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Record W4385738280 · doi:10.1016/j.ccell.2023.07.007

Proteogenomic insights suggest druggable pathways in endometrial carcinoma

2023· article· en· W4385738280 on OpenAlexaff
Yongchao Dou, Lizabeth Katsnelson, Yingwei Hu, Boris Reva, Runyu Hong, Yi-Ting Wang, Iga Kołodziejczak, Rita Jui-Hsien Lu, Chia‐Feng Tsai, Wen Bu, Wenke Liu, Xiaofang Guo, Eunkyung An, Rebecca C. Arend, Jasmin Bavarva, Lijun Chen, Rosalie Chu, Andrzej Czekański, Teresa Davoli, Elizabeth G. Demicco, Deborah F. DeLair, Kelly A. Devereaux, Saravana M. Dhanasekaran, Peter R. Dottino, Bailee Dover, Thomas Fillmore, McKenzie E. Foxall, Catherine Hermann, Tara Hiltke, Galen Hostetter, Marcin Jędryka, Scott D. Jewell, Isabelle Johnson, Andrea G. Kahn, Amy T. Ku, Chandan Kumar‐Sinha, Paweł Kurzawa, Alexander J. Lazar, Rossana Lazcano, Jonathan T. Lei, Yi Li, Yuxing Liao, T. Mamie Lih, Tai‐Tu Lin, John A. Martignetti, Ramya P. Masand, Rafał Matkowski, Wilson McKerrow, Mehdi Mesri, Matthew Monroe, Jamie Moon, Ronald Moore, Michael Nestor, Chelsea J. Newton, Tatiana Omelchenko, Gilbert S. Omenn, Samuel Payne, Vladislav Petyuk, Ana I. Robles, Henry Rodriguez, Kelly V. Ruggles, Dmitry Rykunov, Sara R. Savage, Athena Schepmoes, Tujin Shi, Zhiao Shi, Jimin Tan, Mason D. Taylor, Mathangi Thiagarajan, Joshua M. Wang, Karl Weitz, Bo Wen, Claire Williams, Yige Wu, Matthew A. Wyczalkowski, Xinpei Yi, Xu Zhang, Rui Zhao, David G. Mutch, Arul M. Chinnaiyan, Richard Smith, Alexey I. Nesvizhskii, Pei Wang, Maciej Wiznerowicz, Li Ding, D.R. Mani, Hui Zhang, Matthew L. Anderson, Karin Rodland, Bing Zhang, Tao Liu, David Fenyö, Andrzej Antczak, Meenakshi Anurag, Thomas Bauer, Chet Birger, Michael J. Birrer, Melissa Borucki, Shuang Cai, Anna Calinawan, Steven A. Carr, Patricia Castro, Sandra Cerda, Daniel W. Chan, David Chesla, Marcin Cieślik, Sandra Cottingham, Rajiv Dhir, Marcin J. Domagalski, Brian Druker, Elizabeth R. Duffy, Nathan Edwards, Robert A. Edwards, Matthew J. Ellis, Jennifer Eschbacher, Mina Fam, Brenda Fevrier-Sullivan, Jesse Francis, John Freymann, Stacey Gabriel, Gad Getz, Michael A. Gillette, Andrew K. Godwin, Charles A. Goldthwaite, Pamela Grady, Jason Hafron, Pushpa Hariharan, Barbara Hindenach, Katherine A. Hoadley, Jasmine Huang, Michael Ittmann, Ashlie Johnson, Corbin D. Jones, Karen A. Ketchum, Justin Kirby, Toan Le, Avi Ma’ayan, Rashna Madan, Sailaja Mareedu, Peter B. McGarvey, Francesmary Modugno, Rebecca Montgomery, Kristen Nyce, Amanda G. Paulovich, Barbara L. Pruetz, Liqun Qi, Shannon Richey, Eric E. Schadt, Yvonne Shutack, Shilpi Singh, Michael Smith, Darlene Tansil, Ratna R. Thangudu, Matt Tobin, Ki Sung Um, Negin Vatanian, Alex Webster, George D. Wilson, Jason N. Wright, Kakhaber Zaalishvili, Zhen Zhang, Grace Zhao

Bibliographic record

VenueCancer Cell · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicPI3K/AKT/mTOR signaling in cancer
Canadian institutionsUniversity of TorontoMount Sinai Hospital
FundersNational Institute of Environmental Health SciencesNational Cancer InstituteNational Institutes of HealthCancer Prevention and Research Institute of TexasNational Institute of General Medical SciencesBattelleU.S. Department of DefenseU.S. Department of EnergyPacific Northwest National LaboratoryLeidos
KeywordsDruggabilityCancer researchWnt signaling pathwayBiologyProtein kinase BPhosphorylationCarcinomaBioinformaticsImmunotherapyMedicineOncologyInternal medicineSignal transductionCancerGeneGenetics

Abstract

fetched live from OpenAlex

We characterized a prospective endometrial carcinoma (EC) cohort containing 138 tumors and 20 enriched normal tissues using 10 different omics platforms. Targeted quantitation of two peptides can predict antigen processing and presentation machinery activity, and may inform patient selection for immunotherapy. Association analysis between MYC activity and metformin treatment in both patients and cell lines suggests a potential role for metformin treatment in non-diabetic patients with elevated MYC activity. PIK3R1 in-frame indels are associated with elevated AKT phosphorylation and increased sensitivity to AKT inhibitors. CTNNB1 hotspot mutations are concentrated near phosphorylation sites mediating pS45-induced degradation of β-catenin, which may render Wnt-FZD antagonists ineffective. Deep learning accurately predicts EC subtypes and mutations from histopathology images, which may be useful for rapid diagnosis. Overall, this study identified molecular and imaging markers that can be further investigated to guide patient stratification for more precise treatment of EC.

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 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 score0.080
Threshold uncertainty score0.797

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 head0.021
GPT teacher head0.250
Teacher spread0.228 · 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.

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

Citations53
Published2023
Admission routes1
Has abstractyes

Explore more

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