Pooling in high-throughput drug screening.

Pooling in HTS refers to the act of testing mixtures of compounds in a primary screen to accurately identify hits for secondary screening. The reduction in the number of tests needed to screen a compound library by pooling can also be extended to achieve much-needed error tolerance in HTS. Despite the success of HTS in other biological experiments, pooling in high-throughput drug screening has been a controversial and often marginalized paradigm. At first appearance, pooling appears to promise gains from reduced effort, or possibly could create more problems than solutions. However, this article demonstrates that pooling is a practical and necessary part of HTS: discussions include the rationale for pooling compounds in HTS, a unifying view of pooling design theory, a review of past attempts at pooling and their success, and recent advances in the field.

[1]  Alan Dove,et al.  Drug screening—beyond the bottleneck , 1999, Nature Biotechnology.

[2]  Jacqueline M. Hughes-Oliver,et al.  Pooling Experiments for Blood Screening and Drug Discovery , 2006, Screening.

[3]  Caroline Engeloch,et al.  Statistical evaluation of a self-deconvoluting matrix strategy for high-throughput screening of the CXCR3 receptor. , 2005, Assay and drug development technologies.

[4]  D. Balding,et al.  Efficient pooling designs for library screening. , 1994, Genomics.

[5]  Brian Hudson,et al.  Strategic Pooling of Compounds for High-Throughput Screening , 1999, J. Chem. Inf. Comput. Sci..

[6]  Wolfgang Stadje,et al.  Group testing procedures with incomplete identification and unreliable testing results , 2006 .

[7]  Nicolas Thierry-Mieg,et al.  A new pooling strategy for high-throughput screening: the Shifted Transversal Design , 2006, BMC Bioinformatics.

[8]  Annalisa De Bonis,et al.  Optimal Two-Stage Algorithms for Group Testing Problems , 2005, SIAM J. Comput..

[9]  W. Patrick Walters,et al.  A guide to drug discovery: Designing screens: how to make your hits a hit , 2003, Nature Reviews Drug Discovery.

[10]  Scott L Diamond,et al.  Evaluation of an orthogonal pooling strategy for rapid high-throughput screening of proteases. , 2008, Assay and drug development technologies.

[11]  Brian K Shoichet,et al.  Synergy and antagonism of promiscuous inhibition in multiple-compound mixtures. , 2006, Journal of medicinal chemistry.

[12]  Houghten,et al.  Drug discovery and vaccine development using mixture-based synthetic combinatorial libraries. , 2000, Drug discovery today.

[13]  Gilles Bailly,et al.  Interpool: interpreting smart-pooling results , 2008, Bioinform..

[14]  Niklaus Wirth,et al.  Algorithms and Data Structures , 1989, Lecture Notes in Computer Science.

[15]  Robert Nadon,et al.  Statistical practice in high-throughput screening data analysis , 2006, Nature Biotechnology.

[16]  Peter J. Woolf,et al.  poolHiTS: A Shifted Transversal Design based pooling strategy for high-throughput drug screening , 2008, BMC Bioinformatics.

[17]  Ely Porat,et al.  Search Methodologies , 2022 .

[18]  H. Uehara,et al.  A Positive Detecting Code and Its Decoding Algorithm for DNA Library Screening , 2009, IEEE/ACM Transactions on Computational Biology and Bioinformatics.

[19]  J. Lehár,et al.  Systematic discovery of multicomponent therapeutics , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[20]  S M Freier,et al.  Deconvolution of combinatorial libraries for drug discovery: experimental comparison of pooling strategies. , 1996, Journal of medicinal chemistry.

[21]  Minge Xie,et al.  Group Testing With Blockers and Synergism , 2001 .