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Record W4410600065 · doi:10.1186/s13059-025-03609-3

Incorporating scale uncertainty in microbiome and gene expression analysis as an extension of normalization

2025· article· en· W4410600065 on OpenAlexaff
Michelle Pistner Nixon, Gregory B. Gloor, Justin D. Silverman

Bibliographic record

VenueGenome biology · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMetabolomics and Mass Spectrometry Studies
Canadian institutionsWestern University
FundersNational Institute of General Medical SciencesNational Institutes of Health
KeywordsBiologyNormalization (sociology)Computational biologyHuman geneticsMicrobiomeEvolutionary biologyGeneticsGene expressionGene expression profilingScale (ratio)GeneCartography

Abstract

fetched live from OpenAlex

Statistical normalizations are used in differential analyses to address sample-to-sample variation in sequencing depth. Yet normalizations make strong, implicit assumptions about the scale of biological systems, such as microbial load, leading to false positives and negatives. We introduce scale models as a generalization of normalizations, which allows researchers to model potential errors in these modeling assumptions, thereby enhancing the transparency and robustness of data analyses. In practice, scale models can drastically reduce false positives and false negatives rates. We introduce updates to the popular ALDEx2 software package, available on Bioconductor, facilitating scale model analysis.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.114
Threshold uncertainty score0.367

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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 head0.006
GPT teacher head0.260
Teacher spread0.254 · 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 teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
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

Citations9
Published2025
Admission routes1
Has abstractyes

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