1) Researchers developed a consensus fingerprint data mining method using 400 medicinally relevant functional groups to classify molecules and mine databases. 2) The method was validated on a dataset of over 300,000 compounds classified into 538 biological target classes, showing an average of 37.7-87.9% of active compounds recovered within the top hits. 3) Using a consensus approach that overlapped the functional group fingerprint predictions with Daylight fingerprint predictions resulted in a 50% reduction in false positives compared to the individual methods.

1. Data Mining Using Consensus Fingerprint Searches AstraZeneca CNS Chemistry, Wilmington, USA * Cancer and Infection Chemistry, Alderley Park, UK ^ James R. Arnold * Charles L. Lerman * William F. Michne * David A. Cosgrove ^ James R. Damewood *

3. Fingerprint Based Classification and Data Mining Classification is based on 400 medicinally relevant functional groups. Imigran (1): GSK, 1.07 billion dollar treatment for migraine in 2000.

4. * The exclusions make the functional group definitions specific and make the entire set as orthogonal as possible. Pattern Matching Rules

5. Classification Quality: Coverage and Overlap of Definitions Ideal Coverage Ideal Overlap Testing in medicinally relevant databases. Roughly 90% coverage and 10% overlap. Coverage : All heteroatoms in molecule are classified. Overlap : A heteroatom in molecule classified in > 1 functional group. CMC = 8,545 MDDR = 135,342 MedCh = 145,158

9. The circles are drawn to scale according to the number of actives recovered at given Tanimoto distances. Consensus Approach: Overlap of True Positives from FG Count and Daylight

10. Number of true and false positives for the Functional Group Fingerprint counts, Daylight fingerprint and consensus (logical “AND”) approaches for the five hundred and thirty eight biological target classes at Tanimoto distances of 0.0, 0.1, 0.2, and 0.3. The three methods are binned at the various Tanimoto distances and are reported in the order of counts, Daylight, consensus, and are listed as FG, D and C, respectively. Performance of the FG Count, Daylight and Consensus Approaches in Terms of True and False Positives 50% reduction false positives FG = FG Count D = Daylight C = Consensus