date generated: 2024-11-26

Background

Mitch performs unidimensional and multidimensional gene set enrichment analysis. The concept behind this dates to work by Cox and Mann (https://doi.org/10.1186/1471-2105-13-S16-S12). This implementation is suited to R based workflows of multi-omics datasets. This software was developed by Antony Kaspi and Mark Ziemann. Learn more about Mitch at the website: https://github.com/markziemann/Mitch

Input profiles

Here is the first few lines of the input profile.

The profiling data being passed to mitch
rna2 k9a2
A2M 3.415090 2.7880123
AAAS -2.962096 3.4898251
ABRA 10.673777 13.3060357
AC004453.8 -2.076975 0.8679133
AC006480.1 -2.155952 1.8189543
AC013437.7 -3.810378 -0.0657374

Here are some metrics about the input data profile:

Profiling data metrics
Profile metrics
num_genes_in_profile 1000
duplicated_genes_present 0
num_profile_genes_in_sets 192
num_profile_genes_not_in_sets 808
profile_pearson_correl 0.23499
profile_spearman_correl 0.22935

Here is a plot of the input profiles. Note the dynamic ranges.

Here is the contour plot of the profile including all detected genes.

Input genesets

Here are some metrics about the gene sets used:

GMT file of genesets:
Gene set metrics
Gene sets metrics
num_genesets 200
num_genesets_excluded 195
num_genesets_included 5

Gene sets by quadrant


Number of significant gene sets (FDR<0.05)= 1

Interactive enrichment scatterplot

All sets with FDR<0.05. Try hovering over the points.

Top N sets irrespective of FDR. Try hovering over the points.

A heatmap of S values for top results


A plot of effect size versus significance


Significance is the -log2(p.adjustMANOVA) and effect size is the s.dist which is the hypotenuse of the s scores.

Results table

Top N= 3 gene sets
set setSize pMANOVA p.adjustMANOVA s.dist s.rna2 s.k9a2 p.rna2 p.k9a2
Biological oxidations 10 0.0090 0.045 0.5570 -0.5560 -0.0414 0.00243 0.8220
Antigen processing: Ubiquitination & Proteasome degradation 20 0.0597 0.149 0.2890 -0.0555 0.2840 0.67100 0.0296
Adaptive Immune System 44 0.5300 0.672 0.0978 0.0000 0.0978 1.00000 0.2730


Results (complete table)


Click HERE to show results for all gene sets

Complete results
set setSize pMANOVA p.adjustMANOVA s.dist s.rna2 s.k9a2 p.rna2 p.k9a2
Biological oxidations 10 0.0090 0.045 0.5570 -0.55600 -0.0414 0.00243 0.8220
Antigen processing: Ubiquitination & Proteasome degradation 20 0.0597 0.149 0.2890 -0.05550 0.2840 0.67100 0.0296
Adaptive Immune System 44 0.5300 0.672 0.0978 0.00000 0.0978 1.00000 0.2730
Asparagine N-linked glycosylation 17 0.5380 0.672 0.1440 -0.13600 0.0459 0.33600 0.7450
Axon guidance 48 0.9450 0.945 0.0264 0.00696 -0.0255 0.93500 0.7650



Detailed Gene set reports


Biological oxidations
Biological oxidations
metric value
setSize 10
pMANOVA 0.009
p.adjustMANOVA 0.045
s.dist 0.557
s.rna2 -0.556
s.k9a2 -0.0414
p.rna2 0.00243
p.k9a2 0.822



Top 20 genes
Gene rna2 k9a2
GGT5 -188 -74

Click HERE to show all gene set members

All member genes
rna2 k9a2
BPHL -12 386
CES3 -293 87
CYP2J2 -218 480
GGT5 -188 -74
GSS -203 726
GSTM2 -295 361
GSTP1 -131 276
HSP90AB1 327 851
MTR 219 526
SULT1A1 -152 11





Antigen processing: Ubiquitination & Proteasome degradation
Antigen processing: Ubiquitination & Proteasome degradation
metric value
setSize 20
pMANOVA 0.0597
p.adjustMANOVA 0.149
s.dist 0.289
s.rna2 -0.0555
s.k9a2 0.284
p.rna2 0.671
p.k9a2 0.0296



Top 20 genes
Gene rna2 k9a2
PSMB7 -268 620
UBE2E3 -125 557
WSB1 -137 508
ANAPC7 -206 326
PSMA4 -99 610
PSMB5 -209 97

Click HERE to show all gene set members

All member genes
rna2 k9a2
ANAPC7 -206 326
ASB7 130 262
FBXL14 286 579
HECTD1 196 771
HERC1 382 769
HERC2 318 3
HUWE1 221 525
ITCH 263 452
LTN1 24 671
NEDD4 185 869
PJA2 297 764
PSMA4 -99 610
PSMB5 -209 97
PSMB7 -268 620
RNF19A 161 677
TRIP12 343 407
UBE2C 647 127
UBE2E3 -125 557
WSB1 -137 508
ZBTB16 657 857





