Introduction to Bioinformatics: Understanding the Basics of What is Bioinformatics - Prof., Lab Reports of Bioinformatics

Download Introduction to Bioinformatics: Understanding the Basics of What is Bioinformatics - Prof. and more Lab Reports Bioinformatics in PDF only on Docsity! #1 - What is Bioinformatics 8/20/07 BCB 444/544 Fall 07 Dobbs 1 8/20/07BCB 444/544 F07 ISU Dobbs #1 - What is Bioinformatics? 1 Lecture 1 What is Bioinformatics? (Genomics? Computational Biology?) #1_Aug20 BCB 444/544 Thanks to Mark Gerstein (Yale) & Eric Green (NIH) for many borrowed & modified PPTs 8/20/07BCB 444/544 F07 ISU Dobbs #1 - What is Bioinformatics? 2 8/20/07BCB 444/544 F07 ISU Dobbs #1 - What is Bioinformatics? 3 Introduction to Bioinformatics Instructors: Drena Dobbs ddobbs@iastate.edu Michael Terribilini terrible@iastate.edu Jae-Hyung Lee jhlee777@iastate.edu TAs: Jeff Sander jdsander@iastate.edu Pete Zaback petez@iastate.edu Lab: MBB 106, 4-4991 BCB 444/544 8/20/07BCB 444/544 F07 ISU Dobbs #1 - What is Bioinformatics? 4 BCB 444/544 - Website http://bindr.gdcb.iastate.edu/bcb544 • Syllabus • Lecture & Lab Schedules (with Homework Assignments) • Lecture PPTs • Lab Exercises • Practice Exams • Grading Policy • Project Guidelines, etc. • Links • Check regularly for updates! 8/20/07BCB 444/544 F07 ISU Dobbs #1 - What is Bioinformatics? 5 Meets in 1304 MBB every week EXCEPT this week: Current schedule: Thurs 1-3 PM Conflicts? Alternatives? BCB 444/544 - Computer Lab 1st Lab meets in Library Rm 32 8/20/07BCB 444/544 F07 ISU Dobbs #1 - What is Bioinformatics? 6 Essential Bioinformatics Jin Xiong, Cambridge, 2006 ISBN-13: 9780521600828 Textbook Companion Website: Not much of one for Xiong: Xiong resources but check out companion sites for optional texts (next slide - URLs also provided on class website) BCB 444/544 - Required Textbook #1 - What is Bioinformatics 8/20/07 BCB 444/544 Fall 07 Dobbs 2 8/20/07BCB 444/544 F07 ISU Dobbs #1 - What is Bioinformatics? 7 BCB 444/544 - Optional Textbooks Please don't buy these yet! Completely optional, perhaps useful, references. All are available from ISU Bookstore but are cheaper from online booksellers. • Mount - good reference for both "biologists" and "computer scientists" - but a bit out of date; Online resources - include lists of applications with URLs • Pevsner - great overview, esp. for those with little biology background; Online resources - excellent: many links & PPTs. • Jones & Pevzner - good introduction to basic algorithms, esp. for biologists with little computer science background; Online resources - very good: problems, links & PPTs. 8/20/07BCB 444/544 F07 ISU Dobbs #1 - What is Bioinformatics? 8 Required Reading (after today, must read before lecture) Wed Aug 22 - for Lecture #2 • Xiong Textbook: • Chp 1 - Introduction • Chp 2 - Biological Databases Thurs Aug 23 - for Lab #1: • Literature Resources for Bioinformatics Andrea Dinkelman, see Lab Schedule for URL Fri Aug 24 • Genomics & Its Impact on Science & Society: Genomics & Human Genome Project Primer see Lecture Schedule for URL 8/20/07BCB 444/544 F07 ISU Dobbs #1 - What is Bioinformatics? 