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Eliminating accidental deviations to minimize generalization error and maximize reliability: applications in connectomics and genomics

Eric W. Bridgeford, Shangsi Wang, Zhi Yang, 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, Consortium for Reliability and Reproducibility, View ORCID ProfileJoshua T. Vogelstein
doi: https://doi.org/10.1101/802629
Eric W. Bridgeford
1Johns Hopkins University
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Shangsi Wang
1Johns Hopkins University
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Zhi Yang
2Shanghai Jiaotong University
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Zeyi Wang
1Johns Hopkins University
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Ting Xu
3Child Mind Institute
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Cameron Craddock
3Child Mind Institute
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Jayanta Dey
1Johns Hopkins University
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Gregory Kiar
1Johns Hopkins University
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William Gray-Roncal
1Johns Hopkins University
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Carlo Colantuoni
1Johns Hopkins University
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Christopher Douville
1Johns Hopkins University
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Stephanie Noble
4Yale University
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Carey E. Priebe
1Johns Hopkins University
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Brian Caffo
1Johns Hopkins University
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Michael Milham
3Child Mind Institute
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Xi-Nian Zuo
2Shanghai Jiaotong University
5Beijing Normal University, Nanning Normal University, University of Chinese Academy of Sciences
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Joshua T. Vogelstein
1Johns Hopkins University
5Progressive Learning
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  • ORCID record for Joshua T. Vogelstein
  • For correspondence: jovo@jhu.edu
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Abstract

Reproducibility, the ability to replicate scientific findings, is a prerequisite for scientific discovery and clinical utility. Troublingly, we are in the midst of a reproducibility crisis. A key to reproducibility 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 reproducibility 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 reproducibility crisis, and more generally, mitigating accidental measurement error.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Revised according to new feedback

  • https://neurodata.io/mgc

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted December 17, 2020.
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Eliminating accidental deviations to minimize generalization error and maximize reliability: applications in connectomics and genomics
Eric W. Bridgeford, Shangsi Wang, Zhi Yang, 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, Consortium for Reliability and Reproducibility, Joshua T. Vogelstein
bioRxiv 802629; doi: https://doi.org/10.1101/802629
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Eliminating accidental deviations to minimize generalization error and maximize reliability: applications in connectomics and genomics
Eric W. Bridgeford, Shangsi Wang, Zhi Yang, 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, Consortium for Reliability and Reproducibility, Joshua T. Vogelstein
bioRxiv 802629; doi: https://doi.org/10.1101/802629

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