BSC 4934: Q'BIC Capstone Workshop in Bioinformatics - Course Information and Overview - Pr, Study Guides, Projects, Research of Biology

Download BSC 4934: Q'BIC Capstone Workshop in Bioinformatics - Course Information and Overview - Pr and more Study Guides, Projects, Research Biology in PDF only on Docsity! 06/24/09 Q'BIC Bioinformatics 1 BSC 4934: Q BIC Capstone Workshop Giri Narasimhan ECS 254A; Phone: x3748 giri@cis.fiu.edu http://www.cis.fiu.edu/~giri/teach/BSC4934_Su09.html 24 June through 8 July, 2009 06/24/09 Q'BIC Bioinformatics 2 Overview of Course Sequence Alignment; Multiple Sequence Alignment Sequence Analysis Sequencing and Mapping Phylogenetic Analysis Gene prediction techniques Pattern discovery techniques Protein structure alignment and analysis Genomics, Functional Genomics, Proteomics Gene Expression Data Analysis RNA Secondary structure RNA interference and small RNA Ribozymes and Riboswitches Databases & Software Packages Statistics for Bioinformatics Computational Learning & Predictive Methods Biomedical Image Analysis Emerging Biotechnologies 06/24/09 Q'BIC Bioinformatics 5 Evaluation Homework Assignments (35 %) Exam (35 %) Semester Project (25 %) Class Participation (5 %) Course Homepage http://www.cis.fiu.edu/~giri/teach/BSC4934_Su09.html Lecture notes, required reading material, homework, announcements, etc. 06/24/09 Q'BIC Bioinformatics 6 Introduction 1. What is Bioinformatics? Analysis of biological data with computing & statistical tools. 2. The different aspects of Informatics? Data Management (Database Technology, Internet Programming) Analysis/Interpretation of Data (Data Mining, Modeling, Statistical Tools) Development of Algorithms/ Data Structures Visualization and Interface Design (HCI, Graphics) 3. How to assist biological research? propose new models or correlations based on data from experiments verify a proposed model using known data propose new experiments based on model or analysis use predicted information to narrow down search in a biological investigation 06/24/09 Q'BIC Bioinformatics 7 Overall Goals Gene Protein Structure Function DNA Sequence Gene Regulatory Networks Molecular Interaction and Reaction Networks PPI Networks Metabolic Pathways 06/24/09 Q'BIC Bioinformatics 10 Genome Sizes Organism Size Date Est. # genes HIV type 1 9.2 Kb 1997 9 H. influenzae 1.8 Mb 1995 1,740 M. genitalium 0.58 Mb 1998 525 E. coli 4.7 Mb 1997 4,000 S. cerevisiae 12.1 Mb 1996 6,034 C. elegans 97 Mb 1998 19,099 A. thaliana 100 Mb 2000 25,000 D. melanogaster 180 Mb 2000 13,061 M. musculus 3 Gb 2002 ~30,000 H. sapiens 3 Gb 2001 32,000+ 06/24/09 Q'BIC Bioinformatics 11 Short Homework Find the organism with the largest genome known! How many chromosomes does it have? Do you think a larger genome implies a “more evolved” organism or a “less evolved” organism? 06/24/09 Q'BIC Bioinformatics 12 Caenorhabditis Elegans Entire genome – 1998; 8 year effort 1st animal; 2nd eukaryote (after yeast) Nematode (phylum) Easy to experiment with; Easily observable 97 million bases; 20,000 genes; 12,000 with known function; 6 Chromosomes; GC content 36% 959 cells; 302-cell nervous system 36% of proteins common with human 15 Kb mitochondrial genome Results in ACeDB 25% of genes in operons Important for HGP: technology, software, scale/efficiency 182 genes with alternative splice variants universe-review.ca