Representing DNA Structure and Using Metaphors & Analogies

1. Representing DNA Structure andUsing Metaphors & Analogies Srinivas Narayanan Vinay K. Chaudhri

2. Hypothesis • Knowledge is grounded in small number of building blocks that are extended by composition and analogy

3. Our Work • Investigate metaphors as an organizational principle in the knowledge base • Orthogonal to taxonomic organization • Represent about 20-30 metaphors grounded in processes and forces • Use structural invariants as a basis for analogical inference propagation and validation

4. Contribution to E2E Goals • A more natural organization for the KB • Provide some of the building blocks for the core knowledge • Be able to use structure mapping in the E2E system

5. Outline • Representing DNA Structure • Pump priming • A first cut representation • Metaphors used in DNA representation • Chemical bond and connector • Holding together • Sample Questions • Constructing RNA representation from DNA • Using Analogy GUI from NWU

6. Outine

7. DNA Structure • A DNA molecule consists of two long polynucleotide chains composed of four types of nucleotide subunits. • The two chains are held together by hydrogen bonds between the base portions of the nucleotides. As we saw in Chapter 2, nucleotides are composed of a five-carbon sugar to which are attached one or more phosphate group. • The nucleotides are covalently linked together in a chain through the sugars and phosphates, which thus form a backbone of alternating sugar-phosphate-sugar-phosphate.

8. Pump Priming • Domain-specific concepts that should already be in the KB • Nucleotide • Chemical Bond • Five Carbon Sugar • Phosphate Group • Covalent Bond • Ribose and Deoxyribose • Chemical Elements: Nitrogen, Hydrogen, etc.

9. Representing Nucleotide (every Nucleotide has (parts ((a RingCompound with ((name ((Base))) (parts ((a Nitrogen with (linkedTo ((the FiveCarbonSugar parts of Self)))))))) (a FiveCarbonSugar with (instance-of ((constraint ((:set Ribose Deoxyribose) includes TheValue))))) (a PhosphateGroup with (linkedTo ((the FiveCarbonSugar parts of Self)))) (at-least 1 PhosphateGroup) (exactly 1 Base) (exactly 1 FiveCarbonSugar)))) (MELD Translation is available)

10. Technical Issues • SMEs must be able to specialize by adding additional constraints • Simply connecting the components does not seem to be enough • Possible Solutions • GKB-style constraint editing • Use dialogs to elicit constraints

11. Representing DNA Chains • A DNA chain consists of Nucleotide element each of which has one of Adenine, Gyanine, Thymine, or Cytosine as a base • Ends of the DNA chain have polarity (a 5’ and a 3’ end).

12. Representing DNA Chain (every DNA-Chain has ((prettyName (("DNA Chain" "DNA Strand"))) (name ((DNA-Chain DNA-Strand))) (chainEnd ((the1 chainElement of Self with ((name ((threeprimeEnd))) (parts ((a DeoxyRibose with (exactly 0 connectedTo)))))) (the last chainElement of Self with ((name ((fiveprimeEnd))) (parts ((a PhosphateGroup with (exactly 0 connectedTo)))))))) (chainElement ((must-be-a a Nucleotide with ((constraint ((instance-of (:set Adenine Gyanine Cytosine Thymine))))) (orientation ((VectorFromToFn FiveMinuteEnd ThreeMinuteEnd))))))

13. Technical Issues • Need a generic representation component modeling chains • Need to state spatial direction

14. Representing DNA Molecule • A DNA molecule has the shape of a double helix. • A DNA molecule consists of a pair of DNA chains. • The Chains are anti-parallel. • The Chains are held together by chemical bonds between the complementary bases along each chain. The complementary bases are A-T and C-G. The bonds are AT-bond and CG bond.

15. Representing DNA Molecule (every DNA-Molecule has ((shape ((DoubleHelix))) (parts ((:seq ((a DNA-Chain with ((chainElement ((a Nucleotide with ((parts ((a Base with ((location ((the interior of Self))) (heldBy ((a ChemicalBond with ((held ((Self) (a chainElement of (the2 DNA-Chain part of Self)))) constraint ((instance-of (:set AT-Bond GC-Bond)))))))) (exactly 1 heldby))) ……..

16. Technical Issues • Need representation components for Hold Together. • Need representation of Bonds.

17. Representing Holds • Holding objects in place involves the application of a holding force which maintains the relative position and orientation of the objects. • Holding Together is a hold whose holding force is directed inward (relative to the objects). The tendency of the objects is to move apart. • Holding Apart is a hold whose holding force is directed outward (relative to the objects). The tendency of the objects is to move toward each other.

