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Record W2525513041

Molecular Biomarker Discovery in Psoriatic Arthritis

2016· dissertation· en· W2525513041 on OpenAlexfundno aff
Remy A. Pollock

Bibliographic record

VenueTSpace (University of Toronto) · 2016
Typedissertation
Languageen
FieldMedicine
TopicCytokine Signaling Pathways and Interactions
Canadian institutionsnot available
FundersCanadian Institutes of Health ResearchKrembil FoundationUniversity of TorontoNational Psoriasis Foundation
KeywordsPsoriatic arthritisBiomarkerBiomarker discoveryMedicineArthritisComputational biologyData scienceComputer scienceBiologyInternal medicineProteomicsGeneticsGene
DOInot available

Abstract

fetched live from OpenAlex

Aim: Psoriatic arthritis (PsA) is an inflammatory arthritis of unknown etiology that develops in approximately 30% of individuals with psoriasis. No objectively measurable biomarker has been identified for PsA, due in part to insufficient knowledge of its etiopathogenesis. This work aims to identify candidate biomarkers of PsA by studying its underlying transcriptomic and epigenomic mechanisms. Methods: Psoriasis (PsC) and PsA patients from a prospective cohort were analyzed. Whole blood, serum, and semen samples were obtained from subsets of patients and unaffected controls for transcriptomic, protein, and epigenomic analyses, respectively. Potential epigenetic mechanisms were also analyzed using self-reported family history data from the entire PsC and PsA cohort to further explore the parent-of-origin effect. Results: Transcriptomic analyses identified several genes involved in innate immunity, particularly toll-like receptor signalling as differentially expressed in whole blood of PsA and PsC patients. Four candidate gene expression biomarkers CXCL10, NOTCH2NL, HAT1, and SETD2 were replicated in an independent cohort of PsC and PsA patients. Soluble CXCL10 was significantly elevated in baseline serum samples of psoriasis patients who later developed PsA compared to patients who did not develop PsA. Excessive paternal transmission was found in PsC and PsA patients, as well as genetic anticipation manifesting as increased disease severity during male transmission. DNA methylation profiling of sperm cells revealed several germ line variations associated with psoriasis and PsA occurring near or within genes involved in inflammatory and immune system processes, including HCG26 within the major histocompatibility complex. Conclusions: Whole blood transcriptomic and serum protein analysis identified the chemokine CXCL10 as a putative predictive biomarker of PsA in PsC patients. Evidence of a parent-of-origin effect, genetic anticipation, and the identification of germ line DNA methylation variations in patients suggest a role for epigenetic mechanisms in psoriatic disease etiopathogenesis, and a potential new avenue of biomarker discovery.

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)0.001
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: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0020.002
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.001

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 head0.012
GPT teacher head0.262
Teacher spread0.250 · 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

Citations0
Published2016
Admission routes1
Has abstractyes

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