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Record W4402620139 · doi:10.1038/s41467-024-52283-9

DNA Methylation signatures underpinning blood neutrophil to lymphocyte ratio during first week of human life

2024· article· en· W4402620139 on OpenAlexaff
David Martino, Nina Kresoje, Nelly Amenyogbe, Rym Ben-Othman, Bing Cai, Mandy Lo, Olubukola T. Idoko, Oludare A. Odumade, Reza Falsafi, Travis M. Blimkie, Andy An, Casey P. Shannon, Sebastiano Montante, Bhavjinder K. Dhillon, Joann Diray‐Arce, Al Ozonoff, Kinga K. Smolen, Ryan R. Brinkman, Kerry McEnaney, Asimenia Angelidou, Peter Richmond, Scott J. Tebbutt, Beate Kampmann, Ofer Levy, Robert E. W. Hancock, Amy Huei‐Yi Lee, Tobias R. Kollmann

Bibliographic record

VenueNature Communications · 2024
Typearticle
Languageen
FieldMedicine
TopicNeonatal Respiratory Health Research
Canadian institutionsSimon Fraser UniversityBC Cancer AgencyPrevention of Organ FailureDalhousie UniversityBC Children's HospitalUniversity of British ColumbiaSNC-Lavalin (Canada)St. Paul's Hospital
FundersNational Institute on Minority Health and Health DisparitiesNational Institute of Allergy and Infectious DiseasesMedical Research CouncilNational Institutes of HealthU.S. Department of Health and Human Services
KeywordsEpigeneticsDNA methylationBiologyImmune systemImmunologyMethylationImmunityDifferentially methylated regionsEpigenomicsGeneticsGeneGene expression

Abstract

fetched live from OpenAlex

Understanding of newborn immune ontogeny in the first week of life will enable age-appropriate strategies for safeguarding vulnerable newborns against infectious diseases. Here we conducted an observational study exploring the immunological profile of infants longitudinally throughout their first week of life. Our Expanded Program on Immunization - Human Immunology Project Consortium (EPIC-HIPC) studies the epigenetic regulation of systemic immunity using small volumes of peripheral blood samples collected from West African neonates on days of life (DOL) 0, 1, 3, and 7. Genome-wide DNA methylation and single nucleotide polymorphism markers are examined alongside matched transcriptomic and flow cytometric data. Integrative analysis reveals that a core network of transcription factors mediates dynamic shifts in neutrophil-to-lymphocyte ratios (NLR), which are underpinned by cell-type specific methylation patterns in the two cell types. Genetic variants are associated with lower NLRs at birth, and healthy newborns with lower NLRs at birth are more likely to subsequently develop sepsis. These findings provide valuable insights into the early-life determinants of immune system development. Evaluating the immune status of newborns helps recognition of those who are at higher risk for serious infectious diseases. Here authors identify lower, epigenetically inferred, neutrophil-to-lymphocyte ratios during the first week of life as risk factor for sepsis and provide insight into the underpinning epigenetic and transcriptional patterns.

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)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
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 integrity0.0000.000
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 head0.065
GPT teacher head0.402
Teacher spread0.338 · 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 designObservational
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
Published2024
Admission routes1
Has abstractyes

Explore more

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