date generated: 2021-02-09

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.

##                x
## STK25   15.96852
## CCDC80  15.13535
## TLR4   -11.86789
## TFB2M  -10.84115
## SH2B3  -10.74626
## MRGBP  -10.27617

Here are some metrics about the input data profile:

Profile metrics
Profile metrics
num_genesets 5
num_genes_in_profile 15982
duplicated_genes_present 0
num_profile_genes_in_sets 263
num_profile_genes_not_in_sets 15719

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 sets metrics
Gene sets metrics
num_genesets 5
num_genesets_excluded 0
num_genesets_included 5

Differential pathway expression


Interactive enrichment scatterplot

Significance is calculated by -log10(p-value). All points shown are FDR<0.05.

Significance is calculated by -log10(p-value). Top N sets shown irrespective of FDR.

Results table

Top N= 5 gene sets

set setSize pANOVA s.dist p.adjustANOVA
tRNA processing in the mitochondrion 24 3.01e-05 -0.492 5.01e-05
Complex I biogenesis 52 7.46e-05 -0.318 9.32e-05
The citric acid (TCA) cycle and respiratory electron transport 147 1.56e-08 -0.270 7.79e-08
Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. 103 4.32e-06 -0.262 1.08e-05
Regulation of lipid metabolism by PPARalpha 106 5.37e-04 -0.195 5.37e-04


Results (complete table)


Click HERE to show results for all gene sets

Complete results
set setSize pANOVA s.dist p.adjustANOVA
tRNA processing in the mitochondrion 24 3.01e-05 -0.492 5.01e-05
Complex I biogenesis 52 7.46e-05 -0.318 9.32e-05
The citric acid (TCA) cycle and respiratory electron transport 147 1.56e-08 -0.270 7.79e-08
Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. 103 4.32e-06 -0.262 1.08e-05
Regulation of lipid metabolism by PPARalpha 106 5.37e-04 -0.195 5.37e-04



Detailed Gene set reports



tRNA processing in the mitochondrion

tRNA processing in the mitochondrion
5
set tRNA processing in the mitochondrion
setSize 24
pANOVA 3.01e-05
s.dist -0.492
p.adjustANOVA 5.01e-05



Top enriched genes

Top 20 genes
GeneID Gene Rank
MT-ND2 -8080
MT-CO2 -7984
MT-ND1 -7938
MT-CO1 -7848
MT-ATP6 -7777
MT-CO3 -7751
MT-CYB -7639
MT-ND5 -7183
MT-ATP8 -7080
MT-ND3 -6630
MT-ND4L -5673
MT-ND4 -4961
MT-ND6 -4202
MT-TP -4196
MT-TW -3435
MT-TT -2837
ELAC2 -2355
MT-RNR2 -1452
MT-TA -892
TRMT10C -756

Click HERE to show all gene set members

All member genes
GeneID Gene Rank
MT-ND2 -8080
MT-CO2 -7984
MT-ND1 -7938
MT-CO1 -7848
MT-ATP6 -7777
MT-CO3 -7751
MT-CYB -7639
MT-ND5 -7183
MT-ATP8 -7080
MT-ND3 -6630
MT-ND4L -5673
MT-ND4 -4961
MT-ND6 -4202
MT-TP -4196
MT-TW -3435
MT-TT -2837
ELAC2 -2355
MT-RNR2 -1452
MT-TA -892
TRMT10C -756
MT-RNR1 -287
HSD17B10 142
MT-TI 1672
TRNT1 7180



Complex I biogenesis

Complex I biogenesis
1
set Complex I biogenesis
setSize 52
pANOVA 7.46e-05
s.dist -0.318
p.adjustANOVA 9.32e-05



Top enriched genes

Top 20 genes
GeneID Gene Rank
MT-ND2 -8080
MT-ND1 -7938
NDUFA8 -7430
MT-ND5 -7183
NDUFB4 -6860
MT-ND3 -6630
NDUFB10 -6591
NDUFB11 -6464
NDUFC2 -6106
NDUFS3 -5923
NDUFS8 -5602
NDUFB2 -5271
NDUFC1 -5207
NDUFAB1 -5189
NDUFAF6 -5069
MT-ND4 -4961
NDUFA11 -4865
NDUFS7 -4748
NUBPL -4437
NDUFS1 -4228

