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Sequence Analysis

Sequence Analysis. Programme. A Motif-based Framework for Recognizing Sequence Families Sharan, Myers 9:45-10:10am 10:10-10:40am Coffee Break An HMM Posterior Decoder for Sequence Feature Prediction that Includes Homology Information Käll, Krogh, Sonnhammer 10:40-11:05am

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Sequence Analysis

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  1. Sequence Analysis

  2. Programme • A Motif-based Framework for Recognizing Sequence FamiliesSharan, Myers9:45-10:10am 10:10-10:40am Coffee Break • An HMM Posterior Decoder for Sequence Feature Prediction that Includes Homology InformationKäll, Krogh, Sonnhammer10:40-11:05am • Self-Organized Clustering Methods for Familial Binding ProfilesMahony, Golden, Smith, Benos11:05-11:30am 12:15-1:30pm ISCB Open Business Meeting • Statistics of Local Multiple AlignmentsPrakash, Tompa1:45-2:10pm • Computing the P-value of the Information Content from an Alignment of Multiple SequencesNagarajan, Jones, Keich2:10-2:35pm

  3. What Controls Gene Expression? • Transcription factors • Regulatory RNAs • miRNA • smRNA • siRNA • Methylation • Chromatin

  4. Wasserman and Sandelin, (2004) Applied Bioinformatics for the identification of regulatory elements Nature Reviews Genetics (5): 276-287.

  5. Transcription Factors • Proteins which bind DNA • Enhance or repress gene expression • Families e.g.: • Homeodomain (Hox) • POU domain (Oct-1) • Helix-loop-Helix (c-Myc) • Zinc Fingers (TFIIIA) • Leucine Zipper (c/EBP) • Winged Helix (Fox family) • Approx 10% of genes in Human genome are TF’s

  6. 577 TFBS TF Noise

  7. TF Problems • TFBS are small and degenerate • TGTGGT AML-1a • NNNWAAAYAAAYANNNNN FOXJ2_1 • AYMAYAATATTTKN FOXJ2_2 • TYAAGTG NKX2-5 • Upstream sequences (even conserved) are large

  8. Wasserman and Sandelin, (2004)

  9. 577 TFBS 101 TFBS Conserved Sites

  10. Motifs Collections? • Databases/experimental data • Transfac • Jaspar • De novo searches/motif finding • Xiaohui Xie, Jun Lu, EJ. Kulbokas, Todd Golub, Vamsi Mootha, Kerstin Lindblad-Toh, Eric Lander, Manolis Kellis (2005) Systematic discovery of regulatory motifs in human promoters and 3' UTRs by comparison of several mammals Nature, 2005 Feb 27, doi:10.1038/nature03441

  11. Motif Finding • From unaligned DNA? • Pattern finding • local multiple alignment • Benchmark test sets • M. Tompa, N. Li, T. L. Bailey , G. M. Church , B. De Moor, E. Eskin, A. V. Favorov, M. C. Frith, Y. Fu, W. J. Kent, V. J. Makeev, A. A. Mironov, W. S. Noble, G. Pavesi, G. Pesole, M. Regnier, N. Simonis, S. Sinha, G. Thijs, J. van Helden, M. Vandenbogaert, Z. Weng, C. Workman, C. Ye, and Z. Zhu (2005) Assessing Computational Tools for the Discovery of Transcription Factor Binding Sites. Nature Biotechnology, vol. 23, no. 1, 137 - 144. • Compared 13 motif finders: AlignACE, ANN-Spec, Consensus, GLAM, Improbizer, MEME, MEME3, MITRA, MotifSampler, oligo/dyad-analysis, QuickScore, SeSiMCMC, Weeder, YMF

  12. TFBS frequency? Cre-bp1_c_Jun 7.7 HSF2 13.0 Cart-1 17.4 ER 22.1 : HSF 80.4 SP1 86.7 …so how do we determine significance?

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