Drug design for ever, from hype to hope

In its first 25 years JCAMD has been disseminating a large number of techniques aimed at finding better medicines faster. These include genetic algorithms, COMFA, QSAR, structure based techniques, homology modelling, high throughput screening, combichem, and dozens more that were a hype in their time and that now are just a useful addition to the drug-designers toolbox. Despite massive efforts throughout academic and industrial drug design research departments, the number of FDA-approved new molecular entities per year stagnates, and the pharmaceutical industry is reorganising accordingly. The recent spate of industrial consolidations and the concomitant move towards outsourcing of research activities requires better integration of all activities along the chain from bench to bedside. The next 25 years will undoubtedly show a series of translational science activities that are aimed at a better communication between all parties involved, from quantum chemistry to bedside and from academia to industry. This will above all include understanding the underlying biological problem and optimal use of all available data

Evolutionary Granular Kernel Machines

Kernel machines such as Support Vector Machines (SVMs) have been widely used in various data mining applications with good generalization properties. Performance of SVMs for solving nonlinear problems is highly affected by kernel functions. The complexity of SVMs training is mainly related to the size of a training dataset. How to design a powerful kernel, how to speed up SVMs training and how to train SVMs with millions of examples are still challenging problems in the SVMs research. For these important problems, powerful and flexible kernel trees called Evolutionary Granular Kernel Trees (EGKTs) are designed to incorporate prior domain knowledge. Granular Kernel Tree Structure Evolving System (GKTSES) is developed to evolve the structures of Granular Kernel Trees (GKTs) without prior knowledge. A voting scheme is also proposed to reduce the prediction deviation of GKTSES. To speed up EGKTs optimization, a master-slave parallel model is implemented. To help SVMs challenge large-scale data mining, a Minimum Enclosing Ball (MEB) based data reduction method is presented, and a new MEB-SVM algorithm is designed. All these kernel methods are designed based on Granular Computing (GrC). In general, Evolutionary Granular Kernel Machines (EGKMs) are investigated to optimize kernels effectively, speed up training greatly and mine huge amounts of data efficiently

Bayesian Ensemble of Regression Trees for Multinomial Probit and Quantile Regression

This dissertation proposes multinomial probit Bayesian additive regression trees (MPBART), ordered multiclass Bayesian additive classification trees (O-MBACT) and Bayesian quantile additive regression trees (BayesQArt) as extensions of BART - Bayesian additive regression trees for tackling multinomial choice, multiclass classification, ordinal regression and quantile regression problems. The proposed models exhibit very good predictive performances. In particular, ranking among the top performing procedures when non-linear relationships exist between the response and the predictors. The proposed procedures can readily be applied on data sets with the number of predictors larger than the number of observations. MPBART is sufficiently flexible to allow inclusion of predictors that describe the observed units as well as the available choice alternatives and it can also be used as a general multiclass classification procedure. Through two simulation studies and four real data examples, we show that MPBART exhibits very good out-ofsample predictive performance in comparison to other discrete choice and multiclass classification methods. To implement MPBART, the R package mpbart is freely available from CRAN repositories. When ordered gradation is exhibited by a multinomial response, ordinal regression is an appealing framework. Ensemble of trees models, while widely used for binary classification, multiclass classification and continuous response regression, have not been extensively applied to solve ordinal regression problems. This work fills this void with Bayesian sum of regression trees. The predictive performance of our ordered Bayesian ensemble of trees model is illustrated through simulation studies and real data applications. Ensemble of regression trees have become popular statistical tools for the estimation of conditional mean given a set of predictors. However, quantile regression trees and their ensembles have not yet garnered much attention despite the increasing popularity of the linear quantile regression model. This work proposes a Bayesian quantile additive regression trees model that shows very good predictive performance illustrated using simulation studies and real data applications. Further extension to tackle binary classification problems is also considered