Mathematical correction for fingerprint similarity measures to improve chemical retrieval

Abstract

In many modern chemoinformatics systems, molecules are represented by long binary fingerprint vectors recording the presence or absence of particular features or substructures, such as labeled paths or trees, in the molecular graphs. These long fingerprints are often compressed to much shorter fingerprints using a simple modulo operation. As the length of the fingerprints decreases, their typical density and overlap tend to increase, and so does any similarity measure based on overlap, such as the widely used Tanimoto similarity. Here we show that this correlation between shorter fingerprints and higher similarity can be thought of as a systematic error introduced by the fingerprint folding algorithm and that this systematic error can be corrected mathematically. More precisely, given two molecules and their compressed fingerprints of a given length, we show how a better estimate of their uncompressed overlap, hence of their similarity, can be derived to correct for this bias. We show how the correction can be implemented not only for the Tanimoto measure but also for all other commonly used measures. Experiments on various data sets and fingerprint sizes demonstrate how, with a negligible computational overhead, the correction noticeably improves the sensitivity and specificity of chemical retrieval. © 2007 American Chemical Society.