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Record W4226066106 · doi:10.1371/journal.pcbi.1010020

Survival analysis of pathway activity as a prognostic determinant in breast cancer

2022· article· en· W4226066106 on OpenAlexfundno aff
Gustavo S. Jeuken, Nicholas P. Tobin, Lukas Käll

Bibliographic record

VenuePLoS Computational Biology · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicBioinformatics and Genomic Networks
Canadian institutionsnot available
FundersBC Cancer AgencyStiftelsen för Strategisk ForskningStiftelsen för Strategisk ForskningCancer Research UK
KeywordsBiological pathwayPathway analysisComputational biologyCell survivalSignal transductionBiologyMetabolic pathwaySystems biologyBioinformaticsGeneticsGene expressionGeneApoptosis

Abstract

fetched live from OpenAlex

High throughput biology enables the measurements of relative concentrations of thousands of biomolecules from e.g. tissue samples. The process leaves the investigator with the problem of how to best interpret the potentially large number of differences between samples. Many activities in a cell depend on ordered reactions involving multiple biomolecules, often referred to as pathways. It hence makes sense to study differences between samples in terms of altered pathway activity, using so-called pathway analysis. Traditional pathway analysis gives significance to differences in the pathway components' concentrations between sample groups, however, less frequently used methods for estimating individual samples' pathway activities have been suggested. Here we demonstrate that such a method can be used for pathway-based survival analysis. Specifically, we investigate the pathway activities' association with patients' survival time based on the transcription profiles of the METABRIC dataset. Our implementation shows that pathway activities are better prognostic markers for survival time in METABRIC than the individual transcripts. We also demonstrate that we can regress out the effect of individual pathways on other pathways, which allows us to estimate the other pathways' residual pathway activity on survival. Furthermore, we illustrate how one can visualize the often interdependent measures over hierarchical pathway databases using sunburst plots.

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: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.158
Threshold uncertainty score0.352

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 head0.011
GPT teacher head0.256
Teacher spread0.244 · 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 designObservational
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

Citations21
Published2022
Admission routes1
Has abstractyes

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