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pmid:39487182

Characterization of metastasis-specific macrophages in colorectal cancer for prognosis prediction and immunometabolic remodeling.

Yang Hua · Xiukun Ma · Xinyu Zhao · Xiaomeng Wei · Xiaojing Mu · XiPeng Zhang

Scientific reports · 2024 doi:10.1038/s41598-024-77248-2

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complete

Experiment

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Data

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Analysis

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Characterization of metastasis-specific macrophages in colorectal cancer for prognosis prediction and immunometabolic remodeling.
doi
10.1038/s41598-024-77248-2
pmid
39487182
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Yang Hua
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Xiukun Ma
[2]
Xinyu Zhao
[3]
Xiaomeng Wei
[4]
Xiaojing Mu
[5]
XiPeng Zhang
journal
Scientific reports
year
2024
abstract
This study develops a prognostic model to predict metastasis and prognosis in colorectal cancer liver metastases by identifying distinct macrophage subsets. Using scRNA-seq data from primary colorectal cancer and liver metastases, we dissected the cellular landscape to find unique macrophage subpopulations, particularly EEF1G + macrophages, which were prevalent in liver metastases. The study leveraged data from GSE231559, TCGA, and GEO databases to construct an 8-gene risk model named EMGS, based on the EEF1G + macrophage gene signature. Patients were divided into high-risk and low-risk groups using the median EMGS score, with the high-risk group showing significantly worse survival. This group also demonstrated upregulated pathways associated with tumor progression, such as epithelial-mesenchymal transition and angiogenesis, and downregulated metabolic pathways. Moreover, the high-risk group presented an immunosuppressive microenvironment, with a higher TIDE score indicating lower effectiveness of immunotherapy. The study identifies potential drugs targeting the high-risk group, suggesting therapeutic avenues to improve survival. Conclusively, the EMGS score identifies colorectal cancer patients at high risk of liver metastases, highlighting the role of specific macrophage subsets in tumor progression and providing a basis for personalized treatment strategies.
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Subsequently, these genes were assessed using the least absolute shrinkage and selection operator (LASSO) method in Cox proportional hazards regression, employing the ‘glmnet’ package in R.
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Subsequently, these genes were assessed using the least absolute shrinkage and selection operator (LASSO) method in Cox proportional hazards regression, employing the ‘glmnet’ package in R.
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We sourced the single-cell RNA-seq dataset from the Gene Expression Omnibus (GEO) database using the accession number GSE231559. The TCGA-COAD cohort dataset was obtained from The Cancer Genome Atlas (TCGA) portal, available at https://portal.gdc.cancer.gov/. For validation purposes, we also retrieved datasets GSE29621, GSE17536, and GSE39582 from the GEO database.
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We sourced the single-cell RNA-seq dataset from the Gene Expression Omnibus (GEO) database using the accession number GSE231559. The TCGA-COAD cohort dataset was obtained from The Cancer Genome Atlas (TCGA) portal, available at https://portal.gdc.cancer.gov/. For validation purposes, we also retrieved datasets GSE29621, GSE17536, and GSE39582 from the GEO database.
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In the TCGA-COAD training set, the EMGS-high group demonstrated significantly higher mortality risk and lower overall survival rates (Fig. 4A, HR = 2.5, 95% CI: 1.77–3.54, P < 0.0001).
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In the TCGA-COAD training set, the EMGS-high group demonstrated significantly higher mortality risk and lower overall survival rates (Fig. 4A, HR = 2.5, 95% CI: 1.77–3.54, P < 0.0001).
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sections[6] "Performance of the EMGS Signature in training and validation cohorts" paragraph 2
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In the TCGA-COAD training set, the EMGS-high group demonstrated significantly higher mortality risk and lower overall survival rates (Fig. 4A, HR = 2.5, 95% CI: 1.77–3.54, P < 0.0001).
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In the TCGA-COAD training set, the EMGS-high group demonstrated significantly higher mortality risk and lower overall survival rates (Fig. 4A, HR = 2.5, 95% CI: 1.77–3.54, P < 0.0001).
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Metastasis Gene Expression Profile Predicts Recurrence and Death in Colon Cancer Patients (Moffitt Samples)
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[22]
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[23]
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[24]
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[25]
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[26]
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[27]
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[28]
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[29]
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[30]
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[31]
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[32]
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[33]
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[34]
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[35]
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[36]
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[37]
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[38]
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[39]
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[40]
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[41]
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[42]
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[43]
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[44]
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[45]
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[46]
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[47]
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[48]
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[49]
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[50]
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[51]
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[52]
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[53]
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[54]
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[55]
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[56]
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[57]
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[58]
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[59]
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[60]
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[61]
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[63]
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[64]
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[65]
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[66]
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[67]
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[68]
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[69]
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[70]
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[71]
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[72]
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[73]
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[74]
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[75]
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[76]
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[77]
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[80]
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[81]
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[82]
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[83]
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[100]
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[127]
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[130]
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[131]
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[132]
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[134]
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[140]
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[142]
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[143]
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[144]
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[145]
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[146]
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[147]
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[148]
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[149]
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[150]
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[151]
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[152]
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[153]
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[154]
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[155]
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[156]
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[157]
