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 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://127.0.0.1:37517 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 KEAP1 1.851134e-09 KEAP1 -6.010359 9.255671e-07 STK11 1.409734e-05 STK11 -4.342340 3.524335e-03 TRPM6 1.818257e-03 TRPM6 3.118416 3.030428e-01 PRKDC 3.428469e-03 PRKDC -2.926457 4.167011e-01 CPED1 4.167011e-03 CPED1 2.865234 4.167011e-01 DSCAM 7.793411e-03 DSCAM -2.660891 6.494510e-01 RP1L1 1.773061e-02 RP1L1 2.371196 8.575677e-01 CNTNAP4 1.950163e-02 CNTNAP4 2.335801 8.575677e-01 ZNF831 2.027714e-02 ZNF831 2.321180 8.575677e-01 ITPRID1 2.187583e-02 ITPRID1 2.292517 8.575677e-01 >>> Result of Wilcoxon test (top 10) p.value names statistic adjust_pvalue KEAP1 1.855700e-09 KEAP1 26226 9.278498e-07 STK11 1.412697e-05 STK11 18723 3.531744e-03 TRPM6 1.821939e-03 TRPM6 5773 3.036565e-01 PRKDC 3.435223e-03 PRKDC 10346 4.175075e-01 CPED1 4.175075e-03 CPED1 5616 4.175075e-01 DSCAM 7.805885e-03 DSCAM 12753 6.504904e-01 RP1L1 1.775059e-02 RP1L1 14371 8.590259e-01 CNTNAP4 1.953062e-02 CNTNAP4 7558 8.590259e-01 ZNF831 2.030351e-02 ZNF831 10113 8.590259e-01 ITPRID1 2.191164e-02 ITPRID1 5892 8.590259e-01 All mutation types: mut. Warning: You defined `cell_fun` for a heatmap with more than 100 rows or columns, which might be very slow to draw. Consider to use the vectorized version `layer_fun`. All mutation types: mut. Warning: You defined `cell_fun` for a heatmap with more than 100 rows or columns, which might be very slow to draw. Consider to use the vectorized version `layer_fun`. >>>> Result of Cuzick Test p.value names statistic adjust_pvalue KEAP1 1.851134e-09 KEAP1 -6.010359 9.255671e-07 STK11 1.409734e-05 STK11 -4.342340 3.524335e-03 TRPM6 1.818257e-03 TRPM6 3.118416 3.030428e-01 PRKDC 3.428469e-03 PRKDC -2.926457 4.167011e-01 CPED1 4.167011e-03 CPED1 2.865234 4.167011e-01 DSCAM 7.793411e-03 DSCAM -2.660891 6.494510e-01 RP1L1 1.773061e-02 RP1L1 2.371196 8.575677e-01 CNTNAP4 1.950163e-02 CNTNAP4 2.335801 8.575677e-01 ZNF831 2.027714e-02 ZNF831 2.321180 8.575677e-01 ITPRID1 2.187583e-02 ITPRID1 2.292517 8.575677e-01 >>> Result of Wilcoxon test (top 10) p.value names statistic adjust_pvalue KEAP1 1.855700e-09 KEAP1 26226 9.278498e-07 STK11 1.412697e-05 STK11 18723 3.531744e-03 TRPM6 1.821939e-03 TRPM6 5773 3.036565e-01 PRKDC 3.435223e-03 PRKDC 10346 4.175075e-01 CPED1 4.175075e-03 CPED1 5616 4.175075e-01 DSCAM 7.805885e-03 DSCAM 12753 6.504904e-01 RP1L1 1.775059e-02 RP1L1 14371 8.590259e-01 CNTNAP4 1.953062e-02 CNTNAP4 7558 8.590259e-01 ZNF831 2.030351e-02 ZNF831 10113 8.590259e-01 ITPRID1 2.191164e-02 ITPRID1 5892 8.590259e-01 All mutation types: mut. Warning: You defined `cell_fun` for a heatmap with more than 100 rows or columns, which might be very slow to draw. Consider to use the vectorized version `layer_fun`. All mutation types: mut. Warning: You defined `cell_fun` for a heatmap with more than 100 rows or columns, which might be very slow to draw. Consider to use the vectorized version `layer_fun`. ℹ Follow-up time ranges from 0.13 to 238.42 months WT Mutated 481 8 ℹ Maximum follow-up time is 238.4 months; divided into 6 sections ℹ Reference group not defined, using alphabetical order Warning in survival::Surv(time, status) : Invalid status value, converted to NA ℹ Follow-up time ranges from 0.13 to 238.42 months WT Mutated 481 8 ℹ Maximum follow-up time is 238.4 months; divided into 6 sections ℹ Reference group not defined, using alphabetical order Warning in survival::Surv(time, status) : Invalid status value, converted to NA ℹ Follow-up time ranges from 0.13 to 238.42 months WT Mutated 481 8 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" Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [79 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [6 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [73 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [6 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [73 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [19 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [56 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [4 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [6 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [73 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [19 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [56 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [4 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [19 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [56 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [4 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [26 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [33 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [16 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [4 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [19 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [56 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [4 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [26 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [33 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [16 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [4 