Click HERE to show all gene set members

All member genes
GeneID Gene Rank
MT-ND2 -8080
MT-ND1 -7938
NDUFA8 -7430
MT-ND5 -7183
NDUFB4 -6860
MT-ND3 -6630
NDUFB10 -6591
NDUFB11 -6464
NDUFC2 -6106
NDUFS3 -5923
NDUFS8 -5602
NDUFB2 -5271
NDUFC1 -5207
NDUFAB1 -5189
NDUFAF6 -5069
MT-ND4 -4961
NDUFA11 -4865
NDUFS7 -4748
NUBPL -4437
NDUFS1 -4228
MT-ND6 -4202
NDUFB5 -3964
NDUFA1 -3660
NDUFA13 -3464
NDUFB9 -3430
NDUFAF3 -3381
NDUFA2 -3043
NDUFAF1 -2932
NDUFB8 -2347
NDUFV3 -1759
NDUFA10 -1721
ACAD9 -1698
NDUFA9 -1513
NDUFA12 -1478
NDUFS4 -1134
NDUFB1 -1011
NDUFV2 -658
NDUFB3 -508
NDUFA5 -138
NDUFB7 -137
NDUFS6 -61
NDUFAF4 -37
ECSIT 356
TMEM126B 739
NDUFB6 1090
NDUFS2 1246
NDUFS5 1410
NDUFAF5 1819
NDUFAF7 3012
NDUFAF2 3099
NDUFV1 3204
TIMMDC1 5450



The citric acid (TCA) cycle and respiratory electron transport

The citric acid (TCA) cycle and respiratory electron transport
4
set The citric acid (TCA) cycle and respiratory electron transport
setSize 147
pANOVA 1.56e-08
s.dist -0.27
p.adjustANOVA 7.79e-08



Top enriched genes

Top 20 genes
GeneID Gene Rank
MT-ND2 -8080
MT-CO2 -7984
OGDH -7979
MT-ND1 -7938
VDAC1 -7931
PDHX -7915
MT-CO1 -7848
MT-ATP6 -7777
MT-CO3 -7751
SDHB -7689
MT-CYB -7639
FH -7612
FAHD1 -7584
ETFB -7522
NDUFA8 -7430
COX8A -7282
MT-ND5 -7183
MT-ATP8 -7080
CS -6993
NDUFB4 -6860

Click HERE to show all gene set members

All member genes
GeneID Gene Rank
MT-ND2 -8080
MT-CO2 -7984
OGDH -7979
MT-ND1 -7938
VDAC1 -7931
PDHX -7915
MT-CO1 -7848
MT-ATP6 -7777
MT-CO3 -7751
SDHB -7689
MT-CYB -7639
FH -7612
FAHD1 -7584
ETFB -7522
NDUFA8 -7430
COX8A -7282
MT-ND5 -7183
MT-ATP8 -7080
CS -6993
NDUFB4 -6860
MT-ND3 -6630
NDUFB10 -6591
SLC16A3 -6551
DLST -6517
NDUFB11 -6464
MDH2 -6461
ETFA -6239
UQCRFS1 -6210
NDUFC2 -6106
GSTZ1 -6058
PDHB -5935
UQCRC1 -5934
NDUFS3 -5923
COX20 -5920
NDUFS8 -5602
SDHA -5373
UCP2 -5364
NDUFB2 -5271
NDUFC1 -5207
NDUFAB1 -5189
COX6B1 -5164
NDUFAF6 -5069
PDK2 -5044
MT-ND4 -4961
COX5A -4887
NDUFA11 -4865
SUCLG1 -4749
NDUFS7 -4748
PDHA1 -4645
PDPR -4472
NUBPL -4437
SCO2 -4325
COX5B -4316
NDUFS1 -4228
MT-ND6 -4202
SURF1 -4188
NDUFB5 -3964
RXRA -3861
PDP2 -3807
NDUFA1 -3660
UQCR10 -3653
COX6A1 -3518
BSG -3476
NDUFA13 -3464
NDUFB9 -3430
NDUFAF3 -3381
MPC1 -3309
IDH3A -3100
SDHD -3052
NDUFA2 -3043
PDK3 -2979
NDUFAF1 -2932
LRPPRC -2923
SUCLG2 -2819
PPARD -2757
COX11 -2665
COX16 -2500
COX7B -2391
NDUFB8 -2347
CYC1 -2316
ACO2 -1905
MPC2 -1858
UQCRH -1815
NDUFV3 -1759
NDUFA10 -1721
ACAD9 -1698
DLAT -1598
PDK1 -1538
NDUFA4 -1522
NDUFA9 -1513
NDUFA12 -1478
IDH3G -1473
ME2 -1412
L2HGDH -1218
TACO1 -1193
NDUFS4 -1134
NDUFB1 -1011
SLC16A1 -885
NDUFV2 -658
NDUFB3 -508
HAGH -308
NDUFA5 -138
NDUFB7 -137
NDUFS6 -61
NDUFAF4 -37
COX7C -13
COX14 59
IDH3B 71
PDK4 130
LDHB 279
DLD 354
ECSIT 356
COX6C 526
IDH2 672
TMEM126B 739
UQCRC2 973
NDUFB6 1090
UQCRQ 1230
NDUFS2 1246
NDUFS5 1410
UQCR11 1481
TRAP1 1519
SLC25A14 1543
NDUFAF5 1819
UQCRB 2069
GLO1 2337
COX7A2L 2355
D2HGDH 2356
CYCS 2582
LDHA 2651
NNT 2723
COQ10A 2761
ME1 2791
NDUFAF7 3012
NDUFAF2 3099
NDUFV1 3204
COX4I1 3895
SDHC 4485
SCO1 5234
TIMMDC1 5450
SLC25A27 5503
SUCLA2 5766
COX19 5879
COX18 6716
COQ10B 7223
ETFDH 7224
PDP1 7449



Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.

Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.
3
set Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.
setSize 103
pANOVA 4.32e-06
s.dist -0.262
p.adjustANOVA 1.08e-05



Top enriched genes

Top 20 genes
GeneID Gene Rank
MT-ND2 -8080
MT-CO2 -7984
MT-ND1 -7938
MT-CO1 -7848
MT-ATP6 -7777
MT-CO3 -7751
SDHB -7689
MT-CYB -7639
ETFB -7522
NDUFA8 -7430
COX8A -7282
MT-ND5 -7183
MT-ATP8 -7080
NDUFB4 -6860
MT-ND3 -6630
NDUFB10 -6591
NDUFB11 -6464
ETFA -6239
UQCRFS1 -6210
NDUFC2 -6106

Click HERE to show all gene set members

All member genes
GeneID Gene Rank
MT-ND2 -8080
MT-CO2 -7984
MT-ND1 -7938
MT-CO1 -7848
MT-ATP6 -7777
MT-CO3 -7751
SDHB -7689
MT-CYB -7639
ETFB -7522
NDUFA8 -7430
COX8A -7282
MT-ND5 -7183
MT-ATP8 -7080
NDUFB4 -6860
MT-ND3 -6630
NDUFB10 -6591
NDUFB11 -6464
ETFA -6239
UQCRFS1 -6210
NDUFC2 -6106
UQCRC1 -5934
NDUFS3 -5923
COX20 -5920
NDUFS8 -5602
SDHA -5373
UCP2 -5364
NDUFB2 -5271
NDUFC1 -5207
NDUFAB1 -5189
COX6B1 -5164
NDUFAF6 -5069
MT-ND4 -4961
COX5A -4887
NDUFA11 -4865
NDUFS7 -4748
NUBPL -4437
SCO2 -4325
COX5B -4316
NDUFS1 -4228
MT-ND6 -4202
SURF1 -4188
NDUFB5 -3964
NDUFA1 -3660
UQCR10 -3653
COX6A1 -3518
NDUFA13 -3464
NDUFB9 -3430
NDUFAF3 -3381
SDHD -3052
NDUFA2 -3043
NDUFAF1 -2932
LRPPRC -2923
COX11 -2665
COX16 -2500
COX7B -2391
NDUFB8 -2347
CYC1 -2316
UQCRH -1815
NDUFV3 -1759
NDUFA10 -1721
ACAD9 -1698
NDUFA4 -1522
NDUFA9 -1513
NDUFA12 -1478
TACO1 -1193
NDUFS4 -1134
NDUFB1 -1011
NDUFV2 -658
NDUFB3 -508
NDUFA5 -138
NDUFB7 -137
NDUFS6 -61
NDUFAF4 -37
COX7C -13
COX14 59
ECSIT 356
COX6C 526
TMEM126B 739
UQCRC2 973
NDUFB6 1090
UQCRQ 1230
NDUFS2 1246
NDUFS5 1410
UQCR11 1481
TRAP1 1519
SLC25A14 1543
NDUFAF5 1819
UQCRB 2069
COX7A2L 2355
CYCS 2582
COQ10A 2761
NDUFAF7 3012
NDUFAF2 3099
NDUFV1 3204
COX4I1 3895
SDHC 4485
SCO1 5234
TIMMDC1 5450
SLC25A27 5503
COX19 5879
COX18 6716
COQ10B 7223
ETFDH 7224



