Finding Regulatory Signals in Genomes 24.11.5 60 min..ppt

* Finding Regulatory Signals in Genomes 24.11.5 60 min. The Biological Problem Different Kinds of Signals Promotors Enhancers Splicing Signals Different Organisms Information Beyond the sequences Data - known/unknown signal Aligned Unaligned The Computational Problem Measures of Performance Quality Performance of Different Methods Regulation in Eukaryotes Promotor Transcription Factors - TF Transcription Factor binding Sites - TFBS Cis-regulatory modules - CRM Transcription Start Site - TSS TATA boxes CG richness Phylogenetic Footprinting Combinatorial Interaction Enhancers Wasserman and Sandelin (2004) ‘Applied Bioinformatics for the Identification of Regulatory Elements” Nature Review Genetics 5.4.276 Regulatory Protein-DNA Complexes Moses et al.(2003) “Position specific variation in the rate fo evolution of transcription binding sites” BMC Evolutionary Biology 3.19- Luscome et al.(2000) An overview of the structure of protein-DNA complexes Genome Biology 1.1.1-37 Databases with the 3-D structure of combined DNA -Protein Data bases with known promotors Weight Matrices,Sequence Logos Wasserman and Sandelin (2004) ‘Applied Bioinformatics for the Identification of Regulatory Elements” Nature Review Genetics 5.4.276 Very high frequency of false positives. A model for binding of MyoD will yield 106 binding sites, while only 103 might be real. Motifs in Biological Sequences 1990 Lawrence Reilly “An Expectation Maximisation (EM) Algorithm for the identification and Characterization of Common Sites in Unaligned Biopolymer Sequences Proteins 7.41-51. 1992 Cardon and Stormo Expectation Maximisation Algorithm for Identifying Protein-binding sites with variable lengths from Unaligned DNA Fragments L.Mol.Biol. 223.159-170 1993 Lawrence… Liu “Detecting subtle sequence signals: a Gibbs sampling strategy for multiple alignment” Science 262, 208-214. (R,l) 1 K Q=(q1,A,…,qw,T) probability of diff