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August 2012 This work is licensed under the Creative Commons Attribution 3.0 Unported License. To view a copy of this license, visit

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Presentation on theme: "August 2012 This work is licensed under the Creative Commons Attribution 3.0 Unported License. To view a copy of this license, visit"— Presentation transcript:

1 August 2012 This work is licensed under the Creative Commons Attribution 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by/3.0/ or send a letter to Creative Commons, 444 Castro Street, Suite 900, Mountain View, California, 94041, USA. BEL Framework v2.0.0

2 BEL Framework Overview Current version 2.0.0 released June 29, 2012 – Open source The BEL Framework includes: – BEL Compiler – KAM store – Tools – Web and Java APIs API = Application Programming Interface – Can be used by software to access information from KAMs KAM Navigator uses the Web API Whistle uses the Java API – Web Server

3 Knowledge User Workflow: BEL Framework and Applications Multiple KAMs can be imported for use by the application BEL Compiler Encrypted portable KAM BEL Framework BEL Framework API KAM Store Application BEL Documents 3

4 Contents KAMs and the KAM store BEL Compiler – Running the BEL Compiler – Phase I - Compiler Expansions – Phase II - Equivalencing – Phase III – Compiler Augmentations BEL Framework Tools 4

5 Knowledge Assembly Model (KAM) A knowledge base in network form Composed of Nodes (KamNode) and Edges (KamEdge) Each KamNode represents one or more BEL Terms drawn from one or more BEL Documents Each KamEdge represents one or more BEL Statements from from one or more BEL Documents 5

6 KamNodes Nodes represent one or more BEL terms KamNodes are coalesced wherever possible by the equivalencing engine (Phase II) 6

7 KamEdges Represent assertions supported by one or more BEL Statements Querying a KamEdge will return: – Each BEL Statement supporting the assertion – Assertions are coalesced based solely on semantic triple after equivalencing, independent of Annotations Querying a BEL Statement will return: – The BEL Document the statement was recorded in – The list of assertions for the statement 7

8 KAM Store The database that stores KAMs Default database is Derby – Can configure to use MySQL or other databases Put KAMs into the KAM Store by: – Compiling a KAM (belc.cmd) – Importing a KAM (tools\KamManager.cmd --import) Access KAMs via: – APIs – Exporting a KAM (tools\KamManager.cmd –export) © 2012, Open BEL Community8

9 Contents KAMs and the KAM store BEL Compiler – Running the BEL Compiler – Phase I - Compiler Expansions – Phase II - Equivalencing – Phase III – Compiler Augmentations BEL Framework Tools 9

10 KAMs Are Compiled from BEL Documents The BEL Compiler compiles one or more BEL Documents into a Knowledge Assembly Model (KAM) Multi-Phase compiler/assembler: 1.Compiler – compiles each BEL Document into a proto-network 2.Equivalencer – merges proto-networks by equivalencing analogous nodes across namespaces 3.Augmenter – increases KAM computability by injecting terms and relationships from additional sources of prior knowledge (e.g. relationships connecting RNAs to their corresponding proteins) 4.Assembler – Generates final network and supporting evidence structures Users can change compiler parameters to control the knowledge assembly process 10

11 KAM Compilation Phases CompilerEquivalencerAugmentor Final Assembler Compiled KAM BEL Documents Equivalence Tables Other Prior Knowledge Namespace & Annotation Tables Network Resources 11

12 Contents KAMs and the KAM store BEL Compiler – Running the BEL Compiler – Phase I - Compiler Expansions – Phase II - Equivalencing – Phase III – Compiler Augmentations BEL Framework Tools 12

13 Running the BEL Compiler From BEL Framework folder: – belc.cmd (Windows) – belc.sh (Linux or OS X) Ensure that the server is not running Required: – BEL document(s) Specify filename(s) with –f OR specify path to folder of BEL documents with -p – KAM name Specify with -k – KAM description Specify with –d 13 >belc.cmd –f myDoc.bel –k myKAM –d "my KAM description"

14 Contents KAMs and the KAM store BEL Compiler – Running the BEL Compiler – Phase I - Compiler Expansions – Phase II - Equivalencing – Phase III – Compiler Augmentations BEL Framework Tools 14

15 Phase I Expansions List expansions Inner terms Protein modifications Reactions Nested statements Reciprocal statements 15

