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Record W4412673238 · doi:10.1101/2025.07.23.663512

RASGRP4 is a key factor in KRAS activation mediated by SOS in Y1 mouse tumor cell line

2025· preprint· en· W4412673238 on OpenAlexaff
Fabio Montoni, Rosangela A.M. Wailemann, Thompson E.P. Torres, Cecilia Sella Fonseca, Marcelo S. Reis, Hugo A. Armelin

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicProtein Tyrosine Phosphatases
Canadian institutionsArtificial Intelligence in Medicine (Canada)
FundersFundação de Amparo à Pesquisa do Estado de São PauloInstituto Butantan
KeywordsKRASKey (lock)Factor (programming language)Cancer researchLine (geometry)Cell biologyChemistryBiologyComputer scienceGeneticsMutationComputer securityMathematicsProgramming language

Abstract

fetched live from OpenAlex

The Y1 mouse adrenocortical carcinoma cell line presents amplification of the KRas oncogene and high-basal levels of KRAS-GTP mediated by the GEF SOS. In this research, we developed a dynamic model based on ordinary differential equations of the KRAS-GTP activation mediated by SOS in Y1 cells, which showed that SOS only is not sufficient to reach the high-basal levels of KRAS-GTP experimentally observed for this cell line. Interestingly, a modification in this system, which added another GEF in the model, made the model reach the expected levels of KRAS activation, leading to the hypothesis that there was a missing element in this system. To find this missing element, a PCR panel of RasGEFs was performed and the GEF Rasgrp4 was found highly expressed in parental Y1 cell lines, indicating that this was the missing element in the system. Finally, tumor growth assays in Balb/c-NUDE mice with the Y1 cell versus RASGRP4 CRISPR depleted Y1 cells, showed reduced tumor growth and frequency for the RASGRP4 depleted cells.

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)0.000
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: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

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)0.0010.000

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 head0.008
GPT teacher head0.219
Teacher spread0.211 · 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
Published2025
Admission routes1
Has abstractyes

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Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicProtein Tyrosine PhosphatasesFrench-language works237,207