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[158]
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[159]
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[160]
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[161]
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[162]
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[163]
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[164]
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[165]
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[166]
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[167]
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[168]
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[169]
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[170]
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[171]
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[172]
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[173]
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[174]
GSM972112
[175]
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[176]
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[177]
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[178]
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[179]
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[180]
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[181]
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[182]
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[183]
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[184]
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[185]
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[186]
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[187]
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[188]
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[189]
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[190]
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[191]
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[192]
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[193]
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[194]
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[195]
GSM972133
[196]
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[197]
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[198]
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[199]
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[200]
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[201]
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[202]
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[203]
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[204]
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[205]
GSM972143
[206]
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[207]
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[208]
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[209]
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[210]
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[211]
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[212]
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[213]
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[214]
GSM972152
[215]
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[216]
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[217]
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[218]
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[219]
GSM972157
[220]
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[221]
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[222]
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[223]
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[224]
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[225]
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[226]
GSM972164
[227]
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[228]
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[229]
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[230]
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[231]
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[232]
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[233]
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[234]
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[235]
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[236]
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[237]
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[238]
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[239]
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[240]
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[241]
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[242]
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[243]
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[244]
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[245]
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[246]
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[247]
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[248]
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[249]
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[250]
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[251]
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[252]
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[253]
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[254]
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[255]
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[256]
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[257]
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[258]
GSM972196
[259]
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[260]
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[261]
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[262]
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[263]
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[264]
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[265]
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[266]
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[267]
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[268]
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[269]
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[270]
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[271]
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[272]
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[273]
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[274]
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[275]
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[276]
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[277]
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[278]
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[279]
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[280]
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[281]
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[282]
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[283]
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[284]
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[285]
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[286]
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[287]
GSM972225
[288]
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[289]
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[290]
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[291]
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[292]
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[293]
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[294]
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[295]
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[296]
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[297]
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[298]
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[299]
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[300]
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[301]
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[302]
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[303]
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[304]
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[305]
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[306]
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[307]
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[308]
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[309]
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[310]
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[311]
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[312]
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[313]
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[314]
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[315]
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[316]
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[317]
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[318]
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[319]
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[320]
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[321]
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[322]
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[323]
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[324]
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[325]
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[326]
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[327]
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[328]
