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Record W2920946515 · doi:10.1093/bioinformatics/btz189

Significance tests for analyzing gene expression data with small sample sizes

2019· article· en· W2920946515 on OpenAlexafffund
Insha Ullah, S. R. Paul, Zhenjie Hong, You‐Gan Wang

Bibliographic record

VenueBioinformatics · 2019
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGene expression and cancer classification
Canadian institutionsUniversity of Windsor
FundersAustralian Research Council Centre of Excellence for Mathematical and Statistical FrontiersNatural Sciences and Engineering Research Council of Canada
KeywordsSample size determinationVariance (accounting)Monte Carlo methodStatistical hypothesis testingComputer scienceStatisticTest statisticDegrees of freedom (physics and chemistry)Sample (material)Distribution (mathematics)StatisticsMathematicsExpression (computer science)Scripting languageAlgorithm

Abstract

fetched live from OpenAlex

MOTIVATION: Under two biologically different conditions, we are often interested in identifying differentially expressed genes. It is usually the case that the assumption of equal variances on the two groups is violated for many genes where a large number of them are required to be filtered or ranked. In these cases, exact tests are unavailable and the Welch's approximate test is most reliable one. The Welch's test involves two layers of approximations: approximating the distribution of the statistic by a t-distribution, which in turn depends on approximate degrees of freedom. This study attempts to improve upon Welch's approximate test by avoiding one layer of approximation. RESULTS: We introduce a new distribution that generalizes the t-distribution and propose a Monte Carlo based test that uses only one layer of approximation for statistical inferences. Experimental results based on extensive simulation studies show that the Monte Carol based tests enhance the statistical power and performs better than Welch's t-approximation, especially when the equal variance assumption is not met and the sample size of the sample with a larger variance is smaller. We analyzed two gene-expression datasets, namely the childhood acute lymphoblastic leukemia gene-expression dataset with 22 283 genes and Golden Spike dataset produced by a controlled experiment with 13 966 genes. The new test identified additional genes of interest in both datasets. Some of these genes have been proven to play important roles in medical literature. AVAILABILITY AND IMPLEMENTATION: R scripts and the R package mcBFtest is available in CRAN and to reproduce all reported results are available at the GitHub repository, https://github.com/iullah1980/MCTcodes. SUPPLEMENTARY INFORMATION: Supplementary data is available at Bioinformatics online.

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)0.047
metaresearch head score (Gemma)0.284
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 score0.047
Threshold uncertainty score0.249

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0470.284
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0030.003
Bibliometrics0.0040.005
Science and technology studies0.0010.006
Scholarly communication0.0020.003
Open science0.0050.003
Research integrity0.0030.007
Insufficient payload (model declined to judge)0.0100.002

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 head0.042
GPT teacher head0.281
Teacher spread0.239 · 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

Citations11
Published2019
Admission routes2
Has abstractyes

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