Last updated: 2022-02-03

Checks: 4 3

Knit directory: MS_lesions/

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  • causes_of_variability_wm
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  • coefs_w_varying_pcs_other
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  • deg_barplot_wm
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  • gm_neuron_propns_layers
  • gm_vs_wm_proportions
  • grp17_cell_abundances
  • gwas_coloc
  • gwas_de_barplots
  • gwas_manhattan
  • logfc_vs_donor_sd_gm
  • logfc_vs_donor_sd_wm
  • module_scores_opc_oligo
  • module_top_oligo_genes
  • mofa_factor_heatmap_wm
  • muscat_vs_sd
  • oligo_barplot_gm
  • oligo_barplot_wm
  • paga_on_oligos
  • random_effects_model_example
  • sample_summary
  • sccaf_summary
  • session_info
  • session-info-chunk-inserted-by-workflowr
  • top_genes_factor1
  • top_genes_factor2
  • top_genes_factor3
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  • umap_opc_oligo
  • variance_explained
  • wm_logfc_profile_clusters

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Setup / definitions

Libraries

Helper functions

source('code/ms00_utils.R')
library("knitr")

Figure 1

B

UMAP applied to subset of 100k cells (subset because of memory limits), using parameters min_dist = 1, spread = 2, otherwise defaults. Clusters are determined by Louvain clustering applied to the conos graph, followed by post-hoc splitting of two clusters based on biological expectations (COPs and immune cells), and merging of very similar clusters (using SCCAF).

include_graphics("figure/ms12_markers.Rmd/plot_umap_final_celltypes_sel-1.png", error = FALSE)

Version Author Date
7fb1b95 wmacnair 2021-11-25

C

UMAP plot as in B-1, restricted to just oligodendrocyte and OPC celltypes.

include_graphics("figure/ms12_markers.Rmd/plot_umap_opc_oligo_only-1.png", error = FALSE)

Version Author Date
7fb1b95 wmacnair 2021-11-25

D

Median oNMF module score per fine celltype for OPC and oligo modules and cells. Columns are scaled to have max value equal to 1.

include_graphics("figure/ms08_modules.Rmd/plot_scores_by_type_scaled-1.png", error = FALSE)

Version Author Date
d2a327c wmacnair 2022-01-20
9af1539 wmacnair 2021-12-13
7fb1b95 wmacnair 2021-11-25

E

Expression of top genes for each oligo-OPC module (gene selected if weight >2%). Expression calculated across all cells and samples.

include_graphics("figure/ms08_modules.Rmd/plot_genes_dotplot-2.png", error = FALSE)

Version Author Date
d2a327c wmacnair 2022-01-20
1d30bcb wmacnair 2022-01-17
9af1539 wmacnair 2021-12-13
7fb1b95 wmacnair 2021-11-25

F

PAGA applied to oligodendrocytes and OPCs / COPs across all samples.

include_graphics("figure/ms11_paga.Rmd/plot_paga_olg_wm_gm-1.png", error = FALSE)

Version Author Date
6ae0432 wmacnair 2022-01-07
93fa77e wmacnair 2022-01-05
ff2b8fb wmacnair 2021-12-15
7fb1b95 wmacnair 2021-11-25

Figure 2

A

Proportions of fine celltypes in healthy GM and healthy WM. Neuronal celltypes excluded. Negative binomial model fit to absolute numbers for each celltype, using total number of cells in sample as offset. FDR calculated across all celltypes.

include_graphics("figure/ms09_ancombc_mixed.Rmd/plot_wm_vs_gm-1.png", error = FALSE)

Version Author Date
9ee5eee wmacnair 2021-12-08
7fb1b95 wmacnair 2021-11-25

B

Contribution to variability in celltype abundances explained by lesion + patient in WM.

include_graphics("figure/ms09_ancombc_mixed.Rmd/plot_lrt_results-1.png", error = FALSE)

