ONLINE RESOURCES Introduction to Molecular Biology and Bioinformatics (IMBB) 2014

Dedan Githae Email: [email protected] BecA-ILRI Hub; Nairobi, Kenya 16 May, 2014 The larger picture..

• Lower cost, Improved efficiency and modern technology: The sequencers, computers, and rate at which data is being produced have all increased in speed - huge amounts of biological data produced at a FASTER rate than interpreted. • Storage and Exchange of data: Need to improve database design, develop better software for database access / manipulation, harmonize data-entry procedures to compensate for the varied computer procedures and systems used in different laboratories

Computing power, access to information (data) and right software (tools) has enabled scientists increase rate at answering research questions and new discoveries Online Bioinformatics resources

• INFORMATION • Journals / publications, • biological research data.

• TOOLS – Programs to analyse data Information

 Journal Website: Almost every major journal has a web access to abstracts is usually free, even when the content is subscription.  E-journals: Some electronic journals are online-only journals; some are online versions of printed journals, and some consist of the online equivalent of a printed journal, but with additional online-only (sometimes video and interactive media) material. Information

 Servers (eg NCBI Pubmed; ; ) A search engine to search references and abstracts on life sciences and biomedical topics in multiple databases

Sequence Databases

Primary Databases: International Nucleotide Sequence Database Collaboration comprises of • GenBank (USA), • European Nucleotide Archive (Europe) and • DNA DataBase of Japan.

http://www.ncbi.nlm.nih.gov

They cooperate to make all publicly available sequences available.

http://www.ebi.ac.uk/ena/ Sequence Databases

Secondary Databases UniProt: It is a database of protein sequence and functional information. Information about the biological function of proteins derived from the research literature

Available under Uniprot SWISS PROT: Manually annotated and reviewed TrEMBL: Automatically annotated and not reviewed.

Uniprot: www.uniprot.org

Other Databases

Multigenome: ensembl: genome databases for vertebrates and other eukaryotic species,

Genome specific databases: eg Wormbase; Saccharomyces database; Vectorbase; Flu DB; Zebrafish Model Organisms, Flybase etc. NB: You can also access to these genomes from the public databases

Biochemical pathway databases: Biological activities are orchestrated by various molecules These include KEGG; ExPASY; MetaCyc; BioPath

Gene expression Data: DNA Microarrays: array of probe molecules that can bind specific DNA / mRNA. Fluoro- labelling enables viewing level of expression of genes; eg NCBI Geo (Gene experssion omnibus) Expression Atlas (EBI)

2D PAGE: allows quantitative study of protein concentration inwww.yeastgenome.org/ the cell. Eg SWISS- 2D PAGE http://www.ncbi.nlm.nih.gov/geo/ www.fudb.org http://www.ebi.ac.uk/gxa www.zfin.org http://world-2dpage.expasy.org/swiss-2dpage/ www.wormbase.org/ http://vectorbase.org/ http://www.metacyc.org/ KEGG: http://www.genome.jp http://web.expasy.org/pathways/ http://www.molecular-networks.com/databases/biopath Protein Structure Databases

Protein Databank (PDB) (experimentally validated)

Secondary & Others: ModBase: A database of annotated comparative protein structure models Modelled proteins) SCOP: Structural classification of Proteins Depending on α ; β ; α+β ; membrane & cell surface proteins; small proteins; coiled coil proteins, etc CATH: hierarchical domain classification of protein structures in the Protein Data Bank (Class | Architecture | Topology | Homologous superfamilies)

www.pdb.org https://modbase.compbio.ucsf.edu/modweb/

Softwares / Tools

Sources of (informative) tools:

• Journals eg Bioinformatics, Nucleic Acids Research, Journal of Molecular Biology, Protein science publish papers on cutting edge developments and innovations in methods • Most biological databases have software resource listings- eg Sequence searching, visualisation resources (genome / alignment / genome level). • Web servers: “Simple” web implementation of the softwares. Clear inputs, outputs, parameters, graphical data representation and downloadable results. Basic tasks