18. Representing Hold (every Hold has ((holdingForce ((a Force with ((experiencer ((the patient of Self))))))) (patient ((a PartiallyTangible))) (maintainsInPosition ((the experiencer of Self))) (pcs-list ((:triple (forall (the held of Self)) location ?loc) (:triple (forall (the held of Self)) orientation ?orientation) (:triple (the magnitude of holdingForce) > 0))))) Issue: How is maintainsInPosition represented?

19. Variations of Hold (every HoldTogether has ((patient ((:seq (a PartiallyTangible with (potentialDirectionOfMotion ((VectorFromToFn (the2 patient of Self) (the1 patient of Self))))) (a PartiallyTangible with (potentialDirectionOfMotion ((VectorFromToFn (the1 patient of Self) (the2 patient of Self))))))) (holdingForce ((a Force with (composedOf ((a Force with ((direction ((VectorFromToFn (the1 patient of Self) (the2 patient of Self)))) (experiencer (the1 patient of Self)))) (a Force with ((direction ((VectorFromToFn (the2 patient of Self) (the1 patient Of Self)))) ………. OTHER VARIATIONS: HOLD APART, HOLD AT A DISTANCE, HOLD IN

20. Technical Issues Need a general structure that captures more complicated force interactions and processes.

21. Chemical Bonds as Connectors Instance of the General Metaphor Mapping Forces => Force-bearing Objects Chemical Bonds are broken, created, fragile, weak, destroyed, etc. (every Connector has (primaryFunction ((HoldTogether))) (ChemicalBond has ((construedAs ((Connector)))))

22. Representing Metaphors in the Knowledge Base (every DomainMap has ((source ((a Thing))) (target ((a Thing))))) (*ConnectorBondMap with (source ((a Connector))) (target ((a ChemicalBond with ((primaryFunction ((the primaryFunction of Self))))

23. Sample Questions • The nucleotide sequence of one DNA strand of a DNA double helix is 5’-GGATTTTCCCAAGG-3’. What is the sequence of the other strand? • Follows from the structure of DNA and the definition of AT and CG bonds • Need to figure out if KM inference engine will do this inference

24. Sample Questions • Which of the following DNAs would melt first? • 5’-GCGGGGCCAGCCT-3’ • 3’-CGCCCCGGTCGGA-5’ • 5’-AAATTTTAAAAGAAA-3’ • 3’-TTTAAAATTTTCTTT-5’ • Involves use of problem solving knowledge • Need to represent qualitative relations

25. Outline • Representing DNA Structure • Pump priming • A first cut representation • Metaphors used in DNA representation • Chemical bond and connector • Holding together • Sample Questions • Constructing RNA representation from DNA • Using Analogy GUI from NWU

26. INITIAL SCREEN OLD CASE NEW CASE Target Case Domain Base Case Domain Original Individuals New Individuals Original Statements New Statements Correspondences Candidate Inferences New Delete Accept

27. BASE LOADED OLD CASE NEW CASE Target Case Domain Base Case DNA Domain Cell New Individuals Original Individuals # [1] DNA [2] AT- Bond [3] CG-Bond [4] DNA-Chain [5] Phosphodigester Linkage Original Statements New Statements # [7] DNA HAS SHAPE Double Helix [9] DNA HAS PART DNA-Chain [19] DNA-Chain HAS PART Nucleotide [21] Nucleotide HAS PART Deoxyribpse Correspondences Candidate Inferences New Delete Accept

28. TARGET WITH INDIVIDUALS OLD CASE NEW CASE Target Case Domain Base Case DNA Domain Cell RNA Cell New Individuals Original Individuals # # [1] DNA [66] RNA [2] AT- Bond [67] AU- Bond [3] CG-Bond [69] CG- Bond [4] DNA-Chain [70] RNA-Chain [5] Phosphodigester Linkage [74] Phosphodigester Linkage Original Statements New Statements # # [7] DNA HAS SHAPE Double Helix [9] DNA HAS PART DNA-Chain [19] DNA-Chain HAS PART Nucleotide [21] Nucleotide HAS PART Deoxyribpse Correspondences Candidate Inferences #N Original Individual #N New Individual New Delete Accept

29. ADDING TARGET ISA STATEMENTS OLD CASE NEW CASE Target Case Domain Base Case DNA Domain Cell RNA Cell New Individuals Original Individuals # # [1] DNA [66] RNA [2] AT- Bond [67] AU- Bond [3] CG-Bond [69] CG- Bond [4] DNA-Chain [70] RNA-Chain [5] Phosphodigester Linkage [74] Phosphodigester Linkage Original Statements New Statements # # [7] DNA HAS SHAPE Double Helix [33] RNA ISA Chemical Compound [9] DNA HAS PART DNA-Chain [34] RNA-Chain ISA Chain [19] DNA-Chain HAS PART Nucleotide [21] Nucleotide HAS PART Deoxyribpse Correspondences Candidate Inferences #N Original Individual #N New Individual New Delete Accept

