RESUMEN
MOTIVATION: Standard statistical techniques often assume that data are normally distributed, with constant variance not depending on the mean of the data. Data that violate these assumptions can often be brought in line with the assumptions by application of a transformation. Gene-expression microarray data have a complicated error structure, with a variance that changes with the mean in a non-linear fashion. Log transformations, which are often applied to microarray data, can inflate the variance of observations near background. RESULTS: We introduce a transformation that stabilizes the variance of microarray data across the full range of expression. Simulation studies also suggest that this transformation approximately symmetrizes microarray data.
Asunto(s)
Perfilación de la Expresión Génica/instrumentación , Perfilación de la Expresión Génica/métodos , Modelos Genéticos , Modelos Estadísticos , Análisis de Secuencia por Matrices de Oligonucleótidos/instrumentación , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Algoritmos , Análisis de Varianza , Calibración/normas , Interpretación Estadística de Datos , Perfilación de la Expresión Génica/normas , Funciones de Verosimilitud , Análisis de Secuencia por Matrices de Oligonucleótidos/normas , Estándares de Referencia , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Programas InformáticosRESUMEN
The development of treatment strategies for drug intoxication has been hindered in part by the lack of clinically useful antagonists. Consequently, the major goal of these studies was to determine whether a monoclonal antibody Fab fragment (of IgG) could be used as an effective drug class-selective antagonist and to understand better the dose-response relationships for reversing CNS drug toxicity. Changes in drug-induced locomotor effects in a rat model were used to assess the ability of the antiphencyclidine (anti-PCP) Fab to reverse the behavioral effects of PCP and other potent arylcyclohexylamines. In experiments to determine the pharmacodynamics of Fabinduced antagonism of behavioral effects, the Fab completely reversed all PCP-induced locomotor effects in a Fab dose-dependent manner with a minimal effective dose of 0.18 mole-equivalents of Fab and an ED50 value of about one-third mole-equivalent. The anti-PCP Fab also completely reversed the locomotor effects induced by two other structurally related potent analogs of PCP: 1-[1-(2-thienyl)cyclohexyl]piperidine and N-ethyl-1-phenylcyclohexylamine. In addition, pharmacological and immunological selectivity was further tested by treatment of the behavioral effects induced by the structurally unrelated locomotor stimulant (+)methamphetamine. The antibody did not effectively reverse the effects of methamphetamine-induced locomotor activity. These results indicate that antibody-based medications can be developed to treat toxicity caused by classes of drugs as well as by individual drugs.