16 List Expansion - hasMembers Phase I expands hasMembers relationships to individual hasMember relationships All hasMembers relationship statements are removed p(PFH:"AKT Family") hasMember p(HGNC:AKT1) p(PFH:"AKT Family") hasMember p(HGNC:AKT2) p(PFH:"AKT Family") hasMember p(HGNC:AKT3 ) becomes 16 p(PFH:"AKT Family") hasMembers \ list(p(HGNC:AKT1),p(HGNC:AKT2),p(HGNC:AKT3))

17 List Expansion - hasComponents Phase I expands hasComponents relationships to individual hasComponent relationships All hasComponents relationship statements are removed 17 complex(NCH:"IkappaB Kinase Complex") hasComponent p(HGNC:CHUK) complex(NCH:"IkappaB Kinase Complex") hasComponent p(HGNC:IKBKB) complex(NCH:"IkappaB Kinase Complex") hasComponent p(HGNC:IKBKG) becomes complex(NCH:"IkappaB Kinase Complex") hasComponents \ list(p(HGNC:CHUK), p(HGNC:IKBKB), p(HGNC:IKBKG))

18 complexAbundance Expansion Phase I preprocesses complexAbundance() terms and injects individual hasComponent relationships 18 complex(p(HGNC:GTF2E1),p(HGNC:GTF2E2)) complex(p(HGNC:GTF2E1),p(HGNC:GTF2E2))\ hasComponent p(HGNC:GTF2E1) complex(p(HGNC:GTF2E1),p(HGNC:GTF2E2))\ hasComponent p(HGNC:GTF2E2) becomes complex(p(HGNC:GTF2E1),p(HGNC:GTF2E2))

19 compositeAbundance Expansion Phase I preprocesses compositeAbundance() terms and injects individual includes relationships composite(a(CHEBI:"deoxyribonucleic acid"), a(CHEBI:"NAD(+)")) composite(a(CHEBI:"deoxyribonucleic acid"), a(CHEBI:"NAD(+)")) includes \ a(CHEBI:"deoxyribonucleic acid"), composite(a(CHEBI:"deoxyribonucleic acid"), a(CHEBI:"NAD(+)")) includes \ a(CHEBI:"NAD(+)") becomes 19 composite(a(CHEBI:"deoxyribonucleic acid"), a(CHEBI:"NAD(+)")) \ -> ribo(p(HGNC:PARP1))

20 Inner Terms Expansion Phase I expands inner terms to relate abundances to activity terms using actsIn relationships becomes phos(p(HGNC:DUSP1)) =| kin(p(HGNC:MAPK8)) p(HGNC:DUSP1) actsIn phos(p(HGNC:DUSP1)) p(HGNC:MAPK8) actsIn kin(p(HGNC:MAPK8)) 20 phos(p(HGNC:DUSP1)) =| kin(p(HGNC:MAPK8))

21 Protein Modification Expansion Phase I expands proteinModification() sub-terms to associate a modified protein abundance with the root protein abundance p(HGNC:MAPK1, pmod(P, T)) => kin(p(HGNC:MAPK1)) p(HGNC:MAPK1) hasModification p(HGNC:MAPK1, pmod(P,T)) p(HGNC:MAPK1) actsIn kin(p(HGNC:MAPK1)) becomes 21 p(HGNC:MAPK1, pmod(P,T)) => kin(p(HGNC:MAPK1))

22 Variant Expansion Phase I expands fusion(), truncation(), and substitution() sub-terms to associate a protein variant abundance with the parent (reference) protein abundance p(HGNC:KRAS, sub(G,12,V)) p(HGNC:KRAS) hasVariant p(HGNC:KRAS, sub(G,12,V)) becomes 22 p(HGNC:KRAS, sub(G,12,V))

23 Reaction Expansion Phase I expands reactants() and products() reaction sub-terms to associate the reactant and product lists with their abundances reaction(reactants(a(CHEBI:superoxide)), \ products(a(CHEBI:"hydrogen peroxide"),a(CHEBI:oxygen)) a(CHEBI:superoxide) reactantIn \ reaction(reactants(a(CHEBI:superoxide)), \ products(a(CHEBI:"hydrogen peroxide"),a(CHEBI:oxygen)) reaction(reactants(a(CHEBI:superoxide)), \ products(a(CHEBI:"hydrogen peroxide"),a(CHEBI:oxygen)) \ hasProduct a(CHEBI:"hydrogen peroxide") reaction(reactants(a(CHEBI:superoxide)), \ products(a(CHEBI:"hydrogen peroxide"),a(CHEBI:oxygen)) \ hasProduct a(CHEBI:oxygen) becomes 23 reaction(reactants(a(CHEBI:superoxide)), products(a(CHEBI:"hydrogen peroxide"),a(CHEBI:oxygen))