Version Author Date
47a3ec8 wmacnair 2021-12-08
7fb1b95 wmacnair 2021-11-25

C

Contribution to variability in celltype abundances explained by lesion + patient in GM, no layers.

include_graphics("figure/ms09_ancombc_mixed.Rmd/plot_lrt_results-2.png", error = FALSE)

Version Author Date
47a3ec8 wmacnair 2021-12-08
7fb1b95 wmacnair 2021-11-25

D

Differential abundance results for WM.

include_graphics("figure/ms09_ancombc_mixed.Rmd/plot_bootstraps_lesions_signif-1.png", error = FALSE)

Version Author Date
270e5fc wmacnair 2021-11-26

E

Differential abundance results for GM (with layers factored out).

include_graphics("figure/ms09_ancombc_mixed.Rmd/plot_bootstraps_lesions_signif-6.png", error = FALSE)

Version Author Date
270e5fc wmacnair 2021-11-26

Figure 3

A

include_graphics("figure/ms99_deg_figures_gm.Rmd/plot_de_barplot_sel-1.png", error = FALSE)

Version Author Date
d83826d wmacnair 2022-01-27

B

include_graphics("figure/ms99_deg_figures_wm.Rmd/plot_de_barplot_sel-1.png", error = FALSE)

Version Author Date
d83826d wmacnair 2022-01-27

C

Dotplot of Hallmark module results for GM.

[IN PRODUCTION]

D

Dotplot of Hallmark module results for WM.

[IN PRODUCTION]

E

Heatmap of selected interferon genes.

[IN PRODUCTION]

F

Genetic enrichment of differentially expressed genes.

include_graphics("figure/gwas_figures/de_barplots.png", error = FALSE)

Version Author Date
b1e52a7 wmacnair 2022-01-06

G

Clustering of WM fold change profiles. Restricted to genes where at least one lesion type has FDR < 5%. Clusters split so that average logFC difference between clusters is > log(4); clusters with fewer than 5 genes not shown; clusters ordered in descending order of mean logFC.

include_graphics("figure/ms99_deg_figures_wm.Rmd/plot_fc_cluster_profiles-1.png", error = FALSE)

Version Author Date
d83826d wmacnair 2022-01-27

Figure 4

A

Clustered expression heatmap of WM genes.

include_graphics("figure/ms15_mofa_sample_wm_final_meta_bigger.Rmd/fig_overview_expression-2.png", error = FALSE)

Version Author Date
8bc5188 wmacnair 2022-01-27

B

Variance explained

include_graphics("figure/ms15_mofa_sample_wm_final_meta_bigger.Rmd/fig_factor_r2s-1.png", error = FALSE)

Version Author Date
8bc5188 wmacnair 2022-01-27

C

First two PCs of CLRs of oligodendroglia proportions.

include_graphics("figure/ms09_ancombc_mixed.Rmd/plot_sample_splits_clrs_oligos-6.png", error = FALSE)

Version Author Date
8364a6f wmacnair 2021-12-13

D

Patient stratification via MOFA factors.

include_graphics("figure/ms15_mofa_sample_wm_final_meta_bigger.Rmd/plot_factors_heatmap_few-1.png", error = FALSE)

Version Author Date
8bc5188 wmacnair 2022-01-27

E

Factor 1 top genes

include_graphics("figure/ms15_mofa_sample_wm_final_meta_bigger.Rmd/fig_factor1-1.png", error = FALSE)

Version Author Date
8bc5188 wmacnair 2022-01-27

F

Factor 3 top genes

include_graphics("figure/ms15_mofa_sample_wm_final_meta_bigger.Rmd/fig_factor3-1.png", error = FALSE)

Version Author Date
8bc5188 wmacnair 2022-01-27

G

Factor 5 top genes

include_graphics("figure/ms15_mofa_sample_wm_final_meta_bigger.Rmd/fig_factor5-1.png", error = FALSE)

Version Author Date
8bc5188 wmacnair 2022-01-27

Supplementary figures

S1

Post-QC summary of samples

include_graphics("de_reports/figure/ms03_SampleQC.Rmd/plot_totals_split_by_meta-1.png", error = FALSE)

