Multiple testing subsets

High-throughput analyses are subject to problems of noise and multiple testing and involve the necessity to select reliable, informative, and biologically reasonable subsets. 

In these scenarios, the allele frequency of the variant is not considered to be different between the disease cohort and an appropriate control population. However, the hypothesis being tested is whether the polymorphism is associated with some relevant clinical characteristic, a defined phenotype, or a clinical subset of a heterogeneous syndrome. As discussed earlier, it may be difficult to ascertain disease risk when a variant from a single gene is one of several from multiple genes that together ascertain risk. Furthermore, disease modification effects may be part of a pharmacogenetic influence. In many cases, it is not ethical to withdraw or standardize therapy for all patients, so statistical methods need to be utilized to ascertain medication use as a confounder in analysis of a polymorphism s disease modification potential. 

Schema-based assessment puts the what and the why of assessment first, and it does so by supplying an integrated picture of memory, learning, and assessment. The schema comprises multiple knowledge components, each made up potentially of many different pieces of information. Any test item for a schema will call for some subset of one or more of these knowledge components. The task of the test developer is to create items to test various subsets and thereby estimate efficiently the completeness of an individual s schema knowledge.

There is also a need for cell systems that express a multiplicity of metabolic enzymes and transporters to assess dmg disposition in vivo. Cell line modification through cDNA expression can be used to add missing functions to cells that are known to express only a subset of needed enzymes or transporters known to be present in vivo. Cell lines can also be modified by deleting a natively expressed transporter so that the cell lines are more selective for other transporters. In both ways, the in vitro testing models can be improved. 

Brown-DeGane AM, McGlone J Multiple chemical sensitivity a test of the olfactory-limbic model. J Occup Environ Med 41 366-377, 1999 Caccappolo E, Kipen H, Kelly-McNeil K, et al Odor perception multiple chemical sensitivities, chronic fatigue, and asthma. J Occup Environ Med 42 629-638, 2000 Cone JE, Harrison R, Reiter R Patients with multiple chemical sensitivities clinical diagnostic subsets among an occupational health clinic population. Occup Med 2 721-738, 1987... 

BioActivity summary provides a set of functions that allows one to revise the substance/compound and assay sets. For example, one may focus only on a subset of compounds that are active in one or more of the selected assays using the Compound I Select Active link, or explore additional screen sets where the given compounds were considered active using the Assay I Add Active link. PubChem provides multiple access points for this service. For compounds or substances tested found in Entrez, one can launch this service for each individual record using the direct "BioActivity Analysis" link, or, for all of the records from an Entrez search, through the launching point at the "Tool" area. 

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