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A “Fair and Balanced” Assessment of Protein Function Prediction Servers <ul><ul><li>Iddo Friedberg, Martin Jambon, Andrei ...
Outline <ul><li>What is function? </li></ul><ul><li>Describing function </li></ul><ul><li>Describing function similarity <...
What is Function? <ul><li>Biochemical </li></ul><ul><li>Pathway/location </li></ul><ul><li>Phenotypic </li></ul>10 -6  m 1...
Outline <ul><li>What is function? </li></ul><ul><li>Describing function </li></ul><ul><li>Describing function similarity <...
Describing Function: From English to Keywords “ HAL—which is the first enzyme in the degradation pathway of L-histidine—ca...
Describing Function: From English to Keywords “ HAL—which is the first enzyme in the degradation pathway of L-histidine—ca...
Outline <ul><li>What is function? </li></ul><ul><li>Describing function </li></ul><ul><li>Describing function similarity <...
Keyword Similarity Measurements <ul><li>Represent each document as a set of words </li></ul><ul><li>Use set theory to norm...
Keywords and Semantics “ HAL —which is the first  enzyme  in the  degradation pathway  of  L-histidine — catalyzes  the no...
Ontology: beyond keywords <ul><li>Ontologies serve to establish the semantic function of words </li></ul><ul><li>Ontologie...
EC1 oxidoreductases EC2 transferases EC3 hydrolases EC4 lyases EC5 isomaerase EC6 ligases EC4.1 carbon-carbon EC4.2 carbon...
EC4 lyases EC4.3 carbon-nitrogen EC 4.3.1 ammonia lyases EC 4.3.1.3 histidine ammonia lyase Enzyme Commission Classificati...
Gene Ontology: Function Beyond Enzymes <ul><li>GO describes function beyond the enzymatic </li></ul><ul><li>Three function...
GO: molecular function of HAL Histidine ammonia-lyase activity (GO:003456)‏ ammonia-lyase activity C-N lyase activity lyas...
GO: biological process  of HAL Histidine biosynthesis Histidine family biosynthesis Histidine metabolism Physiological pro...
Outline <ul><li>What is function? </li></ul><ul><li>Describing function </li></ul><ul><li>Describing function similarity <...
The Gene Ontology <ul><li>GO is a hierarchy of  terms . A directed acyclic graph. </li></ul><ul><li>A  node  contains a si...
The Problem with Path Distance Some terms are more  informative  than others! General terms are less informative An absurd...
Information Content Based Distance <ul><li>A  concept  occurs if each term, or its children, occurs. </li></ul><ul><li>The...
Outline <ul><li>What is function? </li></ul><ul><li>Describing function </li></ul><ul><li>Describing function similarity <...
Selecting Targets <ul><li>Ideally  targets should be: </li></ul><ul><ul><li>Without obvious homologs (sequence or structur...
Selecting Targets Cont'd <ul><li>Thermotoga maritima : a hyperthermophilic deep ocean eubacteria.  </li></ul><ul><li>Genom...
Outline <ul><li>What is function? </li></ul><ul><li>Describing function </li></ul><ul><li>Describing function similarity <...
Assessed Servers
Server Scorecard (empty)‏ Spearmint ___ RuleBase ___ AnnoLite ___ PFP ___ PhydBac ___ ProKnow ___ Proteome Analyst __ GOPE...
T7: an aspartate oxidase or dehydrogenase? <ul><li>Novel enzyme, aspartate dehydrogenase, non-orthologous replacement for ...
in cluster FIG ID Function TM ID #1 ASPDH: Aspartate dehydrogenase [same functional role as] (EC  1.4.3.16 ) TM1643* #2 QS...
T7: GO Tree and Probabilities Oxidoreductase CH-NH 2  bonds Molecular Function Catalytic Oxidoreductase Oxidoreductase CH-...
T7: summary <ul><li>A “new” enzyme: aspartate dehydrogenase </li></ul><ul><li>Non orthologous replacement of aspartate oxi...
