Slides on Genomics - Introduction to Bioinformatics | BCB 544, Study notes of Bioinformatics

Download Slides on Genomics - Introduction to Bioinformatics | BCB 544 and more Study notes Bioinformatics in PDF only on Docsity! Genomics 11/14/05 D Dobbs ISU - BCB 444/544X 1 11/16/05 D Dobbs ISU - BCB 444/544X: Genomics 1 11/16/05 Genomics 11/16/05 D Dobbs ISU - BCB 444/544X: Genomics 2 Bioinformatics Seminars Nov 17 Thurs 4:10 BBMB Seminar in 1414 MBB C2 and PH Domains: Diverse regulators of membrane signaling events Joe Falke, UC Boulder Nov 18 Fri 12:10 BCB Seminar in E164 Lago Using P-Values for the Planning and Analysis of Microarray Experiments Dan Nettleton, Stat 11/16/05 D Dobbs ISU - BCB 444/544X: Genomics 3 Protein Structure Prediction Genome Analysis Mon Protein 3' structure prediction Wed Genome analysis & genome projects Comparative genomics; ENCODE, SNPs, HapMaps, medical genomics Thur Lab Protein structure prediction, SNPs Fri Experimental approaches: microarrays, proteomics, metabolomics, chemical genomics 11/16/05 D Dobbs ISU - BCB 444/544X: Genomics 4 Reading Assignment (for Mon-Fri) Mount Bioinformatics • Chp 11 Genome Analysis http://www.bioinformaticsonline.org/ch/ch11/index.html • pp. 495 - 547 • Ck Errata: http://www.bioinformaticsonline.org/help/errata2.html 11/16/05 D Dobbs ISU - BCB 444/544X: Genomics 5 BCB 544 Additional Readings Required: • Gene Prediction • Burge & Karlin 1997 JMB 268:78 Prediction of complete gene structures in human genomic DNA • Human HapMap (Nature 437, Oct 27, 2005) • Commentary (437:1233) http://www.nature.com/nature/journal/v437/n7063/full/4371233a.html • News & Views (437: 1241) http://www.nature.com/nature/journal/v437/n7063/full/4371241a.html Optional: • Article (437:1299) A haplotype map of the human genome The International HapMap Consortium 11/16/05 D Dobbs ISU - BCB 444/544X: Genomics 6 Review last lecture: Protein Structure Prediction focus on: Threading Genomics 11/14/05 D Dobbs ISU - BCB 444/544X 2 11/16/05 D Dobbs ISU - BCB 444/544X: Genomics 7 1. Align target sequence with template structures (fold library) from the Protein Data Bank (PDB) 2. Calculate energy (score) to evaluate goodness of fit between target sequence and template structure 3. Rank models based on energy scores (assumption: native- like structures have lowest energy) Target Sequence Structure Templates ALKKGF…HFDTSE Protein Structure Prediction using Threading 11/16/05 D Dobbs ISU - BCB 444/544X: Genomics 8 Protein Threading: typical energy function MTYKLILNGKTKGETTTEAVDAATAEKVFQYANDNGVDGEWTYTE How well does a specific residue fit structural environment? What is "probability" that two specific residues are in contact? Alignment gap penalty? Total energy: Ep + Es + Eg Find a sequence-structure alignment that minimizes the energy function 11/16/05 D Dobbs ISU - BCB 444/544X: Genomics 9 A Rapid Threading Approach for Protein Structure Prediction Kai-Ming Ho, Physics Haibo Cao Yungok Ihm Zhong Gao James Morris Cai-zhuang Wang Drena Dobbs, GDCB Jae-Hyung Lee Michael Terribilini Jeff Sander Trick for Fast Threading? ALKKGF…HFDTSE (1D – 3D problem)Sequence – Structure (1D – 2D problem) (1D – 1D problem) Sequence – Contact Matrix Sequence – 1D Profile Ihm 2004 11/16/05 D Dobbs ISU - BCB 444/544X: Genomics 11 Template structure (reduced) representation ,1=ijC 5.6!ijr Åif (contact) ,0=ijC Otherwise A neighbor in sequence (non-contact) i j 1 N Template structure ( contact matrix)C NN ! Ihm 2004 11/16/05 D Dobbs ISU - BCB 444/544X: Genomics 12 Energy function Assumption: At residue level, pair-wise hydrophobic interaction is dominant: E = Σi,j Cij Uij Cij : contact matrix Uij = U(residue I , residue J) • MJ matrix : U = Uij • LTW : U = Qi*Qj • HP model : U = {1,0} Ihm 2004