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Record W2943637588 · doi:10.1101/622050

TimeTeller: a New Tool for Precision Circadian Medicine and Cancer Prognosis

2019· preprint· en· W2943637588 on OpenAlexaff
Denise Vlachou, Georg A. Bjarnason, Sylvie Giacchetti, Françis Lévi, D.A.J. Rand

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2019
Typepreprint
Languageen
FieldNeuroscience
TopicCircadian rhythm and melatonin
Canadian institutionsHealth Sciences CentreSunnybrook Health Science Centre
FundersBiotechnology and Biological Sciences Research CouncilEngineering and Physical Sciences Research CouncilUniversity of WarwickDirectorate for Biological SciencesInstitut National de la Santé et de la Recherche MédicaleCancer Research UK
KeywordsCircadian rhythmCircadian clockBreast cancerBiomarkerMetric (unit)CancerInternal medicinePrecision medicineOncologyMedicineDiseaseBioinformaticsComputational biologyBiologyPathologyEngineering

Abstract

fetched live from OpenAlex

Abstract Recent studies have established that the circadian clock influences onset, progression and therapeutic outcomes in a number of diseases including cancer and heart disease. Therefore, there is a need for tools to measure the functional state of the circadian clock and its downstream targets in patients. We provide such a tool and demonstrate its clinical relevance by an application to breast cancer where we find a strong link between survival and our measure of clock dysfunction. We use a machine-learning approach and construct an algorithm called TimeTeller which uses the multi-dimensional state of the genes in a transcriptomics analysis of a single biological sample to assess the level of circadian clock dysfunction. We demonstrate how this can distinguish healthy from malignant tissues and demonstrate that the molecular clock dysfunction metric is a potentially new prognostic and predictive breast cancer biomarker that is independent of the main established prognostic factors.

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)0.001
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
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 score0.173
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0010.001
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 head0.036
GPT teacher head0.265
Teacher spread0.229 · 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.

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

Citations20
Published2019
Admission routes1
Has abstractyes

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