T1: the little Thiamine synthesis enzyme who couldn't (and neither could we)‏
T1: the Thiamine synthesis hypothesis Beck & Downs, JB 1998
T1 is not involved directly in the Thiamine pathway <ul><li>ApbE is present in bacteria with and without the thiamine bios...
T1 Beck & Downs, JB 1998 ApbE
T1: a non oligomerizing T-fold T-fold: normally forms homo-oligomeric barrels Uricase T1 Active site Oligomerization regio...
T1: predictions <ul><li>Cellular Process (Thiamine  biosynthesis)  found by: Spearmint, Rulebase, PFP, ProKnow </li></ul><...
T1 - conclusions <ul><li>It is possible to have extensive knowledge of a protein, inc. structure, pathway yet know little ...
T2 <ul><li>TM1622. ORFan. </li></ul><ul><li>MF:  GTPase  binding.  </li></ul><ul><ul><li>Evidence: structural similarity t...
T2 aligned to Ran-GTPASE MOVIE
T2 Predictions binding Protein binding Enzyme binding GTPase binding Small GTPase binding p=0.45; gosim=113 p=0.21 gosim=2...
T4: Pantothenate Kinase <ul><li>TM0883 </li></ul><ul><li>Pantothenate kinase activity  GO:0004594 E.C. 2.7.1.33 </li></ul>...
T4: Pantothenate Kinase,  CoA synthesis Boxes: enzymes Circles: substrates/products Arrows: “preferred” reaction direction...
Brand, L. A. et al. J. Biol. Chem. 2005;280:20185-20188 Cluster analysis of the predicted coaX gene in selected organisms
T4: server predictions <ul><li>ProKnow : kinase activity; ATP binding </li></ul><ul><li>Many servers erroneously provided ...
T5: Growth Arrest; GDNF Receptor SwissProt: GAS1_HUMAN <ul><li>Contributed by Michal Linial </li></ul><ul><li>Cellular pro...
T5: Growth Arrest; GDNF Receptor Signal transducer Receptor activity X-membrane receptor activity hematopoein/interferon-c...
Server Scorecard (empty)‏ Spearmint ___ RuleBase ___ AnnoLite ___ PFP ___ PhydBac ___ ProKnow ___ Proteome Analyst __ GOPE...
Server Scorecard (Full)‏ Spearmint ___ RuleBase ___ AnnoLite ___ PFP ___ PhydBac ___ ProKnow ___ Proteome Analyst __ GOPET...
Thanks <ul><li>Adam Godzik </li></ul><ul><li>Andrei Osterman </li></ul><ul><li>Michal Linial </li></ul><ul><li>Martin Jamb...
Points for Discussion <ul><li>Future target selection: a call for 2006 </li></ul><ul><li>Assessment strategies </li></ul><...
Points for Discussion: Target selection: a call for 2006 <ul><li>Experimentally verified </li></ul><ul><li>Not yet publish...
Points for Discussion: Assessment strategies <ul><li>Ontology based / other? </li></ul><ul><li>Additional and new distance...
