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Record W4413342628 · doi:10.1073/pnas.2424203122

Minimizing and quantifying uncertainty in AI-informed decisions: Applications in medicine

2025· article· en· W4413342628 on OpenAlexaff
Samuel D. Curtis, Sambit Panda, Adam Li, Haoyin Xu, Yuhang Bai, Itsuki Ogihara, Eliza O’Reilly, Yuxuan Wang, Lisa Dobbyn, Maria Popoli, Janine Ptak, Nadine T. Nehme, Natalie Silliman, Jeanne Tie, Peter Gibbs, Lan T. Ho‐Pham, Ngoc Bich Tran, Thach Tran, Tuan V. Nguyen, Ehsan Irajizad, Michael Goggins, Christopher L. Wolfgang, Tian‐Li Wang, Ie‐Ming Shih, Amanda N. Fader, Anne Marie Lennon, Ralph H. Hruban, Chetan Bettegowda, Lucy Gilbert, Kenneth W. Kinzler, Nickolas Papadopoulos, Bert Vogelstein, Joshua T Vogelstein, Christopher Douville

Bibliographic record

VenueProceedings of the National Academy of Sciences · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer Genomics and Diagnostics
Canadian institutionsMcGill University Health Centre
FundersNational Health and Medical Research CouncilNational Institutes of HealthDepartment of Health and Aged Care, Australian Government
KeywordsFalse positive paradoxComputer scienceNonparametric statisticsUncertainty quantificationSensitivity (control systems)Parametric statisticsFalse positives and false negativesVariable (mathematics)Set (abstract data type)Data miningMachine learningArtificial intelligenceAlgorithmStatisticsMathematics

Abstract

fetched live from OpenAlex

AI is now a cornerstone of modern dataset analysis. In many real world applications, practitioners are concerned with controlling specific kinds of errors, rather than minimizing the overall number of errors. For example, biomedical screening assays may primarily be concerned with mitigating the number of false positives rather than false negatives. Quantifying uncertainty in AI-based predictions, and in particular those controlling specific kinds of errors, remains theoretically and practically challenging. We develop a strategy called multidimensional informed generalized hypothesis testing (MIGHT) which we prove accurately quantifies uncertainty and confidence given sufficient data, and concomitantly controls for particular error types. Our key insight was that it is possible to integrate canonical cross-validation and parametric calibration procedures within a nonparametric ensemble method. Simulations demonstrate that while typical AI based-approaches cannot be trusted to obtain the truth, MIGHT can be. We apply MIGHT to answer an open question in liquid biopsies using circulating cell-free DNA (ccfDNA) in individuals with or without cancer: Which biomarkers, or combinations thereof, can we trust? Performance estimates produced by MIGHT on ccfDNA data have coefficients of variation that are often orders of magnitude lower than other state of the art algorithms such as support vector machines, random forests, and Transformers, while often also achieving higher sensitivity. We find that combinations of variable sets often decrease rather than increase sensitivity over the optimal single variable set because some variable sets add more noise than signal. This work demonstrates the importance of quantifying uncertainty and confidence-with theoretical guarantees-for the interpretation of real-world data.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.029
metaresearch head score (Gemma)0.112
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Theoretical or conceptual · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.029
Threshold uncertainty score0.156

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0290.112
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0030.002
Bibliometrics0.0030.003
Science and technology studies0.0010.006
Scholarly communication0.0040.005
Open science0.0030.005
Research integrity0.0040.006
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.054
GPT teacher head0.373
Teacher spread0.319 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designTheoretical or conceptual
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations4
Published2025
Admission routes1
Has abstractyes

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