An Introduction to Bioinformatics. CSE, Marmara University mimoza.marmara.edu.tr/~m.sakalli/cse546 Oct/12/09 Source http://bio.fsu.edu/~stevet/BSC5936/BioDataBases.ppt

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An Introduction to Bioinformatics.CSE, Marmara
University mimoza.marmara.edu.tr/m.sakalli/cse54
6Oct/12/09Source http//bio.fsu.edu/stevet/BS
C5936/BioDataBases.ppt
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Terminology

• Bioinformatics using computational techniques to
  access, analyze, and interpret the biological
  information. Tool Building. Biocomputing and
  computational biology are the synonyms.
• Sequence analysis is the study of molecular
  sequence data.
• Genomics analyzes the context of genes or
  complete genomes.
• Proteomics is the subdivision of genomics
  concerned with analyzing the protein complement,
  i.e. the proteome.
• The Human Genome Project and numerous the data
  coming at alarming rates.
• Homo sapiens the 3.2 billion base pairs
  Estimates of the number of genes were around
  100,000 range but turns out to be twice as many
  as a fruit fly, between 25 and 35,000!
• The protein coding region of the genome is only
  about 1 or so, a bunch of the remainder is
  jumping selfish DNA of which much may be
  involved in regulation and control.

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• Three major databases with their own specific
  format. Mirrored among each other and sharing
  accession codes, but NOT identifier names
• 1) National Center for Biotechnology Information
  (NCBI),/the National Library of Medicine (NLM),
  at the NIH, (Gene bank and GenPept).
• http//www.ncbi.nlm.nih.gov/
• http//www.ncbi.nlm.nih.gov/Genbank/GenbankOvervie
  w.html
• Georgetown Universitys National Biomedical
  Research Foundation Protein Identification
  Resource and Naval Research Lab sequences of
  three-dimensional structure.
• http//www-nbrf.georgetown.edu/
• http//www-nbrf.georgetown.edu/pirwww/dbinfo/nrl3d
  .html
• 2)
• European Molecular Biology Laboratory
• http//www.ebi.ac.uk/embl/index.html,
  http//www.embl-heidelberg.de/
• European Bioinformatics Institute,
• http//www.ebi.ac.uk/
• Swiss Institute of Bioinformatics (SIB), Expert
  Protein Analysis System
• http//www.expasy.ch/, http//www.expasy.org/links
  .html
• Nucleotide Sequence Database, amino acid sequence
  databases
• http//expasy.cbr.nrc.ca/sprot/
• 3)
• http//www.ddbj.nig.ac.jp/

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• Atlas of Protein Sequence and Structure The
  first well recognized protein sequence database,
  mid sixties, by Dr. Margaret Dayhoff.
• DDBJ began in 1984, GenBank in 1982, and EMBL in
  1980. They are all attempts at establishing an
  organized, reliable, comprehensive and openly
  available library of genetic sequences.
• Each program needs to recognize particular
  aspects of the sequence files flexibility of the
  program is a headache. NCBIs ASN.1 format and
  its Entrez interface attempt to reduce these
  prbls.
• Unfortunately, not like ieee working groups for
  internet taskforce, RFCies for example, format
  issues are the most confusing and troubling
  aspect of working with primary sequence data.
• Sequence database installations are commonly a
  complex ASCII/Binary mix, but neither relational
  nor OOP (often proprietary).
• Contain several very long text files each
  containing different types of information all
  related to particular sequences.
• Software is usually required to interact with
  these databases. ReadSeq of Don Gilbert (a
  reformatting program, for DNA and protein
  sequences, accepting single or multiple inputs in
  18 different formats, converting to a specified
  format. )

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• http//www.molecularevolution.org/
• AWTY (Are We There Yet?) is a system for
  graphically exploring convergence of Markov Chain
  Monte Carlo (MCMC) chains in Bayesian
  phylogenetic inference (Nylander et al. 2008).
• FigTree to graphically view phylogenetic trees.
• Clustal W (Thompson et al. 1994) is for global
  multiple sequence alignment. Using a progressive
  alignment algorithm with affine gap penalties and
  a guide tree based on sequence similarity to
  align DNA or amino acid sequences. The affine gap
  cost model penalizes insertions and deletions
  using a linear function in which one term is
  length independent, and the other is length
  dependent. Gap penalty Gapopen Len
  Gapextend. Recent reviews comparing multiple
  alignment algorithms (e.g., Hickson et al. 2000,
  Thompson et al. 1999, and McClure et al. 1994).
  Morrison and Ellis (1997) discuss the effects of
  nucleotide sequence alignment on the estimation
  of phylogenetic hypotheses. The current version
  is Clustal W2 (Larkin et al. 2007). The program
  is also available with a graphical user
  interface, Clustal X.
• BEAST, (Beauti), -Bayesian Evolutionary Analysis
  Sampling Trees- is for evolutionary inference of
  molecular sequences, Andrew Rambaut and Alexei
  Drummond (Drummond et al. 2002 2005 2006).
• FASTA compares pairs of protein or DNA sequences
  as well as comparing a single protein or DNA
  sequence to a database or library. Fast and local
  or remote services.
• GARLI (Genetic Algorithm for Rapid Likelihood
  Inference) performs phylogenetic searches on
  aligned nucleotide datasets using the maximum
  likelihood criterion.
• MAFFT implements FFT to optimize protein
  alignments based on physical properties of the
  amino acids (Katoh et al., 2002 2005). The
  program uses progressive alignment followed by
  refinement, also known as iterative alignment.