S2A

[TO DO: summaries of post-QC QC metrics]

S2B

[TO UPDATE: cluster mixing; need to update to merged version]

include_graphics("figure/ms04_conos.Rmd/plot_conos_mixing-1.png", error = FALSE)

Version Author Date
7fb1b95 wmacnair 2021-11-25

S3A

Expression of marker genes selected for broad celltypes, and for fine celltypes. Expression calculated across all cells and samples.

include_graphics("figure/ms12_markers.Rmd/plot_dotplot_dheeraj_compact-1.png", error = FALSE)

Version Author Date
7fb1b95 wmacnair 2021-11-25

S3B

[Eneritz to provide: comparing oligo cell types in this paper and previous nature paper]

S3C

[TO DO: astrocyte module genes]

S4A

Proportions of neuronal compartment per sample, split by layer-specificity of neurons. L1 and L2/L3 neurons account for relatively low proportions of NAGM samples, while L5 and L6 neurons account for high proportions of NAGM samples; vice versa for GML samples, while ctrl GM lies in the middle. This indicates that, on average, the samples are roughly ordered as follows: NAGM is deeper than ctrl GM, which is deeper than GML.

include_graphics("figure/ms09_ancombc_mixed.Rmd/plot_propns_layers-1.png", error = FALSE)

Version Author Date
9ee5eee wmacnair 2021-12-08
7fb1b95 wmacnair 2021-11-25

S4B

Principal components of GM neuronal layer centred log ratios (CLRs; see Methods). y-axis shows absolute Spearman correlation between PC loadings and neuronal layer numbers (excluding neuronal clusters without an assigned layer number). x-axis shows the variance explained by each PC (on a log scale). Dashed lines show thresholds at 0.2 Spearman correlation, and 1% variance explained, giving up to 7 PCs that could be relevant to layers.

include_graphics("figure/ms09_ancombc_mixed.Rmd/plot_layer_var_exp-1.png", error = FALSE)

Version Author Date
afba18d wmacnair 2021-12-20
9ee5eee wmacnair 2021-12-08
7fb1b95 wmacnair 2021-11-25

S4C

Bootstrapped ANCOM-BC results including varying numbers of PCs as covariates. Number of PCs used varies from 0 to 7 (see S4B for rationale for 7). Grey lines show 95% bootstrapped confidence interval, coloured lines show 80% confidence interval; based on 20k bootstraps (large number taken to give reliable estimates of tails; see [ref: Hesterberg 2011]).

include_graphics("figure/ms09_ancombc_mixed.Rmd/plot_effect_of_pcs_lesions-1.png", error = FALSE)

Version Author Date
270e5fc wmacnair 2021-11-26
7fb1b95 wmacnair 2021-11-25
include_graphics("figure/ms09_ancombc_mixed.Rmd/plot_effect_of_pcs_lesions-2.png", error = FALSE)

Version Author Date
270e5fc wmacnair 2021-11-26
7fb1b95 wmacnair 2021-11-25

S5A

Proportions of all non-contaminated genes with MS effect and / or donor effect, in WM. MS effect defined as: FDR < 1% for at least one lesion type, and abs(logFC) > log(1.5) (i.e. expression change of +/-50%). Donor effect defined as: ANOVA for inclusion of random effect in model has FDR < 1%, and SD(random effects) > log(1.5).

include_graphics("figure/ms99_deg_figures_wm.Rmd/plot_causes_of_variability-1.png", error = FALSE)

Version Author Date
d83826d wmacnair 2022-01-27
79b10e2 wmacnair 2022-01-24

S5B

Proportions of all non-contaminated genes with MS effect and / or donor effect, in GM. MS effect defined as: FDR < 1% for at least one lesion type, and abs(logFC) > log(1.5) (i.e. expression change of +/-50%). Donor effect defined as: ANOVA for inclusion of random effect in model has FDR < 1%, and SD(random effects) > log(1.5).