The End
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Critical Assessment of Function Annotation, 2005

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A talk I gave at the Automated Function Prediction meeting, 2005. Highlights different challenges in running a competition between protein function prediction servers. Talks of the use of semantic similarity in Gene Ontology as a metric for assessment, the problems in determining a "Gold Standard" and more

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Critical Assessment of Function Annotation, 2005

  1. 1. A “Fair and Balanced” Assessment of Protein Function Prediction Servers <ul><ul><li>Iddo Friedberg, Martin Jambon, Andrei Osterman and Adam Godzik </li></ul></ul>
  2. 2. Outline <ul><li>What is function? </li></ul><ul><li>Describing function </li></ul><ul><li>Describing function similarity </li></ul><ul><li>Selecting Targets </li></ul><ul><li>Assessing servers </li></ul><ul><li>Thoughts for the future </li></ul>
  3. 3. What is Function? <ul><li>Biochemical </li></ul><ul><li>Pathway/location </li></ul><ul><li>Phenotypic </li></ul>10 -6 m 1m 10 -9 m Mutation: Histidinemia (Mental retardation and speech defect)‏ Histidine amino lyase (HAL, Histidase)‏ L-histidine Urocanate +NH 3
  4. 4. Outline <ul><li>What is function? </li></ul><ul><li>Describing function </li></ul><ul><li>Describing function similarity </li></ul><ul><li>Selecting Targets </li></ul><ul><li>Assessing servers </li></ul><ul><li>Thoughts for the future </li></ul>
  5. 5. Describing Function: From English to Keywords “ HAL—which is the first enzyme in the degradation pathway of L-histidine—catalyzes the non-oxidative deamination of its substrate to trans-urocanic acid”. László Poppe, (2001) COCB “ HAL— which is the first enzyme in the degradation pathway of L-histidine — catalyzes the non-oxidative deamination of its substrate to trans -urocanic acid ”.
  6. 6. Describing Function: From English to Keywords “ HAL—which is the first enzyme in the degradation pathway of L-histidine—catalyzes the non-oxidative deamination of its substrate to trans-urocanic acid”. László Poppe, (2001) COCB “ HAL— which is the first enzyme in the degradation pathway of L-histidine — catalyzes the non-oxidative deamination of its substrate to trans -urocanic acid ”. “ HAL — which is the first enzyme in the degradation pathway of L-histidine — catalyzes the non-oxidative deamination of its substrate to trans -urocanic acid ”. “ HAL — which is the first enzyme in the degradation pathway of L-histidine — catalyzes the non-oxidative deamination of its substrate to trans -urocanic acid ”. “ HAL — which is the first enzyme in the degradation pathway of L-histidine — catalyzes the non-oxidative deamination of its substrate to trans -urocanic acid ”.
  7. 7. Outline <ul><li>What is function? </li></ul><ul><li>Describing function </li></ul><ul><li>Describing function similarity </li></ul><ul><li>Selecting Targets </li></ul><ul><li>Assessing servers </li></ul><ul><li>Thoughts for the future </li></ul>
  8. 8. Keyword Similarity Measurements <ul><li>Represent each document as a set of words </li></ul><ul><li>Use set theory to normalize a common word count </li></ul><ul><li>Problem: does not take into account the corpus word count </li></ul><ul><li>Represent each document as a vector of (weighted by frequency) words </li></ul><ul><li>Document similarity based on the angle between the vectors </li></ul><ul><li>Problem: dimensions not really orthogonal (co-dependence of words)‏ </li></ul>
