Sequential screening

Van Rhee AM. Use of recursion forests in the sequential screening process consensus selection by multiple recursion trees. J Chem Inf Comput Sci 2003 43 941-8. 

We have worked in the field of cheminformatics for about a decade, and in particular we have developed statistical and computer science technology for sequential screening and advocated a paradigm shift to its adoption within the pharmaceutical and biotechnology industries (see Fig. 17.2). 

Jones-Hertzog DK, Mukhopadhyay P, Keefer CE, Young SS. Use of recursive partitioning in the sequential screening of G-protein-coupled receptors. J Pharmacol Toxicol 2000 10 207-15. 

Figure 4.64 Schematicofa mixer-tube reactor set-up used forhigh-throughput sequential screening of (i) catalysts and (N) substrates. The substrate (S) is thus treated to form the product (P) [110. ...

A strategy for the enantioseparation of basic compounds was described by SokolieP and Koller [35] and is displayed in Figure 3.7. All steps from method development till validation are included in the flow chart. Perhaps a disadvantage in this approach is that sequential screening and optimization steps are used (i.e., every factor is optimized individually). The use of the developed scheme was demonstrated for one compound, for which the method was developed, optimized, and validated. The generic applicability of this approach was not considered and is unknown. 

In our study we compare two diversity-driven design methods (uniform cell coverage and clustering), two analysis methods motivated by similarity (cell-based analysis and cluster-classification), and two descriptor sets (BCUT and constitutional). Thus, our study addresses some of the many questions arising in a sequential screen how to choose the initial screen, how to analyze the structure-activity data, and what molecular descriptor set to use. The study is limited to one assay and thus cannot be definitive, but it at least provides preliminary insights and reveals some trends. 

Key Words Decision trees, high throughput screening initial screening sets random recursive partitioning recursive partitioning sequential screening. 

We decided to examine only one sample size for the design, 4096. Abt et al. (6) examined sample size, among other factors, when studying sequential screening. Yi et al. (20) also used a sample size of 4096 when studying the optimization of a statistical analysis method for this dataset. Both studies indicated that relatively small sample sizes of 5000 to 10,000 compounds could be used to produce useful trees. Clearly, large sample sizes should lead to better... 

The hits identified by screening a small percentage of the database can be followed up using 2D methods and/or 3D pharmacophore-based further exploration of the database to retrieve more actives in a sequential screening fashion. The goal is to minimize the number of compounds screened and maximize the number of actives retrieved at the end of the screening rounds such that the relevant chemical space is explored with an optimal use of resources. 

The authors would like to acknowledge Dr. Marvin Waldman and Dr. Chien-Tin Lin of Accelrys for exciting scientific discussions and for information on algorithms on fingerprints. The authors would also like to acknowledge Dr. Frank Brown of Johnson Johnson Pharmaceutical Research and Development for discussions on sequential screening. 

Dynamic Sequential Screening in Liquid/Liquid and Gas/Liquid Reactors... 

Reactor 24 [R 24] High-throughput Gas/Liquid and Liquid/Liquid Dynamic Sequential Screening Reactor... 

Engels, M. F. M., Thielemans, T., Verbinnen, D., Tollenaere, J. P., and Verbeeck, R. (2000). Cerberus A system supporting the sequential screening process. Journal of Chemical Information and Computer Sciences, 40, 241-245. 

The expected number of runs required by a sequential screening plan depends, sometimes heavily, on (1) whether a response value may be used only once in the analysis immediately following the experimental stage in which it is acquired or may be reused in subsequent analyses, and (2) whether the experimental designs... 

Comput. Set., 40 (2), 241 (2000). CerBeruS A System Supporting the Sequential Screening Process. 

Shaughnessy et al. (155) reported the rapid, sequential screening of three phosphine ligand libraries L22-L24 in a Heck coupling reaction involving a fluorescent substrate 9.92 and the supported aryl bromide 9.93, whose structure and synthesis are reported in Fig. 9.36. 

Crisman TJ, Jenkins JL, Parker CN, Hill WAG, Bender A, Deng Z, Nettles JH, Davies JW, Ghck M. Plate Cherry Picking a novel semi-sequential screening paradigm for cheaper, faster, information-rich compound selection. J Biomol Screen 2007 12 320-327. 

Young SS, Lam RL, Welch WJ. Initial compound selection for sequential screening. Curr Opin Drug Discov Dev 2002 May 5(3) 422-427. 

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