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Record W2024463309 · doi:10.1002/ijc.24535

A comprehensive catalogue of functional genetic variations in the EGFR pathway: Protein–protein interaction analysis reveals novel genes and polymorphisms important for cancer research

2009· article· en· W2024463309 on OpenAlexafffund
Sevtap Savas, Joseph Geraci, Igor Jurišica, Geoffrey Liu

Bibliographic record

VenueInternational Journal of Cancer · 2009
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicBioinformatics and Genomic Networks
Canadian institutionsPrincess Margaret Cancer CentreUniversity of TorontoOntario Institute for Cancer Research
FundersNatural Sciences and Engineering Research Council of CanadaCanadian Institutes of Health ResearchNathaniel Wharton FundPrincess Margaret Hospital FoundationGenome Canada
KeywordsSingle-nucleotide polymorphismBiologyGeneSNPFYNGeneticsIn silicoComputational biologySignal transductionGenotypeProto-oncogene tyrosine-protein kinase Src

Abstract

fetched live from OpenAlex

The EGFR pathway is a critical signaling pathway deregulated in many solid tumors. In addition to the initiation and progression of cancer, the EGFR pathway is also implicated in variable treatment responses and prognoses. Genetic variation in the form of Single Nucleotide Polymorphisms (SNPs) can affect the function/expression of the EGFR pathway genes. Here, we applied a systematic and comprehensive approach utilizing diverse public databases and in silico analysis tools to select putative functional genetic variations from 244 genes involved in the EGFR pathway. Our data comprises 649 SNPs. Three hundred sixty SNPs are predicted to have biological consequences (functional SNPs). These SNPs can be directly used in further studies to test their association with risk, treatment response and prognosis in cancer. To systematically cover the EGFR pathway, we also performed a network-based analysis to further select putative functional SNPs from the genes whose protein products physically interact with the EGFR pathway proteins. We utilized protein-protein interaction information and focused on 14 proteins that have a high degree of connectivity (interacting with > or = 10 proteins) with the EGFR pathway genes identified to have functional SNPs (f-EGFR genes). Two of these proteins (FYN and LCK) had interactions with 17 of the f-EGFR genes, yet both lacked any putative functional SNP. However, our analysis indicated the presence of potentially functional SNPs in 9 other highly interactive proteins. The genes and their SNPs identified in the network-based analysis represent potential candidates for gene-gene and SNP-SNP interaction studies in cancer research.

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: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.004
Threshold uncertainty score0.012

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0040.007
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0040.001

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 head0.036
GPT teacher head0.342
Teacher spread0.306 · 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

Citations12
Published2009
Admission routes2
Has abstractyes

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