9 Xiong: Chps 1 & 2 SECTION I INTRODUCTION AND BIOLOGICAL DATABASES 1 Introduction What Is Bioinformatics? Goal Scope Applications Limitations New Themes Further Reading 2 Introduction to Biological Databases What Is a Database? Types of Databases Biological Databases Pitfalls of Biological Databases Information Retrieval from Biological Databases Summary Further Reading 8/20/07BCB 444/544 F07 ISU Dobbs #1 - What is Bioinformatics? 10 Assignment #1: Tell us about you Due: Wed, Aug 22 1- Complete HW1_Aug20 for Drena 8/20/07BCB 444/544 F07 ISU Dobbs #1 - What is Bioinformatics? 11 A tutorial on genomic sequencing, gene structure, genes prediction Howard Hughes Medical Institute (HHMI) Cold Spring Harbor Laboratory (CSHL) Assignment #2 (& for Fun): DNA Interactive "Genomes" 1. Take the Tour 2. Read about the Project 3. Do some Genome Mining with:  Nothing to turn in - just do it! http://www.dnai.org/c/index.html 8/20/07BCB 444/544 F07 ISU Dobbs #1 - What is Bioinformatics? 12 What is Bioinformatics? Wikipedia: • Bioinformatics and computational biology involve the use of techniques including: applied mathematics informatics statistics computer science artificial intelligence chemistry & biochemistry (& engineering) to solve biological problems usually on the molecular level • Research in computational biology often overlaps with systems biology (& genomics) #1 - What is Bioinformatics 8/20/07 BCB 444/544 Fall 07 Dobbs 5 8/20/07BCB 444/544 F07 ISU Dobbs #1 - What is Bioinformatics? 25 1st Draft Human Genome: "Finished" in 2001 Modified from Eric Green 8/20/07BCB 444/544 F07 ISU Dobbs #1 - What is Bioinformatics? 26 Human Genome Sequencing Two approaches: • Public (government) - International Consortium (mainly 6 countries, NIH-funded in US) • Hierarchical cloning & BAC-to-BAC sequencing • Map-based assembly • Private (industry) - Celera, Craig Venter, CEO • Whole genome random "shotgun" sequencing • Computational assembly (took advantage of public maps & sequences, too) Guess which human genome they sequenced? Craig's How many genes? ~ 20,000 (Science, May 2007) 8/20/07BCB 444/544 F07 ISU Dobbs #1 - What is Bioinformatics? 27 Public Sequencing: International Consortium Modified from Eric Green 8/20/07BCB 444/544 F07 ISU Dobbs #1 - What is Bioinformatics? 28 So, having a list of parts is not enough! BIG QUESTION? SYSTEMS BIOLOGY How do parts work together to form a functional system? What is a system? Macromolecular complex, pathway, network, cell, tissue, organism, ecosystem… 8/20/07BCB 444/544 F07 ISU Dobbs #1 - What is Bioinformatics? 29 Is this Bioinformatics? • Creating digital libraries • Automated bibliographic search and text comparison • Knowledge bases for biological literature • Methods for structure determination • Computational X-ray crystallography • NMR structure determination • Distance geometry • Metabolic pathway simulation YES YES YES Modified from Mark Gerstein 8/20/07BCB 444/544 F07 ISU Dobbs #1 - What is Bioinformatics? 30 • Gene identification by sequence inspection • Prediction of splice sites, promoters, etc. • DNA methods in forensics • Modeling populations of organisms • Ecological Modeling • Genomic sequencing methods • Assembling contigs • Physical and genetic mapping • Linkage analysis • Linking specific genes to various traits YES YES YES YES YES Modified from Mark Gerstein Is this Bioinformatics? #1 - What is Bioinformatics 8/20/07 BCB 444/544 Fall 07 Dobbs 6 8/20/07BCB 444/544 F07 ISU Dobbs #1 - What is Bioinformatics? 