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Record W2122995782 · doi:10.1101/024745

Data science identifies novel drug interactions that prolong the QT interval

2015· preprint· en· W2122995782 on OpenAlexfundno aff
Tal Lorberbaum, Kevin J. Sampson, Raymond L. Woosley, Robert S. Kass, Nicholas P. Tatonetti

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2015
Typepreprint
Languageen
FieldComputer Science
TopicComputational Drug Discovery Methods
Canadian institutionsnot available
FundersNational Institute of General Medical SciencesHamilton Health Sciences Foundation
KeywordsQT intervalTorsades de pointesLong QT syndromeMedicineDrugObservational studyCardiologyInternal medicinePharmacology

Abstract

fetched live from OpenAlex

Drug-induced prolongation of the QT interval on the electrocardiogram (long QT syndrome, LQTS) can lead to a potentially fatal ventricular arrhythmia called Torsades de Pointes (TdP). 180 drugs with both cardiac and non-cardiac indications have been found to increase risk for TdP, but drug-drug interactions contributing to LQTS (QT-DDIs) remain poorly characterized. Traditional methods for mining observational healthcare data are poorly equipped to detect QT-DDI signals due to low reporting numbers and a lack of direct evidence for LQTS. In this study we present an integrative data science pipeline that effectively circumvents these limitations by identifying latent signals for QT-DDIs in the FDA?s Adverse Event Reporting System and retrospectively validating these predictions using electrocardiogram data in electronic health records. We present 26 novel QT-DDIs flagged using this method that warrant further investigation.

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)0.005
metaresearch head score (Gemma)0.018
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: none
GenreCandidate signal: Methods · Consensus signal: Methods
Teacher disagreement score0.005
Threshold uncertainty score0.025

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0050.018
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.002
Bibliometrics0.0040.003
Science and technology studies0.0010.001
Scholarly communication0.0030.002
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 head0.086
GPT teacher head0.323
Teacher spread0.237 · 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 designSimulation or modeling
Domainnot available
GenreMethods

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
Published2015
Admission routes1
Has abstractyes

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