Estimating the proportion of true null hypotheses and adaptive false discovery rate control in discrete paradigm.

Storey's estimator for the proportion of true null hypotheses, originally proposed under the continuous framework, has been modified in this work under the discrete framework. The modification results in improved estimation of the parameter of interest. The proposed estimator is used to formulate an adaptive version of the Benjamini-Hochberg procedure. Control over the false discovery rate by the proposed adaptive procedure has been proved analytically. The proposed estimate is also used to formulate an adaptive version of the Benjamini-Hochberg-Heyse procedure. Simulation experiments establish the conservative nature of this new adaptive procedure. Substantial amount of gain in power is observed for the new adaptive procedures over the standard procedures. For demonstration of the proposed method, two important real life gene expression data sets, one related to the study of HIV and the other related to methylation study, are used.

Bias-corrected estimators for proportion of true null hypotheses: application of adaptive FDR-controlling in segmented failure data.

Two recently introduced model-based bias-corrected estimators for proportion of true null hypotheses ( π 0 ) under multiple hypotheses testing scenario have been restructured for random observations under a suitable failure model, available for each of the common hypotheses. Based on stochastic ordering, a new motivation behind formulation of some related estimators for π 0 is given. The reduction of bias for the model-based estimators are theoretically justified and algorithms for computing the estimators are also presented. The estimators are also used to formulate a popular adaptive multiple testing procedure. Extensive numerical study supports superiority of the bias-corrected estimators. The necessity of the proper distributional assumption for the failure data in the context of the model-based bias-corrected method has been highlighted. A case-study is done with a real-life dataset in connection with reliability and warranty studies to demonstrate the applicability of the procedure, under a non-Gaussian setup. The results obtained are in line with the intuition and experience of the subject expert. An intriguing discussion has been attempted to conclude the article that also indicates the future scope of study.

Two-stage test of means of unordered pairs.

The problem of testing equality of means of a bivariate normal distribution on the basis of a sample of size n has been considered when the labels of the observations are either missing or not known. The problem may arise in many applied settings, especially in genetics. Classical likelihood ratio test fails here because of identifiability problems. We propose a two-stage testing procedure using a recently developed test in the context of penalized splines. The proposed testing procedure is found to outperform the tests proposed in the literature. Copyright © 2017 John Wiley & Sons, Ltd.

Simultaneous identification of growth law and estimation of its rate parameter for biological growth data: a new approach.

Scientific formalizations of the notion of growth and measurement of the rate of growth in living organisms are age-old problems. The most frequently used metric, "Average Relative Growth Rate" is invariant under the choice of the underlying growth model. Theoretically, the estimated rate parameter and relative growth rate remain constant for all mutually exclusive and exhaustive time intervals if the underlying law is exponential but not for other common growth laws (e.g., logistic, Gompertz, power, general logistic). We propose a new growth metric specific to a particular growth law and show that it is capable of identifying the underlying growth model. The metric remains constant over different time intervals if the underlying law is true, while the extent of its variation reflects the departure of the assumed model from the true one. We propose a new estimator of the relative growth rate, which is more sensitive to the true underlying model than the existing one. The advantage of using this is that it can detect crucial intervals where the growth process is erratic and unusual. It may help experimental scientists to study more closely the effect of the parameters responsible for the growth of the organism/population under study.

Comparative efficacies of artemisinin combination therapies in Plasmodium falciparum malaria and polymorphism of pfATPase6, pfcrt, pfdhfr, and pfdhps genes in tea gardens of Jalpaiguri District, India.

In India, chloroquine has been replaced by a combination of artesunate and sulfadoxine-pyrimethamine (AS-SP) for uncomplicated P. falciparum malaria. Other available combinations, artemether-lumefantrine (AM-LF) and artesunate-mefloquine (AS-MQ), not included in the national program, are widely used by private practitioners. Little is known about the therapeutic efficacy of these artemisinin combinations and the prevalence of molecular markers associated with antimalarial drug resistance. A total of 157 patients with P. falciparum monoinfection were recruited and randomized into three study groups (AS-SP, AM-LF, and AS-MQ). All patients were followed up for 42 days to study the clinical and parasitological responses according to the WHO protocol (2009). We assessed the polymorphism of the pfATPase6, pfcrt, pfdhfr, and pfdhps genes by the DNA-sequencing method. The PCR-corrected therapeutic efficacies of AS-SP, AM-LF, and AS-MQ were 90.6% (95% confidence interval [CI], 0.793 to 0.969), 95.9% (95% CI, 0.860 to 0.995), and 100% (95% CI, 0.927 to 1.00), respectively. No specific mutational pattern was observed in the pfATPase6 gene. All isolates had a K76T mutation in the pfcrt gene. In the pfdhfr-pfdhps genotype, quadruple mutation was frequent, and quintuple mutation was documented in 6.3% of P. falciparum isolates. The significant failure rate of AS-SP (9.5%), although within the limit (10%) for drug policy change, was due to SP failure because of prevailing mutations in pfdhfr, I(51)R(59)N(108), with pfdhps, G(437) and/or E(540). The efficacy of this ACT needs periodic monitoring. Artemether-lumefantrine and artesunate-mefloquine are effective alternatives to the artesunate-sulfadoxine-pyrimethamine combination.