1.  What is MSA (Multiple Sequence Alignment)? What is it good for? How do I use it?  Software and algorithms The programs How they work? Which to use?  In practice Get the sequences Reformat them Evaluate the alignment Realign or modify the alignment Add or subtract sequence We have alredy discussed Lec 09

2. Sunday, November 28, 7:49:01 PM Lec 09 Platform, software and algorithm selection  Software's The best What’s available The easiest to use The best output  Algorithm The most accurate The best for your problem What’s available What you are familiar with Web-basedCentral serverLocal computer  Platforms

3. Sunday, November 28, 7:49:01 PM Main applications of MSA Lec 09

4. Sunday, November 28, 7:49:01 PM Get the sequences: databases GenBank: An annotated collection of all publicly available nucleotide and protein sequences. RefSeq: NCBI non-redundant set of reference sequences, including genomic DNA, transcript (RNA), and protein products. UniProt Consortium Database: Universal protein knowledgebase, a central resource of protein sequence and function from Swiss-Prot, TrEMBL and PIR. Entrez Gene: Gene-centered information at NCBI. UniGene: Unified clusters of ESTs and full-length mRNA sequences. OMIM: Online Mendelian inheritance in man: a catalog of human genetic and genomic disorders. Model Organism Genome Databases: MGD, RGD, SGD, Flybase… GeneCards: Integrated database of human genes, maps, proteins and diseases. SNP Consortium Database. Lec 09

5. Sunday, November 28, 7:49:01 PM Get the sequences: Entrez Text Searches Lec 09 http://www.ncbi.nlm.nih.gov/sites/gquery

6. Sunday, November 28, 7:49:01 PM Entrez Gene Lec 09 http://www.ncbi.nlm.nih.gov/gene

7. Sunday, November 28, 7:49:01 PM UniProt Consortium Databases (http://www.uniprot.org)http://www.uniprot.org Lec 09  Number of explicitly cross-referenced databases: 126

8. Sunday, November 28, 7:49:01 PM UniProt Text Search Lec 09 http://www.uniprot.org/

9. Sunday, November 28, 7:49:01 PM UniProt Sequence Report Lec 09

10. Sunday, November 28, 7:49:01 PM PIR Text Search Lec 09 http://pir.georgetown.edu/pirwww/search/textsearch.shtml

11. Sunday, November 28, 7:49:01 PM OMIM: Online Mendelian Inheritance in Man Lec 09 http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim&TabCmd=Limits

12. Sunday, November 28, 7:49:01 PM Protein Family Databases  Whole Proteins PIRSF: A Network Classification System of Protein Families COG (Clusters of Orthologous Groups) of Complete Genomes ProtoNet: Automated Hierarchical Classification of Proteins  Protein Domains Pfam: Alignments and HMM Models of Protein Domains SMART: Protein Domain Families CDD: Conserved Domain Database  Protein Motifs PROSITE: Protein Patterns and Profiles BLOCKS: Protein Sequence Motifs and Alignments PRINTS: Protein Sequence Motifs and Signatures  Integrated Family Databases iProClass: Superfamilies/Families, Domains, Motifs, Rich Links InterPro: Integrate Pfam, PRINTS, PROSITES, ProDom, SMART, PIRSF, SuperFamily Lec 09

13. Sunday, November 28, 7:49:01 PM Lec 09 http://pir.georgetown.edu/pirwww/dbinfo/pirsf.shtml PIRSF: A Network Classification System of Protein Families

14. Sunday, November 28, 7:49:01 PM COG: Clusters of Orthologous Groups of proteins Lec 09 http://www.ncbi.nlm.nih.gov/COG/

15. Sunday, November 28, 7:49:01 PM Domain Classification Lec 09 http://pir.georgetown.edu/pirwww/dbinfo/iproclass.shtml

16. Sunday, November 28, 7:49:01 PM Lec 09 Domain Classification InterPro Gene3D

17. Sunday, November 28, 7:49:01 PM Protein Motifs Lec 09

18. Sunday, November 28, 7:49:01 PM Databases of Protein Functions  Metabolic Pathways, Enzymes, and Compounds Enzyme Classification: Classification and Nomenclature of Enzyme-Catalysed Reactions (EC-IUBMB) KEGG (Kyoto Encyclopedia of Genes and Genomes): Metabolic Pathways LIGAND (at KEGG): Chemical Compounds, Reactions and Enzymes EcoCyc: Encyclopedia of E. coli Genes and Metabolism MetaCyc: Metabolic Encyclopedia (Metabolic Pathways) BRENDA: Enzyme Database UM-BBD: Microbial Biocatalytic Reactions and Biodegradation Pathways  Cellular Regulation and Gene Networks EpoDB: Genes Expressed during Human Erythropoiesis BIND: Descriptions of interactions, molecular complexes and pathways DIP: Catalogs experimentally determined interactions between proteins BioCarta: Biological pathways of human and mouse GO: Gene Ontology Consortium Database Lec 09

19. Sunday, November 28, 7:49:01 PM KEGG Metabolic & Regulatory Pathways  KEGG is a suite of databases and associated software, integrating our current knowledge on molecular interaction networks, the information of genes and proteins, and of chemical compounds and reactions. http://www.genome.jp/kegg/pathway.html http://www.genome.jp/kegg/pathway.html#metabolism Lec 09

20. Sunday, November 28, 7:49:01 PM Multiple Genome Alignment MultiPipMaker - output MGA Michael Höhl, Stefan Kurtz,Enno Ohlebusch Efficient Multiple Genome Alignment Bioinformatics, Vol. 18 (S1): S312-S320, 2002 http://bibiserv.techfak.uni- bielefeld.de/mga/ref.html PipMaker and MultiPipMaker Schwartz S, Elnitski L, Li M, et al. MultiPipMaker and supporting tools: alignments and analysis of multiple genomic DNA sequences NUCLEIC ACIDS RES 31 (13): 3518-3524 JUL 1 2003 http://bio.cse.psu.edu/pipmaker/ MAVID Bray N and Pachter L,MAVID multiple alignment server, Nucleic Acids Research 2003 31: 3525- 3526 http://baboon.math.berkeley.edu/mavid/ http://www-gsd.lbl.gov/vista/ Lec 09

21. Sunday, November 28, 7:49:01 PM Multiple Genome Alignment Lec 09 Genomic Targets for Comparative Sequencing http://genome.ucsc.edu/