What is Bioinformatics

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What is Bioinformatics?

• Bioinformatics collection and storage of
  biological information
• Computational biology development of algorithms
  and statistical models to analyze biological data

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Jobs for bioinformaticians
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Databases make biological data available to
scientists

• As biology has increasingly turned into a
  data-rich science, the need for storing and
  communicating large datasets has grown
  tremendously.
• Nucleotide, protein sequences
• Protein structure
• Expression data
• Gene/protein networks

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Nucleotide Databases

• EMBL www.ebi.ac.uk/embl/
• The EMBL (European Molecular Biology Laboratory)
  nucleotide sequence database is maintained by the
  European Bioinformatics Institute (EBI) in
  Hinxton, Cambridge, UK.

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Nucleotide Databases cont.

• GenBank maintained by the National Center for
  Biotechnology Information (NCBI) contains Entrez
  for accession to nucleotides, proteins,
  annotations, etc.
• www.ncbi.nlm.nih.gov/Genbank/
• UniGene a non-redundant set of gene-oriented
  clusters www.ncbi.nlm.nih.gov/UniGene/

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Protein Databases

• SWISS-PROT SWISS-PROT is a protein sequence
  database to provide a high level of annotations
  (such as the description of the function of a
  protein, its domains structure,
  post-translational modifications, variants,
  etc.), a minimal level of redundancy and high
  level of integration with other databases.
  www.expasy.ch/sprot/

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Protein Databases

• PIR
• http//pir.georgetown.edu/
• -The Protein Information Resource (PIR) is a
  division of the National Biomedical Research
  Foundation (NBRF) in the US. It is involved in a
  collaboration with the Munich Information Center
  for Protein Sequences (MIPS) and the Japanese
  International Protein Sequence Database (JIPID).
  Release 67.00 (31 Dec 2000) contains 198,801
  entries.

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Sequence Motif Databases

• Pfam
• www.sanger.ac.uk/Software/Pfam/
• Pfam is a database of protein families defined as
  domains (contiguous segments of entire protein
  sequences). For each domain, it contains a
  multiple alignment of a set of defining sequences
  (the seeds) and the other sequences in SWISS-PROT
  that can be matched to that alignment.

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3D-Structure Databases

• PDB
• www.rcsb.org/pdb/
• -The PDB is the main primary database for 3D
  structures of biological macromolecules
  determined by X-ray crystallography and NMR.
  Structural biologists usually deposit their
  structures in the PDB on publication, and some
  scientific journals require this before accepting
  a paper. It also accepts the experimental data
  used to determine the structures.

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How to get sequences?

• Entrez Database provides nucleotide and protein
  sequences in different formats.
• One of the formats is FASTA

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FASTA FORMAT

• Each sequence begins with a description line gt

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A protein in FASTA format

• gtHBA_ALLMI
• VLSMEDKSNVKAIWGKASGHLEEYGAEALEMFCAYPQTKIYFPHFDMSH
  NSAQIRAHGKKVFSALHEAVNHIDDLPGALCRLSELHAHSLRVDPVNFKF
  LAHCVLVVFAIHHPSALSPEIHASLDKFLCAVSAVLTSKYR
• The first line is the description line, starts
  with a character 'gt' shows that the description
  line of a sequence follows the string following
  the 'gt' and ending at the first space (' ') is
  the sequence id (HBA_ALLMI).

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A DNA sequence in Fasta

• gtX sequence
• ATGAATAGCACAGAGAGACCAAGAGAGAGAGAGAGACCCAGATATATCA
  GATAGAGA

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Why align sequences?

• Find evolutionary relationship between species
  and/or genes.
• Identify novel genes and define similar genes in
  other species.
• Study genomes and how they change.

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Sequence Alignment

• Homology means that two (or more) sequences have
  a common ancestor.
• An example to sequence alignment

Sequence 1
Sequence 2
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CLUSTALW A software for aligning sequences
http//www.ebi.ac.uk/clustalw/
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Genome Databases

• www.ensembl.org

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Genome Databases Gene Prediction

• Define the location of genes (coding sequences,
  regulatory regions)
• Gene prediction using software based on rules and
  patterns. Find Open Reading Frames (ORFs), with
  additional criteria for good start sequence for a
  gene.
• Gene identification through alignment with known
  proteins and EST sequences (Expressed Sequence
  Tags mRNA sequences).
• Gene prediction through similarity with proteins
  or ESTs in other organisms.
• Gene prediction through comparison with other
  genomes conserved regions are probably coding or
  regulatory regions.

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Genome Databases Annotation

• Annotation of the genes Compare with
  genes/proteins of known function in other
  organisms.
• Functional classification. Broad groups of
  functional characterization, such as 'ribosomal
  proteins', 'nucleotide metabolism', 'signal
  transduction'.

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Genome Databases Evolution

• Evolutionary history
• Genome duplications
• Gene loss

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Transcription Databases

• Microarrays can analyze 1000s of transcripts
  simultaneously.
• Allow analysis of genes that are high or low in
  expression between normal and disease, for
  example.
• Microarray Databases contain expression data
  (large amounts).
• Stanford Microarray Database

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Signaling Metabolic Pathways

• Analyze how genes/proteins interact and learn
  about function of genes
• KEGG Kyoto Encyclopedia of Genes and Genomes
• http//www.genome.ad.jp/kegg/