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Record W3136342625 · doi:10.1002/jha2.187

DNA methylation analysis improves the prognostication of acute myeloid leukemia

2021· article· en· W3136342625 on OpenAlexafffund
Hanie Samimi, Isha Mehta, Roderick Docking, Aamir Zainulabadeen, Aly Karsan, Habil Zare

Bibliographic record

VenueeJHaem · 2021
Typearticle
Languageen
FieldMedicine
TopicAcute Myeloid Leukemia Research
Canadian institutionsCanada's Michael Smith Genome Sciences Centre
FundersNational Institute on AgingTerry Fox Research InstituteGenome British Columbia
KeywordsDNA methylationEpigenomicsMyeloid leukemiaMethylationOncologyGeneComputational biologyMedicineBioinformaticsInternal medicineBiologyGeneticsGene expression

Abstract

fetched live from OpenAlex

Abstract Integration of orthogonal data could provide new opportunities to pinpoint the underlying molecular mechanisms of hematologic disorders. Using a novel gene network approach, we integrated DNA methylation data from The Cancer Genome Atlas ( n = 194 cases) with the corresponding gene expression profile. Our integrated gene network analysis classified AML patients into low‐, intermediate‐, and high‐risk groups. The identified high‐risk group had significantly shorter overall survival compared to the low‐risk group ( p ‐value ≤). Specifically, our approach identified a particular subgroup of nine high‐risk AML cases that died within 2 years after diagnosis. These high‐risk cases otherwise would be incorrectly classified as intermediate‐risk solely based on cytogenetics, mutation profiles, and common molecular characteristics of AML. We confirmed the prognostic value of our integrative gene network approach using two independent datasets, as well as through comparison with European LeukemiaNet and LSC17 criteria. Our approach could be useful in the prognostication of a subset of borderline AML cases. These cases would not be classified into appropriate risk groups by other approaches that use gene expression, but not DNA methylation data. Our findings highlight the significance of epigenomic data, and they indicate integrating DNA methylation data with gene coexpression networks can have a synergistic effect.

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)0.001
Version: codex-gemma-dda1882f352aValidation 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 score0.307
Threshold uncertainty score0.326

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.002
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 head0.019
GPT teacher head0.310
Teacher spread0.291 · 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 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

Citations9
Published2021
Admission routes2
Has abstractyes

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