SBMLmerge and MIRIAM support

Transcription

1 SBMLmerge and MIRIAM support Marvin Schulz Max Planck Institute for Molecular Genetics Biomodels.net training camp

2 What exactly does SBMLmerge do? Small parts of the glycolysis

3 SBMLmerge... merges SBML files

4 Problems when merging SBML files syntactical requirements semantical problems

5 Problems when merging SBML files syntactical requirements no id used twice, semantical problems

6 Problems when merging SBML files syntactical requirements no id used twice, no circles in rule dependencies,... glucose = 2 g6p g6p = 1 2 glucose semantical problems

7 Problems when merging SBML files syntactical requirements no id used twice, no circles in rule dependencies,... glucose = 2 g6p g6p = 1 2 glucose semantical problems identification of identical entities

8 Could both refer to identical biological entities? <species id="glucose six phosphate" compartment="cytosol" > <species id="s1" name="g6p" compartment="cytosol" >

9 Problems when merging SBML files syntactical requirements no id used twice, no circles in rule dependencies,... glucose = 2 g6p g6p = 1 2 glucose semantical problems identification of identical entities dependent quantities (overlapping compartments, cell mitochondrion)

10 Problems when merging SBML files syntactical requirements no id used twice, no circles in rule dependencies,... glucose = 2 g6p g6p = 1 2 glucose semantical problems identification of identical entities dependent quantities (overlapping compartments, cell mitochondrion) does merging make sense? (models from different organisms)

11 Steps in merging SBML files Flowchart of SBMLmerge

12 Steps in merging SBML files SBMLannotate Helps user to assign MIRIAM annotations to compartments, species, and reactions step by step. Flowchart of SBMLmerge

13 Steps in merging SBML files SBMLannotate Helps user to assign MIRIAM annotations to compartments, species, and reactions step by step. SBMLcheck performs various consistency checks on the files Flowchart of SBMLmerge

14 Steps in merging SBML files SBMLannotate Helps user to assign MIRIAM annotations to compartments, species, and reactions step by step. SBMLcheck performs various consistency checks on the files SBMLmerge finally merges annotated and checked files Flowchart of SBMLmerge

15 Steps in merging SBML files Flowchart of SBMLmerge SBMLannotate Helps user to assign MIRIAM annotations to compartments, species, and reactions step by step. SBMLcheck performs various consistency checks on the files SBMLmerge finally merges annotated and checked files Each module can be executed independently

16 SBMLannotate SBMLannotate currently annotates compartments species reactions

17 SBMLannotate SBMLannotate currently annotates compartments species reactions Steps for each compartment / species:

18 SBMLannotate SBMLannotate currently annotates compartments species reactions Steps for each compartment / species: get potential names <compartment metaid="meta0001" id="c1" name="cytoplasm">

19 SBMLannotate SBMLannotate currently annotates compartments species reactions Steps for each compartment / species: get potential names <compartment metaid="meta0001" id="c1" name="cytoplasm"> search database for similar names

20 SBMLannotate SBMLannotate currently annotates compartments species reactions Steps for each compartment / species: get potential names <compartment metaid="meta0001" id="c1" name="cytoplasm"> search database for similar names suggest their IDs to the user cytoplasm GO:

21 SBMLannotate SBMLannotate currently annotates compartments species reactions Steps for each compartment / species: get potential names <compartment metaid="meta0001" id="c1" name="cytoplasm"> search database for similar names suggest their IDs to the user cytoplasm GO: Assigns MIRIAM annotations

22 Annotating compartments General classification of compartments: name of the compartment tissue organism

23 Annotating compartments General classification of compartments: Ontologies implemented in SBMLannotate name of the compartment Gene Ontology 1 tissue organism Taxonomy 2 (supported in current SBMLmerge alpha version)

24 Nested compartments Another benefit of Gene Ontology cell GO:

25 Nested compartments Another benefit of Gene Ontology cell GO: cytosol GO: nucleus GO: mitochondrion GO: mitochondrial matrix GO: mitochondrial membrane GO: Allows check for overlapping compartments

