Speeding Up Chemical Searches Using the Inverted Index: The Convergence of Chemoinformatics and Text Search Methods

Abstract

In ligand-based screening, retrosynthesis, and other chemoinformatics applications, one of-ten seeks to search large databases of molecules in order to retrieve molecules that are similar to a given query. With the expanding size of molecular databases, the efficiency and scalability of data structures and algorithms for chemical searches are becoming increasingly important. Remarkably, both the chemoinformatics and information retrieval communities have converged on similar solutions whereby molecules or documents are represented by binary vectors, or fingerprints, indexing their substructures such as labeled paths for molecules and n-grams for text, with the same Jaccard-Tanimoto similarity measure. As a result, similarity search methods from one field can be adapted to the other. Here we adapt recent, state-of-the-art, inverted index methods from information retrieval to speed up similarity searches in chemoinformatics. Our results show a several-fold speed-up improvement over previous methods for both thresh-old searches and top-K searches. We also provide a mathematical analysis that allows one to predict the level of pruning achieved by the inverted index approach, and validate the quality of these predictions through simulation experiments. All results can be replicated using data freely downloadable from http://cdb.ics.uci.edu/.

HmSearch

“…Similarity queries with a Tanimoto threshold on binary fingerprints of chemicals are widely used in chemoinformatics applications [10,7,6,19]. There exist many specialized solutions [23,2,18,22,20].…”

“…At query time, a depth first traversal on the tree is performed together with pruning based on the number of 1-bits. One of the latest methods is [20], where each fingerprint is transformed into a set (as in Section 2) and inverted index is built on the set elements. This essentially reduces the original problem into a set overlap search problem, where the DivideSkip method proposed in their earlier work [13] is employed for query processing.…”

“…Two web pages are considered as near-duplicate if their vectors are within Hamming distance 3 [16]. • Similarity search is widely used in Chemical informatics to search and classify known chemicals, virtually screen of chemicals for drug discovery, and predict and optimize the properties of existing active compounds [10,20]. A fundamental query is to find all the molecules whose 881-bit fingerprints have Tanimoto similarity no less than t to the fingerprint of a query molecule.…”

On-Chip Reconfigurable Hardware Accelerators for Popcount Computations

“…Similarity search is widely used in chemical informatics to predict and optimize properties of existing compounds [13,14]. A fundamental problem is to find all the molecules whose fingerprints have Tanimoto similarity no less than a given value.…”

ChemCom: A Software Program for Searching and Comparing Chemical Libraries

“…As more HTS facilities are established and the number of available chemicals increases rapidly, performing large-scale searches and comparisons are becoming even more common and important. 3 Numerous methods have been developed to help speed up searches against chemical libraries [1][2][3][4][5][6][7][8] . Chemical fingerprinting, for example, is a common method of simplifying chemical representation by describing the structural properties of a chemical as a one-dimensional feature string.…”