Evaluating point-prediction uncertainties in neural networks for protein-ligand binding prediction.

Neural Network (NN) models provide potential to speed up the drug discovery process and reduce its failure rates. The success of NN models requires uncertainty quantification (UQ) as drug discovery explores chemical space beyond the training data distribution. Standard NN models do not provide uncertainty information. Some methods require changing the NN architecture or training procedure, limiting the selection of NN models. Moreover, predictive uncertainty can come from different sources. It is important to have the ability to separately model different types of predictive uncertainty, as the model can take assorted actions depending on the source of uncertainty. In this paper, we examine UQ methods that estimate different sources of predictive uncertainty for NN models aiming at protein-ligand binding prediction. We use our prior knowledge on chemical compounds to design the experiments. By utilizing a visualization method we create non-overlapping and chemically diverse partitions from a collection of chemical compounds. These partitions are used as training and test set splits to explore NN model uncertainty. We demonstrate how the uncertainties estimated by the selected methods describe different sources of uncertainty under different partitions and featurization schemes and the relationship to prediction error.

A cross-study analysis of drug response prediction in cancer cell lines.

To enable personalized cancer treatment, machine learning models have been developed to predict drug response as a function of tumor and drug features. However, most algorithm development efforts have relied on cross-validation within a single study to assess model accuracy. While an essential first step, cross-validation within a biological data set typically provides an overly optimistic estimate of the prediction performance on independent test sets. To provide a more rigorous assessment of model generalizability between different studies, we use machine learning to analyze five publicly available cell line-based data sets: National Cancer Institute 60, ancer Therapeutics Response Portal (CTRP), Genomics of Drug Sensitivity in Cancer, Cancer Cell Line Encyclopedia and Genentech Cell Line Screening Initiative (gCSI). Based on observed experimental variability across studies, we explore estimates of prediction upper bounds. We report performance results of a variety of machine learning models, with a multitasking deep neural network achieving the best cross-study generalizability. By multiple measures, models trained on CTRP yield the most accurate predictions on the remaining testing data, and gCSI is the most predictable among the cell line data sets included in this study. With these experiments and further simulations on partial data, two lessons emerge: (1) differences in viability assays can limit model generalizability across studies and (2) drug diversity, more than tumor diversity, is crucial for raising model generalizability in preclinical screening.

Optimisation and data mining techniques for the screening of epileptic patients.

Identifying abnormalities or anomalies by visual inspection on neurophysiologic signals such as ElectroEncephaloGrams (EEGs), is extremely challenging. We propose a novel Multi-Dimensional Time Series (MDTS) classification technique, called Connectivity Support Vector Machines (C-SVMs) that integrates brain connectivity network with SVMs. To alter noise in EEG data, Independent Component Analysis based on the Unbiased Quasi Newton Method was applied. C-SVM achieved 94.8% accuracy classifying subjects compared to 69.4% accuracy with standard SVMs. It suggests that C-SVM can be a rapid, yet accurate, technique for online differentiation between epileptic and normal subjects. It may solve other classification MDTS problems too.