include_graphics("figure/ms99_deg_figures_gm.Rmd/plot_causes_of_variability-1.png", error = FALSE)

Version Author Date
d83826d wmacnair 2022-01-27
79b10e2 wmacnair 2022-01-24

S6A

[IN PRODUCTION: DEG barplots for fine celltypes]

S6B

[IN PRODUCTION: dot plot of GM fine type GO terms]

S6C

[IN PRODUCTION: heatmap of selected genes in GM: GRIA1, GRIA2, GRIA4, GRIN2B, GRM1, GRM5, SLC2A12, SLC22A10, SCN1A, SCN1B, SCN2B, SCN4B, KCNA1, KCNA2, KCNC1, OXPHOS, ATP1A1, ATP1B1, NDUFB10, NDUFS3, UQCRH]

S7A

[barplot of DEGs in fine cell types]

S8A

Distribution of model fits for genes for each broad celltype in WM. y-axis shows standard deviation of random (donor) effects for each gene. x-axis shows log2FC of lesion type with smallest p-value for each gene. Horizontal dashed lines show cutoff at SD = log(1.5); vertical dashed lines show cutoff at abs(log2FC) = log(1.5).

include_graphics("figure/ms15_mofa_sample_wm_final_meta_bigger.Rmd/fig_interesting_gs-1.png", error = FALSE)

Version Author Date
8bc5188 wmacnair 2022-01-27

S8B

Distribution of model fits for genes for each broad celltype in GM. y-axis shows standard deviation of random (donor) effects for each gene. x-axis shows log2FC of lesion type with smallest p-value for each gene. Horizontal dashed lines show cutoff at SD = log(1.5); vertical dashed lines show cutoff at abs(log2FC) = log(1.5).

include_graphics("figure/ms15_mofa_sample_gm_w_layers_final_meta.Rmd/fig_interesting_gs-1.png", error = FALSE)

Version Author Date
1d0d7e8 wmacnair 2022-01-21

S9

[show absence of WM oligo pattern in GM: maybe take WM PCs, apply to GM?]

S10A

[MOFA cartoon]

S10B

[CLARIFYING: maybe same as S8A? see comment in manuscript]

S11A

Distributions of MOFA factors. Colour denotes donor; grey is used where only one sample was obtained from a donor.

include_graphics("figure/ms15_mofa_sample_gm_w_layers_final_meta.Rmd/fig_mofa_factors_lesions-1.png", error = FALSE)

Version Author Date
5a1c0c2 wmacnair 2022-01-06
7fb1b95 wmacnair 2021-11-25

S11B

First panel shows variation in expression for each celltype explained by MOFA+ factors; second panel shows extent to which MOFA+ factors can be accounted for by metadata. Variance explained in first panel is per celltype, so the maximum total for each row is 100%. Pseudo-R2 values are calculated by fitting a mixed model to each factor, using model factor_value ~ lesion_type + sex + age_scale + pmi_cat + (1 | donor_id), and the glmmTMB function in package glmmTMB. Pseudo-R2 values are determined by Nakagawa’s R2, showing proportion of variance explained using fixed components only, and including a donor effect (see Methods).

include_graphics("figure/ms15_mofa_sample_gm_w_layers_final_meta.Rmd/fig_factor_r2s-1.png", error = FALSE)

Version Author Date
2372e65 wmacnair 2022-01-18
5a1c0c2 wmacnair 2022-01-06
7fb1b95 wmacnair 2021-11-25

S12

[IN PRODUCTION: plot extent of overlap between factor genes in WM]

S13

[CLARIFYING: see comment in manuscript]

Supplementary tables

Table 3

[DEGs for each broad cell type (fdr <0.01 & log FC > 1.5) with same annotation (specific to cell types, shared between lesions within a cell type and shared between cell types)]

Table 4

[MAGMA MS genes (fdr < 0.05) which are DEGs in pericytes, endo and opc/cops]