31 • Rational drug design • RNA structure prediction • Protein structure prediction • Artificial life simulations • Artificial immunology • Computer security YES Modified from Mark Gerstein Is this Bioinformatics? 8/20/07BCB 444/544 F07 ISU Dobbs #1 - What is Bioinformatics? 32 So, this is Bioinformatics What is it good for? Just a few examples… 8/20/07BCB 444/544 F07 ISU Dobbs #1 - What is Bioinformatics? 33 Designing drugs • Understanding how proteins bind other molecules • Structural modeling & ligand docking • Designing inhibitors or modulators of key proteins Figures adapted from Olsen Group Docking Page at Scripps, Dyson NMR Group Web page at Scripps, and from Computational Chemistry Page at Cornell Theory Center). Modified from Mark Gerstein 8/20/07BCB 444/544 F07 ISU Dobbs #1 - What is Bioinformatics? 34 Finding homologs of "new" human genes Modified from Mark Gerstein 8/20/07BCB 444/544 F07 ISU Dobbs #1 - What is Bioinformatics? 35 Finding WHAT? Homologs - "same genes" in different organisms • Human vs Mouse vs Yeast • Much easier to do experiments on yeast to determine function • Often, function of an ortholog in at least one organism is known Best Sequence Similarity Matches to Date Between Positionally Cloned Human Genes and S. cerevisiae Proteins Human Disease MIM # Human GenBank BLASTX Yeast GenBank Yeast Gene Gene Acc# for P-value Gene Acc# for Description Human cDNA Yeast cDNA Hereditary Non-polyposis Colon Cancer 120436 MSH2 U03911 9.2e-261 MSH2 M84170 DNA repair protein Hereditary Non-polyposis Colon Cancer 120436 MLH1 U07418 6.3e-196 MLH1 U07187 DNA repair protein Cystic Fibrosis 219700 CFTR M28668 1.3e-167 YCF1 L35237 Metal resistance protein Wilson Disease 277900 WND U11700 5.9e-161 CCC2 L36317 Probable copper transporter Glycerol Kinase Deficiency 307030 GK L13943 1.8e-129 GUT1 X69049 Glycerol kinase Bloom Syndrome 210900 BLM U39817 2.6e-119 SGS1 U22341 Helicase Adrenoleukodystrophy, X-linked 300100 ALD Z21876 3.4e-107 PXA1 U17065 Peroxisomal ABC transporter Ataxia Telangiectasia 208900 ATM U26455 2.8e-90 TEL1 U31331 PI3 kinase Amyotrophic Lateral Sclerosis 105400 SOD1 K00065 2.0e-58 SOD1 J03279 Superoxide dismutase Myotonic Dystrophy 160900 DM L19268 5.4e-53 YPK1 M21307 Serine/threonine protein kinase Lowe Syndrome 309000 OCRL M88162 1.2e-47 YIL002C Z47047 Putative IPP-5-phosphatase Neurofibromatosis, Type 1 162200 NF1 M89914 2.0e-46 IRA2 M33779 Inhibitory regulator protein Choroideremia 303100 CHM X78121 2.1e-42 GDI1 S69371 GDP dissociation inhibitor Diastrophic Dysplasia 222600 DTD U14528 7.2e-38 SUL1 X82013 Sulfate permease Lissencephaly 247200 LIS1 L13385 1.7e-34 MET30 L26505 Methionine metabolism Thomsen Disease 160800 CLC1 Z25884 7.9e-31 GEF1 Z23117 Voltage-gated chloride channel Wilms Tumor 194070 WT1 X51630 1.1e-20 FZF1 X67787 Sulphite resistance protein Achondroplasia 100800 FGFR3 M58051 2.0e-18 IPL1 U07163 Serine/threoinine protein kinase Menkes Syndrome 309400 MNK X69208 2.1e-17 CCC2 L36317 Probable copper transporter Modified from Mark Gerstein 8/20/07BCB 444/544 F07 ISU Dobbs #1 - What is Bioinformatics? 36 Comparative Genomics: Genome/Transcriptome/Proteome/Metabolome Databases, statistics • Occurrence of a specific genes or features in a genome • How many kinases in yeast? • Compare Tissues • Which proteins are expressed in cancer vs normal tissues? • Diagnostic tools • Drug target discovery Modified from Mark Gerstein