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [26 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [33 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [16 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [4 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [21 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [20 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [14 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [4 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [20 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [26 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [33 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [16 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [4 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [21 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [20 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [14 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [4 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [20 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [21 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [20 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [14 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [4 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [20 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [18 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [19 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [19 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [14 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [5 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [4 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [21 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [20 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [14 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [4 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [20 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [18 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [19 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [19 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [14 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [5 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [4 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [18 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [19 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [19 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [14 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [5 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [4 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [16 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [19 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [14 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [3 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [5 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [3 != 1 x 1] Warning in matrix(x[cl == i, ], byrow = FALSE, nrow = 1, ncol = ncol(x)) : data length differs from size of matrix: [19 != 1 x 1] ℹ Best number of TME clusters: 2 ℹ Cluster distribution: ℹ Creating heatmap with 3 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 . # A tibble: 5 × 5 # Groups: Stage [5] Stage M_Stage Freq Prop count 1 Stage I M0 9 1 9 2 Stage II M0 37 1 37 3 Stage III M0 16 1 16 4 Stage IV M1 15 1 15 5 2 1 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: "Female" and "Male" ℹ Features: 183 ✔ Wilcoxon test complete ℹ Groups: 2 ("N0" and "N1") ℹ Features: 183 ✔ Kruskal-Wallis test complete ℹ Best number of TME clusters: 4 ℹ Cluster distribution: ℹ Creating heatmap with 2 features ℹ Creating heatmap with 2 features `stat_compare_means()` with `comparisons` displays *unadjusted* p-values (no correction for multiple comparisons). ℹ For p-values adjusted for multiple comparisons, use `geom_pwc()`, or `stat_pvalue_manual()` together with `compare_means(..., p.adjust.method = )`. This message is displayed once per session. ℹ Best number of TME clusters: 4 ℹ Cluster distribution: ℹ Groups: "M0" and "M1" ℹ Features: 183 ✔ Wilcoxon test complete ℹ Creating heatmap with 20 features `height` was translated to `width`. ℹ Creating heatmap with 185 features `height` was translated to `width`. `height` was translated to `width`. ℹ Creating heatmap with 20 features ℹ Survival follow-up time range: 4.11 to 153.72 months ℹ Best cutoff for "Immune_Checkpoint": 1.26 ✔ Best cutoff for "Immune_Checkpoint": 1.26 ℹ High Immune_Checkpoint: 11 ℹ Low Immune_Checkpoint: 68 ℹ Maximum follow-up time is 153.7 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 Follow-up time ranges from 4.11 to 153.72 months Female Male 48 31 ℹ Maximum follow-up time is 153.7 months; divided into 6 sections ℹ Reference group not defined, using alphabetical order 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 ℹ Computing pearson partial correlation for ✔ Partial correlation analysis complete ℹ Calculating spearman correlation (n = 79) ℹ Exact p-value: 4.2e-11 ℹ Groups: "Stage I", "Stage II", "Stage III", and "Stage IV" `geom_smooth()` using formula = 'y ~ x' `geom_smooth()` using formula = 'y ~ x' ℹ Calculating pearson correlation: 2 x 7