24 Nested Statement Expansion The compiler will automatically expand nested statements and create additional relationships from the subject of the statement to the object of the nested statement – can be turned off using the --no-statement-expansion switch 24

25 Default Nested Statement Expansion Phase I expands nested statements to link the subject of the statement to the object of the nested statement The original statement is preserved as supporting evidence for the derived assertions p(HGNC:CLSPN) -> p(HGNC:CHEK1, pmod(P)) kin(p(HGNC:ATR)) => p(HGNC:CHEK1, pmod(P)) p(HGNC:ATR) actsIn kin(p(HGNC:ATR)) p(HGNC:CHEK1) hasModification p(HGNC:CHEK1, pmod(P)) becomes 25 p(HGNC:CLSPN) -> (kin(p(HGNC:ATR)) => p(HGNC:CHEK1, pmod(P)))

26 Modified Nested Statement Expansion When the –no-statement-expansion switch is set, the compiler will instantiate the subject of the statement and expand the nested statement but not couple the two together. The original statement is removed becomes 26 kin(p(HGNC:ATR)) => p(HGNC:CHEK1, pmod(P)) p(HGNC:CLSPN) p(HGNC:ATR) actsIn kin(p(HGNC:ATR)) p(HGNC:CHEK1) hasModification p(HGNC:CHEK1, pmod(P)) p(HGNC:CLSPN) -> (kin(p(HGNC:ATR)) => p(HGNC:CHEK1, pmod(P)))

27 Reciprocal Statement Expansion All KAM edges are directed Non-directed BEL relationships (positiveCorrelation, negativeCorrelation, association) are expanded to be expressed in both directions: 27 r(HGNC:IL8) positiveCorrelation path(MESHD:"Lung Neoplasms") path(MESHD:"Lung Neoplasms") positiveCorrelation r(HGNC:IL8) becomes r(HGNC:IL8) positiveCorrelation path(MESHD:"Lung Neoplasms") path(MESHD:"Lung Neoplasms") positiveCorrelation r(HGNC:IL8)

28 Contents KAMs and the KAM store BEL Compiler – Running the BEL Compiler – Phase I - Compiler Expansions – Phase II - Equivalencing – Phase III – Compiler Augmentations BEL Framework Tools 28

29 Phase II Equivalences Nodes are equivalenced based on: – Namespace value UUID In.beleq resource file – Equivalent unordered list complexes, composites, rxns 29

30 The BEL Framework Manages Equivalences Between External IDs Equivalences between terms from different vocabularies are provided to the BEL compiler – AKT3 in the HGNC namespace and Entrez Gene ID 10000 refer to the same gene – p(HGNC:AKT3) and p(EG:10000) coalesce to a single node in a KAM Selection of preferred namespaces “Dialect” slated for future 30

31 Contents KAMs and the KAM store BEL Compiler – Running the BEL Compiler – Phase I - Compiler Expansions – Phase II - Equivalencing – Phase III – Compiler Augmentations BEL Framework Tools 31

32 Phase III Augmentations Gene Scaffolding Protein Families Named Complexes Orthology 32

33 Network Augmentation Order Protein Family Inclusion Protein Family Inclusion Named Complex Inclusion Named Complex Inclusion Protein Family Expansion Protein Family Expansion Named Complex Expansion Named Complex Expansion Gene Scaffolding Gene Scaffolding Optional Stages Basic Stages 33 Orthology

34 Gene Scaffolding Default behavior is to insert p(), r(), and g() nodes and corresponding edges wherever a protein, rna, or gene abundance term is detected The compiler will only insert missing nodes and edges – Can be turned off with the --no-gene-scaffolding switch becomes p(HGNC:KRAS, sub(G, 12, V)) -> \ path(MESH:Neoplasms) p(HGNC:KRAS) hasVariant \ p(HGNC:KRAS, sub(G, 12, V)) r(HGNC:KRAS) >> p(HGNC:KRAS) g(HGNC:KRAS) :> r(HGNC:KRAS) 34 p(HGNC:KRAS, sub(G, 12, V)) -> path(MESHD:Neoplasms)

35 Protein Family Expansion The compiler will automatically include protein family members when a protein family term is identified – Can be turned off using the --no-protein-families switch The compiler can also search for protein families to include when a protein family member is identified – Can be enabled using the --expand-protein-families switch The compiler will automatically connect protein family activity terms with the corresponding family member activity terms 35

