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Daniel J. Wilson

Publications and source records attributed to Daniel J. Wilson.

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Doublethink: simultaneous Bayesian-frequentist model-averaged hypothesis testing

Establishing the frequentist properties of Bayesian approaches widens their appeal and offers new understanding. In hypothesis testing, Bayesian model averaging addresses the problem that conclusions are sensitive to variable selection. But Bayesian false discovery rate (FDR) guarantees are sensitive to subjective prior assumptions. Here we show that Bayesian model-averaged hypothesis testing is a closed testing procedure that controls the frequentist familywise error rate (FWER) in the strong sense. To quantify the FWER, we use the theory of regular variation and likelihood asymptotics to derive a chi-squared tail approximation for the model-averaged posterior odds. Convergence is pointwise as the sample size grows and, in a simplified setting subject to a minimum effect size assumption, uniform. The 'Doublethink' method computes simultaneous posterior odds and asymptotic p-values for model-averaged hypothesis testing. We explore Doublethink through a Mendelian randomization study and simulations, comparing to approaches like LASSO, stepwise regression, the Benjamini-Hochberg procedure, the harmonic mean p-value and e-values. We consider the limitations of the approach, including finite-sample inflation, and mitigations, like testing groups of correlated variables. We discuss the benefits of Doublethink, including post-hoc variable selection, and its wider implications for the theory and practice of hypothesis testing.

stat.ME

The Lévy combination test

A novel class of methods for combining $p$-values to perform aggregate hypothesis tests has emerged that exploit the properties of heavy-tailed Stable distributions. These methods offer important practical advantages including robustness to dependence and better-than-Bonferroni scaleability, and they reveal theoretical connections between Bayesian and classical hypothesis tests. The harmonic mean $p$-value (HMP) procedure is based on the convergence of summed inverse $p$-values to the Landau distribution, while the Cauchy combination test (CCT) is based on the self-similarity of summed Cauchy-transformed $p$-values. The CCT has the advantage that it is analytic and exact. The HMP has the advantage that it emulates a model-averaged Bayes factor, is insensitive to $p$-values near 1, and offers multilevel testing via a closed testing procedure. Here I investigate whether other Stable combination tests can combine these benefits, and identify a new method, the Lévy combination test (LCT). The LCT exploits the self-similarity of sums of Lévy random variables transformed from $p$-values. Under arbitrary dependence, the LCT possesses better robustness than the CCT and HMP, with two-fold worst-case inflation at small significance thresholds. It controls the strong-sense familywise error rate through a multilevel test uniformly more powerful than Bonferroni. Simulations show that the LCT behaves like Simes' test in some respects, with power intermediate between the HMP and Bonferroni. The LCT represents an interesting and attractive addition to combined testing methods based on heavy-tailed distributions.

stat.ME

Rapid host switching in generalist Campylobacter strains erodes the signal for tracing human infections

Campylobacter jejuni and Campylobacter coli are the biggest causes of bacterial gastroenteritis in the developed world, with human infections typically arising from zoonotic transmission associated with infected meat, especially poultry. Because this organism is not thought to survive well outside of the gut, host associated populations are genetically isolated to varying degrees. Therefore the likely origin of most Campylobacter strains can be determined by host-associated variation in the genome. This is instructive for characterizing the source of human infection at the population level. However, some common strains appear to have broad host ranges, hindering source attribution. Whole genome sequencing has the potential to reveal fine-scale genetic structure associated with host specificity within each of these strains. We found that rates of zoonotic transmission among animal host species in ST-21, ST-45 and ST-828 clonal complexes were so high that the signal of host association is all but obliterated. We attributed 89% of clinical cases to a chicken source, 10% to cattle and 1% to pig. Our results reveal that common strains of C. jejuni and C. coli infectious to humans are adapted to a generalist lifestyle, permitting rapid transmission between different hosts. Furthermore, they show that the weak signal of host association within these complexes presents a challenge for pinpointing the source of clinical infections, underlining the view that whole genome sequencing, powerful though it is, cannot substitute for intensive sampling of suspected transmission reservoirs.

q-bio.PE