26 Annotating species Database IDs currently used in annotating species: KEGG 3 Gene Ontology 4 ChEBI 5 CAS 6 PubChem 7 3DMET

27 Name search in practice When searching for D-Glukose-sechs-Phosphat we get the results (1) d-glucose 6-phosphate KEGG:C00092 CAS: PubChem:3392 ChEBI:15954 (2) d-glucose 1-phosphate CAS: PubChem:3403 KEGG:C00103 ChEBI:16077 (3) d-xylulose-5-phosphate PubChem:3530 KEGG:C00231 ChEBI:16332 (4) d-xylose-5-phosphate PubChem:9033 KEGG:C06814 (5) d-glucose 1,6-bisphosphate CAS: PubChem:3929 KEGG:C00660 ChEBI:17680 (6) glucose-6-phosphatase GO: CAS: EC: (7) glucose-1-phosphatase GO: CAS: EC:

28 Annotating reactions Annotating reactions is based on KEGG:

29 Annotating reactions Annotating reactions is based on KEGG: Get KEGG ids from all reactants and products

30 Annotating reactions Annotating reactions is based on KEGG: Get KEGG ids from all reactants and products Get reactions all species ids are associated with

31 Annotating reactions Annotating reactions is based on KEGG: Get KEGG ids from all reactants and products Get reactions all species ids are associated with Suggest this list to the user to select one item

32 Annotating reactions in practice For the reaction alpha-d-glucose alpha-d-glucose-6-phosphate we get the following suggestions: R01786: ATP + alpha-d-glucose ADP + alpha-d-glucose 6-phosphate R01788: alpha-d-glucose 6-phosphate + H2O alpha-d-glucose + Orthophosphate R02189: (Phosphate)n + alpha-d-glucose (Phosphate)n + alpha-d-glucose 6-phosphate

33 Quality of the list of suggested reaction ids The quality of the list of suggested reaction ids depends on:

34 Quality of the list of suggested reaction ids The quality of the list of suggested reaction ids depends on: does the reaction appear in KEGG

35 Quality of the list of suggested reaction ids The quality of the list of suggested reaction ids depends on: does the reaction appear in KEGG detailedness of the modelling

36 Quality of the list of suggested reaction ids The quality of the list of suggested reaction ids depends on: does the reaction appear in KEGG detailedness of the modelling annotation status of the document

37 Recognizing links <species id="species1953" name="1-phosphatidylinositol 4-kinase" compartment="c1"> <annotation>... <rdf:li rdf:resource=" <rdf:li rdf:resource=" </annotation> </species> generic database id recognition

38 Recognizing links <species id="species1953" name="1-phosphatidylinositol 4-kinase" compartment="c1"> <annotation>... <rdf:li rdf:resource=" <rdf:li rdf:resource=" </annotation> </species> generic database id recognition based on regular expressions for database names and IDs

39 Recognizing links <species id="species1953" name="1-phosphatidylinositol 4-kinase" compartment="c1"> <annotation>... <rdf:li rdf:resource=" <rdf:li rdf:resource=" </annotation> </species> generic database id recognition based on regular expressions for database names and IDs ignores links inside tags haspart ispartof hasversion isversionof

40 Recognizing links <species id="species1953" name="1-phosphatidylinositol 4-kinase" compartment="c1"> <annotation>... <rdf:li rdf:resource=" <rdf:li rdf:resource=" </annotation> </species> generic database id recognition based on regular expressions for database names and IDs ignores links inside tags haspart ispartof hasversion isversionof support for these terms is planned

41 Storing links Currently SBMLannotate only supports the Dublin Core term RELATION.

42 Storing links Currently SBMLannotate only supports the Dublin Core term RELATION. <species metaid="species1953" id="species1953" name="1-phosphatidylinositol 4-kinase" compartment="c1"> <annotation> <rdf:rdf xmlns:rdf=" xmlns:dc=" <rdf:description rdf:about="#species1953"> <dc:relation> <rdf:bag> <rdf:li rdf:resource=" <rdf:li rdf:resource=" </rdf:bag> </dc:relation> </rdf:description> </rdf:rdf> </annotation> </species>

