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Record W4412754255 · doi:10.1101/2025.07.24.666661

NanoString Technologies Neuropathology Panel Produces Unreliable Measurements of Mouse Hippocampal Gene Expression

2025· preprint· en· W4412754255 on OpenAlexaff
Justin S. Rhodes, Meghan G. Connolly

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMolecular Biology Techniques and Applications
Canadian institutionsUniversity of Alberta
FundersNational Institutes of HealthNational Aeronautics and Space Administration
KeywordsNeuropathologyHippocampal formationNeuroscienceGene expressionHippocampusBiologyGeneComputational biologyCell biologyMedicinePathologyGenetics

Abstract

fetched live from OpenAlex

Abstract Technologies for measuring gene expression (i.e., the number of RNA transcripts) of large numbers of genes simultaneously in specific tissues have exploded in recent years. Current methods include high-throughput RNA sequencing (RNA-seq), transcript counting platforms like NanoString’s nCounter®, and spatially resolved techniques based on fluorescent in situ hybridization (FISH). Several studies have evaluated the reliability of these different methods and performance in comparison to one another. Typically, technical reliability, as measured by Pearson’s correlation of two measurements of the same sample, is usually well above 90%, and is statistically significant even for small sample sizes (e.g., 8 samples measured twice). We performed an experiment where we aimed to compare hippocampal gene expression between 3 groups (n=5 per group) of young adult male C57BL/6J mice. Before sampling, the groups were treated with either repeated injections of PBS (vehicle), extracellular vesicles taken from the blood plasma of sedentary mice (SedVs) or exercising mice (ExerVs). The hippocampus was dissected, and RNA purified using standard methods. The samples were analyzed using the NanoString Neuropathology panel, that measures 770 genes simultaneously. To estimate reliability, we measured 8 of the samples twice in two separate assays. Surprisingly, only 85 genes showed a significant Pearson’s correlation (p<0.05), and none of these met false discovery significance (all q<0.05). To confirm that no errors were made transferring labels, the individual samples were permuted to see whether a different assignment could recover a greater number of positive correlations. Results showed that the original assignment was best suggesting no errors in sample assignments were made. We conclude that the Nanostring neuropathology panel produces unreliable data for mouse hippocampal gene expression.

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)0.003
metaresearch head score (Gemma)0.003
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: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.017

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.003
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.001
Science and technology studies0.0010.001
Scholarly communication0.0010.000
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.001

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 head0.023
GPT teacher head0.242
Teacher spread0.219 · 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
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

Citations0
Published2025
Admission routes1
Has abstractyes

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