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Record W3013451229 · doi:10.1101/2020.03.23.002972

Finding associations in a heterogeneous setting: Statistical test for aberration enrichment

2020· preprint· en· W3013451229 on OpenAlexaff
Aziz M. Mezlini, Sudeshna Das, Anna Goldenberg

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2020
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGene expression and cancer classification
Canadian institutionsHospital for Sick Children
Fundersnot available
KeywordsStatistical powerVariance (accounting)Statistical hypothesis testingDiseaseDNA methylationStatistical modelComputer scienceAnalysis of varianceMultiple comparisons problemGeneGene expressionComputational biologyStatisticsBioinformaticsBiologyMedicineMathematicsMachine learningGeneticsInternal medicine

Abstract

fetched live from OpenAlex

Abstract Most two-group statistical tests are implicitly looking for a broad pattern such as an overall shift in mean, median or variance between the two groups. Therefore, they operate best in settings where the effect of interest is uniformly affecting everyone in one group versus the other. In real-world applications, there are many scenarios where the effect of interest is heterogeneous. For example, a drug that works very well on only a proportion of patients and is equivalent to a placebo on the remaining patients, or a disease associated gene expression dysregulation that only occurs in a proportion of cases whereas the remaining cases have expression levels indistinguishable from the controls for the considered gene. In these examples with heterogeneous effect, we believe that using classical two-group statistical tests may not be the most powerful way to detect the signal. In this paper, we developed a statistical test targeting heterogeneous effects and demonstrated its power in a controlled simulation setting compared to existing methods. We focused on the problem of finding meaningful associations in complex genetic diseases using omics data such as gene expression, miRNA expression, and DNA methylation. In simulated and real data, we showed that our test is complementary to the traditionally used statistical tests and is able to detect disease-relevant genes with heterogeneous effects which would not be detectable with previous approaches.

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)0.039
metaresearch head score (Gemma)0.190
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: Methods · Consensus signal: Methods
Teacher disagreement score0.039
Threshold uncertainty score0.208

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0390.190
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0020.002
Bibliometrics0.0030.002
Science and technology studies0.0010.006
Scholarly communication0.0020.002
Open science0.0020.003
Research integrity0.0020.003
Insufficient payload (model declined to judge)0.0040.000

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 head0.022
GPT teacher head0.269
Teacher spread0.248 · 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
GenreMethods

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
Published2020
Admission routes1
Has abstractyes

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