43 Storing links Currently SBMLannotate only supports the Dublin Core term RELATION. <species metaid="species1953" id="species1953" name="1-phosphatidylinositol 4-kinase" compartment="c1"> <annotation> <rdf:rdf xmlns:rdf=" xmlns:dc=" <rdf:description rdf:about="#species1953"> <dc:relation> <rdf:bag> <rdf:li rdf:resource=" <rdf:li rdf:resource=" </rdf:bag> </dc:relation> </rdf:description> </rdf:rdf> </annotation> </species> Support for HAS PART is planned.

44 SBMLcheck Checks syntactical or semantical validity of an annotated model

45 SBMLcheck Checks syntactical or semantical validity of an annotated model e.g. completeness of reactions (missing metabolites) alpha-d-glucose alpha-d-glucose-6-phosphate,

46 SBMLcheck Checks syntactical or semantical validity of an annotated model e.g. completeness of reactions (missing metabolites) alpha-d-glucose alpha-d-glucose-6-phosphate, and other mistakes in model construction

47 SBMLmerge Input: annotated and checked files <species id="glucose 6 phosphate" compartment="cytosol"> <annotation>... <rdf:li rdf:resource=" </annotation></species>

48 SBMLmerge Input: annotated and checked files <species id="glucose 6 phosphate" compartment="cytosol"> <annotation>... <rdf:li rdf:resource=" </annotation></species> 1 Merge the lists of compartments, species,...

49 SBMLmerge Input: annotated and checked files <species id="glucose 6 phosphate" compartment="cytosol"> <annotation>... <rdf:li rdf:resource=" </annotation></species> 1 Merge the lists of compartments, species,... 2 Find identical / contradicting elements in the input files rules: glucose = 1 2 g6p glucose = 2 g6p

50 SBMLmerge Input: annotated and checked files <species id="glucose 6 phosphate" compartment="cytosol"> <annotation>... <rdf:li rdf:resource=" </annotation></species> 1 Merge the lists of compartments, species,... 2 Find identical / contradicting elements in the input files rules: glucose = 1 2 g6p glucose = 2 g6p 3 Resolve conflicts with user interaction

51 SBMLmerge Input: annotated and checked files <species id="glucose 6 phosphate" compartment="cytosol"> <annotation>... <rdf:li rdf:resource=" </annotation></species> 1 Merge the lists of compartments, species,... 2 Find identical / contradicting elements in the input files rules: glucose = 1 2 g6p glucose = 2 g6p 3 Resolve conflicts with user interaction 4 Some small automatic adaptions e.g. changing constant attribute

52 Identical / contradicting elements Comparison mainly based on annotations <species id="glucose six phosphate">... <rdf:li rdf:resource= " <species id="s1" name="g6p">... <rdf:li rdf:resource= "

53 Identical / contradicting elements Comparison mainly based on annotations <species id="glucose six phosphate">... <rdf:li rdf:resource= " In their absence <species id="s1" name="g6p">... <rdf:li rdf:resource= " IDs / metaids / variables (rules) are compared

54 Identical / contradicting elements Comparison mainly based on annotations <species id="glucose six phosphate">... <rdf:li rdf:resource= " In their absence <species id="s1" name="g6p">... <rdf:li rdf:resource= " IDs / metaids / variables (rules) are compared afterwards core attributes are compared <species id="glucose" compartment="cytosol"> <species id="glucose" compartment="mitochondrion">

55 Elements we do not annotate Currently we do not annotate parameters events Problem: missing ontologies

56 Qualified relations and different databases Problems with entities we do annotate: limited database no complex molecules

57 Qualified relations and different databases Problems with entities we do annotate: limited database no complex molecules Possible solutions: include qualified relations and new databases. UniProt Reactome ChemBank DrugBank BIND Ensembl InterPro OMIM PIRSF

58 Webversion All programs are also available via a user friendly web interface:

59 The end Thank you for your attention For more information visit This work is funded by the