Regulation of lipid metabolism by PPARalpha

Regulation of lipid metabolism by PPARalpha
2
set Regulation of lipid metabolism by PPARalpha
setSize 106
pANOVA 0.000537
s.dist -0.195
p.adjustANOVA 0.000537



Top enriched genes

Top 20 genes
GeneID Gene Rank
CDK8 -8142
MED13 -7911
AHRR -7895
SLC27A1 -7885
G0S2 -7853
PPARA -7816
PPARG -7740
ALAS1 -7559
TNFRSF21 -7540
NFYA -7501
MED12 -7448
MED20 -7384
MED6 -7297
PPARGC1A -7167
PLIN2 -7106
NR1H2 -7089
MTF1 -6750
CCNC -6627
SP1 -6498
SIN3A -6401

Click HERE to show all gene set members

All member genes
GeneID Gene Rank
CDK8 -8142
MED13 -7911
AHRR -7895
SLC27A1 -7885
G0S2 -7853
PPARA -7816
PPARG -7740
ALAS1 -7559
TNFRSF21 -7540
NFYA -7501
MED12 -7448
MED20 -7384
MED6 -7297
PPARGC1A -7167
PLIN2 -7106
NR1H2 -7089
MTF1 -6750
CCNC -6627
SP1 -6498
SIN3A -6401
MED29 -6389
NCOA2 -6386
MED14 -6318
ACOX1 -6107
NCOA1 -6063
MED16 -5807
NCOA6 -5718
HDAC3 -5428
NPAS2 -5226
MED25 -5176
MED8 -5154
NCOA3 -5126
MED22 -5110
PPARGC1B -5066
NCOR2 -4774
CARM1 -4620
TIAM2 -4534
MED19 -4496
SIN3B -4389
CHD9 -4312
EP300 -4071
MED15 -3901
RXRA -3861
ARNTL -3694
CDK19 -3620
CPT1A -3477
MED17 -3469
ARNT -3459
NR1H3 -3270
CYP1A1 -3001
RORA -2829
MED24 -2748
SMARCD3 -2703
CPT2 -2616
TRIB3 -2512
NCOR1 -2380
MED23 -2237
MED13L -2076
ACSL1 -1850
CREBBP -1636
ABCB4 -1490
MED26 -1239
MED27 -970
SREBF2 -606
MED1 -401
SREBF1 -118
MED11 213
ESRRA 313
GRHL1 364
ANKRD1 370
THRAP3 382
MED9 769
TGS1 1039
NFYC 1211
ACADM 1344
TXNRD1 1443
NRF1 1798
PEX11A 2077
GLIPR1 2234
ARNT2 2432
MED31 2646
ME1 2791
FHL2 2943
MED28 3112
TBL1X 3314
MED10 3402
FADS1 3435
MED21 3591
FDFT1 3706
NR1D1 3739
MED4 3810
HELZ2 4209
GPS2 4580
TBL1XR1 4631
MED18 4649
MED7 4793
HMGCR 4931
NFYB 5119
MED30 5562
RGL1 5713
AHR 6261
ABCA1 6440
HMGCS1 6470
ANGPTL4 6489
CLOCK 7650
NR1H4 7719