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• All sequence databases contain (in their own
  format)
• Name (Genetic identifiers) LOCUS, ENTRY, ID
• Definition A brief, one-line, textual sequence
  description.
• Accession Number A constant data identifier.
• Source and classification (taxonomy) information.
• Complete literature references.
• Comments and keywords.
• The all important FEATURE table!
• A summary or checksum line.
• The sequence itself.

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• LOCUS HSEF1AR 1506 bp
  mRNA linear PRI 12-SEP-1993
• DEFINITION Human mRNA for elongation factor 1
  alpha subunit (EF-1 alpha).
• ACCESSION X03558
• VERSION X03558.1 GI31097
• KEYWORDS elongation factor elongation factor
  1.
• SOURCE human.
• ORGANISM Homo sapiens
• Eukaryota Metazoa Chordata
  Craniata Vertebrata Euteleostomi
• Mammalia Eutheria Primates
  Catarrhini Hominidae Homo.
• REFERENCE 1 (bases 1 to 1506)
• AUTHORS Brands,J.H., Maassen,J.A., van
  Hemert,F.J., Amons,R. and Moller,W.
• TITLE The primary structure of the alpha
  subunit of human elongation
• JOURNAL Eur. J. Biochem. 155 (1), 167-171
  (1986)
• MEDLINE 86136120
• FEATURES Location/Qualifiers
• source 1..1506
• /organism"Homo sapiens"
• /db_xref"taxon9606"
• CDS 54..1442

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EMBL and SWISS-PROT

• ID EF11_HUMAN STANDARD PRT 462 AA.
• AC P04720 P04719
• DT 13-AUG-1987 (Rel. 05, Created)
• DE Elongation factor 1-alpha 1 (EF-1-alpha-1)
  (Elongation factor 1 A-1)
• DE (eEF1A-1) (Elongation factor Tu) (EF-Tu).
• GN EEF1A1 OR EEF1A OR EF1A.
• OS Homo sapiens (Human),
• OS Bos taurus (Bovine), and
• OS Oryctolagus cuniculus (Rabbit).
• OC Eukaryota Metazoa Chordata Craniata
  Vertebrata Euteleostomi
• OC Mammalia Eutheria Primates Catarrhini
  Hominidae Homo.
• OX NCBI_TaxID9606, 9913, 9986
• RN 1
• RP SEQUENCE FROM N.A.
• RC SPECIESHuman
• RX MEDLINE86136120 PubMed3512269
• RA Brands J.H.G.M., Maassen J.A., van Hemert
  F.J., Amons R., Moeller W.
• RT "The primary structure of the alpha subunit
  of human elongation . -binding sites."
• RL Eur. J. Biochem. 155167-171(1986).

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PIR/NBRF format

• ENTRY EFHU1 type complete
  iProClass View of EFHU1
• TITLE translation elongation factor
  eEF-1 alpha-1 chain - human
• ALTERNATE_NAMES translation elongation factor Tu
• ORGANISM formal_name Homo sapiens
  common_name man
• cross-references taxon9606
• DATE 30-Jun-1988 sequence_revision
  05-Apr-1995 text_change..
• ACCESSIONS B24977 A25409 A29946 A32863
  I37339
• REFERENCE A93610
• authors Rao, T.R. Slobin, L.I.
• journal Nucleic Acids Res. (1986) 142409
• title Structure of the amino-terminal
  end of mammalian elongation
• accession B24977
• molecule_type mRNA
• residues 1-82,'A',84-94 label RAO
• cross-references EMBLX03689 NIDg31109
  PIDNCAA27325.1
• PIDg31110.
• GENETICS
• gene GDBEEF1A1 EEF1A EF1A
• cross-references GDB118791 OMIM130590

