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Robert F Harrison

Publications and source records attributed to Robert F Harrison.

6 recordsLinked to original sources

Evaluation of machine-learning methods for ligand-based virtual screening.

Machine-learning methods can be used for virtual screening by analysing the structural characteristics of molecules of known (in)activity, and we here discuss the use of kernel discrimination and naive Bayesian classifier (NBC) methods for this purpose. We report a kernel method that allows the processing of molecules represented by binary, integer and real-valued descriptors, and show that it is little different in screening performance from a previously described kernel that had been developed specifically for the analysis of binary fingerprint representations of molecular structure. We then evaluate the performance of an NBC when the training-set contains only a very few active molecules. In such cases, a simpler approach based on group fusion would appear to provide superior screening performance, especially when structurally heterogeneous datasets are to be processed.

Artificial Intelligence↗

Artificial neural network models for prediction of acute coronary syndromes using clinical data from the time of presentation.

STUDY OBJECTIVE: Clinical and ECG data from presentation are highly discriminatory for diagnosis of acute coronary syndromes, whereas definitive diagnosis from serial ECG and cardiac marker protein measurements is usually not available for several hours. Artificial neural networks are computer programs adept at pattern recognition tasks and have been used to analyze data from chest pain patients with a view to developing diagnostic algorithms that might improve triage practices in the emergency department. The aim of this study is to develop and optimize artificial neural network models for diagnosis of acute coronary syndrome, to test these models on data collected prospectively from different centers, and to establish whether the performance of these models was superior to that of models derived using a standard statistical technique, logistic regression. METHODS: The study used data from 3,147 patients presenting to 3 hospitals with acute chest pain. Data from hospital 1 were used to train the models, which were then tested on independent data from the other 2 hospitals. From 40 potential factors, variables were selected according to the logarithm of their likelihood ratios to produce models using 8, 13, 20, and 40 factors. Identical data were used for logistic regression and artificial neural network models. Calibration and performance were assessed, the latter using receiver operating characteristic (ROC) curve analysis. RESULTS: Although the performance of artificial neural network models generally increased with increasing numbers of factors, this was insignificant. The 13-factor model was therefore used for the rest of the study owing to its marginally improved calibration over the smallest model. Area under the ROC curve (with standard error) was 0.97 (0.006). The overall sensitivity and specificity of this model for acute coronary syndrome diagnosis using the training data was 0.93. ROC curves for logistic regression and artificial neural network models applied to data from the 3 hospitals were identical. For the 13-factor artificial neural network model tested on data from hospitals 2 and 3, area under the ROC curves (standard error) were 0.93 (0.006) and 0.95 (0.009), respectively. Investigation of the performance of the artificial neural network models throughout the range of predicted probabilities showed that they were well calibrated. CONCLUSION: This study confirms that artificial neural networks can offer a useful approach for developing diagnostic algorithms for chest pain patients; however, the exceptional performance and simplicity of the logistic model militates in favor of logistic regression for the present task. Our artificial neural network models were well calibrated and performed well on unseen data from different centers. These issues have not been addressed in previous studies. However, and unlike in previous studies, we did not find the performance of artificial neural network models to be significantly different from that of suitably optimized logistic regression models.

Adolescent↗

Virtual screening using binary kernel discrimination: analysis of pesticide data.

This paper discusses the use of binary kernel discrimination (BKD) for identifying potential active compounds in lead-discovery programs. BKD was compared with established virtual screening methods in a series of experiments using pesticide data from the Syngenta corporate database. It was found to be superior to methods based on similarity searching and substructural analysis but inferior to a support vector machine. Similar conclusions resulted from application of the methods to a pesticide data set for which categorical activity data were available.

Algorithms↗

Virtual screening using binary kernel discrimination: effect of noisy training data and the optimization of performance.

Binary kernel discrimination (BKD) uses a training set of compounds, for which structural and qualitative activity data are available, to produce a model that can then be applied to the structures of other compounds in order to predict their likely activity. Experiments with the MDL Drug Data Report database show that the optimal value of the smoothing parameter, and hence the predictive power of BKD, is crucially dependent on the number of false positives in the training set. It is also shown that the best results for BKD are achieved using one particular optimization method for the determination of the smoothing parameter that lies at the heart of the method and using the Jaccard/Tanimoto coefficient in the kernel function that is used to compute the similarity between a test set molecule and the members of the training set.

Algorithms↗