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Record W3138760652 · doi:10.1101/2021.03.21.436232

Identifying Differential Methylation in Cancer Epigenetics via a Bayesian Functional Regression Model

2021· preprint· en· W3138760652 on OpenAlexafffund
Farhad Shokoohi, David A. Stephens, Celia M.T. Greenwood

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2021
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicEpigenetics and DNA Methylation
Canadian institutionsMcGill University
FundersNatural Sciences and Engineering Research Council of Canada
KeywordsCategorical variableRegressionComputational biologyComputer scienceBayesian probabilityCovariateDNA methylationMethylationEpigeneticsBiologyData miningArtificial intelligenceMachine learningGeneticsGeneMathematicsStatistics

Abstract

fetched live from OpenAlex

Abstract DNA methylation plays an essential role in regulating gene activity, modulating disease risk, and determining treatment response. Researchers can obtain insight into methylation patterns at a single nucleotide level utilizing next-generation sequencing technologies. However, complex features inherent in the data obtained via these technologies pose challenges beyond the typical big data problems. Identifying differentially methylated cytosines (dmc) or regions is one of such challenges. Current methodologies for identifying dmcs fall short in handling low read-depth data and missing values, capturing functional data patterns, granting multiple covariates (categorical, continuous, or combination), and multiple group comparisons. We have developed an efficient method to identify dmcs based on a Bayesian functional regression approach, termed DMCFB , that tackles these shortcomings. Through simulation studies, we establish that DMCFB outperforms current methods and results in better smoothing, and efficient imputation. We apply the proposed method to analyze a dataset containing patients with acute promyelocytic leukemia and control samples. With DMCFB , we discovered many new dmcs, and more importantly, exhibited enhanced consistency of differential methylation within islands and at their adjacent shores. Furthermore, we detected differential methylation at more of the binding sites of the fused gene involved in this cancer.

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)0.009
metaresearch head score (Gemma)0.014
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: Simulation or modeling
GenreCandidate signal: Methods · Consensus signal: Methods
Teacher disagreement score0.037
Threshold uncertainty score0.073

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0090.014
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0020.002
Bibliometrics0.0020.002
Science and technology studies0.0010.001
Scholarly communication0.0010.001
Open science0.0030.001
Research integrity0.0020.002
Insufficient payload (model declined to judge)0.0030.001

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 head0.026
GPT teacher head0.269
Teacher spread0.243 · 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

Citations2
Published2021
Admission routes2
Has abstractyes

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