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Record W2040626959 · doi:10.1093/nar/gkp573

Importance of randomization in microarray experimental designs with Illumina platforms

2009· article· en· W2040626959 on OpenAlexafffund
Ricardo A. Verdugo, Christian F. Deschepper, Gloria Muñoz, Daniel Pomp, Gary A. Churchill

Bibliographic record

VenueNucleic Acids Research · 2009
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGene expression and cancer classification
Canadian institutionsMontreal Clinical Research Institute
FundersNational Institute of General Medical SciencesCanadian Institutes of Health Research
KeywordsNormalization (sociology)BiologyDNA microarrayDesign of experimentsComputational biologyConfoundingStatistical powerFalse discovery rateRandomizationComputer scienceStatistical hypothesis testingStatisticsBioinformaticsData miningGeneticsMathematicsGene expressionGeneClinical trial

Abstract

fetched live from OpenAlex

Measurements of gene expression from microarray experiments are highly dependent on experimental design. Systematic noise can be introduced into the data at numerous steps. On Illumina BeadChips, multiple samples are assayed in an ordered series of arrays. Two experiments were performed using the same samples but different hybridization designs. An experiment confounding genotype with BeadChip and treatment with array position was compared to another experiment in which these factors were randomized to BeadChip and array position. An ordinal effect of array position on intensity values was observed in both experiments. We demonstrate that there is increased rate of false-positive results in the confounded design and that attempts to correct for confounded effects by statistical modeling reduce power of detection for true differential expression. Simple analysis models without post hoc corrections provide the best results possible for a given experimental design. Normalization improved differential expression testing in both experiments but randomization was the most important factor for establishing accurate results. We conclude that lack of randomization cannot be corrected by normalization or by analytical methods. Proper randomization is essential for successful microarray experiments.

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)0.165
metaresearch head score (Gemma)0.352
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesMetaresearch
Consensus categoriesnone
DomainCandidate signal: Methods · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.835
Threshold uncertainty score0.873

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.1650.352
Meta-epidemiology (narrow)0.0020.003
Meta-epidemiology (broad)0.0040.002
Bibliometrics0.0020.004
Science and technology studies0.0020.005
Scholarly communication0.0050.004
Open science0.0040.004
Research integrity0.0030.007
Insufficient payload (model declined to judge)0.0030.002

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 head0.041
GPT teacher head0.341
Teacher spread0.300 · 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.

Study designSimulation or modeling
DomainMethods
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

Citations29
Published2009
Admission routes2
Has abstractyes

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