Unused figure / supp figs I haven’t sorted out yet

Sx

[SCCAF]

include_graphics("de_reports/figure/ms03_SampleQC.Rmd/plot_totals_split_by_meta-1.png", error = FALSE)

Sx

WM oligodendroglia proportions barplot

include_graphics("figure/ms09_ancombc_mixed.Rmd/plot_sample_splits_bars_oligos-1.png", error = FALSE)

Version Author Date
97aa6f8 wmacnair 2021-12-08
47a3ec8 wmacnair 2021-12-08

Sx

Comparison of Sarah’s validation of GPR17-expressing cells

include_graphics("figure/ms09_ancombc_mixed.Rmd/plot_no_gpr17_cells-1.png", error = FALSE)

Version Author Date
afba18d wmacnair 2021-12-20

Sx

Contribution to variability in celltype abundances explained by lesion + patient in GM, including 4 layer PCs

include_graphics("figure/ms09_ancombc_mixed.Rmd/plot_lrt_results-6.png", error = FALSE)

Version Author Date
47a3ec8 wmacnair 2021-12-08
7fb1b95 wmacnair 2021-11-25

Sx

DA results for GM, no layers

include_graphics("figure/ms09_ancombc_mixed.Rmd/plot_bootstraps_lesions-2.png", error = FALSE)

Version Author Date
47a3ec8 wmacnair 2021-12-08
7fb1b95 wmacnair 2021-11-25

Sx

include_graphics("figure/ms15_mofa_sample_gm_w_layers_final_meta.Rmd/fig_overview_expression-2.png", error = FALSE)

Version Author Date
1d0d7e8 wmacnair 2022-01-21

Sx

Effect of including PCs, neurons

include_graphics("figure/ms09_ancombc_mixed.Rmd/plot_effect_of_pcs_lesions-1.png", error = FALSE)

Version Author Date
270e5fc wmacnair 2021-11-26
7fb1b95 wmacnair 2021-11-25

Sx

Effect of including PCs, other celltypes

include_graphics("figure/ms09_ancombc_mixed.Rmd/plot_effect_of_pcs_lesions-2.png", error = FALSE)

Version Author Date
270e5fc wmacnair 2021-11-26
7fb1b95 wmacnair 2021-11-25

Sx

GM oligodendroglia proportions barplot

include_graphics("figure/ms09_ancombc_mixed.Rmd/plot_sample_splits_bars_oligos-2.png", error = FALSE)

Version Author Date
97aa6f8 wmacnair 2021-12-08
47a3ec8 wmacnair 2021-12-08

Sx

Illustration of random effects model

include_graphics("figure/ms15_mofa_sample_wm_final_meta_bigger.Rmd/fig_random_effects_example-3.png", error = FALSE)

Version Author Date
8bc5188 wmacnair 2022-01-27

Sx

Disease effect vs donor effect

include_graphics("figure/ms15_mofa_sample_wm_final_meta_bigger.Rmd/fig_muscat_vs_sd-1.png", error = FALSE)

Sx

MOFA factors

include_graphics("figure/ms15_mofa_sample_wm_final_meta_bigger.Rmd/fig_mofa_factors_diagnosis-1.png", error = FALSE)

Version Author Date
8bc5188 wmacnair 2022-01-27

Sx

Manhattan plot of MAGMA differentially expressed genes

include_graphics("figure/gwas_figures/manhattan.png", error = FALSE)

Version Author Date
b1e52a7 wmacnair 2022-01-06

Sx

Example of a coloc gene that is differentially expressed

include_graphics("figure/gwas_figures/coloc_example_gene_NR1H3_microglia.png", error = FALSE)

Version Author Date
b1e52a7 wmacnair 2022-01-06

Sx

Expression heatmap of WM genes, ordered by lesion type.

include_graphics("figure/ms15_mofa_sample_wm_final_meta_bigger.Rmd/fig_overview_expression-4.png", error = FALSE)

