Comparing Objective and Subjective Bayes Factors for the Two-Sample Comparison: The Classification Theorem in Action.

Many Bayes factors have been proposed for comparing population means in two-sample (independent samples) studies. Recently, Wang and Liu (2015) presented an "objective" Bayes factor (BF) as an alternative to a "subjective" one presented by Gönen et al. (2005).

Teaching Principal Components Using Correlations.

Introducing principal components (PCs) to students is difficult. First, the matrix algebra and mathematical maximization lemmas are daunting, especially for students in the social and behavioral sciences. Second, the standard motivation involving variance maximization subject to unit length constraint does not directly connect to the "variance explained" interpretation.

Pathway crosstalk effects: Shrinkage and disentanglement using a Bayesian hierarchical model.

Identifying the biological pathways that are related to various clinical phenotypes is an important concern in biomedical research. Based on estimated expression levels and/or p-values, over-representation analysis (ORA) methods provide rankings of pathways, but they are tainted because pathways overlap. This crosstalk phenomenon has not been rigorously studied and classical ORA does not take into consideration: (i) that crosstalk effects in cases of overlapping pathways can cause incorrect rankings of pathways, (ii) that crosstalk effects can cause both excess type I errors and type II errors, (iii) that rankings of small pathways are unreliable and (iv) that type I error rates can be inflated due to multiple comparisons of pathways.

Rewriting yeast central carbon metabolism for industrial isoprenoid production.

A bio-based economy has the potential to provide sustainable substitutes for petroleum-based products and new chemical building blocks for advanced materials. We previously engineered Saccharomyces cerevisiae for industrial production of the isoprenoid artemisinic acid for use in antimalarial treatments. Adapting these strains for biosynthesis of other isoprenoids such as β-farnesene (CH), a plant sesquiterpene with versatile industrial applications, is straightforward.

Closed Testing in Pharmaceutical Research: Historical and Recent Developments.

In pharmaceutical research, making multiple statistical inferences is standard practice. Unless adjustments are made for multiple testing, the probability of making erroneous determinations of significance increases with the number of inferences. Closed testing is a flexible and easily explained approach to controlling the overall error rate that has seen wide use in pharmaceutical research, particularly in clinical trials settings.

Kurtosis as Peakedness, 1905 - 2014. .

The incorrect notion that kurtosis somehow measures "peakedness" (flatness, pointiness or modality) of a distribution is remarkably persistent, despite attempts by statisticians to set the record straight. This article puts the notion to rest once and for all. Kurtosis tells you virtually nothing about the shape of the peak - its only unambiguous interpretation is in terms of tail extremity; i.

Analysis and correction of crosstalk effects in pathway analysis.

Identifying the pathways that are significantly impacted in a given condition is a crucial step in understanding the underlying biological phenomena. All approaches currently available for this purpose calculate a P-value that aims to quantify the significance of the involvement of each pathway in the given phenotype. These P-values were previously thought to be independent.

High-level semi-synthetic production of the potent antimalarial artemisinin.

In 2010 there were more than 200 million cases of malaria, and at least 655,000 deaths. The World Health Organization has recommended artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated malaria caused by the parasite Plasmodium falciparum. Artemisinin is a sesquiterpene endoperoxide with potent antimalarial properties, produced by the plant Artemisia annua.

Production of amorphadiene in yeast, and its conversion to dihydroartemisinic acid, precursor to the antimalarial agent artemisinin.

Malaria, caused by Plasmodium sp, results in almost one million deaths and over 200 million new infections annually. The World Health Organization has recommended that artemisinin-based combination therapies be used for treatment of malaria. Artemisinin is a sesquiterpene lactone isolated from the plant Artemisia annua.

On using the bootstrap for multiple comparisons.

There are many ways to bootstrap data for multiple comparisons procedures. Methods described here include (i) bootstrap (parametric and nonparametric) as a generalization of classical normal-based MaxT methods, (ii) bootstrap as an approximation to exact permutation methods, (iii) bootstrap as a generator of realistic null data sets, and (iv) bootstrap as a generator of realistic non-null data sets. Resampling of MinP versus MaxT is discussed, and the use of the bootstrap for closed testing is also presented.

Industrial fermentation of renewable diesel fuels.

In commodity chemicals, cost drives everything. A working class family of four drives up to the gas pumps and faces a choice of a renewable diesel or petroleum diesel. Renewable diesel costs $0.

How well do multiple testing methods scale up when both n and k increase?

With increasingly massive data sets in biopharmaceutical research, particularly in genomic and related applications, there is concern about how well multiple comparisons methods "scale up" with increasing number of tests (k). Familywise error rate-controlling methods do not scale up well, and false discovery rate-controlling methods do scale up well with increasing k. But neither method scales up well with increasing sample size (n) when testing point nulls.

Permutational Multiple Testing Adjustments With Multivariate Multiple Group Data.

