Function-process links The theory

Why bother? To improve the ontology To fill in annotation gaps As an aid to annotation –Suggest new annotations –Avoid redundant annotation effort –Annotation cross-products Better integration with pathway databases To present annotations to users in more useful ways –e.g. more informative AmiGO displays

GO in 2008

Filling in annotation gaps GO: kinase activity GO: kinase activity GO: phosphorylation |P| = 3640 |F| = 6053 |F ∩ P| = 2230 |F ∩ not P| = July 2008

Filling in annotation gaps GO: kinase activity GO: kinase activity GO: phosphorylation Future

Improved presentation to users

part_of

annotations propagate over part_of KIC1 IDA

part_of annotations propagate over part_of KIC1 IDA

part_of annotations propagate over part_of NDK1 IDA

part_of annotations propagate over part_of NDK1 IDA

A quick review of part_of Means “always part of some” –Example: nucleus part_of cell EVERY nucleus is part_of SOME cell

Mining pathway DBs for links glycolysis fructose bisphosphatase activity of fructose 1 6 bisphosphatase 2 _cytosol glucose 6 phosphate isomerase activity of glucose 6 phosphate isomerase dimer_cytosol glycolysis fructose- bisphosphate aldolase activity glucose-6- phosphate isomerase activity reactome GO MF BP

Mining pathway DBs for links glycolysis fructose bisphosphatase activity of fructose 1 6 bisphosphatase 2 _cytosol glucose 6 phosphate isomerase activity of glucose 6 phosphate isomerase dimer_cytosol glycolysis fructose- bisphosphate aldolase activity glucose-6- phosphate isomerase activity reactome GO xref

Mining pathway DBs for links glycolysis fructose bisphosphatase activity of fructose 1 6 bisphosphatase 2 _cytosol glucose 6 phosphate isomerase activity of glucose 6 phosphate isomerase dimer_cytosol glycolysis fructose- bisphosphate aldolase activity glucose-6- phosphate isomerase activity reactome GO xref has_part

xrefs: not necessarily equivalent glycolysis [human] glycolysis [human] fructose bisphosphatase activity of fructose 1 6 bisphosphatase 2 _cytosol glucose 6 phosphate isomerase activity of glucose 6 phosphate isomerase dimer_cytosol glycolysis fructose- bisphosphate aldolase activity glucose-6- phosphate isomerase activity reactome GO equivalent has_part? GO:new is_a GO:new is_a

xrefs: not necessarily equivalent glycolysis [human] glycolysis [human] fructose bisphosphatase activity of fructose 1 6 bisphosphatase 2 _cytosol glucose 6 phosphate isomerase activity of glucose 6 phosphate isomerase dimer_cytosol glycolysis fructose- bisphosphate aldolase activity glucose-6- phosphate isomerase activity reactome GO equivalent some_has_part GO:new is_a GO:new is_a has_part

xrefs: not necessarily equivalent glycolysis [human] glycolysis [human] fructose bisphosphatase activity of fructose 1 6 bisphosphatase 2 _cytosol glucose 6 phosphate isomerase activity of glucose 6 phosphate isomerase dimer_cytosol glycolysis fructose- bisphosphate aldolase activity glucose-6- phosphate isomerase activity reactome GO xref some_has_part has_part

Specifics Low Hanging Fruit –Function to process links Mostly part_of links Some regulates links Pathways –Process to function has_part –Mining from pathways databases & curation

Function-process links Conclusions of the electron transport working group.

UTP:glucose-1-phosphate uridylyltransferase activity α-D-glucose 1-phosphate + UTP -> UDP-D-glucose + diphosphate glucose metabolic process UDP-glucose metabolic process galactose metabolic process biosynthetic process colanic acid biosynthetic process response to desiccation carbohydrate catabolic process Function Process hp

urea cycle arginosuccinate synthase activity Catalysis of the reaction: ATP + L-citrulline + L-aspartate = AMP +diphosphate + (N(omega)-L-arginino)succinate arginine biosynthetic process polyamine biosynthesis Function Process hp

carbamoyl-phosphate synthase activity Catalysis of a reaction that results in the formation of carbamoyl phosphate. Urea cycle and metabolism of amino groups Glutamate metabolism Arginine and proline metabolism Nitrogen metabolism Function Process hp

Lysine biosynthesis pathways

lysine biosynthesis lysine biosynthesis 1 lysine biosynthesis 3 lysine biosynthesis 2 lysine biosynthesis 4 lysine biosynthesis 5 lysine biosynthesis 6 Function Process is_a lysine biosynthesis 7? is_a

Process Function Lysine Biosynthesis Shared function? = has_part Non-shared function new GO term existing GO term

Process Function Lysine Biosynthesis Process B Shared function? = has_part Non-shared function new GO term existing GO term

Process Function Lysine Biosynthesis Process BProcess C Shared function? = has_part Non-shared function new GO term existing GO term

Process Function Lysine Biosynthesis Process BProcess C Relationship explosion (or Editorial office explosion)

Where do pathways start and end? A B C D process 1 process 2 process 3

Use cases Can we slim from function up to process? Can we infer annotations to process from those to function?

has_part has_function but only as part_of polyamine biosynthesis has_function but only as part_of urea cycle polyamine biosynthesis arginosuccinate synthase activity Gene product x Gene product y Function Process Gene products

has_part has_function urea cycle polyamine biosynthesis Gene product x Gene product y Function Process Gene products ?

has_part has_function urea cycle polyamine biosynthesis Gene product x Gene product y Function Process Gene products No has_part cannot be used for slimming.

Can we infer annotations to process from those to function? No. There is too much variation in process details, and too many functions are shared.

So what can we do?

phosphorylation kinase activity Function Process part_of We can make relationships between single step processes and their respective functions.

glucose transport glucose transporter activity Function Process part_of We can make any obvious relationship where part_of holds, and this will allow useful slimming.

We can mine the other links from pathway databases and make non-curated sometimes_part_of links.

sometimes_part_of What does this buy us? Very full coverage of function-process links. No manual link curation. What work does it involve? We maintain the mapping files e.g. reactome2go. We write the mining scripts. Work with pathway dbs to unify exchange formats and make data interoperable

Acknowledgements Michelle Gwinn-Giglio Debbie Siegele Ingrid Keseler Harold Drabkin Jennifer Deegan Chris Mungall Peifen Zhang