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ConSAT: a database and tool for
protein function prediction using
consensus domain architectures
Alfonso E. Romero [1], Tamás Nepusz [2],
Rajkumar Sasidharan [3], Alberto Paccanaro [1]
aeromero@cs.rhul.ac.uk – http://www.cs.rhul.ac.uk/~aeromero
http://paccanarolab.org
[1] Royal Holloway, University of London
[2] Model College, Molde (Norway)
[3] UCLA
Outline
1.Domains and function prediction
2.The ConSAT method for function prediction
3.ConSAT: web server and database
● Domain → conserved part of protein sequence
– Stable and exist in many proteins
– Evolve independently
– Often autonomous folding units
– Individual function
● Example: zinc finger domains
Domains and function prediction
Domains and function prediction
● Single domain proteins:
Protein ↔ Domain ↔ Function
● Multiple domain proteins (most common case):
Protein Functions?
Domain1
Domain2
…
DomainN
Domains and function prediction
● Domain combination can create new functions
● Domain combination can modify or suppress any of
the individual domain functions
● Function is determined by the domain arrangement
(architecture) and not just by the aggregation of the
individual domain functions.
Bashton M, Chothia C. The generation of new protein functions by the
combination of domains. Structure. 2007 Jan;15(1):85-99.
Domains and function prediction
● Protein architecture
– Domain juxtaposition
– Domain insertion
Insertions can be recursive
Aroul-Selvam R, Hubbard T, and Sasidharan R. Domain insertions
in protein structures. J Mol Biol. 2004. 338(4):633-41.
Domains and function prediction
● Finding domains:
– Computational models (signatures)
– Domain databases (Pfam, CATH-Gene3D, PANTHER, …)
– Use InterPro as a starting point:
● Agglutinates the main databases
● Common name for several signatures of the same domain (IPR
domain identifiers)
● InterPro2GO (IPR domains → GO terms)
● Issues:
– Different databases do not agree in the output
– Different domain boundaries for same IPR domain
Domains and function prediction
● Issues (graphically):
– 2 and 4 overlap (one of them is probably wrong)
– 1 and 3 seem to be the same
● Solution: Consensus domain architecture
The ConSAT method for FP
Two steps:
1.Given the InterPro output for a sequence, obtain the
consensus domain architecture
2. Assign functions to each architecture
The ConSAT method for FP
● Step 1: consensus domain architecture
The ConSAT method for FP
● Step 2: function prediction methods (GO terms)
The ConSAT method for FP
● Step 2: function prediction methods (weighted
English words)
Prot 1
Prot 2
...
Prot N
Abs 1
Abs 2
...
Abs M
Cleaning
Stopwords
Stemming
TF x IDF
Retina 0.356
Cancer 0.281
Immune 0.148
Mammal 0.121
...
1
Abs 1
Abs 2
...
Abs M
2 3
ConSAT: web server and database
http://paccanarolab.org/consat
https://github.com/alfonsoeromero/ConSAT
@consat_web
www.facebook.com/consatweb
ConSAT: web server and database
● Web server: run ConSAT given a set of
sequences + InterPro
● Database: precomputed architectures and
functions for all UniProtKB sequences. Easily
accessible. Also raw datasets.
ConSAT: web server and database
● Database:
– Search facilities (by gene(s), by protein(s), GO
term, IPR domain, by words…)
– Detail pages for protein, architecture, domain and
word
→ Try it now!
→ Feedback is accepted (and very useful!)
→ Suggestions and other opinions as well!
ConSAT: web server and database
ConSAT: web server and database
ConSAT: web server and database
ConSAT: web server and database
Thanks for your attention!
Questions, comments?
Anyone hiring? :)

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Presentation alfonso romero

  • 1. ConSAT: a database and tool for protein function prediction using consensus domain architectures Alfonso E. Romero [1], Tamás Nepusz [2], Rajkumar Sasidharan [3], Alberto Paccanaro [1] aeromero@cs.rhul.ac.uk – http://www.cs.rhul.ac.uk/~aeromero http://paccanarolab.org [1] Royal Holloway, University of London [2] Model College, Molde (Norway) [3] UCLA
  • 2. Outline 1.Domains and function prediction 2.The ConSAT method for function prediction 3.ConSAT: web server and database
  • 3. ● Domain → conserved part of protein sequence – Stable and exist in many proteins – Evolve independently – Often autonomous folding units – Individual function ● Example: zinc finger domains Domains and function prediction
  • 4. Domains and function prediction ● Single domain proteins: Protein ↔ Domain ↔ Function ● Multiple domain proteins (most common case): Protein Functions? Domain1 Domain2 … DomainN
  • 5. Domains and function prediction ● Domain combination can create new functions ● Domain combination can modify or suppress any of the individual domain functions ● Function is determined by the domain arrangement (architecture) and not just by the aggregation of the individual domain functions. Bashton M, Chothia C. The generation of new protein functions by the combination of domains. Structure. 2007 Jan;15(1):85-99.
  • 6. Domains and function prediction ● Protein architecture – Domain juxtaposition – Domain insertion Insertions can be recursive Aroul-Selvam R, Hubbard T, and Sasidharan R. Domain insertions in protein structures. J Mol Biol. 2004. 338(4):633-41.
  • 7. Domains and function prediction ● Finding domains: – Computational models (signatures) – Domain databases (Pfam, CATH-Gene3D, PANTHER, …) – Use InterPro as a starting point: ● Agglutinates the main databases ● Common name for several signatures of the same domain (IPR domain identifiers) ● InterPro2GO (IPR domains → GO terms) ● Issues: – Different databases do not agree in the output – Different domain boundaries for same IPR domain
  • 8. Domains and function prediction ● Issues (graphically): – 2 and 4 overlap (one of them is probably wrong) – 1 and 3 seem to be the same ● Solution: Consensus domain architecture
  • 9. The ConSAT method for FP Two steps: 1.Given the InterPro output for a sequence, obtain the consensus domain architecture 2. Assign functions to each architecture
  • 10. The ConSAT method for FP ● Step 1: consensus domain architecture
  • 11. The ConSAT method for FP ● Step 2: function prediction methods (GO terms)
  • 12. The ConSAT method for FP ● Step 2: function prediction methods (weighted English words) Prot 1 Prot 2 ... Prot N Abs 1 Abs 2 ... Abs M Cleaning Stopwords Stemming TF x IDF Retina 0.356 Cancer 0.281 Immune 0.148 Mammal 0.121 ... 1 Abs 1 Abs 2 ... Abs M 2 3
  • 13. ConSAT: web server and database http://paccanarolab.org/consat https://github.com/alfonsoeromero/ConSAT @consat_web www.facebook.com/consatweb
  • 14. ConSAT: web server and database ● Web server: run ConSAT given a set of sequences + InterPro ● Database: precomputed architectures and functions for all UniProtKB sequences. Easily accessible. Also raw datasets.
  • 15. ConSAT: web server and database ● Database: – Search facilities (by gene(s), by protein(s), GO term, IPR domain, by words…) – Detail pages for protein, architecture, domain and word → Try it now! → Feedback is accepted (and very useful!) → Suggestions and other opinions as well!
  • 16. ConSAT: web server and database
  • 17. ConSAT: web server and database
  • 18. ConSAT: web server and database
  • 19. ConSAT: web server and database
  • 20. Thanks for your attention! Questions, comments? Anyone hiring? :)