  9. 9. Keywords and Semantics “ HAL —which is the first enzyme in the degradation pathway of L-histidine — catalyzes the non-oxidative deamination of its substrate to trans-urocanic acid ”. László Poppe, (2001) COCB “ Histidase catalyzes the elimination of the alpha-amino group of histidine using a 4-methylidene-imidazole-5-one (MIO), which is formed autocatalytically from the internal peptide segment 142Ala-Ser-Gly.” Baedecker & Schultz, (2002) Eur J Biochem <ul><li>Keyword based methods are semantically blind </li></ul><ul><li>What do we do if there are no shared keywords? </li></ul>
  10. 10. Ontology: beyond keywords <ul><li>Ontologies serve to establish the semantic function of words </li></ul><ul><li>Ontologies are 'specifications of a relational vocabulary': sets of defined terms like the sort that you would find in a dictionary, but the terms are networked. (from the GO site)‏ </li></ul>
  11. 11. EC1 oxidoreductases EC2 transferases EC3 hydrolases EC4 lyases EC5 isomaerase EC6 ligases EC4.1 carbon-carbon EC4.2 carbon-oxygen EC4.3 carbon-nitrogen EC4.5 phosphorus-oxygen EC4.99 others EC4.4 carbon-sulfur EC 4.3.1 ammonia lyases EC 4.3.1.1 aspartate ammonia lyase EC 4.3.1.2 met-aspartate ammonia lyase EC 4.3.1.3 histidine ammonia lyase EC 4.3.3 amine lyases Enzyme Commission Classification Enzyme
  12. 12. EC4 lyases EC4.3 carbon-nitrogen EC 4.3.1 ammonia lyases EC 4.3.1.3 histidine ammonia lyase Enzyme Commission Classification <ul><li>E.C. Provides a semantically accurate description by </li></ul><ul><li>1) Using a controlled vocabulary </li></ul><ul><li>2) Going from the general to the specific </li></ul><ul><li>3) Defining the scope of interest </li></ul>
  13. 13. Gene Ontology: Function Beyond Enzymes <ul><li>GO describes function beyond the enzymatic </li></ul><ul><li>Three functional aspects are described: </li></ul><ul><ul><li>Molecular function </li></ul></ul><ul><ul><li>Biological process </li></ul></ul><ul><ul><li>Cellular location </li></ul></ul><ul><li>Terms are related by “is-a” and “part-of” relationships </li></ul>
  14. 14. GO: molecular function of HAL Histidine ammonia-lyase activity (GO:003456)‏ ammonia-lyase activity C-N lyase activity lyase activity Molecular Function
  15. 15. GO: biological process of HAL Histidine biosynthesis Histidine family biosynthesis Histidine metabolism Physiological process Cellular process Biological process
  16. 16. Outline <ul><li>What is function? </li></ul><ul><li>Describing function </li></ul><ul><li>Describing function similarity </li></ul><ul><ul><li>Keywords </li></ul></ul><ul><ul><li>Ontology </li></ul></ul><ul><li>Selecting targets </li></ul><ul><li>Assessing servers </li></ul><ul><li>Thoughts for the future </li></ul>
  17. 17. The Gene Ontology <ul><li>GO is a hierarchy of terms . A directed acyclic graph. </li></ul><ul><li>A node contains a single term which is one of the following aspects : </li></ul><ul><ul><li>molecular function </li></ul></ul><ul><ul><li>cellular component </li></ul></ul><ul><ul><li>cellular process </li></ul></ul><ul><li>Problem: how do we create a distance/similarity measure? </li></ul><ul><li>Solution 1: measure the shortest path distance between terms </li></ul>His-NH 3 lyase Serine-NH 3 lyase NH 3 -lyase C-S lyase lyase activity hydrolase Catalytic activity d(His- NH 3 lyase,C-S lyase) = 3 <ul><ul><ul><li>(Lord et. al Bioinformatics 2003)‏ </li></ul></ul></ul>
