Mar 25, 2020

Patterns of 'Analytical Irreproducibility' in Multimodal Diseases

BioRxiv : the Preprint Server for Biology
A. R. BassonAlexander Rodriguez-Palacios


Multimodal diseases are those in which affected individuals can be divided into subtypes (or data modes); for instance, mild vs. severe, based on (unknown) modifiers of disease severity. Studies have shown that despite the inclusion of a large number of subjects, the causal role of the microbiome in human diseases remains uncertain. The role of the microbiome in multimodal diseases has been studied in animals; however, findings are often deemed irreproducible, or unreasonably biased, with pathogenic roles in 95% of reports. As a solution to repeatability, investigators have been told to seek funds to increase the number of human-microbiome donors (N) to increase the reproducibility of animal studies (doi:10.1016/j.cell.2019.12.025). Herein, through simulations, we illustrate that increasing N will not uniformly/universally enable the identification of consistent statistical differences (patterns of analytical irreproducibility), due to random sampling from a population with ample variability in disease and the presence of disease data subtypes (or modes). We also found that studies do not use cluster statistics when needed (97.4%, 37/38, 95%CI=86.5,99.5), and that scientists who increased N, concurrently reduced the number ...Continue Reading

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Mentioned in this Paper

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Sequence Determinations, DNA

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