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Record W2070003798 · doi:10.1089/dna.2006.0570

Gene Set Enrichment Analyses Revealed Several Affected Pathways in Niemann-Pick Disease Type C Fibroblasts

2007· article· en· W2070003798 on OpenAlex
Aloys De Windt, Myriam Rai, Leena Kytömäki, Karin Thelen, Dieter Lütjohann, Lise Bernier, Jean Davignon, Juhani T. Soini, Massimo Pandolfo, Reijo Laaksonen

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueDNA and Cell Biology · 2007
Typearticle
Languageen
FieldMedicine
TopicLysosomal Storage Disorders Research
Canadian institutionsMontreal Clinical Research Institute
Fundersnot available
KeywordsBiologyNPC1Downregulation and upregulationNeurodegenerationGene expressionCell biologyBiological pathwayCancer researchDrug discoveryGeneGene expression profilingDiseaseBioinformaticsEndosomeGeneticsInternal medicineIntracellularMedicine

Abstract

fetched live from OpenAlex

Niemann-pick type C (NPC) disease is characterized by endosomal and lysosomal accumulation of lipids, impaired tubulovesicular trafficking, and neurodegeneration leading to premature death. Current treatment options are limited to mainly symptomatic treatments. Thus, new and efficient drug targets are needed, and therefore we performed a Gene Set Enrichment Analysis (GSEA) on NPC and healthy fibroblasts to identify globally affected pathways in NPC that could serve as targets for later drug discovery programs. Cell lines were characterized by analyzing cellular concentrations of cholesterol, its precursors and metabolites, as well as cellular plant sterol levels. Gene expression analyses were performed with Sentrix Human-8 Expression BeadChips, analyzing 23,000 transcripts. Pathway analysis of the expression data was performed using the GSEA method. Twenty-seven upregulated and 33 downregulated pathways emerged as globally affected in the GSEA analysis. These pathways included, for example, mitochondrial pathway, caspase cascade, as well as prostaglandin and leukotriene metabolism. Based on the present results and earlier published data, anti-inflammatory and antiapoptotic treatment could be beneficial in NPC.

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.

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)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.709
Threshold uncertainty score0.476

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
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)0.0000.000

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 head0.040
GPT teacher head0.336
Teacher spread0.295 · 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