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Record W4381250708 · doi:10.1016/j.mcpro.2023.100602

Proteomic Dynamics of Breast Cancer Cell Lines Identifies Potential Therapeutic Protein Targets

2023· article· en· W4381250708 on OpenAlexafffund
Rui Sun, Weigang Ge, Yi Zhu, Azin Sayad, Augustin Luna, Mengge Lyu, Shuang Liang, Luis Tobalina, Vinodh N. Rajapakse, Chen-Huan Yu, Huanhuan Zhang, Jie Fang, Fang Wu, Hui Xie, Julio Sáez-Rodríguez, Huazhong Ying, William C. Reinhold, Chris Sander, Yves Pommier, Benjamin G. Neel, Ruedi Aebersold, Tiannan Guo

Bibliographic record

VenueMolecular & Cellular Proteomics · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA modifications and cancer
Canadian institutionsPrincess Margaret Cancer CentreUniversity of TorontoUniversity Health Network
FundersH2020 European Research CouncilNational Cancer InstituteNatural Science Foundation of Zhejiang ProvinceSystemsX.chNational Natural Science Foundation of ChinaNational Institutes of HealthCanada Research ChairsSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungPrincess Margaret Hospital FoundationSanofiNational Science FoundationAstex PharmaceuticalsPfizerEuropean Research Council
KeywordsPI3K/AKT/mTOR pathwayProteomicsProteomeTriple-negative breast cancerComputational biologyCancer researchProtein kinase BBiologyBreast cancerCell growthBioinformaticsSignal transductionCancerCell biologyGeneticsGene

Abstract

fetched live from OpenAlex

Treatment and relevant targets for breast cancer (BC) remain limited, especially for triple-negative BC (TNBC). We identified 6091 proteins of 76 human BC cell lines using data-independent acquisition (DIA). Integrating our proteomic findings with prior multi-omics datasets, we found that including proteomics data improved drug sensitivity predictions and provided insights into the mechanisms of action. We subsequently profiled the proteomic changes in nine cell lines (five TNBC and four non-TNBC) treated with EGFR/AKT/mTOR inhibitors. In TNBC, metabolism pathways were dysregulated after EGFR/mTOR inhibitor treatment, while RNA modification and cell cycle pathways were affected by AKT inhibitor. This systematic multi-omics and in-depth analysis of the proteome of BC cells can help prioritize potential therapeutic targets and provide insights into adaptive resistance in TNBC.

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 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 categoriesMeta-epidemiology (narrow)
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 score0.029
Threshold uncertainty score1.000

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 head0.006
GPT teacher head0.229
Teacher spread0.223 · 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 teacher head, not a consensus.

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

Citations19
Published2023
Admission routes2
Has abstractyes

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