Pattern databases in protein analysis

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Pattern databases in protein analysis

• Arthur Gruber

Instituto de Ciências Biomédicas Universidade de
São Paulo
AG-ICB-USP
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Protein databases

• Genpept protein sequence database translated
  from GenBank
• UniProtKB/TrEMBL is a computer-annotated
  protein sequence database complementing the
  UniProtKB/Swiss-Prot Protein Knowledgebase.
• UniProtKB/Swiss-Prot is a curated protein
  sequence database that provides a high level of
  annotation, a minimal level of redundancy and a
  high level of integration with other databases.

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How to assign protein functions?

• Similar proteins may share common functions, but
  proteins that share common domains may have
  evolved to perform distinct functions
• Proteins that exert similar function may share
  common domains, but domain sequences are not
  always very similar more refined are requires
  than simply similarity searches
• Proteins may share common domains, but have
  different architectures no single domain are
  necessarily involved with protein function. Many
  proteins use multiple domains to perform their
  activities

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Some conclusions

• Similarity searches may reveal proteins that
  share very similar sequences and functions
  high similarity over the full length of the query
  sequence
• An output with no significant hits or with hits
  to unannotated proteins will no unravel the
  possible function of the query protein
• Similarity searches do not differentiate
  orthologues from paralogues
• When matching multidomain proteins, it may not be
  appropriate to transfer the functional annotation
  the context is important!

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So what do proteins with similar function have in
common?
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residues, motifs, domains, architecture
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Pattern databases

• Databases that contain patterns of residue
  conservation within groups of related sequences
• There are several methods to determine patterns
• There are many different pattern databases

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Pattern databases
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Common protein pattern databases

• Prosite patterns regular expressions
• Prosite profiles weight matrices (profiles)
• Pfam database of protein domain families.
  Contains curated multiple sequence alignments for
  each family and corresponding HMMs
• Prints database of groupf of motifs that in the
  context of being together, are more potent for
  assign protein function
• Prodom automatedly generated databases based on
  a recursive use of PSI-BLAST similarity searches
• Interpro an integrated databaes that combines
  different protein signature recognition methods
  in one single resource

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How to start building a pattern database?

• Prosite patterns regular expressions
• Prosite profiles weight matrices (profiles)
• Pfam database of protein domain families.
  Contains curated multiple sequence alignments for
  each family and corresponding HMMs
• Prints database of groupf of motifs that in the
  context of being together, are more potent for
  assign protein function
• Prodom automatedly generated databases based on
  a recursive use of PSI-BLAST similarity searches
• Interpro an integrated databaes that combines
  different protein signature recognition methods
  in one single resource

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How to start building a pattern database?
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How to start building a pattern database?

• With multiple sequence alignments of functionally
  related proteins

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Some definitions

• Protein motif a single conserved region
• Prosite pattern a consensus expression of a
  conserved region
• Frequency matrices (PRINTS) matrices that
  contain the frequencies in which residures occur
  in a given motif
• PSSM position specific score (weight) matrices
  (BLOCKS) add a scoring scheme to the frequency
  matrices
• HMMs profiles probabilistic models derived from
  alignment profiles
• Protein domain - is a part of protein sequence
  and structure that can evolve, function, and
  exist independently of the rest of the protein
  chain.

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