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Examples of DBs with specialized type of sequences

• Almost all the links Human Genome Ensemble
  Project at http//www.ensembl.org/
• Patterns, motifs, and profiles REBASE, EPD,
  PROSITE,
• Aligned multiple sequence entries. RDP and ALN.
• Functionally, structurally, or phylogenetically
  ordered iProClass and HOVERGEN vertebrate gene
  db.
• HIV Database, and the Giardia lamblia Genome
  Project.
• 3D Structure, atomic coordinate data is necessary
  to define the tertiary shape of a particular
  biological molecule. Protein DB and Rutgers
  Nucleic Acid Db.
• MolBio Molecular visualization with special
  software.
• Genomic linkage mapping databases for H. sapiens,
  Mus, Drosophila, C. elegans, Saccharomyces,
  Arabidopsis, E. coli.
• OMIM Online Mendelian Inheritance in Man
• Phylogenetic Tree Databases e.g. the Tree of
  Life.

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• Theres a bewildering assortment of different
  databases and ways to access and manipulate the
  information within them. The key is to learn how
  to use that information in the most efficient
  manner.
• For example Given a novel genome sequence, find
  all genes and p-genes.
• I want to design "sequence capture" probes for
  the exons of 40 genes that cause RP.
• Obtain the exonic sequence, with at least 100
  nt's flanking, and 1000 nts of the promoter from
  transcription start
• I propose a new way to find disease-causing
  mutations in humans. I want to only look in
  genes that have regions that are 1) highly
  conserved across species, 2) have known
  functional protein domains (ex. transmembrane
  domains), and 3) have mRNA secondary structure.
  Is this a good idea?
• 1859 of Charles Darwins The Origin of Species
• Basic Mendelian Genetics
• Mendels laws
• independent assortment
• independent segregation
• mitosis and meiosis
• dominant/recessive and pedigrees (the graphs of
  phenotype)
• alleles
• Basic molecular genetics
• DNA
• RNA

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Pearson FastA format GCG single
sequence format

• gtEFHU1 PIR1 release 71.01
• MGKEKTHINIVVIGHVDSGKSTTTGHLIYKCGGIDKRTIEKFEKEAAEMG
  
• KGSFKYAWVLDKLKAERERGITIDISLWKFETSKYYVTIIDAPGHRDFIK
  
• NMITGTSQADCAVLIVAAGVGEFEAGISKNGQTREHALLAYTLGVKQLIV
  
• GVNKMDSTEPPYSQKRYEEIVKEVSTYIKKIGYNPDTVAFVPISGWNGDN
  
• MLEPSANMPWFKGWKVTRKDGNASGTTLLEALDCILPPTRPTDKPLRLPL
  
• QDVYKIGGIGTVPVGRVETGVLKPGMVVTFAPVNVTTEVKSVEMHHEALS
  
• EALPGDNVGFNVKNVSVKDVRRGNVAGDSKNDPPMEAAGFTAQVIILNHP
  
• GQISAGYAPVLDCHTAHIACKFAELKEKIDRRSGKKLEDGPKFLKSGDAA
  
• IVDMVPGKPMCVESFSDYPPLGRFAVRDMRQTVAVGVIKAVDKKAAGAGK
  
• VTKSAQKAQKAK

!!AA_SEQUENCE 1.0 P1EFHU1 - translation
elongation factor eEF-1 alpha-1 chain -
human NAlternate names translation elongation
factor Tu F1-223/Domain eEF-1 alpha domain I,
GTP-binding status predicted ltEF1gt F8-156/Domain
translation elongation factor Tu homology
ltETUgt F14-21/Region nucleotide-binding motif A
(P-loop) F153-156/Region GTP-binding NKXD
motif F245-330/Domain eEF-1 alpha domain II,
tRNA-binding status predicted ltEF2gt F332-462/Dom
ain eEF-1 alpha domain III, tRNA-binding status
predicted ltEF3gt F36,55,79,165,318/Modified site
N6,N6,N6-trimethyllysine (Lys) status
predicted F301,374/Binding site
glycerylphosphorylethanolamine (Glu) (covalent)
status predicted EFHU1 Length 462 January 14,
2002 1949 Type P Check 5308 .. 1
MGKEKTHINI VVIGHVDSGK STTTGHLIYK CGGIDKRTIE
KFEKE 401 IVDMVPGKPM CVESFSDYPP
LGRFAVRDMR QTVAVGVIKA VDKKAAGAGK 351
GQISAGYAPV LDCHTAHIAC KFAELKEKID RRSGKKLEDG
PKFLKSGDAA 451 VTKSAQKAQK AK