Eliminating accidental deviations to minimize generalization error and maximize replicability: Applications in connectomics and genomics

Eric W. Bridgeford, Shangsi Wang, Zeyi Wang, Ting Xu, Cameron Craddock, Jayanta Dey, Gregory Kiar, William Gray-Roncal, Carlo Colantuoni, Christopher Douville, Stephanie Noble, Carey E. Priebe, Brian Caffo, Michael Milham, Xi Nian Zuo, Joshua T. Vogelstein

Research output: Contribution to journalArticlepeer-review


Replicability, the ability to replicate scientific findings, is a prerequisite for scientific discovery and clinical utility. Troublingly, we are in the midst of a replicability crisis. A key to replicability is that multiple measurements of the same item (e.g., experimental sample or clinical participant) under fixed experimental constraints are relatively similar to one another. Thus, statistics that quantify the relative contributions of accidental deviations—such as measurement error—as compared to systematic deviations—such as individual differences—are critical. We demonstrate that existing replicability statistics, such as intra-class correlation coefficient and fingerprinting, fail to adequately differentiate between accidental and systematic deviations in very simple settings. We therefore propose a novel statistic, discriminability, which quantifies the degree to which an individual’s samples are relatively similar to one another, without restricting the data to be univariate, Gaussian, or even Euclidean. Using this statistic, we introduce the possibility of optimizing experimental design via increasing discriminability and prove that optimizing discriminability improves performance bounds in subsequent inference tasks. In extensive simulated and real datasets (focusing on brain imaging and demonstrating on genomics), only optimizing data discriminability improves performance on all subsequent inference tasks for each dataset. We therefore suggest that designing experiments and analyses to optimize discriminability may be a crucial step in solving the replicability crisis, and more generally, mitigating accidental measurement error.

Original languageEnglish (US)
Article numbere1009279
JournalPLoS computational biology
Issue number9
StatePublished - Sep 2021
Externally publishedYes

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Modeling and Simulation
  • Ecology
  • Molecular Biology
  • Genetics
  • Cellular and Molecular Neuroscience
  • Computational Theory and Mathematics


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