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[329]
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[330]
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[331]
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[332]
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[333]
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[334]
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[335]
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[336]
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[337]
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[338]
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[339]
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[340]
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[341]
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[342]
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[343]
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[344]
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[345]
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[346]
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[347]
GSM972285
[348]
GSM972286
[349]
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[350]
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[351]
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[352]
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[353]
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[354]
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[355]
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[356]
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[357]
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[358]
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[359]
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[360]
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[361]
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[362]
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[363]
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[364]
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[365]
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[366]
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[367]
GSM972305
[368]
GSM972306
[369]
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[370]
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[371]
GSM972309
[372]
GSM972310
[373]
GSM972311
[374]
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[375]
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[376]
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[377]
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[378]
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[379]
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[380]
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[381]
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[382]
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[383]
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[384]
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[385]
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[386]
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[387]
GSM972325
[388]
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[389]
GSM972327
[390]
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[391]
GSM972329
[392]
GSM972330
[393]
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[394]
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[395]
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[396]
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[397]
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[398]
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[399]
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[400]
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[401]
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[402]
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[403]
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[404]
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[405]
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[406]
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[407]
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[408]
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[409]
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[410]
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[411]
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[412]
GSM972350
[413]
GSM972351
[414]
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[415]
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[416]
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[417]
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[418]
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[419]
GSM972357
[420]
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[421]
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[422]
GSM972360
[423]
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[424]
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[425]
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[426]
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[427]
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[428]
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[429]
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[430]
GSM972368
[431]
GSM972369
[432]
GSM972370
[433]
GSM972371
[434]
GSM972372
[435]
GSM972373
[436]
GSM972374
[437]
GSM972375
[438]
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[439]
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[440]
GSM972378
[441]
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[442]
GSM972380
[443]
GSM972381
[444]
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[445]
GSM972383
[446]
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[447]
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[448]
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[449]
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[450]
GSM972388
[451]
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[452]
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[453]
GSM972391
[454]
GSM972392
[455]
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[456]
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[457]
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[458]
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[459]
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[460]
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[461]
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[462]
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[463]
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[464]
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[465]
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[466]
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[467]
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[468]
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[469]
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[470]
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[471]
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[472]
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[473]
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[474]
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[475]
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[476]
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[477]
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[478]
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[479]
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[480]
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[481]
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[482]
GSM972420
[483]
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[484]
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[485]
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[486]
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[487]
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[488]
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[489]
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[490]
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[491]
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[492]
GSM972430
[493]
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[494]
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[495]
GSM972433
[496]
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[497]
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[498]
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[499]
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[500]
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[501]
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[502]
GSM972440
[503]
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[504]
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[505]
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[506]
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[507]
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[510]
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[511]
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[512]
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[513]
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[514]
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[515]
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[516]
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[517]
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[518]
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[519]
