su: ignoring --preserve-environment, it's mutually exclusive with --login Attaching package: ‘DT’ The following objects are masked from ‘package:shiny’: dataTableOutput, renderDataTable Attaching package: ‘bs4Dash’ The following objects are masked from ‘package:shiny’: actionButton, column, insertTab, navbarMenu, tabsetPanel The following object is masked from ‘package:graphics’: box Attaching package: ‘shinyWidgets’ The following object is masked from ‘package:bs4Dash’: progressBar Attaching package: ‘zip’ The following objects are masked from ‘package:utils’: unzip, zip Loading required package: DBI Attaching package: ‘dplyr’ The following objects are masked from ‘package:stats’: filter, lag The following objects are masked from ‘package:base’: intersect, setdiff, setequal, union Attaching package: ‘dbplyr’ The following objects are masked from ‘package:dplyr’: ident, sql ========================================================================== IOBR v2.2.3.9000 Immuno-Oncology Biological Research For Documentation: https://iobr.github.io/IOBR/ For Tutorial: https://iobr.github.io/book/ For Help: https://github.com/IOBR/IOBR/issues If you use IOBR in published research, please cite: DQ Zeng, YR Fang, ..., GC Yu*, WJ Liao*, Enhancing immuno-oncology investigations through multidimensional decoding of tumor microenvironment with IOBR 2.0. Cell Rep Methods 4, 100910 (2024). & YR Fang, ..., WJ Liao*, DQ Zeng*, Systematic Investigation of Tumor Microenvironment and Antitumor Immunity With IOBR, Med Research (2025). https://onlinelibrary.wiley.com/doi/epdf/10.1002/mdr2.70001 ========================================================================== IOBRportal database mode: enabled. Listening on http://127.0.0.1:44363 ℹ Best number of TME clusters: 2 ℹ Cluster distribution: User session ended. Running garbage collection... User session ended. Running garbage collection... ℹ Best number of TME clusters: 3 ℹ Cluster distribution: ℹ Groups: 3 ("TME1", "TME2", and "TME3") ℹ Features: 183 ✔ Kruskal-Wallis test complete ℹ Creating heatmap with 20 features tidyHeatmap says: (once per session) from release 1.7.0 the scaling is set to "none" by default. Please use scale = "row", "column" or "both" to apply scaling tidyHeatmap says: If you use tidyHeatmap for scientific research, please cite: Mangiola, S. and Papenfuss, A.T., 2020. 'tidyHeatmap: an R package for modular heatmap production based on tidy principles.' Journal of Open Source Software. doi:10.21105/joss.02472. This message is displayed once per session. Warning: `when()` was deprecated in purrr 1.0.0. ℹ Please use `if` instead. ℹ The deprecated feature was likely used in the tidyHeatmap package. Please report the issue at . User session ended. Running garbage collection... User session ended. Running garbage collection... User session ended. Running garbage collection... ℹ Best number of TME clusters: 2 ℹ Cluster distribution: ℹ Best number of TME clusters: 4 ℹ Cluster distribution: User session ended. Running garbage collection... ℹ Best number of TME clusters: 2 ℹ Cluster distribution: ℹ Survival follow-up time range: 0.1 to 122.37 months ℹ Best cutoff for "TMEscoreA_plus": 2.73 ✔ Best cutoff for "TMEscoreA_plus": 2.726 ℹ High TMEscoreA_plus: 93 ℹ Low TMEscoreA_plus: 293 ℹ Maximum follow-up time is 122.4 months; divided into 6 sections Warning: Using `size` aesthetic for lines was deprecated in ggplot2 3.4.0. ℹ Please use `linewidth` instead. ℹ The deprecated feature was likely used in the ggpubr package. Please report the issue at . Ignoring unknown labels: • colour : "Strata" Ignoring unknown labels: • colour : "Strata" Ignoring unknown labels: • colour : "Strata" Ignoring unknown labels: • colour : "Strata" Ignoring unknown labels: • colour : "Strata" Ignoring unknown labels: • colour : "Strata" ℹ Survival follow-up time range: 0.1 to 122.37 months ℹ Best cutoff for "TMEscoreB_plus": -1.55 ✔ Best cutoff for "TMEscoreB_plus": -1.547 ℹ High TMEscoreB_plus: 240 ℹ Low TMEscoreB_plus: 146 ℹ Maximum follow-up time is 122.4 months; divided into 6 sections Ignoring unknown labels: • colour : "Strata" Ignoring