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

sessionInfo()
## R version 4.0.3 (2020-10-10)
## Platform: x86_64-pc-linux-gnu (64-bit)
## Running under: Ubuntu 20.04.2 LTS
## 
## Matrix products: default
## BLAS:   /usr/lib/x86_64-linux-gnu/blas/libblas.so.3.9.0
## LAPACK: /usr/lib/x86_64-linux-gnu/lapack/liblapack.so.3.9.0
## 
## 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       
## 
## attached base packages:
## [1] parallel  stats4    stats     graphics  grDevices utils     datasets 
## [8] methods   base     
## 
## other attached packages:
##  [1] pkgload_1.1.0               GGally_2.0.0               
##  [3] reshape2_1.4.4              beeswarm_0.2.3             
##  [5] gtools_3.8.2                echarts4r_0.3.3            
##  [7] vioplot_0.3.5               zoo_1.8-8                  
##  [9] sm_2.2-5.6                  mitch_1.2.2                
## [11] gplots_3.1.0                fgsea_1.16.0               
## [13] DESeq2_1.30.0               SummarizedExperiment_1.20.0
## [15] Biobase_2.50.0              MatrixGenerics_1.2.0       
## [17] matrixStats_0.57.0          GenomicRanges_1.42.0       
## [19] GenomeInfoDb_1.26.0         IRanges_2.24.0             
## [21] S4Vectors_0.28.0            BiocGenerics_0.36.0        
## [23] forcats_0.5.0               stringr_1.4.0              
## [25] dplyr_1.0.2                 purrr_0.3.4                
## [27] readr_1.4.0                 tidyr_1.1.2                
## [29] tibble_3.0.4                ggplot2_3.3.2              
## [31] tidyverse_1.3.0            
## 
## loaded via a namespace (and not attached):
##  [1] colorspace_2.0-0       ellipsis_0.3.1         rprojroot_1.3-2       
##  [4] XVector_0.30.0         fs_1.5.0               rstudioapi_0.12       
##  [7] bit64_4.0.5            AnnotationDbi_1.52.0   fansi_0.4.1           
## [10] lubridate_1.7.9        xml2_1.3.2             splines_4.0.3         
## [13] geneplotter_1.68.0     knitr_1.30             jsonlite_1.7.1        
## [16] broom_0.7.2            annotate_1.68.0        dbplyr_2.0.0          
## [19] shiny_1.5.0            compiler_4.0.3         httr_1.4.2            
## [22] backports_1.2.0        assertthat_0.2.1       Matrix_1.2-18         
## [25] fastmap_1.0.1          cli_2.1.0              later_1.1.0.1         
## [28] htmltools_0.5.0        tools_4.0.3            gtable_0.3.0          
## [31] glue_1.4.2             GenomeInfoDbData_1.2.4 fastmatch_1.1-0       
## [34] Rcpp_1.0.5             cellranger_1.1.0       vctrs_0.3.4           
## [37] xfun_0.19              ps_1.4.0               testthat_3.0.0        
## [40] rvest_0.3.6            mime_0.9               lifecycle_0.2.0       
## [43] XML_3.99-0.5           zlibbioc_1.36.0        MASS_7.3-53           
## [46] scales_1.1.1           hms_0.5.3              promises_1.1.1        
## [49] RColorBrewer_1.1-2     yaml_2.2.1             memoise_1.1.0         
## [52] gridExtra_2.3          reshape_0.8.8          stringi_1.5.3         
## [55] RSQLite_2.2.1          highr_0.8              genefilter_1.72.0     
## [58] desc_1.2.0             caTools_1.18.0         BiocParallel_1.24.1   
## [61] rlang_0.4.8            pkgconfig_2.0.3        bitops_1.0-6          
## [64] evaluate_0.14          lattice_0.20-41        htmlwidgets_1.5.2     
## [67] bit_4.0.4              tidyselect_1.1.0       plyr_1.8.6            
## [70] magrittr_1.5           R6_2.5.0               generics_0.1.0        
## [73] DelayedArray_0.16.0    DBI_1.1.0              pillar_1.4.6          
## [76] haven_2.3.1            withr_2.3.0            survival_3.2-7        
## [79] RCurl_1.98-1.2         modelr_0.1.8           crayon_1.3.4          
## [82] KernSmooth_2.23-18     rmarkdown_2.5          locfit_1.5-9.4        
## [85] grid_4.0.3             readxl_1.3.1           data.table_1.13.2     
## [88] blob_1.2.1             reprex_0.3.0           digest_0.6.27         
## [91] xtable_1.8-4           httpuv_1.5.4           munsell_0.5.0         
## [94] tcltk_4.0.3

END of report