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Target Gene Predictions for MyoD Genome-Wide Dr. Barbara Wold’s Lab (Caltech) Sean Caonguyen SoCalBSI 8/15/2007 Outline Background Approach Cistematic Python Package UCSC Genome Browser Findings Regulation of Muscle Development Chromatin Immunoprecipitation Sequencing (ChIPSeq) RNA Sequencing (RNASeq) Biological Significance Distance from MyoD Regions and Peaks to closest Gene Compare close genes to the expressed genes Future Directions Regulation of Muscle Development Why are Muscles Important? For daily activities To maintain biological composition TO LIVE!! Myogenic Regulatory Factors (MRFs) Myf 5 MyoD Myogenin Mrf 4 Early http://files.myopera.com/honeybe/blog/wCars002%2520-%2520car%2520cartoon.jpg Chromatin Immunoprecipitation Sequencing (ChIPSeq) MyoD DNA CHROMOSOMAL DNA Each red box denotes a sequence read Map sequence to genome Johnson, D.S., et al. (2007) and Fields, S. (2007) Are the Close Genes Expressed? Solexa Nearby Genes Genomic DNA RNA Sequencing (RNASeq) Introns DNA Exons Transcription 5’ cap Processing… AAAAA mRNA AAAAA Reverse Transcription DNA Size Selected Solexa/Illumina Pre-mRNA How are Genes Expressed? Solexa/Illumina Introns Exons Genomic DNA Biological Significance of Analysis Help understand regulation for the muscle network genes Problems with Muscle Atrophy: Disuse of muscles Aging Zero Gravity Study Muscular Dystrophy Diseases Improve drug development Preventive care for genetic diseases Regulation is the key http://cj_whitehound.madasafish.com/Rats_Nest/artwork/clipart/greenish_sick_rat_in_bed.gif http://www.westyrell.com/lin/spaceman.gif Location of Regulators DNA Gene C Site Gene A Gene B Approach to Project Tools Cistematic Python Package created by Ali Mortazavi Data and Code from Ali Mortazavi and Qing Yuan UCSC Genome Browser Tasks Look at MyoD enriched regions Find distance to nearby genes Determine which genes are expressed or suppressed Find Neighborhood Genes Look for genes in 20kbp radius of the MyoD sequence-tag-enriched regions Also determine distance to the peaks in regions MyoD Region Gene Gene Gene Gene Gene Gene DNA Hits at Peaks and in Regions MyoD Region Search by Peak or Region Midpoint? 5155 Genes 115 Genes Region 5270 Genes 1635 Genes Peak ∑ = 6905 Genes 6790 Genes Contributions Tools Cistematic Past Python Code UCSC Genome Broswer ChIP Seq Find Genes within 20Kbp of Potential MyoD Sites on the genome RNA Seq See if Expression Level of Genes Average Findings Future Directions Look at correlations of MyoD sites to distances to genes Potential regulation distances Isolated top hits for further analysis: Close Far Bidirectional High Mid Low Closer look at MyoD sites with no neighborhood gene Reusable analysis for other proteins Acknowledgements Mentor Wold Lab Biological Investigators Jamil Momand Sandy Sharp Nancy Warter-Perez Wendie Johnston Funding by: DOE and NASA NSF, NIH, and Economic & Workforce Development Computational Gurus Brian Williams Ali Mortazavi SoCalBSI Faculty and staff Barbara Wold Diane Trout Brandon King Cory Tobin Fellow Colleagues Qing Yuan Herbert Lee