unknown labels: • colour : "Strata" Ignoring unknown labels: • colour : "Strata" Ignoring unknown labels: • colour : "Strata" Ignoring unknown labels: • colour : "Strata" Ignoring unknown labels: • colour : "Strata" ℹ Survival follow-up time range: 0.1 to 122.37 months ℹ Best cutoff for "TMEscoreA_plus": 2.73 ✔ Best cutoff for "TMEscoreA_plus": 2.726 ℹ High TMEscoreA_plus: 93 ℹ Low TMEscoreA_plus: 293 ℹ Maximum follow-up time is 122.4 months; divided into 6 sections Ignoring unknown labels: • colour : "Strata" Ignoring unknown labels: • colour : "Strata" Ignoring unknown labels: • colour : "Strata" Ignoring unknown labels: • colour : "Strata" Ignoring unknown labels: • colour : "Strata" Ignoring unknown labels: • colour : "Strata" ℹ Survival follow-up time range: 0.1 to 122.37 months ℹ Best cutoff for "TMEscoreA_plus": 2.73 ✔ Best cutoff for "TMEscoreA_plus": 2.726 ℹ High TMEscoreA_plus: 93 ℹ Low TMEscoreA_plus: 293 ℹ Maximum follow-up time is 122.4 months; divided into 6 sections Ignoring unknown labels: • colour : "Strata" Ignoring unknown labels: • colour : "Strata" Ignoring unknown labels: • colour : "Strata" Ignoring unknown labels: • colour : "Strata" Ignoring unknown labels: • colour : "Strata" Ignoring unknown labels: • colour : "Strata" User session ended. Running garbage collection... ℹ Best number of TME clusters: 2 ℹ Cluster distribution: ℹ Survival follow-up time range: 0.1 to 122.37 months ℹ Best cutoff for "TMEscoreA_plus": 2.73 ✔ Best cutoff for "TMEscoreA_plus": 2.726 ℹ High TMEscoreA_plus: 93 ℹ Low TMEscoreA_plus: 293 ℹ Maximum follow-up time is 122.4 months; divided into 6 sections Ignoring unknown labels: • colour : "Strata" Ignoring unknown labels: • colour : "Strata" Ignoring unknown labels: • colour : "Strata" Ignoring unknown labels: • colour : "Strata" Ignoring unknown labels: • colour : "Strata" Ignoring unknown labels: • colour : "Strata" User session ended. Running garbage collection... User session ended. Running garbage collection... User session ended. Running garbage collection... User session ended. Running garbage collection... User session ended. Running garbage collection... User session ended. Running garbage collection... User session ended. Running garbage collection... User session ended. Running garbage collection... User session ended. Running garbage collection... User session ended. Running garbage collection... User session ended. Running garbage collection... User session ended. Running garbage collection... User session ended. Running garbage collection... ℹ Best number of TME clusters: 4 ℹ Cluster distribution: ℹ Creating heatmap with 22 features ℹ Creating heatmap with 22 features ℹ Follow-up time ranges from 0.1 to 122.37 months TME1 TME2 TME3 TME4 84 91 106 105 ℹ Maximum follow-up time is 122.4 months; divided into 6 sections Registered S3 methods overwritten by 'ggpp': method from heightDetails.titleGrob ggplot2 widthDetails.titleGrob ggplot2 Ignoring unknown labels: • colour : "Strata" User session ended. Running garbage collection... User session ended. Running garbage collection... User session ended. Running garbage collection... User session ended. Running garbage collection... User session ended. Running garbage collection... User session ended. Running garbage collection... User session ended. Running garbage collection... ℹ Best number of TME clusters: 3 ℹ Cluster distribution: ℹ Creating heatmap with 7 features ℹ Creating heatmap with 7 features User session ended. Running garbage collection... User session ended. Running garbage collection... IOBRportal database mode: enabled. User session ended. Running garbage collection... User session ended. Running garbage collection... IOBRportal database mode: enabled. User session ended. Running garbage collection... User session ended. Running garbage collection... User session ended. Running garbage collection... User session ended. Running garbage collection... User session ended. Running garbage collection... User session ended. Running garbage collection... User session ended. Running garbage collection... User session ended. Running garbage