Evidence map›Paper›PMID 33859388›Full record

ArticleNature biomedical engineering2021

Converging genetic and epigenetic drivers of paediatric acute lymphoblastic leukaemia identified by an information-theoretic analysis.

Michael A Koldobskiy, Garrett Jenkinson, Jordi Abante, Varenka A Rodriguez DiBlasi, Weiqiang Zhou, Elisabet Pujadas, Adrian Idrizi, Rakel Tryggvadottir, Colin Callahan, Challice L Bonifant and 5 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature biomedical engineering, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.6field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Structure-guided design of 7-azaindole DNMT1 inhibitors active against hypomethylating agent-resistant acute myeloid leukemia.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Gene Characteristics and Prognostic Values of mJournal of healthcare engineering · 2021
    Article
  15. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 2 institutions in 3 countries.

Michael A KoldobskiyCenter for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Garrett JenkinsonCenter for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0003-2548-098X
Jordi AbanteWhitaker Biomedical Engineering Institute, Johns Hopkins University, Baltimore, MD, USA.ORCID http://orcid.org/0000-0003-4137-2858
Varenka A Rodriguez DiBlasiCenter for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Weiqiang ZhouDepartment of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
Elisabet PujadasCenter for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0003-4795-7945
Adrian IdriziCenter for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Rakel TryggvadottirCenter for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Colin CallahanCenter for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Challice L BonifantPediatric Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0001-9028-1683
Karen R RabinDepartment of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine, Houston, TX, USA.ORCID http://orcid.org/0000-0002-4081-8195
Patrick A BrownPediatric Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-8653-1069
Hongkai JiDepartment of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-6480-0141
John GoutsiasWhitaker Biomedical Engineering Institute, Johns Hopkins University, Baltimore, MD, USA. goutsias@jhu.edu.ORCID http://orcid.org/0000-0002-0192-3857
Andrew P FeinbergCenter for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA. afeinberg@jhu.edu.ORCID http://orcid.org/0000-0002-8364-1991
Johns Hopkins University · USBaylor College of Medicine · US

Funding

MOLECULAR PATHOLOGY OF WILMS TUMOR RELATED GENES 11PR01CA054358 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ANDREW P. FEINBERG · 1991 to 2026
$5.5M
Epigenetic Drivers of Intrinsic Phenotypic Variability in Metabolic DiseaseDP1DK119129 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI FEINBERG, ANDREW P. · 2018 to 2023
$3.9M
Computational Tools for Mining Large Amounts of ChIP and Gene Expression DataR01HG006282 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI JI, HONGKAI · 2012 to 2016
$2.0M
RADIOTHERAPY EFFECTS ON BRAIN FUNCTIONING IN ADULTSR01CA065438 · NCI · CHILDREN'S HOSPITAL OF PHILADELPHIA · PI ARMSTRONG, CAROL L. · 1997 to 2001
$987k
NCI NIH HHS R01 CA054358NCI NIH HHS R01 CA065438NHGRI NIH HHS R01 HG006282NIDDK NIH HHS DP1 DK119129
6 · The paper itself

Abstract

In cancer, linking epigenetic alterations to drivers of transformation has been difficult, in part because DNA methylation analyses must capture epigenetic variability, which is central to tumour heterogeneity and tumour plasticity. Here, by conducting a comprehensive analysis, based on information theory, of differences in methylation stochasticity in samples from patients with paediatric acute lymphoblastic leukaemia (ALL), we show that ALL epigenomes are stochastic and marked by increased methylation entropy at specific regulatory regions and genes. By integrating DNA methylation and single-cell gene-expression data, we arrived at a relationship between methylation entropy and gene-expression variability, and found that epigenetic changes in ALL converge on a shared set of genes that overlap with genetic drivers involved in chromosomal translocations across the disease spectrum. Our findings suggest that an epigenetically driven gene-regulation network, with UHRF1 (ubiquitin-like with PHD and RING finger domains 1) as a central node, links genetic drivers and epigenetic mediators in ALL.

Indexed as

Epigenesis, GeneticModels, TheoreticalCCAAT-Enhancer-Binding ProteinsChildCore Binding Factor Alpha 2 SubunitCytogenetic AnalysisDNA MethylationEntropyETS Translocation Variant 6 ProteinGene EditingGene Expression Regulation, NeoplasticHumansOncogene Proteins, FusionPrecursor Cell Lymphoblastic Leukemia-LymphomaRNA-SeqSingle-Cell AnalysisCCAAT-Enhancer-Binding ProteinsCore Binding Factor Alpha 2 SubunitETS Translocation Variant 6 ProteinOncogene Proteins, FusionTEL-AML1 fusion proteinUbiquitin-Protein LigasesUHRF1 protein, human

Identifiers

PMID33859388
PMCPMC8370714
OpenAlexW3154701921

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.