We consider the multiple comparison problem where multiple outcomes are each compared among several different collections of groups in a multiple group setting. In this case there are several different types of hypotheses, with each specifying equality of the distributions of a single outcome over a different collection of groups. Each type of hypothesis requires a different permutational approach.

Multiple McNemar tests.

Methods for performing multiple tests of paired proportions are described. A broadly applicable method using McNemar's exact test and the exact distributions of all test statistics is developed; the method controls the familywise error rate in the strong sense under minimal assumptions. A closed form (not simulation-based) algorithm for carrying out the method is provided.

Multiple testing with minimal assumptions.

Resampling-based multiple testing methods that control the Familywise Error Rate in the strong sense are presented. It is shown that no assumptions whatsoever on the data-generating process are required to obtain a reasonably powerful and flexible class of multiple testing procedures. Improvements are obtained with mild assumptions.

Stress resistance and signal fidelity independent of nuclear MAPK function.

Elevated external solute stimulates a conserved MAPK cascade that elicits responses that maintain osmotic balance. The yeast high-osmolarity glycerol (HOG) pathway activates Hog1 MAPK (mammalian ortholog p38alpha/SAPKalpha), which enters the nucleus and induces expression of >50 genes, implying that transcriptional up-regulation is necessary to cope with hyperosmotic stress. Contrary to this expectation, we show here that cells lacking the karyopherin required for Hog1 nuclear import or in which Hog1 is anchored at the plasma membrane (or both) can withstand long-term hyperosmotic challenge by ionic and nonionic solutes without exhibiting the normal change in transcriptional program (comparable with hog1Delta cells), as judged by mRNA hybridization and microarray analysis.

Clinical trials simulation: a statistical approach.

A generic template for clinical trials simulations that are typically required by statisticians is developed. Realistic clinical trials data sets are created using a unifying model that allows general correlation structures for endpoint*timepoint data and nonnormal distributions (including time-to-event), and computationally efficient algorithms are presented. The model allows for patient dropout and noncompliance.

Simultaneous inference in general parametric models.

Simultaneous inference is a common problem in many areas of application. If multiple null hypotheses are tested simultaneously, the probability of rejecting erroneously at least one of them increases beyond the pre-specified significance level. Simultaneous inference procedures have to be used which adjust for multiplicity and thus control the overall type I error rate.

Fallback tests in dose-response clinical trials.

This article introduces a general testing procedure for performing dose-control comparisons in dose-response trials with one or more endpoints. The procedure (termed multi-stage fallback procedure) is an extension of the fallback test proposed by Wiens (2003). The multi-stage fallback procedure features a simple stepwise form and improves the power of dose-control tests at higher doses by taking into account the ordering of the doses.

Analysis of mitogen-activated protein kinase signaling specificity in response to hyperosmotic stress: use of an analog-sensitive HOG1 allele.

When confronted with a marked increase in external osmolarity, budding yeast (Saccharomyces cerevisiae) cells utilize a conserved mitogen-activated protein kinase (MAPK) signaling cascade (the high-osmolarity glycerol or HOG pathway) to elicit cellular responses necessary to permit continued growth. One input that stimulates the HOG pathway requires the integral membrane protein and putative osmosensor Sho1, which recruits and enables activation of the MAPK kinase kinase Ste11. In mutants that lack the downstream MAPK kinase (pbs2Delta) or the MAPK (hog1Delta) of the HOG pathway, Ste11 activated by hyperosmotic stress is able to inappropriately stimulate the pheromone response pathway.

Decision-theoretic views on simultaneous testing of superiority and noninferiority.

In a simultaneous testing of noninferiority and superiority in clinical trials, there is no multiplicity penalty. Ng (2003), however, argues that even though there is no inflation of the Type I error rate, this type of simultaneous testing is problematic because it may lead to loss of power in the subsequent confirmatory trial. And he recommends to conduct only one test chosen on the basis of the sponsor's preliminary assessment.

Development and validation of an age-risk score for mortality predication after thermal injury.

Background: In burn patients, the risk of mortality typically decreases as children mature, reaches a nadir at age 21, rises linearly thereafter, and levels off in old age. We hypothesized that a single "age-risk score" (AGESCORE), incorporating a cubic functional form, can be used in predictive models for mortality after burns.

Methods: Data from 6,395 thermally injured patients admitted to a single burn center between January 1, 1950, and December 31, 1999, were used.

When the stress of your environment makes you go HOG wild.

When exposed to increased dissolved solute in their environment (hyperosmotic stress), all eukaryotic cells respond by rapidly activating a conserved mitogen-activated protein kinase cascade, known in budding yeast Saccharomyces cerevisiae as the high osmolarity glycerol (HOG) pathway. Intensive genetic and biochemical analysis in this organism has revealed the presumptive osmosensors, downstream signaling components, and metabolic and transcriptional changes that allow cells to cope with this stressful condition. These findings have had direct application to understanding stress sensing and control of transcription by stress-activated mitogen-activated protein kinases in mammalian cells.