RKB – A Semantic Knowledge Base For RNA (RNA ontology consortium meeting)

RKB – A Semantic Knowledge Base for RNA

Michel Dumontier 1, José Cruz-Toledo 1

Marc Parisien 2, Francois Major 2

1 Carleton University2 Université de Montreal

2Carleton University -- Dumontier Lab dumontierlab.com

Objectives

i. To represent biochemistry of nucleic acids and their structural characteristics including base pairing/stacking

ii. Represent context specific knowledge

iii. Capture the structural annotation generated by MC-Annotate

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Guided design

• Modeling with Upper Level Ontologies– interoperability and semantic coherency– New Upper Level Ontology (NULO)

• distinguishes objects, qualities, roles, processes and spatial regions

• Based on BFO/RO, but for OWL

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• Objects– Occupy space

• Nucleic acids, nucleotides, riboses and phosphates

• Qualities– Intrinsic categorical or numeric valued property

• Nucleotide bears the quality of conformation

• Roles– Defined by extrinsic interactions

• A C3’ atom may hold the exo role during some sugar puckering

• Processes– Entities that extend in time

• structure determination, an interaction

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Biological Modeling


Contextual Modeling of Nucleic Acids

• Base stacking varies in different XRD/NMR models• Need to know in which model that info is found• We want to set the stage for representing simulation.

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RKB populated with PDB, MC-Annotate

• The ontology population involved 3 steps:

i. Assigning names

ii. Asserting class membership

iii. Assigning relations between entities

• The following naming convention was used:– Objects:

• Polymer: PDBID_cCHAIN• Residue: PDBID_cCHAIN_rRESIDUE• Atom: PDBID_cCHAIN_rRESIDUE_aAtom

– Quality/Roles• PDBID_mMODEL_cCHAIN_rRESIDUE_type

– Processes• Structure determination: PDBID_mMODEL• Interaction: PDBID_mMODEL_PROCESSTYPE_PARTICIPANT

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Support for Leontis-Westhof Nomenclature

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• The RKB incorporates LW nomenclature • Describes the three edges for H-bonding

interactions in purines (Y) and pyrimidines (R)• Atom composition:

i. Watson-Crick Edge:• A(N6)/G(O6), R(N1), A(C2)/G(N2),

U(O4)/C(N4), Y(N3) and Y(O2)

ii. Hoogsteen Edge (CH edge for R):• A(N6)/G(O6), R(N7), U(O4)/C(N4) and

Y(C5)

iii. Sugar Edge:• A(C2)/G(N2), R(N3), Y(O2) and O2’

• cis and trans orientations • relative orientations of the glycosidic bond

between the sugar and the PO4 group

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Support for LW+ Nomenclature

• Extension incorporates faces to each edge:

– WC edge:• Wh, Ww and Ws faces

– Hoogsteen Edge:• C8(Y), Hh, Hw and Bh

– Sugar Edge:• Bs, Ss(Y), Sw and O2’

• The Bh and Bs faces involve the Hoogsteen side amino/keto group and the sugar side amino/ keto group respectively.

• The C8 face was introduced for the C8-H8 donor group in purines

5/25/2009 Carleton University -- Dumontier Lab dumontierlab.com

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Describing Base Pairs

• Base pairs composed of interactions with the edges or faces of the interacting bases

• Role chains capture additional knowledge:

Objects that participate in sub-processes (face interactions) are also participants of the process whole (base pair)

hasPart ◦ hasParticipant -> hasParticipant

Objects are involved in processes when their qualities are

isBearerOf ◦ isParticipantIn -> isParticipantIn


10Carleton University :: Dumontier Lab :: dumontierlab.com

The RKB is compatible with both the LW and the Saenger nomenclature for base pairs

• The semantics of the RKB enables the usage of consistent bp naming schemes

• The AA BP in model 4 of PDB:1B36 can be classified as the being member of the following classes:– Saenger type II– LW Trans Hoogsteen/Hoogsteen (8)

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A A

NucleotideBasePairand ParallelBasePairand TransBasePairand HoogsteenHoogsteenBasePairand hasAgent exactly 2 AMP


Sugar Puckering

• The ribose ring presents two distinct puckering modes, envelope and twist

• The classification into either geometry is dependent on the relative position of the carbon atoms of the ribose to its C5’ atom

• Carbon atoms in a ribose thus bear either the endo or exo role with respect to the plane formed by the other atoms

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Sugar Puckering (cont’d)

Our implementation of situational modeling assures that objects are represented by a single entity throughout their lifetime, thus avoiding the need to create multiple distinct instances of the same object in each particular spatial-temporal context with different attributes


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RKB is SPARQL accessible

• SPARQL is a graph query language• Loaded instantiated ontology into Virtuoso 6

• SPARQL endpoint– http://codemonkey.dumontierlab.com/sparql/

• Specify Graphs to restrict search– http://semanticscience.org/rkb/mcannotate/pdb/dna– http://semanticscience.org/rkb/mcannotate/pdb/rna

5/25/2009Carleton University :: Dumontier Lab ::

dumontierlab.com

http://codemonkey.dumontierlab.com/sparql/



http://semanticscience.org/rkb/mcannotate/pdb/dna

http://semanticscience.org/rkb/mcannotate/pdb/rna

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Query 1: Find all face interactions (model 1 of PDB:1B36)