www.ucl.ac.uk 06/24/09 Q'BIC Bioinformatics 15 Drosophila Eyeless vs. Human Aniridia Query: 57 HSGVNQLGGVFVGGRPLPDSTRQKIVELAHSGARPCDISRILQVSNGCVSKILGRYYETG 116 HSGVNQLGGVFV GRPLPDSTRQKIVELAHSGARPCDISRILQVSNGCVSKILGRYYETG Sbjct: 5 HSGVNQLGGVFVNGRPLPDSTRQKIVELAHSGARPCDISRILQVSNGCVSKILGRYYETG 64 Query: 117 SIRPRAIGGSKPRVATAEVVSKISQYKRECPSIFAWEIRDRLLQENVCTNDNIPSVSSIN 176 SIRPRAIGGSKPRVAT EVVSKI+QYKRECPSIFAWEIRDRLL E VCTNDNIPSVSSIN Sbjct: 65 SIRPRAIGGSKPRVATPEVVSKIAQYKRECPSIFAWEIRDRLLSEGVCTNDNIPSVSSIN 124 Query: 177 RVLRNLAAQKEQ 188 RVLRNLA++K+Q Sbjct: 125 RVLRNLASEKQQ 136 Query: 417 TEDDQARLILKRKLQRNRTSFTNDQIDSLEKEFERTHYPDVFARERLAGKIGLPEARIQV 476 +++ Q RL LKRKLQRNRTSFT +QI++LEKEFERTHYPDVFARERLA KI LPEARIQV Sbjct: 197 SDEAQMRLQLKRKLQRNRTSFTQEQIEALEKEFERTHYPDVFARERLAAKIDLPEARIQV 256 Query: 477 WFSNRRAKWRREEKLRNQRR 496 WFSNRRAKWRREEKLRNQRR Sbjct: 257 WFSNRRAKWRREEKLRNQRR 276 E-Value = 2e-31 06/24/09 Q'BIC Bioinformatics 16 Motif Detection in Protein Sequences MTDKMQSLALAPVGNLDSYIRAANAWPMLSADEERALAEKLHYHGDLEAA KTLILSHLRFVVHIARNYAGYGLPQADLIQEGNIGLMKAVRRFNPEVGVR LVSFAVHWIKAEIHEYVLRNWRIVKVATTKAQRKLFFNLRKTKQRLGWFN QDEVEMVARELGVTSKDVREMESRMAAQDMTFDLSSDDDSDSQPMAPVLY LQDKSSNFADGIEDDNWEEQAANRLTDAMQGLDERSQDIIRARWLDEDNK STLQELADRYGVSAERVRQLEKNAMKKLRAAIEA MTDKMQSLALAPVGNLDSYIRAANAWPMLSADEERALAEKLHYHGDLEAA KTLILSHLRFVVHIARNYAGYGLPQADLIQEGNIGLMKAVRRFNPEVGVR LVSFAVHWIKAEIHEYVLRNWRIVKVATTKAQRKLFFNLRKTKQRLGWFN QDEVEMVARELGVTSKDVREMESRMAAQDMTFDLSSDDDSDSQPMAPVLY LQDKSSNFADGIEDDNWEEQAANRLTDAMQGLDERSQDIIRARWLDEDNK STLQELADRYGVSAERVRQLEKNAMKKLRAAIEA 06/24/09 Q'BIC Bioinformatics 17 Patterns in Protein Structures 06/24/09 Q'BIC Bioinformatics 20 SIDS 18000 Amish people in Pennsylvania Mostly intermarried due to religious doctrine rare recessive diseases occurred with high frequencies. SIDS: 3000 deaths/year (US); 21 deaths (Amish community) Many research centers failed to identify cause Collaboration between Affymetrix, TGEN & Clinic for special children solved the problem in 2 months Studied 10000 SNPs using microarray technology Their experiments showed that all the sick infants had two mutant copies of a specific gene, and their parents were carriers of the mutant gene. Conclusion: Disease caused by 2 abnormal copies of TSPYL gene Identified genes expressed in key organs (brainstem,testes) http://www.affymetrix.com/community/wayahead/modern_miracle.affx 06/24/09 Q'BIC Bioinformatics 21 Molecular Biology Background 06/24/09 Q'BIC Bioinformatics 22 2 star molecular players DNA Protein 06/24/09 Q'BIC Bioinformatics 25 The building blocks of DNA & RNA Fig 1.1, Zvelebil/Baum 06/24/09 Q'BIC Bioinformatics 26 DNA double helix structure Fig 1.3, Zvelebil/Baum RNA molecule Fig 1.5, Zvelebil/Baum hinge (B) a (A) Ss oO a ao aaa see DD00<o ina Sienna ft muess <cteeeeee ee = << hinge ‘ecccuc 203%, oy 7 Boy 2 < g IST, > H <vbes <<< 000005’ > blll ir inordnt fe “Meier riiit Hibs stttitlieg 2905005 <<ogpec<—oe <9 2003 <onu<co<ed wo st © % 2 §0o oO ae 2 x 2 Sovd>o<e s—<0v—— <k02050<0080 sTLtttid. ap eee LIL bee beg ee eres oe%. ae Cosi aoa sao o - 2 & oes * E o<'3 a Q <u P3-P9 Q'BIC Bioinformatics P4-P6 27 06/24/09 06/24/09 Q'BIC Bioinformatics 30 Central Dogma DNA acts as a template to replicate itself. DNA is transcribed into RNA. RNA is translated into Protein. DNA RNA Protein Transcription Translation Replication 06/24/09 Central