collection... User session ended. Running garbage collection... User session ended. Running garbage collection... User session ended. Running garbage collection... User session ended. Running garbage collection... User session ended. Running garbage collection... User session ended. Running garbage collection... User session ended. Running garbage collection... ℹ Loading cached data: "anno_hug133plus2" ℹ Row number of original eset: 54675 ✔ 83% of probes in expression set were annotated ℹ Found 23366 duplicate symbols, using "mean" method ℹ Row number after filtering duplicated gene symbol: 21752 ℹ Log2 transformation not necessary (data appears to already be log-scaled) User session ended. Running garbage collection... User session ended. Running garbage collection... IOBRportal database mode: enabled. IOBRportal database mode: enabled. ℹ Best number of TME clusters: 4 ℹ Cluster distribution: ℹ Best number of TME clusters: 4 ℹ Cluster distribution: ℹ Creating heatmap with 7 features Warning in sig_box(data = data, signature = input$sig_box_signature, variable = input$sig_box_variable, : internal error 1 in R_decompress1 with libdeflate Warning in sig_box(data = data, signature = input$sig_box_signature, variable = input$sig_box_variable, : restarting interrupted promise evaluation Warning in sig_box(data = data, signature = input$sig_box_signature, variable = input$sig_box_variable, : internal error 1 in R_decompress1 with libdeflate Warning in sig_box(data = data, signature = input$sig_box_signature, variable = input$sig_box_variable, : restarting interrupted promise evaluation Warning in sig_box(data = data, signature = input$sig_box_signature, variable = input$sig_box_variable, : internal error 1 in R_decompress1 with libdeflate # A tibble: 17 × 5 # Groups: Stage [5] Stage cluster Freq Prop count 1 Stage I TME1 1 0.11 9 2 Stage I TME2 2 0.22 9 3 Stage I TME3 4 0.44 9 4 Stage I TME4 2 0.22 9 5 Stage II TME1 15 0.41 37 6 Stage II TME2 8 0.22 37 7 Stage II TME3 12 0.32 37 8 Stage II TME4 2 0.05 37 9 Stage III TME1 8 0.5 16 10 Stage III TME2 2 0.12 16 11 Stage III TME3 5 0.31 16 12 Stage III TME4 1 0.06 16 13 Stage IV TME1 9 0.6 15 14 Stage IV TME3 3 0.2 15 15 Stage IV TME4 3 0.2 15 16 TME3 1 0.5 2 17 TME4 1 0.5 2 ℹ Available categories: box, continue2, continue, random, heatmap, heatmap3, tidyheatmap ℹ Box palettes: nrc, jama, aaas, jco, paired1, paired2, paired3, paired4, accent, set2 '#374E55FF', '#DF8F44FF', '#00A1D5FF', '#B24745FF', '#79AF97FF', '#6A6599FF', '#80796BFF' ℹ Groups: 4 ("TME1", "TME2", "TME3", and "TME4") ℹ Features: 183 ✔ Kruskal-Wallis test complete `height` was translated to `width`. ℹ Survival follow-up time range: 4.11 to 153.72 months ℹ Best cutoff for "Histones": -0.47 ✔ Best cutoff for "Histones": -0.472 ℹ High Histones: 46 ℹ Low Histones: 33 ℹ Maximum follow-up time is 153.7 months; divided into 6 sections Ignoring unknown labels: • colour : "Strata" Ignoring unknown labels: • colour : "Strata" Ignoring unknown labels: • colour : "Strata" Ignoring unknown labels: • colour : "Strata" Ignoring unknown labels: • colour : "Strata" Ignoring unknown labels: • colour : "Strata" ℹ Follow-up time ranges from 4.11 to 153.72 months Stage I Stage II Stage III Stage IV 9 37 16 15 ℹ Maximum follow-up time is 153.7 months; divided into 6 sections Ignoring unknown labels: • colour : "Strata" ℹ Time range: 4.11 to 153.72 ℹ Input data preview: Setting levels: control = 0, case = 1 Setting direction: controls < cases Setting levels: control = 0, case = 1 Setting direction: controls < cases Setting levels: control = 0, case = 1 Setting direction: controls < cases Setting levels: control = 0, case = 1 Setting direction: controls < cases ℹ Input data preview: Setting levels: control = 0, case = 1 Setting direction: controls < cases Setting levels: control = 0, case = 1 Setting direction: controls < cases Setting levels: control = 0, case = 1 Setting direction: controls < cases ℹ Input data preview: Setting levels: control = 0, case = 1 Setting direction: controls < cases Setting levels: control = 0, case = 1 Setting direction: controls < cases Setting