36 Protein Family Example 1 (Default Behavior) becomes p(HGNC:KRAS, sub(G,12,D)) -> kin(p(PFH:"MAPK JNK Family")) p(HGNC:KRAS) hasVariant p(HGNC:KRAS, sub(G,12,D)) p(PFH:"MAPK JNK Family") actsIn kin(p(PFH:"MAPK JNK Family")) p(PFH:"MAPK JNK Family") hasMember p(HGNC:MAPK8) p(PFH:"MAPK JNK Family") hasMember p(HGNC:MAPK9) p(PFH:"MAPK JNK Family") hasMember p(HGNC:MAPK10) Gene scaffolding will also be added to p(HGNC:KRAS), p(HGNC:MAPK8), p(HGNC:MAPK9), and p(HGNC:MAPK10) 36 p(HGNC:KRAS, sub(G,12,D)) -> kin(p(PFH:"MAPK JNK Family"))

37 Protein Family Example 2 (Default Behavior) becomes kin(p(HGNC:AKT1)) -> p(HGNC:RELA) kin(p(PFH:"AKT Family")) =| bp(MESHPP:Apoptosis) p(HGNC:AKT1) actsIn kin(p(HGNC:AKT1)) p(PFH:"AKT Family") actsin kin(p(PFH:"AKT Family")) p(PFH:"AKT Family") hasMember p(HGNC:AKT1) p(PFH:"AKT Family") hasMember p(HGNC:AKT2) p(PFH:"AKT Family") hasMember p(HGNC:AKT3) kin(p(HGNC:AKT1)) isA kin(p(PFH:"AKT Family")) Gene scaffolding would then be applied to p(HGNC:AKT1), p(HGNC:AKT2), p(HGNC:AKT3), and p(HGNC:RELA) 37 kin(p(HGNC:AKT1)) -> p(HGNC:RELA) kin(p(PFH:"AKT Family")) =| bp(MESHPP:Apoptosis)

38 Protein Family Example 3 (--expand-protein-families enabled) becomes kin(p(HGNC:AKT1)) -> p(HGNC:RELA) p(HGNC:AKT1) actsIn kin(p(HGNC:AKT1)) p(PFH:"AKT Family") hasMember p(HGNC:AKT1) p(PFH:"AKT Family") hasMember p(HGNC:AKT2) p(PFH:"AKT Family") hasMember p(HGNC:AKT3) Gene scaffolding would then be applied to p(HGNC:AKT1), p(HGNC:AKT2), p(HGNC:AKT3), and p(HGNC:RELA) 38 kin(p(HGNC:AKT1)) -> p(HGNC:RELA)

39 Named Complex Expansion The compiler will automatically include named complex components when a named complex member is identified – can be turned off using the --no-named-complexes switch The compiler can also search for named complexes to include when a named complex member is identified – Can be enabled using the --expand-named-complexes switch 39

40 Named Complex Expansion (Default Behavior) becomes kin(complex(NCH:"IkappaB Kinase Complex")) => \ p(HGNC:NFKBIA, pmod(P,S,32)) complex(NCH:"IkappaB Kinase Complex") actsIn \ kin(complex(NCH:"IkappaB Kinase Complex")) p(HGNC:NFKBIA) hasModification p(HGNC:NFKBIA, pmod(P, S, 32)) complex(NCH:"IkappaB Kinase Complex") hasComponent p(HGNC:CHUK) complex(NCH:"IkappaB Kinase Complex") hasComponent p(HGNC:IKBKB) complex(NCH:"IkappaB Kinase Complex") hasComponent p(HGNC:IKBKG) Gene scaffolding would then be applied to p(HGNC:CHUK), p(HGNC:NFKBIA), p(HGNC:IKBKB), and p(HGNC:IKBKG) 40 kin(complex(NCH:"IkappaB Kinase Complex")) => \ p(HGNC:NFKBIA, pmod(P,S,32))

41 Contents KAMs and the KAM store BEL Compiler – Running the BEL Compiler – Phase I - Compiler Expansions – Phase II - Equivalencing – Phase III – Compiler Augmentations BEL Framework Tools 41

42 BEL Framework Tools Found in the “tools” folder of the BEL Framework Two versions for each: –.cmd(Windows) –.sh (Linux, OS X) KamManager – Use with –h to get full options list – list KAMs in KAM store, export KAM to XGMML, delete KAM BelCheck – check BEL document validity DocumentConverter – convert between BEL script and xbel formats CacheManager – Manage cached resources 42

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