Version Author Date
8bc5188 wmacnair 2022-01-27

Sx

Patient stratification

include_graphics("figure/ms15_mofa_sample_wm_final_meta_bigger.Rmd/fig_f1_vs_f2-3.png", error = FALSE)

Version Author Date
8bc5188 wmacnair 2022-01-27

End

devtools::session_info()
- Session info ---------------------------------------------------------------
 setting  value                       
 version  R version 4.0.5 (2021-03-31)
 os       CentOS Linux 7 (Core)       
 system   x86_64, linux-gnu           
 ui       X11                         
 language (EN)                        
 collate  en_US.UTF-8                 
 ctype    C                           
 tz       Europe/Zurich               
 date     2022-01-28                  

- Packages -------------------------------------------------------------------
 package       * version date       lib source                            
 assertthat    * 0.2.1   2019-03-21 [2] CRAN (R 4.0.0)                    
 BiocManager     1.30.16 2021-06-15 [1] CRAN (R 4.0.3)                    
 BiocStyle     * 2.18.1  2020-11-24 [1] Bioconductor                      
 bslib           0.3.1   2021-10-06 [2] CRAN (R 4.0.5)                    
 cachem          1.0.6   2021-08-19 [1] CRAN (R 4.0.5)                    
 callr           3.7.0   2021-04-20 [2] CRAN (R 4.0.3)                    
 cellranger      1.1.0   2016-07-27 [2] CRAN (R 4.0.0)                    
 circlize      * 0.4.13  2021-06-09 [1] CRAN (R 4.0.3)                    
 cli             3.0.1   2021-07-17 [1] CRAN (R 4.0.3)                    
 codetools       0.2-18  2020-11-04 [2] CRAN (R 4.0.3)                    
 colorout      * 1.2-2   2021-04-15 [1] Github (jalvesaq/colorout@79931fd)
 colorspace      2.0-2   2021-06-24 [1] CRAN (R 4.0.3)                    
 crayon          1.4.1   2021-02-08 [2] CRAN (R 4.0.3)                    
 data.table    * 1.14.2  2021-09-27 [2] CRAN (R 4.0.5)                    
 DBI             1.1.1   2021-01-15 [2] CRAN (R 4.0.3)                    
 desc            1.4.0   2021-09-28 [1] CRAN (R 4.0.5)                    
 devtools        2.4.2   2021-06-07 [1] CRAN (R 4.0.3)                    
 digest          0.6.28  2021-09-23 [2] CRAN (R 4.0.5)                    
 dplyr           1.0.7   2021-06-18 [2] CRAN (R 4.0.3)                    
 ellipsis        0.3.2   2021-04-29 [2] CRAN (R 4.0.3)                    
 evaluate        0.14    2019-05-28 [2] CRAN (R 4.0.0)                    
 fansi           0.5.0   2021-05-25 [2] CRAN (R 4.0.3)                    
 fastmap         1.1.0   2021-01-25 [2] CRAN (R 4.0.3)                    
 forcats       * 0.5.1   2021-01-27 [2] CRAN (R 4.0.3)                    
 fs              1.5.0   2020-07-31 [2] CRAN (R 4.0.2)                    
 generics        0.1.1   2021-10-25 [2] CRAN (R 4.0.5)                    
 ggplot2       * 3.3.5   2021-06-25 [1] CRAN (R 4.0.3)                    
 git2r           0.28.0  2021-01-10 [1] CRAN (R 4.0.3)                    
 GlobalOptions   0.1.2   2020-06-10 [1] CRAN (R 4.0.3)                    
 glue            1.4.2   2020-08-27 [2] CRAN (R 4.0.3)                    
 gridExtra       2.3     2017-09-09 [2] CRAN (R 4.0.0)                    
 gtable          0.3.0   2019-03-25 [2] CRAN (R 4.0.0)                    
 highr           0.9     2021-04-16 [2] CRAN (R 4.0.3)                    
 htmltools       0.5.2   2021-08-25 [2] CRAN (R 4.0.5)                    
