Computers in chemistryComputers in chemistry V 0380 Active Learning with Support Vector Machines in the Drug Discovery Process. -(WARMUTH*, M. K.; LIAO, J.; RAETSCH, G.; MATHIESON, M.; PUTTA, S.; LEMMEN, C.; J. Chem. Inf. Comput. Sci. 43 (2003) 2, 667-673; Comp. Sci. Dep., Univ. Calif., Santa Cruz, CA 95064, USA; Eng.) -Lindner 22-232

We investigate the following data mining problem from computer-aided drug design: From a large collection of compounds, find those that bind to a target molecule in as few iterations of biochemical testing as possible. In each iteration a comparatively small batch of compounds is screened for binding activity toward this target. We employed the so-called "active learning paradigm" from Machine Learning for selecting the successive batches. Our main selection strategy is based on the maximum margin hyperplane-generated by "Support Vector Machines". This hyperplane separates the current set of active from the inactive compounds and has the largest possible distance from any labeled compound. We perform a thorough comparative study of various other selection strategies on data sets provided by DuPont Pharmaceuticals and show that the strategies based on the maximum margin hyperplane clearly outperform the simpler ones.

Background: Altering a protein's function by changing its sequence allows natural proteins to be converted into useful molecular tools. Current protein engineering methods are limited by a lack of high throughput physical or computational tests that can accurately predict protein activity under conditions relevant to its final application. Here we describe a new synthetic biology approach to protein engineering that avoids these limitations by combining high throughput gene synthesis with machine learning-based design algorithms.

We consider boosting algorithms that maintain a distribution over a set of examples. At each iteration a weak hypothesis is received and the distribution is updated. We motivate these updates as minimizing the relative entropy subject to linear constraints. For example AdaBoost constrains the edge of the last hypothesis w.r.t. the updated distribution to be at most γ = 0. In some sense, AdaBoost is "corrective" w.r.t. the last hypothesis. A cleaner boosting method is to be "totally corrective": the edges of all past hypotheses are constrained to be at most γ, where γ is suitably adapted.Using new techniques, we prove the same iteration bounds for the totally corrective algorithms as for their corrective versions. Moreover with adaptive γ, the algorithms provably maximizes the margin. Experimentally, the totally corrective versions return smaller convex combinations of weak hypotheses than the corrective ones and are competitive with LPBoost, a totally corrective boosting algorithm with no regularization, for which there is no iteration bound known.