levels: control = 0, case = 1 Setting direction: controls < cases Setting levels: control = 0, case = 1 Setting direction: controls < cases ℹ Computing spearman correlation for 184 features Warning in cor.test.default(data[[feat]], data[[target]], method = method, : Cannot compute exact p-value with ties Warning in cor.test.default(data[[feat]], data[[target]], method = method, : Cannot compute exact p-value with ties Warning in cor.test.default(data[[feat]], data[[target]], method = method, : Cannot compute exact p-value with ties ✔ Correlation analysis complete ℹ Computing pearson partial correlation for ✔ Partial correlation analysis complete ℹ Calculating spearman correlation (n = 79) ℹ Exact p-value: 1.3e-01 `geom_smooth()` using formula = 'y ~ x' `geom_smooth()` using formula = 'y ~ x' ℹ Calculating spearman correlation (n = 79) ℹ Exact p-value: 1.3e-01 `geom_smooth()` using formula = 'y ~ x' `geom_smooth()` using formula = 'y ~ x' ℹ Calculating spearman correlation (n = 79) ℹ Exact p-value: 1.7e-07 `geom_smooth()` using formula = 'y ~ x' `geom_smooth()` using formula = 'y ~ x' ℹ Calculating pearson correlation: 4 x 4 Warning: The `size` argument of `element_line()` is deprecated as of ggplot2 3.4.0. ℹ Please use the `linewidth` argument instead. ℹ The deprecated feature was likely used in the IOBR package. Please report the issue at . >>>> Result of Cuzick Test p.value names statistic adjust_pvalue STK11 5.323632e-08 STK11 -5.440148 2.661816e-05 KEAP1 3.140470e-06 KEAP1 -4.661412 7.851174e-04 EGFR 3.380902e-05 EGFR 4.146165 5.634836e-03 DIDO1 2.046619e-03 DIDO1 -3.083383 2.449802e-01 SPAG17 2.590198e-03 SPAG17 -3.012600 2.449802e-01 KRAS 3.139740e-03 KRAS -2.953715 2.449802e-01 ZFHX4 3.429722e-03 ZFHX4 -2.926343 2.449802e-01 PRKDC 4.858698e-03 PRKDC -2.816256 2.925155e-01 COL11A1 5.496426e-03 COL11A1 -2.776402 2.925155e-01 STYXL2 5.850309e-03 STYXL2 -2.756055 2.925155e-01 Warning in find_mutations(mutation_matrix = mut_data(), signature_matrix = sig_data, : restarting interrupted promise evaluation Warning in find_mutations(mutation_matrix = mut_data(), signature_matrix = sig_data, : internal error 1 in R_decompress1 with libdeflate >>>> Result of Cuzick Test p.value names statistic adjust_pvalue STK11 3.454506e-05 STK11 -4.141228 0.01727253 TP53 1.524199e-04 TP53 3.787093 0.03810496 TIAM1 8.800687e-04 TIAM1 -3.326301 0.14591890 LYST 1.193872e-03 LYST 3.240340 0.14591890 RP1L1 1.459189e-03 RP1L1 3.182680 0.14591890 LAMB4 3.027188e-03 LAMB4 -2.964964 0.21834374 ZNF479 3.056812e-03 ZNF479 2.961966 0.21834374 ITPR2 3.599992e-03 ITPR2 2.911238 0.22499950 SLC8A1 5.375058e-03 SLC8A1 2.783653 0.26289018 DLGAP2 5.486400e-03 DLGAP2 -2.776995 0.26289018 Warning in find_mutations(mutation_matrix = mut_data(), signature_matrix = sig_data, : restarting interrupted promise evaluation Warning in find_mutations(mutation_matrix = mut_data(), signature_matrix = sig_data, : internal error 1 in R_decompress1 with libdeflate Warning in coxph.fit(X, Y, istrat, offset, init, control, weights = weights, : Loglik converged before variable 1 ; coefficient may be infinite. ℹ Follow-up time ranges from 0.13 to 238.42 months WT Mutated 248 241 ℹ Maximum follow-up time is 238.4 months; divided into 6 sections ℹ Reference group not defined, using alphabetical order Ignoring unknown labels: • colour : "Strata" >>>> Result of Cuzick Test p.value names statistic adjust_pvalue STK11 3.454506e-05 STK11 -4.141228 0.01727253 TP53 1.524199e-04 TP53 3.787093 0.03810496 TIAM1 8.800687e-04 TIAM1 -3.326301 0.14591890 LYST 1.193872e-03 LYST 3.240340 0.14591890 RP1L1 1.459189e-03 RP1L1 3.182680 0.14591890 LAMB4 3.027188e-03 LAMB4 -2.964964 0.21834374 ZNF479 3.056812e-03 ZNF479 2.961966 0.21834374 ITPR2 3.599992e-03 ITPR2 2.911238 0.22499950 SLC8A1 5.375058e-03 SLC8A1 2.783653 0.26289018 DLGAP2 5.486400e-03 DLGAP2 -2.776995 0.26289018 Warning in find_mutations(mutation_matrix = mut_data(), signature_matrix = sig_data, : restarting interrupted promise evaluation Warning in find_mutations(mutation_matrix = mut_data(), signature_matrix = sig_data, : internal error 1 in R_decompress1 with libdeflate