Nicolas Le Novere

English

AbstractThe Systems Biology Graphical Notation (SBGN) is an effort to standardize the graphical notation used in maps of biochemical and cellular processes studied in systems biology. SBGN is made up of three orthogonal languages, representing different visions of biological systems. Each language defines a comprehensive set of symbols with precise semantics, together with detailed syntactic rules how maps are to be interpreted. In this presentation I recapitulated why SBGN was developed, and discuss the current state of the Entity Relationships language. I then describe the coming evolutions and the pending issues.</jats:p

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Report on the status of SBGN ER and proposed extensionsNature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  Graphs are everywhere in biologyNature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  Can-this be understood by biologists?Nature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  Can-this be understood by biologists?Stimulates? but ... what exactly?Associates into?  Translocates?No idea. Reciprocalstimulation?Is degraded?Stimulates genetranscription?Nature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  Ambiguity of usual representationsNature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  Kohn's Molecular Interaction Maps● Kurt W Kohn (1998) Oncogene, 16: 1065-1075● Kurt W. Kohn (1999) Mol Biol Cell, 10(8):2703-2734Nature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  Kitano's Notation● Kitano (2003) Biosilico, 1: 169-170● Kitano et al (2005)Nat Biotech, 23: 961-966 Nature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  EntersThe Systems Biology Graphical Notationhttp://www.sbgn.org/Nature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  What is SBGN?● An unambiguous way  of graphically  describing and interpreting biochemical and cellular events● Limited amount of symbolsRe-use existing symbols                                             Smooth learning curve● Can represent logical or mechanistic models, biochemical pathways, at different levels of granularity● Detailed technical specification, precise data-models and growing  software support● Initiated by Hiroaki Kitano. Developed over four years by a diverse communityNature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  Graph trinity: three languages in one notationProcess Descriptions Entity Relationships Activity Flows● Unambiguous● Mechanistic● Sequential● Combinatorial explosion● i● i ti● ti l● i t ri l l i● Unambiguous● Mechanistic● Non-sequential● Independence of relationships● i● i ti● - ti l● I  f r l ti i● Ambiguous● Conceptual● Sequential● i● t l● ti lNature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  Three orthogonal projections of biologyNature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  Nature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  http://sbgn.org/Documents/SpecificationsNature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  ABTPIf A exists, the assignment of the value P to the state variable T of B is increased Entity Relationships can be viewed as rules Nature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  ABTPIf A exists, the assignment of the value P to the state variable T of B is increased Entity Relationships can be viewed as rules (A stimulates the phosphorylation of B on the threonine)Nature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  ABTPIf A exists, the assignment of the value P to the state variable T of B is increased CSPEntity Relationships can be viewed as rules If P is assigned to the state variable T of B, the assignment of the value P to the state variable S of C is decreased Nature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  Multi-state and combinatorial explosionEGFRT654T721T845T891T920T992T1045T1068T1086T1101T1148T1173Process Descriptions: “once a state variable value,    always a state variable value”212 = 4096 states (i.e. EPN glyphs) for EGFRand 4096 complexes between EGFR and targetsPtarget1Ptarget2Ptarget3Ptarget4Ptarget5Ptarget6Ptarget7Ptarget8Ptarget9Ptarget10Ptarget11Ptarget12Nature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  Entity Relationships L1 V1 reference cardNature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  Entity Relationships L1 V1 reference cardcontinuants,things that exists (or not)Nature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  Entity Relationships L1 V1 reference cardoccurrents,events that may happen (or not)Nature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  Entity Relationships L1 V1 syntaxNature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  Example of Entity Relationships L1 V1 semanticsNature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  ER map of calcium-regulated synaptic plasticityincreases synaptic weightdecreases synaptic weightNature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  Entity Relationships L1 V2 nested entitiesNature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  A and B are part of X domainA domainBentityXNature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  X interacts with YdomainA domainBentityXentityYNature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  A of X interacts with YdomainA domainBentityXentityYNature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  Translocation of X in the nucleusdomainA domainBentityXnucleusThe value “nucleus” is assigned to the “location” of entityX, domainAand domainBNature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  degradation of XdomainA domainBentityXFThe value “false” is assigned to the “existence” of entityX, domainAand domainBNature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  insertion of B of X in the membranedomainA domainBentityXmembraneThe value “menbrane” is assigned to the “location ” of domainB but notto domainB and entityXNature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  degradation of domain A of XdomainA domainBentityXFThe value “false” is assigned to the “existence” of domainA but notto domainA and entityX that remain trueNature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  Level 1 Version 1autoinhibNature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  Level 1 Version 1Same molecule=> confusingautoinhibNature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  Level 1 Version 1T306 part of both low and high affinity => confusingautoinhibNature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  Level 1 Version 2Nature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  Pending issues● Logical operation on statements: In L1 V1, logical operators only output influences. Implicit XOR on variable assignments. Nothing for interactions.● Topology of domains: Might be necessary if we want adoption by genomics, synthetic biology etc.● Identification of instances: How to differentiate between several instances of the same entity, differentially involved in a relationships (e.g. trans-phosphorylation)?● Identification of generics: How to lump together several entities for a given  relationships? (e.g. MAPK instead of ERK1 and ERK2).Nature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  CVAUBTORNOTANDeither C or the complex of A and B inhibits ...The absence of T stimulates ...U and V are necessary tothe existence of ...Nature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  EImplicit ORvariablevalue1 value2Only ONE arc, not asuperposition of two.variable has value2variable has value1variable has value1or value2Nature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  Logical operator participating to statementsNature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  Consequence: outcomes on influencesEvariablevalue1 value2ORlogic arcassignmentvalue2 is sent tovariablevalue1 is sent tovariablevariable has value1or value2Nature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  On all influences ...AEvariablevalueA stimulates the assignment of value to variablevalue is assigned to variableNature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  Topology of domainsNature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  Instances in ERE1a E1bE2TSPPNature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010  Generics in ERERK1MEK1TPERK2MEK2TPMSK1ERKTP“=”Nature Precedings : doi:10.1038/npre.2010.4963.1 : Posted 8 Oct 2010

Nature Precedings

Report on the status of SBGN ER and proposed extensions

http://precedings.nature.com/documents/4963/version/1/files/npre20104963-1.pdf

Report on the status of SBGN ER and proposed extensions

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