1. Jump to first page Relational Data

2. Jump to first page Inductive Logic Programming (ILP) n Can use ILP to find a set of rules capturing a property that the positive graphs have in common that no negative graph has. n This property is a kind of disjunction of subgraphs, where we allow one node in the graph to possibly play the role of multiple nodes in the subgraph.

3. Jump to first page Rule

4. Jump to first page Pharmacophores n A drug is a (typically) small organic molecule capable of binding to a target protein. n Binding depends on shape and on locations of charged groups, hydrophobic groups, etc. n If exact structure of target site is known, drug design is relatively easy -- but this is rarely known.

5. Jump to first page Example of Binding

6. Jump to first page Typical Practice n Test many molecules (1,000,000) to find some that bind to target (ligands). n Infer (induce) shape of target site from 3D structural similarities. n Shared 3D substructure is called a pharmacophore. n Perfect example of a machine learning task with spatial target.

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8. Pharmacophore expressed in English A Molecule M is active against Pseudomonas Aeruginosa if it has a conformation B such that: M has a hydrophobic group C, M has a hydrogen acceptor D, the distance between C and D in conformation B is 11.7 Angstroms M has a positively-charged atom E, the distance between C and E in conformation B is 4 Angstroms the distance between D and E in conformation B is 9.4 Angstroms M has a positively-charged atom F, the distance between C and F in conformation B is 11.1 Angstroms the distance between D and F in conformation B is 12.6 Angstroms the distance between E and F in conformation B is 8.7 Angstroms Tolerance 1.5 Angstroms

9. Jump to first page Obvious Question 1 n Why don’t we just use one of the ligands (hits) as the drug? n Typically they don’t meet all the other requirements for drugs: u Non-toxic (other side effects) u Active enough (drink 2 gallons) u Metabolism (lasts long enough but not too long in the body) u Take by mouth? (gut-bloodstream)

10. Jump to first page Obvious Question 2 n Why doesn’t a chemist just look at the ligands and figure out what they have in common? n Each molecule has many different shapes (conformers), any one of which might be the active one. Multiple instance problem (Dietterich, Lathrop, Lozano-Perez) n May be many molecules.

11. Jump to first page The Logical Representation of a Pharmacophore

12. Jump to first page ACE Pharmacophore n Molecule A is an ACE inhibitor if: n molecule A contains a zinc-site B, n molecule A contains a hydrogen acceptor C, n the distance between B and C is 7.89 +/- 0.75 A, n molecule A contains a hydrogen acceptor D, n the distance between B and D is 8.48 +/- 0.75 A, n the distance between C and D is 2.13 +/- 0.75 A, n molecule A contains a hydrogen acceptor E, n the distance between B and E is 4.89 +/- 0.75 A, n the distance between C and E is 3.11 +/- 0.75 A, n the distance between D and E is 3.75 +/- 0.75 A.

13. Jump to first page Molecule 1

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15. Protein Function Gene Sequence Structural Motifs Chromosomal Location Gene/Protein LevelInteractions Gene Expression Protein Interactions FUNCTION