Talk:Hit selection
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Absolute need for review from non-RNAi perspective, LeProf
[edit]This article, while apparently written by someone with a decent knowledge-base in screening, engenders overarching biases arising from the fact that the writer's experience/knowledge is focused on a narrow area of HTS data analysis, that of siRNA screens. This is clearly reflected both in the text, and in the citations. Most HT screens performed, both in terms of numbers of screening campaigns, and number of screening conditions examined, are performed on small molecule agents (e.g., in phenotypic or biochemical assays of chemical compound libraries). The issues associated with hit selection in small molecule are distinctly different, and are at odds with the structured description of siRNA screening followup—involving clustering compounds on the basis of molecular similarity, consideration/expansion of singletons through purchase/synthesis, and weighing of chemical structure and property attributes in the active-to-hit decision process. Good HTS analysis goes far beyond mere rank ordering by potency, and a productive HTS very often features selection of series that are only weakly active, or include weakly active hits (because of other favorable structural / assay attributes, including absence of compound alerts and evidence for clear SAR for a series). Bottom line, this article needs a major re-write to bring in these widely encountered, even predominant HTS concepts.
Ditto on previous, and attention called to over-devotion to single author's work. LeProf
[edit]A POV / close-association tag was added to the article, for its overemphasis on SSMD and the exhaustive devotion to the work of a single author. See also... Davis, A.M., Keeling, D.J., Steele, J. et al. (2005) Components of successful lead generation. Curr Topics Medicinal Chem 5, 421-439 -- and using WOS, search for citations moving forward from this classic older HtL review. Any WOS search of "hit to lead" will make clear that this Wikipedia article is narrowly focused, and so missing the bulk of the relevant information on this important subject in drug discovery. The issues with the article are serious enough, that I would recommend pulling it entirely (or leaving a brief stub), rather than letting it -- in its narrowness and bias -- stand in the interim as a broadly accessible, seemingly authoritative encyclopedia entry on this important subject.