PREFIX ss: <http://semanticscience.org/>

select distinct ?faceInteraction where {?pair ss:isProperPartOf <http://semanticscience.org/pdb/1B36_m1> .?pair ss:hasProperPart ?faceInteraction .?faceInteraction rdf:type ss:FaceInteraction .}

5/25/2009Carleton University :: Dumontier Lab ::

dumontierlab.com

Nucleotide base pairs are composed of one or more face interactions. Where known, such as in the MC-Annotate results, we can retrieve all 18 instances of this that satisfy this query.

http://semanticscience.org/

http://semanticscience.org/pdb/1B36_m1

Carleton University -- Dumontier Lab dumontierlab.com 155/25/2009

See results : http://tinyurl.com/porxdb

http://tinyurl.com/porxdb

http://tinyurl.com/porxdb


Query 2: Find all C8 mediated base pairs (model 1 of PDB:1B36)

PREFIX ss: <http://semanticscience.org/>SELECT DISTINCT ?faceInteraction ?residue ?hasC8Face where { ?pair ss:isProperPartOf <http://semanticscience.org/pdb/1B36_m1> . ?pair ss:hasProperPart ?faceInteraction . ?faceInteraction rdf:type ss:FaceInteraction . ?C8Face ss:isAgentIn ?faceInteraction . ?C8Face rdf:type ss:C8Face . ?residue ss:hasQuality ?C8Face

}

Results: http://tinyurl.com/r7b5e4

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Face interactions are mediated by the faces of bases. Nucleotides and their face qualities are related by the hasQuality relation, whereas faces are agents in the face interaction, and are related by the hasAgent relation.

http://tinyurl.com/r7b5e4


Query 3: Find base pairs involving a GMP sugar-sugar face (model 1 of PDB:1B36)

PREFIX ss: <http://semanticscience.org/>

SELECT distinct ?faceInteraction ?residue ?hasSSFace WHERE {?pair ss:isProperPartOf <http://semanticscience.org/pdb/1B36_m1> .?pair ss:hasProperPart ?faceInteraction .?faceInteraction rdf:type ss:FaceInteraction .?hasSSFace rdf:type ss:SugarSugarFace .?hasSSFace ss:isAgentIn ?faceInteraction .?residue ss:hasQuality ?hasSSFace .?residue rdf:type ss:GMP}

Results found at: http://tinyurl.com/qpup8z

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This query builds on Query 2, in that it requires a Ss face to be on an AMP that is participating in a base pair. Two GMPs are found to have this particular face participating with other nucleotides in base pairs in this particular structure

http://tinyurl.com/qpup8z


Query 4: Find Hoogsteen – O2’ face interactions (model 1 of PDB:1B36)

PREFIX ss: <http://semanticscience.org/>SELECT distinct ?faceInteraction ?residue1 ?residue2 ?hasHhFace ?hasO2pFace where {?pair ss:isProperPartOf <http://semanticscience.org/pdb/1B36_m1> .?pair ss:hasProperPart ?faceInteraction .?faceInteraction rdf:type ss:FaceInteraction .?hasHhFace rdf:type ss:HoogsteenHoogsteenFace .?hasHhFace ss:isAgentIn ?faceInteraction .?hasO2pFace rdf:type ss:O2pFace .?hasO2pFace ss:isAgentIn ?faceInteraction .?residue1 ss:hasQuality ?hasHhFace .?residue2 ss:hasQuality ?hasO2pFace}

Results found at: http://tinyurl.com/oo4fp8

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LW+ nomenclature more detailed for base interactions. The result of this query describes a single base pair in this structure.

http://tinyurl.com/oo4fp8


Future Directions

• Specify Saenger nomenclature • Map other structural annotator output (e.g. 3DNA)• Extend structural knowledge with 6 backbone angles

– range restrictions on classes

• SWRL / DL-safe rules or SPARQL query required to specify cyclic motifs

• Publish as part of Bio2RDF network

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RKB Availability

• Creative Commons License.• Google Code Project:

– http://semanticscience.org

• Instructions: http://code.google.com/p/semanticscience/wiki/RKBDownload

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http://semantiscience.org/

http://code.google.com/p/semanticscience/wiki/RKBDownload


References

• Dumontier, M., et al. (2009). RKB: A Semantic Web Knowledge Base for RNA, Accepted in Bio-Ontologies 2009, Stockholm, Sweden

• Smith, B., et al. (2005). Relations in biomedical ontologies. Genome Biol, 6(5): p. R46

• Leontis, N. B. and E. Westhof (2001). Geometric nomenclature and classification of RNA base pairs. RNA, 7(4): 499-512.

• Lemieux, S. and F. Major. (2002). RNA canonical and non-canonical base pairing types: a recognition method and complete repertoire. Nucleic Acids Res, 30(19): p. 4250-63.

• Major, F., Thibault, P., Computer Modeling of RNA Three-Dimensional Structures, in Encyclopedia of Molecular Cell Biology and Molecular Medicine, R.A. Meyers, Editor. 2005, Wiley-VCH Verlag GmbH & Co.: Weinheim. p. 605-636.

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Technology

RKB – A Semantic Knowledge Base For RNA (RNA ontology consortium meeting)