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Relational Data

Relational Data. Inductive Logic Programming (ILP). Can use ILP to find a set of rules capturing a property that the positive graphs have in common that no negative graph has.

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Relational Data

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  1. Relational Data

  2. Inductive Logic Programming (ILP) • Can use ILP to find a set of rules capturing a property that the positive graphs have in common that no negative graph has. • 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. Rule

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

  5. Example of Binding

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

  7. 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

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

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

  10. The Logical Representation of a Pharmacophore

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

  12. Molecule 1

  13. Gene/Protein Level Interactions Gene Expression Gene Sequence Structural Motifs FUNCTION Protein Interactions Chromosomal Location Protein Function

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