title: Artificial neural network--based analysis of high-throughput screening data for improved prediction of active compounds.
abstract: Artificial neural networks (ANNs) are trained using high-throughput screening (HTS) data to recover active compounds from a large data set. Improved classification performance was obtained on combining predictions made by multiple ANNs. The HTS data, acquired from a methionine aminopeptidases inhibition study, consisted of a library of 43,347 compounds, and the ratio of active to nonactive compounds, R(A/N), was 0.0321. Back-propagation ANNs were trained and validated using principal components derived from the physicochemical features of the compounds. On selecting the training parameters carefully, an ANN recovers one-third of all active compounds from the validation set with a 3-fold gain in R(A/N) value. Further gains in R(A/N) values were obtained upon combining the predictions made by a number of ANNs. The generalization property of the back-propagation ANNs was used to train those ANNs with the same training samples, after being initialized with different sets of random weights. As a result, only 10% of all available compounds were needed for training and validation, and the rest of the data set was screened with more than a 10-fold gain of the original R(A/N) value. Thus, ANNs trained with limited HTS data might become useful in recovering active compounds from large data sets.
authors: Department of Electrical Engineering and Computer Science, University of Kansas, Lawrence, KS 66045, USA. chakra@eecs.ku.edu
authors: Swapan
authors: S
authors: Chakrabarti
authors: Stan R
authors: SR
authors: Svojanovsky
authors: Romana
authors: R
authors: Slavik
authors: Gunda I
authors: GI
authors: Georg
authors: George S
authors: GS
authors: Wilson
authors: Peter G
authors: PG
authors: Smith
mesh_terms: D055808:Drug Discovery / Q000379:methods*; D057166:High-Throughput Screening Assays / Q000379:methods*; D016571:Neural Networks, Computer; D025341:Principal Component Analysis; D015203:Reproducibility of Results