Abstract
BackgroundThe enriched biological activity information of compounds in large and freely-accessible chemical databases like the PubChem Bioassay Database has become a powerful research resource for the scientific research community. Currently, 2D fingerprint based conventional similarity search (CSS) is the most common widely used approach for database screening, but it does not typically incorporate the relative importance of fingerprint bits to biological activity.ResultsIn this study, a large-scale similarity search investigation has been carried out on 208 well-defined compound activity classes extracted from PubChem Bioassay Database. An analysis was performed to compare the search performance of three types of 2D similarity search approaches: 2D fingerprint based conventional similarity search approach (CSS), iterative similarity search approach with multiple active compounds as references (ISS), and fingerprint based iterative similarity search with classification (ISC), which can be regarded as the combination of iterative similarity search with active references and a reversed iterative similarity search with inactive references. Compared to the search results returned by CSS, ISS improves recall but not precision. Although ISC causes the false rejection of active hits, it improves the precision with statistical significance, and outperforms both ISS and CSS. In a second part of this study, we introduce the profile concept into the three types of searches. We find that the profile based non-iterative search can significantly improve the search performance by increasing the recall rate. We also find that profile based ISS (PBISS) and profile based ISC (PBISC) significantly decreases ISS search time without sacrificing search performance.ConclusionsOn the basis of our large-scale investigation directed against a wide spectrum of pharmaceutical targets, we conclude that ISC and ISS searches perform better than 2D fingerprint similarity searching and that profile based versions of these algorithms do nearly as well in less time. We also suggest that the profile version of the iterative similarity searches are both better performing and potentially quicker than the standard algorithm.Electronic supplementary materialThe online version of this article (doi:10.1186/s13321-015-0103-5) contains supplementary material, which is available to authorized users.
Highlights
The enriched biological activity information of compounds in large and freely-accessible chemical databases like the PubChem Bioassay Database has become a powerful research resource for the scientific research community
The specific area under the ROC curve (AUC), average recall rates (ARRs) and arithmetic precision rate (APR) values of each activity class returned by six search approach can be found in three heatmaps in Additional file 1: Figure S4
It should be noted that since explicitly annotated inactives were added in each activity class, the precision rate calculation of each similarity search follows a new definition described in the method part below
Summary
The enriched biological activity information of compounds in large and freely-accessible chemical databases like the PubChem Bioassay Database has become a powerful research resource for the scientific research community. 2D fingerprint based conventional similarity search (CSS) is the most common widely used approach for database screening, but it does not typically incorporate the relative importance of fingerprint bits to biological activity. Among the search methods available, 2D fingerprint based conventional similarity search (CSS) is a well-established virtual screening tool [1, 2], in which the similarities between database compounds and the query compound are measured and ranked, and hits are selected from the top of the ranked list. The similarity between the input and compound being searched is usually measured by the Tanimoto coefficient [5], one of the most common approaches for database searching due to its simplicity [6–8], fast speed, easy implementation and results in drug discovery [8–10]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call