Adaptive Immune System
Adaptive Immune System
metric value
setSize 44
pMANOVA 0.53
p.adjustMANOVA 0.672
s.dist 0.0978
s.rna2 0
s.k9a2 0.0978
p.rna2 1
p.k9a2 0.273



Top 20 genes
Gene rna2 k9a2
PSMB7 -268 620
UBE2E3 -125 557
WSB1 -137 508
ANAPC7 -206 326
BTN3A1 -155 403
PSMA4 -99 610
PSMB5 -209 97

Click HERE to show all gene set members

All member genes
rna2 k9a2
ANAPC7 -206 326
ASB7 130 262
BTN3A1 -155 403
BTN3A2 -109 -8
CHUK 178 397
DYNC1H1 266 273
ENAH 366 811
ERAP1 175 241
FBXL14 286 579
HECTD1 196 771
HERC1 382 769
HERC2 318 3
HUWE1 221 525
ICAM1 557 30
ITCH 263 452
KRAS 362 472
LTN1 24 671
MRC1 14 76
NEDD4 185 869
NFATC3 155 491
NFKBIA 177 712
PAK2 93 563
PIK3CA 235 388
PIK3CB 399 494
PIK3R3 637 444
PJA2 297 764
PPP2R1B 10 773
PSMA4 -99 610
PSMB5 -209 97
PSMB7 -268 620
PTPN11 89 182
RICTOR 192 753
RIPK2 308 -21
RNF19A 161 677
SEC24A 72 96
TAP1 158 261
TNFRSF14 -290 -92
TRIP12 343 407
UBE2C 647 127
UBE2E3 -125 557
VASP 490 445
WSB1 -137 508
YES1 497 295
ZBTB16 657 857





Here is the session info with all the versions of packages used.

sessionInfo()
## R version 4.4.2 (2024-10-31)
## Platform: x86_64-pc-linux-gnu
## Running under: Ubuntu 24.04.1 LTS
## 
## Matrix products: default
## BLAS:   /usr/lib/x86_64-linux-gnu/blas/libblas.so.3.12.0 
## LAPACK: /usr/lib/x86_64-linux-gnu/lapack/liblapack.so.3.12.0
## 
## locale:
##  [1] LC_CTYPE=en_US.UTF-8       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       
## 
## time zone: Australia/Melbourne
## tzcode source: system (glibc)
## 
## attached base packages:
## [1] stats     graphics  grDevices utils     datasets  methods   base     
## 
## other attached packages:
##  [1] kableExtra_1.4.0 pkgload_1.4.0    GGally_2.2.1     ggplot2_3.5.1   
##  [5] reshape2_1.4.4   beeswarm_0.4.0   gplots_3.2.0     gtools_3.9.5    
##  [9] tibble_3.2.1     dplyr_1.1.4      echarts4r_0.4.5  stringi_1.8.4   
## [13] mitch_1.19.2    
## 
## loaded via a namespace (and not attached):
##  [1] sass_0.4.9         utf8_1.2.4         generics_0.1.3     tidyr_1.3.1       
##  [5] bitops_1.0-9       xml2_1.3.6         KernSmooth_2.23-24 caTools_1.18.3    
##  [9] digest_0.6.37      magrittr_2.0.3     evaluate_1.0.1     grid_4.4.2        
## [13] RColorBrewer_1.1-3 fastmap_1.2.0      plyr_1.8.9         jsonlite_1.8.9    
## [17] gridExtra_2.3      promises_1.3.1     purrr_1.0.2        fansi_1.0.6       
## [21] viridisLite_0.4.2  scales_1.3.0       jquerylib_0.1.4    cli_3.6.3         
## [25] shiny_1.9.1        rlang_1.1.4        munsell_0.5.1      withr_3.0.2       
## [29] cachem_1.1.0       yaml_2.3.10        parallel_4.4.2     tools_4.4.2       
## [33] colorspace_2.1-1   httpuv_1.6.15      ggstats_0.7.0      vctrs_0.6.5       
## [37] R6_2.5.1           mime_0.12          lifecycle_1.0.4    stringr_1.5.1     
## [41] htmlwidgets_1.6.4  MASS_7.3-61        pkgconfig_2.0.3    pillar_1.9.0      
## [45] bslib_0.8.0        later_1.4.0        gtable_0.3.6       glue_1.8.0        
## [49] Rcpp_1.0.13-1      systemfonts_1.1.0  xfun_0.49          tidyselect_1.2.1  
## [53] rstudioapi_0.17.1  knitr_1.49         farver_2.1.2       xtable_1.8-4      
## [57] htmltools_0.5.8.1  labeling_0.4.3     rmarkdown_2.29     svglite_2.1.3     
## [61] compiler_4.4.2

END of report