information about the human genome Georgia Tech / ORNL Bioinformatics Conference

9. Elliott H. Margulies et al. Genome Res. 2007; 17: 760-774

10. Notes From the Front Lines of the Genomic Revolution • Comparative genomics is providing a wealth of information about the human genome • DNA sequencing is undergoing revolutionary technical advances Georgia Tech / ORNL Bioinformatics Conference

11. 1000 Genomes Project(meeting in Cambridge, UK, Sept. 17-18, 2007) • Goal is to sequence 1000 genomes at sufficient depth to identify nearly all variants with frequency of minor allele greater than 1% (down to 0.2% in exons) • Will be an excellent test of new sequencing technologies • Pilot projects getting underway Georgia Tech / ORNL Bioinformatics Conference

12. http://cancergenome.nih.gov Georgia Tech / ORNL Bioinformatics Conference

13. Georgia Tech / ORNL Bioinformatics Conference

14. Request For Applications (RFA) Number:RFA-CA-08-005 Title:Advanced Genomic Data Analysis and Visualization Methods for the Cancer Genome Atlas (TCGA) Data (R21) Georgia Tech / ORNL Bioinformatics Conference

15. NIH Roadmap for Medical Research ACCELERATING MEDICAL DISCOVERY TO IMPROVE HEALTH Georgia Tech / ORNL Bioinformatics Conference www.nihroadmap.nih.gov

16. http://nihroadmap.nih.gov/hmp The goal of the Human Microbiome Project, funded by the NIH Roadmap, is to characterize the microbial content of sites in the human body and examine whether changes in the microbiome can be related to disease.

17. HMP Roadmap Initiatives • Developing a reference set of microbial genome sequences and preliminary characterization of the human microbiome • Relationship between disease and changes in the human microbiome • Development of new technologies (Computational and Experimental) • Establishing a Data Analysis and Coordinating Center (DACC) • NCBI Short Read Archive Data Repository • Establishing a resource repository • Ethical, legal and social implications (ELSI) of HMP research Georgia Tech / ORNL Bioinformatics Conference

18. NIH Roadmap for Epigenomics • REFERENCE EPIGENOME MAPPING CENTERS • EPIGENOMICS DATA ANALYSIS AND COORDINATION CENTER (EDACC) • NCBI REPOSITORY AND PORTAL FOR EPIGENOMIC DATA • TECHNOLOGY DEVELOPMENT IN EPIGENOMICS • DISCOVERY OF NOVEL EPIGENETIC MARKS IN MAMMALIAN CELLS • EPIGENOMICS OF HUMAN HEALTH AND DISEASE http://nihroadmap.nih.gov/epigenomics/grants.asp Georgia Tech / ORNL Bioinformatics Conference

19. Notes From the Front Lines of the Genomic Revolution • Comparative genomics is providing a wealth of information about the human genome • DNA sequencing is undergoing revolutionary technical advances • Experimental approaches to determining genome function are moving forward rapidly Georgia Tech / ORNL Bioinformatics Conference

22. ENCODE • Scale to ENCODE Project to identify functional elements in the whole genome • Transcripts, protein coding genes, chromatin modications, transcription factor binding sites, promoter elements • Continue some pilot projects • Promoter elements, RNA binding protein sites • Data Coordinating Center and Data Analysis Center

23. modENCODE ENCODE project on model organisms Learn how to identify functional elements in a model system Support projects in Drosophila and C. elegans www.modencode.org Georgia Tech / ORNL Bioinformatics Conference

24. Notes From the Front Lines of the Genomic Revolution • Comparative genomics is providing a wealth of information about the human genome • DNA sequencing is undergoing revolutionary technical advances • Experimental approaches to determining genome function are moving forward rapidly • Genetic factors in many common diseases are being rapidly revealed Georgia Tech / ORNL Bioinformatics Conference

25. Progress in Genotyping Technology 102 ABI TaqMan ABI SNPlex 10 Cost per genotype (Cents, USD) Illumina Golden Gate Affymetrix MegAllele Affymetrix 10K Illumina Infinium/Sentrix Perlegen 1 Affymetrix 100K/500K Nb of SNPs 1 10 102 103 104 105 106 2001 2005 Courtesy S. Chanock, NCI

26. IBD5 NOD2 PPAR CTLA4 KCNJ11 PTPN22 2000 2001 2002 2003 2004 MEIS1 LBXCOR1 BTBD9 C3 8q24 ORMDL3 4q25 TCF2 GCKR FTO C12orf30 ERBB3 KIAA0350 CD226 16p13 PTPN2 SH2B3 FGFR2 TNRC9 MAP3K1 LSP1 8q24 Confirmed genetic contributors to common human diseases (August 2007) CDKN2A 8q24 #2 8q24 #3 8q24 #4 8q24 #5 8q24 #6 ATG16L1 5p13 10q21 IRGMNKX2-3 IL12B 3p21 1q24 PTPN2 TCF2 CDKN2A IGF2BP2 CDKAL1 HHEX SLC30A8 Age Related Macular Degeneration Crohn’s Disease Type 1 Diabetes Systemic Lupus Erythematosus Asthma Restless leg syndrome Gallstone disease Cholesterol Obesity Coronary Disease QT interval Atrial Fibrillation Type 2 Diabetes Prostate cancer Breast cancer Colon cancer NOS1AP IFIH1 PCSK9 CFB/C2 LOC387715 8q24 IL23R TCF7L2 CD25 IRF5 PCSK9 CFH 2005 2006 2007

27. A partnership to advance the genetic analysis of ADHD Diabetic nephropathy Schizophrenia Bipolar illness Psoriasis Major depression Georgia Tech / ORNL Bioinformatics Conference

28. Genes and Environment Initiative EXPOSURE BIOLOGY PROGRAM GENETICS PROGRAM Identify genetic variants Develop technology and biomarkers GXE • Diet • Physical Activity • Environmental Exposures • Psychosocial Stress and Addictive Substances • Database • Function • Translation • GWA Studies • Data Analysis • Replication • Sequencing Georgia Tech / ORNL Bioinformatics Conference

29. Georgia Tech / ORNL Bioinformatics Conference

30. Peter Good National Human Genome Research Institute Goodp@mail.nih.gov Georgia Tech / ORNL Bioinformatics Conference