 httpuv          1.6.3   2021-09-09 [2] CRAN (R 4.0.5)                    
 jquerylib       0.1.4   2021-04-26 [2] CRAN (R 4.0.3)                    
 jsonlite        1.7.2   2020-12-09 [2] CRAN (R 4.0.3)                    
 knitr         * 1.36    2021-09-29 [1] CRAN (R 4.0.5)                    
 later           1.3.0   2021-08-18 [2] CRAN (R 4.0.5)                    
 lifecycle       1.0.1   2021-09-24 [2] CRAN (R 4.0.5)                    
 magrittr      * 2.0.1   2020-11-17 [1] CRAN (R 4.0.3)                    
 memoise         2.0.0   2021-01-26 [1] CRAN (R 4.0.3)                    
 munsell         0.5.0   2018-06-12 [2] CRAN (R 4.0.0)                    
 pillar          1.6.4   2021-10-18 [1] CRAN (R 4.0.5)                    
 pkgbuild        1.2.0   2020-12-15 [1] CRAN (R 4.0.3)                    
 pkgconfig       2.0.3   2019-09-22 [2] CRAN (R 4.0.0)                    
 pkgload         1.2.3   2021-10-13 [2] CRAN (R 4.0.5)                    
 prettyunits     1.1.1   2020-01-24 [2] CRAN (R 4.0.0)                    
 processx        3.5.2   2021-04-30 [2] CRAN (R 4.0.3)                    
 promises        1.2.0.1 2021-02-11 [2] CRAN (R 4.0.3)                    
 ps              1.6.0   2021-02-28 [2] CRAN (R 4.0.3)                    
 purrr           0.3.4   2020-04-17 [2] CRAN (R 4.0.0)                    
 R6              2.5.1   2021-08-19 [2] CRAN (R 4.0.5)                    
 RColorBrewer  * 1.1-2   2014-12-07 [2] CRAN (R 4.0.0)                    
 Rcpp            1.0.7   2021-07-07 [1] CRAN (R 4.0.3)                    
 readxl        * 1.3.1   2019-03-13 [2] CRAN (R 4.0.0)                    
 remotes         2.4.1   2021-09-29 [1] CRAN (R 4.0.5)                    
 rlang           0.4.12  2021-10-18 [2] CRAN (R 4.0.5)                    
 rmarkdown       2.11    2021-09-14 [1] CRAN (R 4.0.5)                    
 rprojroot       2.0.2   2020-11-15 [2] CRAN (R 4.0.3)                    
 sass            0.4.0   2021-05-12 [2] CRAN (R 4.0.3)                    
 scales        * 1.1.1   2020-05-11 [2] CRAN (R 4.0.0)                    
 sessioninfo     1.1.1   2018-11-05 [1] CRAN (R 4.0.3)                    
 shape           1.4.6   2021-05-19 [1] CRAN (R 4.0.1)                    
 stringi         1.7.4   2021-08-25 [1] CRAN (R 4.0.5)                    
 stringr       * 1.4.0   2019-02-10 [2] CRAN (R 4.0.0)                    
 testthat        3.1.0   2021-10-04 [2] CRAN (R 4.0.5)                    
 tibble          3.1.5   2021-09-30 [1] CRAN (R 4.0.5)                    
 tidyselect      1.1.1   2021-04-30 [2] CRAN (R 4.0.3)                    
 usethis         2.1.2   2021-10-25 [1] CRAN (R 4.0.5)                    
 utf8            1.2.2   2021-07-24 [1] CRAN (R 4.0.3)                    
 vctrs           0.3.8   2021-04-29 [2] CRAN (R 4.0.3)                    
 viridis       * 0.6.2   2021-10-13 [1] CRAN (R 4.0.5)                    
 viridisLite   * 0.4.0   2021-04-13 [1] CRAN (R 4.0.1)                    
 whisker         0.4     2019-08-28 [1] CRAN (R 4.0.3)                    
 withr           2.4.2   2021-04-18 [2] CRAN (R 4.0.3)                    
 workflowr     * 1.6.2   2020-04-30 [1] CRAN (R 4.0.3)                    
 xfun            0.27    2021-10-18 [1] CRAN (R 4.0.5)                    
 yaml            2.2.1   2020-02-01 [2] CRAN (R 4.0.3)                    

