Last updated: 2022-01-26

Checks: 4 3

Knit directory: MS_lesions/

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The following chunks had caches available:
  • ancom_bootstrapped_gm_4pcs
  • ancom_bootstrapped_gm
  • ancom_bootstrapped_wm
  • causes_of_variability_gm
  • causes_of_variability_wm
  • dotplot_marker_genes
  • effect_of_including_pcs_neurons
  • effect_of_including_pcs_others
  • expression_heatmap_gm
  • expression_heatmap_wm
  • f1_vs_f2
  • fig_mofa_factors_diagnosis
  • fixed_vs_random_gm_4pcs
  • fixed_vs_random_gm
  • fixed_vs_random_wm
  • gm_vs_wm_proportions
  • grp17_cell_abundances
  • gwas_coloc
  • gwas_de_barplots
  • gwas_manhattan
  • module_go_terms_annotations
  • module_scores_opc_oligo
  • muscat_vs_sd
  • oligo_barplot_gm
  • oligo_barplot_wm
  • random_effects_model_example
  • session_info
  • session-info-chunk-inserted-by-workflowr
  • top_genes_factor1
  • top_genes_factor2
  • umap_all_celltypes
  • umap_opc_oligo
  • variance_explained

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Note that any generated files, e.g. HTML, png, CSS, etc., are not included in this status report because it is ok for generated content to have uncommitted changes.


There are no past versions. Publish this analysis with wflow_publish() to start tracking its development.


Setup / definitions

Libraries

Helper functions

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

Figure 1

B-1

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

B-2

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

C-1

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

C-2

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

C-3

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

D

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

Figure 2

A

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

B

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

C

Differential abundance results for WM

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

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

D

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

Figure 3

A

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

Version Author Date
79b10e2 wmacnair 2022-01-24

B

include_graphics("figure/ms15_mofa_sample_wm_final_meta.Rmd/fig_overview_expression-2.png", error = FALSE)

Version Author Date
1d0d7e8 wmacnair 2022-01-21

D

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

Version Author Date
79b10e2 wmacnair 2022-01-24

E

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

Figure 4

A

Illustration of random effects model

include_graphics("figure/ms15_mofa_sample_wm_final_meta.Rmd/fig_random_effects_example-3.png", error = FALSE)

Version Author Date
24d709c wmacnair 2022-01-18
7fb1b95 wmacnair 2021-11-25

B

Disease effect vs donor effect

include_graphics("figure/ms15_mofa_sample_wm_final_meta.Rmd/fig_muscat_vs_sd-1.png", error = FALSE)

Version Author Date
24d709c wmacnair 2022-01-18
7fb1b95 wmacnair 2021-11-25

C

MOFA factors

include_graphics("figure/ms15_mofa_sample_wm_final_meta.Rmd/fig_mofa_factors_diagnosis-1.png", error = FALSE)

Version Author Date
24d709c wmacnair 2022-01-18
7fb1b95 wmacnair 2021-11-25

D

Variance explained

include_graphics("figure/ms15_mofa_sample_wm_final_meta.Rmd/fig_factor_r2s-1.png", error = FALSE)

Version Author Date
2372e65 wmacnair 2022-01-18
24d709c wmacnair 2022-01-18
7fb1b95 wmacnair 2021-11-25

E

Patient stratification

include_graphics("figure/ms15_mofa_sample_wm_final_meta.Rmd/fig_f1_vs_f2-3.png", error = FALSE)

Version Author Date
24d709c wmacnair 2022-01-18
7fb1b95 wmacnair 2021-11-25

F

Factor 1 top genes

include_graphics("figure/ms15_mofa_sample_wm_final_meta.Rmd/fig_factor1-1.png", error = FALSE)

Version Author Date
24d709c wmacnair 2022-01-18
7fb1b95 wmacnair 2021-11-25

G

Factor 2 top genes

include_graphics("figure/ms15_mofa_sample_wm_final_meta.Rmd/fig_factor2-1.png", error = FALSE)

Version Author Date
24d709c wmacnair 2022-01-18
7fb1b95 wmacnair 2021-11-25

Figure 5

A

Genetic enrichment of differentially expressed genes

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

Version Author Date
b1e52a7 wmacnair 2022-01-06

B

Manhattan plot of MAGMA differentially expressed genes

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

Version Author Date
b1e52a7 wmacnair 2022-01-06

C

Heatmap of MAGMA differentially expressed genes

D

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

Supplementary figures

S1

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

S2

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

S3

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

S4

DA results for GM, 4 layer PCs

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

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

S5

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

S6

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

S7

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

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     2022-01-26                  

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 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] cachem_1.0.6        cli_3.0.1           stringi_1.7.4      
[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