  18. 18. The Problem with Path Distance Some terms are more informative than others! General terms are less informative An absurd situation: Catalytic activity d(His-NH 3 lyase, C-S lyase) = 3 d(His-NH 3 lyase,catalytic activity) = 3 Need to provide a measure based upon term information content, not path distance <ul><ul><ul><li>(Lord et. al Bioinformatics 2003)‏ </li></ul></ul></ul>His-NH 3 lyase Serine-NH 3 lyase NH 3 -lyase C-S lyase lyase activity hydrolase
  19. 19. Information Content Based Distance <ul><li>A concept occurs if each term, or its children, occurs. </li></ul><ul><li>The probability for each concept, p ( c ) increases as we move towards the root </li></ul><ul><li>Let the set shared parents of two terms be S ( c 1, c 2)‏ </li></ul><ul><li>The probability of the minimal subsumer is: </li></ul><ul><li>p(c1, c2) = min({p(c)})‏ </li></ul><ul><li>c ∈ S ( c 1, c 2)‏ </li></ul><ul><li>sim(c1,c2) = -log 2 ( p ms ( c 1, c 2)) gosim (His-NH3 lyase,C-S lyase) = -log 2 (p(Lyase activity)) = 1.57 </li></ul>His-NH3 lyase p=0.000433 Serine-NH3 lyase p=0.0977 NH3-lyase p=0.124 C-S lyase p=0.0281 Lyase activity p=0.15 hydrolase p=0.102 Catalytic activity p=0.5 Molecular Function p=1 <ul><ul><ul><li>(Lord et. al Bioinformatics 2003)‏ </li></ul></ul></ul>gosim (His-NH3 lyase, cat activity) = -log 2 (0.5)=0.7
  20. 20. Outline <ul><li>What is function? </li></ul><ul><li>Describing function </li></ul><ul><li>Describing function similarity </li></ul><ul><li>Selecting targets </li></ul><ul><li>Assessing servers </li></ul><ul><li>Thoughts for the future </li></ul>
  21. 21. Selecting Targets <ul><li>Ideally targets should be: </li></ul><ul><ul><li>Without obvious homologs (sequence or structure)‏ </li></ul></ul><ul><ul><li>Function experimentally determined </li></ul></ul><ul><ul><li>Not yet published </li></ul></ul>Thanks to the target contributers: Adam Godzik TBI, JCSG Subramanian Sri Krishna , JCSG Andrei Osterman, TBI Michal Linial, UW / HUJI
  22. 22. Selecting Targets Cont'd <ul><li>Thermotoga maritima : a hyperthermophilic deep ocean eubacteria. </li></ul><ul><li>Genome wide fold coverage organism of choice for JCSG 1878 protein coding genes </li></ul><ul><li>Very few, “feeler” assessment targets were picked. </li></ul>
  23. 23. Outline <ul><li>What is function? </li></ul><ul><li>Describing function </li></ul><ul><li>Describing function similarity </li></ul><ul><li>Selecting targets </li></ul><ul><li>Assessing servers (target by target)‏ </li></ul><ul><li>Thoughts for the future </li></ul>
  24. 24. Assessed Servers
  25. 25. Server Scorecard (empty)‏ Spearmint ___ RuleBase ___ AnnoLite ___ PFP ___ PhydBac ___ ProKnow ___ Proteome Analyst __ GOPET ___
  26. 26. T7: an aspartate oxidase or dehydrogenase? <ul><li>Novel enzyme, aspartate dehydrogenase, non-orthologous replacement for aspartate oxidase. TM1643 from T. maritima </li></ul><ul><li>Function experimentally verified: Yang Z et al., J Biol Chem. 2003 278(10):8804-8 </li></ul>
  27. 27. in cluster FIG ID Function TM ID #1 ASPDH: Aspartate dehydrogenase [same functional role as] (EC 1.4.3.16 ) TM1643* #2 QSYN: Quinolinate synthetase (EC 4.1.99.-) TM1644 #3 QAPRT: Quinolinate phosphoribosyltransferase [decarboxylating] (EC 2.4.2.19 ) TM1645* *Structures solved Biological Process: NAD/NADP Biosynthesis Summary: Genomic cluster conserved between T,maritima and several methanogenic archaea contains a novel gene* for the first step of NAD biosynthesis I II ASPOX ASPDH NAD + NADH QSYN PRPP IV FAD + FADH III QAPRT PP i Experimentally confirmed by: Z.Yang et al. (Toronto)‏ “ Aspartate Dehydrogenase, a Novel Enzyme Identified from Structural and Functional Studies of TM1643”, J. Biol. Chem., Vol. 278,, 2003 Connecting intermediates I L-Aspartate II Iminoaspartate III Dihydroxyacetone-P IV Quinolinic acid TM1643