Task Objective Tool Sequence similarity Identify homologous BLAST; SSEARCH; FASTA, sequences to gain ENA search information Sequence alignment Identify conserved regions, CLUSTAL; Muscle; domains, motifs Gene finding Identify coding regions in GENSCAN; ORFinder; gDNA sequences GRAIL DNA Translation Convert DNA Sequence to Various servers and tools eg protein ExPasy, Transeq, EBI, and ORFinders Local pairwise alignment Detect short regions of BLAST; FASTA homology in longer sequences Global pairwise alignment Find the best full length ALIGN alignment in 2 sequences http://web.expasy.org/translate/ http://www.ebi.ac.uk/Tools http://www.ebi.ac.uk/Tools Protein Domains

A protein domain is a conserved part of a given protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain. Molecular evolution uses domains as building blocks and these may be recombined in different arrangements to create proteins with different functions. Databases include: SMART; PROSITE; NCBI; CATH

GLYCINAMIDE RIBONUCLEOTIDE SYNTHETASE (GAR-SYN) FROM E. COLI.

http://prosite.expasy.org/ http://smart.embl-heidelberg.de/

Motifs

A motif is a locally, conserved region / short sequence pattern shared by set of sequence; (Multiple sequence analysis)

Thus can be indicative of function / structural similarities. Can be displayed via Sequence logos, or as patterns of amino acids.

Patterns of amino acids [PROSITE]: For example N-glycosylation site motif takes the form: N{P}[ST]{P} To mean: Asn, followed by anything but Pro, followed by either Ser or Thr, followed by anything but Pro DSSP: Wolfgang Kabsch and Chris Sander

EXPASY: seconadary structure prediction

JPRED 3: from university of Dundee

PDB: DSSP prediction Honorable mention

About PredictProtein PredictProtein integrates feature prediction for secondary structure, solvent accessibility, transmembrane helices, globular regions, coiled-coil regions, structural switch regions, B-values, disorder regions, intra- residue contacts, protein-protein and protein-DNA binding sites, sub-cellular localization, domain boundaries, beta-barrels, cysteine bonds, metal binding sites and disulphide bridges. Listed below is a comprehensive list of methods and databases currently incorporated into the server. Integrated Methods Method Name Description Reference Web Server Download PROFphd Prediction of secondary structure and solvent accessibility - - ftp://rostlab.org/profphd PHDhtm Prediction of transmembrane helices - - ftp://rostlab.org/profphd PROFtmb Prediction of transmembrane beta-barrels - - ftp://rostlab.org/proftmb NORSp Predictor of non-regular secondary structure - - ftp://rostlab.org/norsp NCOILS Calculates the probability that the sequence will adopt a coiled-coil conformation - - - SEG Identifies low complexity regions - - - DISULFIND Prediction of disulfide bridges - - ftp://rostlab.org/profbval PROFBval Prediction of residue mobility - - ftp://rostlab.org/profbval NorsNet Prediction protein disordered sites - - ftp://rostlab.org/norsnet UCON Contact based prediction of disordered sites - - METADISORDER Consensus based prediction of protein disorder - - ISIS Prediction of protein-protein interaction sites - - LocTree2 Prediction of sub-cellular localization for all domains of life - - - MetaStudent Prediction of GO terms for Molecular Function and Biological Process - - ftp://rostlab.org/metastudent SNAP2 Prediction of functional changes due to single nucleotide polymorphism - - - ConSurf Prediction of functional changes due to single nucleotide polymorphism - - - Supporting Databases Database Name Description Reference Download UniRef Used for sequence homology searches by PSI-BLAST abstract http://www.uniprot.org/help/uniref PDB The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. abstract http://www.rcsb.org/pdb/download/download.do Pfam A collection of protein families abstract ftp://ftp.sanger.ac.uk/pub/databases/Pfam/releases/ PROSITE Database of biologically significant sites, patterns and profiles abstract ftp://ftp.expasy.org/databases/prosite/ In a Nutshell… There is vast amount of available out there…. There is a vast number of tools out there.. Select best that is applicable for your project..

Thank you

Dedan Githae Bioinformatician BecA-ILRI Hub [email protected]

Online Bioinformatics resources http://hub.africabiosciences.org