Investigation of the Use of Spectral Clustering for the Analysis of Molecular Data

Abstract Image Spectral clustering involves placing objects into clusters based on the eigenvectors and eigenvalues of an associated matrix. The technique was first applied to molecular data by Brewer [J. Chem. Inf. Model. 2007, 47, 1727–1733] who demonstrated its use on a very small dataset of 125 COX-2 inhibitors. We have determined suitable parameters for spectral clustering using a wide variety of molecular descriptors and several datasets of a few thousand compounds and compared the results of clustering using a nonoverlapping version of Brewer’s use of Sarker and Boyer’s algorithm with that of Ward’s and k-means clustering. We then replaced the exact eigendecomposition method with two different approximate methods and concluded that Singular Value Decomposition is the most appropriate method for clustering larger compound collections of up to 100 000 compounds. We have also used spectral clustering with the Tversky coefficient to generate two sets of clusters linked by a common set of eigenvalues and have used this novel approach to cluster sets of fragments such as those used in fragment-based drug design.