  28. 28. T7: GO Tree and Probabilities Oxidoreductase CH-NH 2 bonds Molecular Function Catalytic Oxidoreductase Oxidoreductase CH-NH 2 bonds NAD/NADP acceptor Oxidoreductase CH-NH 2 bonds Oxygen acceptor Aspartate Dehydrogenase Aspartate Oxidoreductase Spearmint : homoserine dehydrogenase A nnoLite : L-lactate dehydrogenase ProKnow: oxidoreductase activity p=1; gosim=0 p=0.26; gosim=192. p=0.03; gosim=484. p=8.65x10 -4 ; gosim=1017 p=4.74x10 -4 ; gosim=1104 PhydBac : nicotinate nuc. dephosphorylase PFP :3-5 nucleotide phosphodiesterase
  29. 29. T7: summary <ul><li>A “new” enzyme: aspartate dehydrogenase </li></ul><ul><li>Non orthologous replacement of aspartate oxidase </li></ul><ul><li>Experimentally characterized two years ago </li></ul><ul><li>Not yet in annotation databases: do we need a standard deposition system like GenBank (Sequence) PDB (structure) MIAME (microarray)? </li></ul><ul><li>Some servers' predictions are better: is GO the ideal similarity scale? </li></ul>
  30. 30. T1: the little Thiamine synthesis enzyme who couldn't (and neither could we)‏
  31. 31. T1: the Thiamine synthesis hypothesis Beck & Downs, JB 1998
  32. 32. T1 is not involved directly in the Thiamine pathway <ul><li>ApbE is present in bacteria with and without the thiamine biosynthesis pathway </li></ul><ul><li>No correlation with genomic presence of thiamine transporters (ThiBPQ or YuAJ)‏ </li></ul><ul><li>Not present in the thi loci </li></ul><ul><li>Lack of the ApbC or ApbE protein results in a defect in Fe-S cluster metabolism (Downs, JB 2003)‏ </li></ul>
  33. 33. T1 Beck & Downs, JB 1998 ApbE
  34. 34. T1: a non oligomerizing T-fold T-fold: normally forms homo-oligomeric barrels Uricase T1 Active site Oligomerization region Catalytic site Cat. site Oligomerization region
  35. 35. T1: predictions <ul><li>Cellular Process (Thiamine biosynthesis) found by: Spearmint, Rulebase, PFP, ProKnow </li></ul><ul><li>Molecular Function: PFP, ProKnow: oxidoreductase, </li></ul><ul><li>Molecular function PFP: transferring glycosyl groups </li></ul><ul><li>Cellular process aspect: mis-annotation due to outdated annotations in the reference databases (Pfam, KEGG)‏ </li></ul><ul><li>We know the structure, active site, fold type, possible pathway </li></ul>Surprise! We do not know the real function (yet)‏
  36. 36. T1 - conclusions <ul><li>It is possible to have extensive knowledge of a protein, inc. structure, pathway yet know little about its actual biochemical function </li></ul>
  37. 37. T2 <ul><li>TM1622. ORFan. </li></ul><ul><li>MF: GTPase binding. </li></ul><ul><ul><li>Evidence: structural similarity to GTPase binders: Mog1, PsbP </li></ul></ul><ul><ul><li>Genomic co-location with the LepA (elongation factor Tu), a GTPase. </li></ul></ul>
  38. 38. T2 aligned to Ran-GTPASE MOVIE
  39. 39. T2 Predictions binding Protein binding Enzyme binding GTPase binding Small GTPase binding p=0.45; gosim=113 p=0.21 gosim=224 p=7.4x10 -3 gosim=707 gosim=1024 gosim=1122 <ul><li>AnnoLite: </li></ul><ul><li>actin binding </li></ul><ul><li>PIP(4,5) binding </li></ul>PFP : Rab interactor
  40. 40. T4: Pantothenate Kinase <ul><li>TM0883 </li></ul><ul><li>Pantothenate kinase activity GO:0004594 E.C. 2.7.1.33 </li></ul><ul><li>Evidence: experimental (Brand & Strauss, JBC May 2005)‏ </li></ul><ul><li>New protein:CoaX </li></ul>
