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Adjusting for gene-specific covariates to improve RNA-seq analysis

2023· article· en· W4385898657 on OpenAlexfundno aff
Hyeongseon Jeon, Kyu‐Sang Lim, Yet Nguyen, Dan Nettleton

Bibliographic record

VenueBioinformatics · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGene expression and cancer classification
Canadian institutionsnot available
FundersNational Institute of Food and AgricultureGenome AlbertaGenome CanadaU.S. Department of Agriculture
KeywordsCovariateEstimatorNull (SQL)Type I and type II errorsContext (archaeology)Computer scienceNull hypothesisVariable (mathematics)Null modelStatisticsMultiple comparisons problemData miningMathematicsBiology

Abstract

fetched live from OpenAlex

SUMMARY: This article suggests a novel positive false discovery rate (pFDR) controlling method for testing gene-specific hypotheses using a gene-specific covariate variable, such as gene length. We suppose the null probability depends on the covariate variable. In this context, we propose a rejection rule that accounts for heterogeneity among tests by using two distinct types of null probabilities. We establish a pFDR estimator for a given rejection rule by following Storey's q-value framework. A condition on a type 1 error posterior probability is provided that equivalently characterizes our rejection rule. We also present a suitable procedure for selecting a tuning parameter through cross-validation that maximizes the expected number of hypotheses declared significant. A simulation study demonstrates that our method is comparable to or better than existing methods across realistic scenarios. In data analysis, we find support for our method's premise that the null probability varies with a gene-specific covariate variable. AVAILABILITY AND IMPLEMENTATION: The source code repository is publicly available at https://github.com/hsjeon1217/conditional_method.

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)0.028
metaresearch head score (Gemma)0.071
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Methods · Consensus signal: Methods
Teacher disagreement score0.028
Threshold uncertainty score0.146

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0280.071
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.002
Bibliometrics0.0010.001
Science and technology studies0.0010.001
Scholarly communication0.0020.002
Open science0.0030.002
Research integrity0.0020.003
Insufficient payload (model declined to judge)0.0050.002

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 head0.026
GPT teacher head0.283
Teacher spread0.256 · 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 designBench or experimental
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

Citations0
Published2023
Admission routes1
Has abstractyes

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