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Record W4295857825 · doi:10.1101/2022.09.06.506800

Effective use of genetically-encoded optical biosensors for profiling signalling signatures in iPSC-CMs derived from idiopathic dilated cardiomyopathy patients

2022· preprint· en· W4295857825 on OpenAlexafffund
Kyla Bourque, Ida Derish, Cara Hawey, Jace Jones-Tabah, Kashif Khan, Karima Alim, Alyson Jiang, Hooman Sadighian, Jeremy Zwaig, Natalie Gendron, Renzo Cecere, Nadia Giannetti, Terence E. Hébert

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2022
Typepreprint
Languageen
FieldMedicine
TopicCardiomyopathy and Myosin Studies
Canadian institutionsRoyal Victoria HospitalMcGill University Health CentreRoyal Victoria Regional Health CentreRoyal Ottawa Mental Health CentreMcGill University
FundersCanadian Institutes of Health ResearchFaculty of Medicine, McGill UniversityCourtois FoundationMitacsMcGill University
KeywordsDilated cardiomyopathyCardiomyopathyHeart failureDiseaseVentricleMedicineComputational biologyDrug developmentTransplantationHeart transplantationCardiologyBiologyBioinformaticsInternal medicinePharmacologyDrug

Abstract

fetched live from OpenAlex

Abstract Dilated cardiomyopathy (DCM) is a cardiovascular condition that develops when the left ventricle of the heart enlarges, compromising its function and diminishing its capacity to pump oxygenated blood throughout the body. After patients are diagnosed with DCM, disease progression can lead to heart failure and the need for a heart transplantation. DCM is a complex disease where underlying causes can be idiopathic, genetic, or environmental. An incomplete molecular understanding of disease progression poses challenges for drug discovery efforts as effective therapeutics strategies remain elusive. Decades of research using primary cells or animal models have increased our understanding of DCM but has been hampered due to the inaccessibility of human cardiomyocytes, to model cardiac disease, in vitro , in a dish. Here, our goal is to leverage patient-derived hiPSC-CMs and to combine them with biosensors to understand how cellular signalling is altered in DCM. With high sensitivity and versatility, optical biosensors represent the ideal tools to dissect the molecular determinants of cardiovascular disease, in an unbiased manner and in real-time at the level of single cells. By characterizing the pathobiology of dilated cardiomyopathy in a patient-specific manner using high content biosensor-based assays, we aim to uncover personalized mechanisms for the occurrence and development of DCM and as a pathway to development of personalized therapeutics.

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)0.000
metaresearch head score (Gemma)0.000
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 score0.001
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

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 integrity0.0010.001
Insufficient payload (model declined to judge)0.0010.000

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 head0.018
GPT teacher head0.237
Teacher spread0.220 · 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

Citations1
Published2022
Admission routes2
Has abstractyes

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