  41. 41. T4: Pantothenate Kinase, CoA synthesis Boxes: enzymes Circles: substrates/products Arrows: “preferred” reaction directionality Color: organism in which enzyme exists UNIVERSAL PATHWAY Fatty Acid metabolism Central Carbon metabolism CoA B5 PANK VI ATP ADP PPCS VIII CTP CMP, PP i VII Cysteine metabolism PPCDC IX CO 2 PPAT X PP i ATP DPCK ADP ATP PANK2 PANK3 PPAT2 present in H.sapiens present in both present in E.coli absent in both
  42. 42. Brand, L. A. et al. J. Biol. Chem. 2005;280:20185-20188 Cluster analysis of the predicted coaX gene in selected organisms
  43. 43. T4: server predictions <ul><li>ProKnow : kinase activity; ATP binding </li></ul><ul><li>Many servers erroneously provided “Bortadella pertussis Bvg accessory factor family”: old Pfam annotation </li></ul><ul><li>The exact function can be inferred (almost) from genomic context: </li></ul><ul><ul><li>T4 is clustered with other proteins in the CoA synthesis pathway in many organisms AND </li></ul></ul><ul><ul><li>There is no other recognizable pantothenate kinase in T. maritima 's genome </li></ul></ul>
  44. 44. T5: Growth Arrest; GDNF Receptor SwissProt: GAS1_HUMAN <ul><li>Contributed by Michal Linial </li></ul><ul><li>Cellular process: </li></ul><ul><ul><li>induces caspase dependent apoptosis. </li></ul></ul><ul><ul><li>Prevents G 0 -> S cell-cycle transition </li></ul></ul><ul><li>Location: membrane; rafts </li></ul><ul><li>Biochemistry: binds glial derived neurotrophic factors (GDNF); GPI binding (Personal communication M. Linial)‏ </li></ul><ul><li>No structure (Robetta model)‏ </li></ul>
  45. 45. T5: Growth Arrest; GDNF Receptor Signal transducer Receptor activity X-membrane receptor activity hematopoein/interferon-class cytokine receptor activity GDNF receptor activity p=0.134; gosim=289 p=0.072 gosim=379 p=0.052 gosim=426 p=2.32x10 -3 ; gosim=875 p=8.4x10 -5 ; gosim=1353 <ul><li>PFP: </li></ul><ul><li>Protein binding </li></ul><ul><li>Receptor activity </li></ul>
  46. 46. Server Scorecard (empty)‏ Spearmint ___ RuleBase ___ AnnoLite ___ PFP ___ PhydBac ___ ProKnow ___ Proteome Analyst __ GOPET ___
  47. 47. Server Scorecard (Full)‏ Spearmint ___ RuleBase ___ AnnoLite ___ PFP ___ PhydBac ___ ProKnow ___ Proteome Analyst __ GOPET ___
  48. 48. Thanks <ul><li>Adam Godzik </li></ul><ul><li>Andrei Osterman </li></ul><ul><li>Michal Linial </li></ul><ul><li>Martin Jambon </li></ul><ul><li>Subramanian Sri Krishna </li></ul>
  49. 49. Points for Discussion <ul><li>Future target selection: a call for 2006 </li></ul><ul><li>Assessment strategies </li></ul><ul><li>Annotation standards </li></ul><ul><li>Should servers standardize their output? </li></ul><ul><li>Towards meta-servers </li></ul><ul><li>PDB 500 unknowns: a collaborative website </li></ul>
  50. 50. Points for Discussion: Target selection: a call for 2006 <ul><li>Experimentally verified </li></ul><ul><li>Not yet published? </li></ul><ul><li>Not trivially discernible </li></ul><ul><li>Promiscuous? (Yes / No)‏ </li></ul><ul><li>Moonlighters? (Yes / No)‏ </li></ul><ul><li>Categorize by functional aspects? </li></ul><ul><li>Categorize by input type (sequence / structure)? </li></ul><ul><li>Estimation of prediction difficulty? </li></ul>
  51. 51. Points for Discussion: Assessment strategies <ul><li>Ontology based / other? </li></ul><ul><li>Additional and new distance measures? </li></ul><ul><li>Different distance measures for different categories? </li></ul>
  52. 52. The End

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