Dogma DNA replication ( ) DNA Rene 3’ 5’ RNA synthesis (transcription) RNA Serr > protein synthesis (translation) PROTEIN Hoh ie > 0-4 COOH amino acids Q'BIC Bioinformatics Fig 1.6, Zvelebil/Baum 31 DNA Replication Fig 1.4, Zvelebil/Baum template strand A Ce ALA A new strand B strandA new strand A strand B parent DNA double helix a al Al B " template strand B 06/24/09 Q'BIC Bioinformatics 32 06/24/09 Q'BIC Bioinformatics 35 Chromosomes The chromosomal locations of several genes believed to be associated with the human BRCA1 gene implicated in breast cancer are highlighted. 06/24/09 Q'BIC Bioinformatics 36 Human Chr 22 Symbol Position Description ABCD1P4 22q11 ATP-binding cassette, sub-family D (ALD) SNAP29 22q11.21 synaptosomal-associated protein • • • 06/24/09 Q'BIC Bioinformatics 37 DNA Molecule Figure 1.1: E. coli Ala RNA QBIC Bioinformatics 06/24/09 Genes EEE DNA [ la aS la GeneA GeneB GeneC 06/24/09 Q'BIC Bioinformatics GeneD GeneE 41  Nucleatides lic pil » ‘ = Sit) ‘ uae Protein fe Amino Acids 06/24/09 Q'BIC Bioinformatics 42  06/24/09 ily, Harvanit University) "BIC Bioinformatics Replication Eee anne ep Re DNA duplicates = OPLPPDBRANSI LOLA ’ wwUVYY, Transcription RNA synthesis RNA | mRNA ATT rp rere TTT MIEN Information cytoplasm nuclear envelope Translation Protein synthesis Protein \ Protein The Central Dogma of Molecular Biology 06/24/09 46 Transcription Fig 1.7, Zvelebil/Baum (A) (B) DNA 35” DNA double 3 He. RNA polymerase as DNA rewinding coding strand noncoding strand | reanscRiPrion direction of transcription active site 5/ / newly synthesized _ short region of RNA transcript DNA/RNA helix 06/24/09 Q'BIC Bioinformatics 47 06/24/09 DNA Transcription g Wy exon WA == QU Chromosomal DNA 4 intron 1 Ld intron 2 Transcription (RNA synthesis) Wd Wd Nuclear RNA WU WY exon2 Messen: ger RNA RNA synthesis and processing 50  start of transcription Transcription ae 1A) Initiation t— @ | a TEND {B) a B TFB 1c TFUF other factors OQ SOS TFUE RNA polymerase Il TEU 10) oe ATP {€) 06/24/09 QBIC [- cr. ore 51 Transcription 06/24/09 RNA polymerase stop signal for RNA polymerase promoter DNA double helix DNA HELIX oN artate for transcription OPENING 8 a 3 8 INITIATION OF RNA CHAIN BY JOINING OF FIRST TWO RIBONUCLEOSIDE TRIPHOSPHATES 8 3 3 3 a RNA CHAIN ELONGATION IN 5'-to-3' DIRECTION BY ADDITION OF RIBONUCLEOSIDE TRIPHOSPHATES continuous _— RNA strand , i short region of displacement and DNA helix DNAVRNA helix re-formation 5 3! TERMINATION AND RELEASE OF POLYMERASE AND. COMPLETED RNA CHAIN 3 5 224 Chapter 6 : Basic Genetic Mechanisms Q'BIC Bioinformatics PSPS LAST YPII SIR Figure 6-2 The synthesis of an RNA molecule by RNA polymerase. The enzyme binds to the promoter sequence on the DNA and begins its synthesis at a start site within the promoter. It completes its synthesisa a stop (termination) signal, whereupon both the polymerase and its completed RNA chain are released. During RNA chain elongation, polymerization rates average about 3) nucleotides per second at 3 Therefore, an RNA chain of 5000 nucleotides takes about 3 minutes to complete. 52 06/24/09 Q'BIC Bioinformatics 55 Protein Synthesis: Incorporation of amino acid into protein 56 @ ; 3 : 5s) > @<+ 6-8 ec ‘ 35 3 : 20 1 ey ie : ak At it "z SIE Oa<o6<6<50<05> ‘ i § ‘| - =< ‘ Z |ZOWOU<E <UG+ U< <UL OF <OFO<d c r §& i c Ss e Ss g = g wo = a a 3S + g Ss 3S