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[520]
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[521]
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[522]
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[523]
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[524]
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[525]
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[526]
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[527]
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[528]
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[529]
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[530]
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[531]
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[532]
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[533]
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[534]
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[535]
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[542]
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[544]
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[583]
GSM972521
[584]
GSM972522
sample_count
585
group_sizes
null
group_sizes_basis
null
platform
570
taxon
Homo sapiens
title
Gene expression Classification of Colon Cancer defines six molecular subtypes with distinct clinical, molecular and survival characteristics [Expression]
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
gaps array · 10 items
[0]
asset:data:geo:GSE17536 not downloaded
[1]
asset:data:geo:GSE17536 licence not read
[2]
asset:data:geo:GSE178318 not downloaded
[3]
asset:data:geo:GSE178318 licence not read
[4]
asset:data:geo:GSE231559 not downloaded
[5]
asset:data:geo:GSE231559 licence not read
[6]
asset:data:geo:GSE29621 not downloaded
[7]
asset:data:geo:GSE29621 licence not read
[8]
asset:data:geo:GSE39582 not downloaded
[9]
asset:data:geo:GSE39582 licence not read
analysis object · 4 fields
state
complete
methods array · 1 item
[0] object · 10 fields
id
method-1
family
survival_analysis
specific
cox_proportional_hazards
label
Survival analysis
dsl_operations array · 1 item
[0]
cox_ph
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
time_to_event_with_censoring
evidence object · 3 fields
score
1
band
verbatim
quote
Subsequently, these genes were assessed using the least absolute shrinkage and selection operator (LASSO) method in Cox proportional hazards regression, employing the ‘glmnet’ package in R.
targets array · 3 items
[0] object · 8 fields
id
target-published-estimate
claim_id
claim-target-result
operation
cox_ph
unit
per cent
tolerance
null
state
complete
note
The published estimate as the reader quoted it from the paper. No tolerance is published because the paper states none.
[1] object · 8 fields
id
target-published-estimate-hazard-ratio
claim_id
claim-target-result
operation
cox_ph
unit
hazard ratio
tolerance
null
state
complete
note
The published estimate as the reader quoted it from the paper. No tolerance is published because the paper states none.
[2] object · 8 fields
id
target-published-estimate-p-value
claim_id
claim-target-result
operation
cox_ph
unit
p-value
tolerance
null
state
complete
note
The threshold the paper applied to its own result, as the paper states it. A run that reproduces the effect is judged against this threshold.
gaps array · 0 items
capability object · 3 fields
state
complete
requirements array · 1 item
[0] object · 6 fields
capability_id
capability:computational_analysis
label
Computational analysis platform
assay_families array · 9 items
[0]
meta_analysis
[1]
machine_learning
[2]
survival_analysis
[3]
statistical_regression
[4]
pca
[5]
molecular_docking
[6]
network_analysis
[7]
differential_expression
[8]
gwas
candidate
Automated Assays Laravel application and simulated adapters
gaps array · 0 items
readiness object · 8 fields
state
complete
tier
R1
blocked_on
nothing:replicable_now
axes object · 3 fields
method object · 5 fields
tier
R1
expressible
true
required_operations array · 1 item
[0]
cox_ph
missing_operations array · 0 items
basis
The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: cox_proportional_hazards.
capability object · 4 fields
tier
R1
capability_id
capability:computational_analysis
availability_state
owned
basis
The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here.
data object · 6 fields
tier
R1
reachable
true
accessions array · 5 items
[0]
GSE231559
[1]
GSE178318
[2]
GSE29621
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GSE17536
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We sourced the single-cell RNA-seq dataset from the Gene Expression Omnibus (GEO) database using the accession number GSE231559. The TCGA-COAD cohort dataset was obtained from The Cancer Genome Atlas (TCGA) portal, available at https://portal.gdc.cancer.gov/. For validation purposes, we also retrieved datasets GSE29621, GSE17536, and GSE39582 from the GEO database.
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The paper names GSE231559, GSE178318, GSE29621, GSE17536, GSE39582 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read.
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entifying distinct macrophage subsets. Using scRNA-seq data from primary colorectal cancer and live
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Subsequently, these genes were assessed using the least absolute shrinkage and selection operator (LASSO) method in Cox proportional hazards regression, employing the ‘glmnet’ package in R.
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["time_to_event_with_censoring"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Subsequently, these genes were assessed using the least absolute shrinkage and selection operator (LASSO) method in Cox proportional hazards regression, employing the ‘glmnet’ package in R."}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "cox_ph", "expected_value": 95.0, "unit": "per cent", "tolerance": null, "state": "complete", "note": "The published estimate as the reader quoted it from the paper. No tolerance is published because the paper states none."}, {"id": "target-published-estimate-hazard-ratio", "claim_id": "claim-target-result", "operation": "cox_ph", "expected_value": 2.5, "unit": "hazard ratio", "tolerance": null, "state": "complete", "note": "The published estimate as the reader quoted it from the paper. No tolerance is published because the paper states none."}, {"id": "target-published-estimate-p-value", "claim_id": "claim-target-result", "operation": "cox_ph", "expected_value": 0.0001, "unit": "p-value", "tolerance": null, "state": "complete", "note": "The threshold the paper applied to its own result, as the paper states it. 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE231559", "GSE178318", "GSE29621", "GSE17536", "GSE39582"], "resolved_accessions": ["GSE231559", "GSE178318", "GSE29621", "GSE17536", "GSE39582"], "statements": ["We sourced the single-cell RNA-seq dataset from the Gene Expression Omnibus (GEO) database using the accession number GSE231559. The TCGA-COAD cohort dataset was obtained from The Cancer Genome Atlas (TCGA) portal, available at https://portal.gdc.cancer.gov/. For validation purposes, we also retrieved datasets GSE29621, GSE17536, and GSE39582 from the GEO database."], "basis": "The paper names GSE231559, GSE178318, GSE29621, GSE17536, GSE39582 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["cox_ph"], "assets": ["source:pmid:39487182", "data:geo:GSE17536"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE17536"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:37:18Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 12924, "completion_tokens": 2400, "cached_tokens": 256}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:39487182", "type": "paper", "label": "pmid:39487182"}, {"id": "source:pmid:39487182", "type": "manuscript", "label": "PMID 39487182 full text"}, {"id": "data:geo:GSE17536", "type": "dataset", "label": "GEO GSE17536"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:39487182", "type": "paper", "label": "pmid:39487182"}, {"id": "source:pmid:39487182", "type": "manuscript", "label": "PMID 39487182 full text"}, {"id": "data:geo:GSE17536", "type": "dataset", "label": "GEO GSE17536"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-39487182", "type": "extraction", "used": ["source:pmid:39487182"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE17536", "type": "accession_resolution", "used": ["data:geo:GSE17536"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:39487182", "parent_hash": "sha256:7e9de9e2c7976fb21eb2c0a76cf1caed0ec4953439fae0435ac7cb184f5d602e", "fork_of": null, "generation": 1}, "gaps": ["asset:data:geo:GSE17536 licence not read", "asset:data:geo:GSE17536 not downloaded", "asset:data:geo:GSE178318 licence not read", "asset:data:geo:GSE178318 not downloaded", "asset:data:geo:GSE231559 licence not read", "asset:data:geo:GSE231559 not downloaded", "asset:data:geo:GSE29621 licence not read", "asset:data:geo:GSE29621 not downloaded", "asset:data:geo:GSE39582 licence not read", "asset:data:geo:GSE39582 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "scrna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "unsupported", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["entifying distinct macrophage subsets. Using scRNA-seq data from primary colorectal cancer and live"], "order_basis": "paper_text_order:248", "id": "assay:1"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Subsequently, these genes were assessed using the least absolute shrinkage and selection operator (LASSO) method in Cox proportional hazards regression, employing the ‘glmnet’ package in R."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}