JSM 2011 Online Program

The views expressed here are those of the individual authors and not necessarily those of the JSM sponsors, their officers, or their staff.

Abstract Details

Activity Number: 472
Type: Contributed
Date/Time: Wednesday, August 3, 2011 : 8:30 AM to 10:20 AM
Sponsor: Biopharmaceutical Section
Abstract - #303136
Title: Enhanced Hit selection through Use of Molecular Descriptors in Analysis of a High-Throughput Screening Assay
Author(s): Minya Pu*+ and Karen Messer and Howard Cottam and Tomoko Hayashi and Maripat Corr and Dennis Carson
Companies: University of California at San Diego and Moores UCSD Cancer Center and University of California at San Diego and University of California at San Diego and University of California at San Diego and University of California at San Diego
Address: , , ,
Keywords: High-throughput screening (HTS) ; Enriched structural family ; Murcko fragments ; Daylight fingerprints ; Top X approach ; HTS hit selection

A high-throughput screening assay of 160,000 small molecules was used to identify compounds that stimulate innate immune receptors. Hits were called using an enrichment strategy based on unsupervised chemoinformatic clustering of the compounds within the screening library, and also by a naïve 'top X' approach which ranked the compounds individually by activity level. Hits were prioritized using enrichment based on two different sets of molecular descriptors, Daylight-style functional class fingerprints and Murcko scaffolds, and the top X approach was used for the remaining data. A total of 2033 hits were carried forward to the confirmation screen, and the confirmation rate (CR) was estimated using a mixture model. The CR was 83.3% by Murcko fragments, 67.3% by Daylight clusters and 40% by Top X approach. ~10,000 compounds screened in both pilot and primary screens were also used to obtain an unbiased estimate of CR for the top X approach, as well as to compare our methods to a more computationally intensive method. Our computationally simple clustering approach performed similarly to the more computationally intensive method, and vastly outperformed the simple top X approach.

The address information is for the authors that have a + after their name.
Authors who are presenting talks have a * after their name.

Back to the full JSM 2011 program

2011 JSM Online Program Home

For information, contact jsm@amstat.org or phone (888) 231-3473.

If you have questions about the Continuing Education program, please contact the Education Department.