[1] /pstore/home/macnairw/lib/conda_r3.12
[2] /pstore/home/macnairw/.conda/envs/r_4.0.3/lib/R/library

sessionInfo()
R version 4.0.5 (2021-03-31)
Platform: x86_64-conda-linux-gnu (64-bit)
Running under: CentOS Linux 7 (Core)

Matrix products: default
BLAS/LAPACK: /pstore/home/macnairw/.conda/envs/r_4.0.3/lib/libopenblasp-r0.3.12.so

locale:
 [1] LC_CTYPE=C                 LC_NUMERIC=C              
 [3] LC_TIME=en_US.UTF-8        LC_COLLATE=en_US.UTF-8    
 [5] LC_MONETARY=en_US.UTF-8    LC_MESSAGES=en_US.UTF-8   
 [7] LC_PAPER=en_US.UTF-8       LC_NAME=C                 
 [9] LC_ADDRESS=C               LC_TELEPHONE=C            
[11] LC_MEASUREMENT=en_US.UTF-8 LC_IDENTIFICATION=C       

attached base packages:
[1] stats     graphics  grDevices utils     datasets  methods   base     

other attached packages:
 [1] knitr_1.36         readxl_1.3.1       forcats_0.5.1      ggplot2_3.3.5     
 [5] scales_1.1.1       viridis_0.6.2      viridisLite_0.4.0  assertthat_0.2.1  
 [9] stringr_1.4.0      data.table_1.14.2  magrittr_2.0.1     circlize_0.4.13   
[13] RColorBrewer_1.1-2 BiocStyle_2.18.1   colorout_1.2-2     workflowr_1.6.2   

loaded via a namespace (and not attached):
 [1] Rcpp_1.0.7          prettyunits_1.1.1   ps_1.6.0           
 [4] rprojroot_2.0.2     digest_0.6.28       utf8_1.2.2         
 [7] R6_2.5.1            cellranger_1.1.0    evaluate_0.14      
[10] highr_0.9           pillar_1.6.4        GlobalOptions_0.1.2
[13] rlang_0.4.12        callr_3.7.0         whisker_0.4        
[16] jquerylib_0.1.4     rmarkdown_2.11      desc_1.4.0         
[19] devtools_2.4.2      munsell_0.5.0       compiler_4.0.5     
[22] httpuv_1.6.3        xfun_0.27           pkgconfig_2.0.3    
[25] pkgbuild_1.2.0      shape_1.4.6         htmltools_0.5.2    
[28] tidyselect_1.1.1    tibble_3.1.5        gridExtra_2.3      
[31] codetools_0.2-18    fansi_0.5.0         crayon_1.4.1       
[34] dplyr_1.0.7         withr_2.4.2         later_1.3.0        
[37] grid_4.0.5          jsonlite_1.7.2      gtable_0.3.0       
[40] lifecycle_1.0.1     DBI_1.1.1           git2r_0.28.0       
[43] cli_3.0.1           stringi_1.7.4       cachem_1.0.6       
[46] remotes_2.4.1       fs_1.5.0            promises_1.2.0.1   
[49] testthat_3.1.0      bslib_0.3.1         ellipsis_0.3.2     
[52] generics_0.1.1      vctrs_0.3.8         tools_4.0.5        
[55] glue_1.4.2          purrr_0.3.4         pkgload_1.2.3      
[58] processx_3.5.2      fastmap_1.1.0       yaml_2.2.1         
[61] colorspace_2.0-2    BiocManager_1.30.16 sessioninfo_1.1.1  
[64] memoise_2.0.0       usethis_2.1.2       sass_0.4.0