30. SUGGESTING CORRESPONDENCES OLD CASE NEW CASE Target Case Domain Base Case DNA Domain Cell RNA Cell New Individuals Original Individuals # # [1] DNA [66] RNA [2] [67] AU- Bond AT- Bond [3] [69] CG- Bond CG-Bond [4] DNA-Chain [70] RNA-Chain [5] Phosphodigester Linkage [74] Phosphodigester Linkage Original Statements New Statements # # [7] DNA HAS SHAPE Double Helix [33] RNA ISA Chemical Compound [9] DNA HAS PART DNA-Chain [34] RNA-Chain ISA Chain [19] DNA-Chain HAS PART Nucleotide [21] Nucleotide HAS PART Deoxyribpse Correspondences Candidate Inferences #N Original Individual #N New Individual New [1] DNA [66] RNA Delete Accept

31. RESULTS OF INITIAL MATCHING OLD CASE NEW CASE Target Case Domain Base Case DNA Domain Cell RNA Cell New Individuals Original Individuals # # [1] DNA [66] RNA [2] [67] AU- Bond AT- Bond [3] [69] CG- Bond CG-Bond [4] DNA-Chain [70] RNA-Chain [5] Phosphodigester Linkage [74] Phosphodigester Linkage Original Statements New Statements # # [7] DNA HAS SHAPE Double Helix [78] RNA HAS PART RNA-Chain [9] DNA HAS PART DNA-Chain [82] RNA -Chain HAS PART Nucleotide [19] DNA-Chain HAS PART Nucleotide [57] Nucleotide HAS PART Deoxyribose [21] Nucleotide HAS PART Deoxyribpse [48] RNA HAS SHAPE Double Helix Correspondences Candidate Inferences #N Original Individual #N New Individual New [1] DNA [66] RNA Delete [2]AT-Bond [67] AU-Bond [3] CG-Bond [69] CG-Bond Accept [4] DNA-Chain [70] RNA-Chain

32. DELETING CORRESPONDENCES OLD CASE NEW CASE Target Case Domain Base Case DNA Domain Cell RNA Cell New Individuals Original Individuals # # [1] DNA [66] RNA [2] [67] AU- Bond AT- Bond [3] [69] CG- Bond CG-Bond [4] DNA-Chain [70] RNA-Chain [5] Phosphodigester Linkage [74] Phosphodigester Linkage Original Statements New Statements # # [7] DNA HAS SHAPE Double Helix [78] RNA HAS PART RNA-Chain [9] DNA HAS PART DNA-Chain [82] RNA-Chain HAS PART Nucleotide [19] DNA-Chain HAS PART D-Nucleotide [57] Nucleotide HAS PART Deoxyribose [21] Nucleotide HAS PART Deoxyribpse [48] RNA HAS SHAPE Double Helix Correspondences Candidate Inferences #N Original Individual #N New Individual New [1] DNA [66] RNA Delete [2]AT-Bond [67] AU-Bond [3] CG-Bond [69] CG-Bond Accept [4] DNA-Chain [70] RNA-Chain

33. ADDING TARGET KNOWLEDGE OLD CASE NEW CASE Target Case Domain Base Case DNA Domain Cell RNA Cell New Individuals Original Individuals # # [1] DNA [66] RNA [2] [67] AU- Bond AT- Bond [3] [69] CG- Bond CG-Bond [4] DNA-Chain [70] RNA-Chain [5] Phosphodigester Linkage [74] Phosphodigester Linkage Original Statements New Statements # # [7] DNA HAS SHAPE Double Helix [78] RNA HAS PART RNA-Chain [9] DNA HAS PART DNA-Chain [82] RNA-Chain HAS PART Nucleotide [19] DNA-Chain HAS PART D-Nucleotide [99] RNA-Chain HAS SHAPE Chain [21] Nucleotide HAS PART Deoxyribpse [101] R-Nucleotide HAS PART Ribose Correspondences Candidate Inferences #N Original Individual #N New Individual New [1] DNA [66] RNA Delete [3] CG-Bond [69] CG-Bond [4] DNA-Chain [70] RNA-Chain Accept

34. Conclusion Representing the structure of DNA draws building blocks from space, force dynamics and event structure metaphors. RNA structure can be specified using a within-domain analogy with DNA. We have a design and are working on an implementation of the relevant concepts.