Single-cell PBMC Example
karltayeb
2022-03-16
Last updated: 2022-03-29
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Knit directory: logistic-susie-gsea/
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Introduction
Our goals here are to run Logistic SuSiE on differential expression results from TCGA. We want to assess:
- If the resulting enrichment results look good/interpretable across multiple/concatenated gene sets
- Assess sensitivity to a range of p-value thresholds
- Evaluate the potential of the summary stat latent model
library(GSEABenchmarkeR)
library(EnrichmentBrowser)
library(tidyverse)
library(susieR)
library(DT)
source('code/load_gene_sets.R')
source('code/utils.R')
source('code/logistic_susie_vb.R')
source('code/logistic_susie_veb_boost.R')
source('code/latent_logistic_susie.R')Setup
Load Gene Sets
loadGeneSetX uniformly formats gene sets and generates the \(X\) matrix We can source any gene set from WebGestaltR::listGeneSet()
gs_list <- WebGestaltR::listGeneSet()
gobp <- loadGeneSetX('geneontology_Biological_Process', min.size=50) # just huge number of gene sets
gobp_nr <- loadGeneSetX('geneontology_Biological_Process_noRedundant', min.size=1)
gomf <- loadGeneSetX('geneontology_Molecular_Function', min.size=1)
kegg <- loadGeneSetX('pathway_KEGG', min.size=1)
reactome <- loadGeneSetX('pathway_Reactome', min.size=1)
wikipathway_cancer <- loadGeneSetX('pathway_Wikipathway_cancer', min.size=1)
wikipathway <- loadGeneSetX('pathway_Wikipathway', min.size=1)
genesets <- list(
gobp=gobp,
gobp_nr=gobp_nr,
gomf=gomf,
kegg=kegg,
reactome=reactome,
wikipathway_cancer=wikipathway_cancer,
wikipathway=wikipathway
)load('data/pbmc-purified/deseq2-pbmc-purified.RData')
convert_labels <- function(y, from='SYMBOL', to='ENTREZID'){
hs <- org.Hs.eg.db::org.Hs.eg.db
gene_symbols <- names(y)
symbol2entrez <- AnnotationDbi::select(hs, keys=gene_symbols, columns=c(to, from), keytype = from)
symbol2entrez <- symbol2entrez[!duplicated(symbol2entrez[[from]]),]
symbol2entrez <- symbol2entrez[!is.na(symbol2entrez[[to]]),]
symbol2entrez <- symbol2entrez[!is.na(symbol2entrez[[from]]),]
rownames(symbol2entrez) <- symbol2entrez[[from]]
ysub <- y[names(y) %in% symbol2entrez[[from]]]
names(ysub) <- symbol2entrez[names(ysub),][[to]]
return(ysub)
}
par(mfrow=c(1,1))
deseq$`CD19+ B` %>% .$padj %>% hist(main='CD19+B p-values')Loading required package: DESeq2
| Version | Author | Date |
|---|---|---|
| a2bdb56 | karltayeb | 2022-03-29 |
Fit logistic SuSiE
logistic_susie_driver = function(db, celltype, thresh){
gs <- genesets[[db]]
data <- deseq[[celltype]]
# set up binary y
y <- data %>%
as.data.frame %>%
rownames_to_column('gene') %>%
dplyr::select(gene, padj) %>%
filter(!is.na(padj)) %>%
mutate(y = as.integer(padj < thresh)) %>%
select(gene, y) %>%
tibble2namedlist %>%
convert_labels('ENSEMBL')
u <- process_input(gs$X, y) # subset to common genes
vb.fit <- logistic.susie( # fit model
u$X, u$y, L=10, init.intercept = 0, verbose=1, maxit=100)
# summarise results
set.summary <- vb.fit$pip %>%
as_tibble(rownames='geneSet') %>%
rename(pip=value) %>%
mutate(
top_component = apply(vb.fit$alpha, 2, which.max),
active_set = top_component %in% vb.fit$sets$cs_index,
top_component = paste0('L', top_component),
cs = purrr::map(top_component, ~tryCatch(
colnames(gs$X)[get(.x, vb.fit$sets$cs)], error = function(e) list())),
in_cs = geneSet %in% cs,
beta = colSums(vb.fit$mu * vb.fit$alpha),
geneListSize = sum(u$y),
geneSetSize = colSums(u$X),
overlap = (u$y %*% u$X)[1,],
nGenes = length(u$y),
propSetInList = overlap / geneSetSize,
oddsRatio = (overlap / (geneListSize - overlap)) / (
(geneSetSize - overlap) / (nGenes - geneSetSize + overlap)),
pValueHypergeometric = phyper(
overlap-1, geneListSize, nGenes, geneSetSize, lower.tail= FALSE),
db = db,
celltype = celltype,
thresh = thresh
) %>% left_join(gs$geneSet$geneSetDes)
return(list(fit = vb.fit, set.summary=set.summary))
}For each celltype, we fit logistic SuSiE using multiple gene set sources at various threshold of padj.
celltypes <- names(deseq)
pthresh <- c(0.1, 0.01, 0.001, 0.0001, 0.00001, 0.000001)
db_name <- names(genesets)
crossed <- cross3(db_name, celltypes, pthresh)
pbmc_res <- xfun::cache_rds({
res <- purrr::map(crossed, purrr::lift_dl(logistic_susie_driver))
for (i in 1:length(res)){ # save some space
res[[i]]$fit$dat <- NULL
}
res
}, file = 'logistic_susie_pbmc_genesets_pthresh.rds'
)
pbmc_res_set_summary <- dplyr::bind_rows(purrr::map(pbmc_res, ~ pluck(.x, 'set.summary')))Summary functions
Just a few functions to help streamline looking at output
pval_focussed_table = function(thresh=1e-3, filter_db=NULL, filter_celltype=NULL, top.n=50){
pbmc_res_set_summary %>%
filter(
case_when(
is.null(filter_db) ~ TRUE,
!is.null(filter_db) ~ db %in% filter_db
) &
thresh == thresh &
case_when(
is.null(filter_celltype) ~ TRUE,
!is.null(filter_celltype) ~ celltype %in% filter_celltype
)
) %>%
dplyr::arrange(celltype, db, pValueHypergeometric) %>%
group_by(celltype, db) %>% slice(1:top.n) %>%
select(celltype, db, geneSet, description, pip, top_component, oddsRatio, propSetInList, pValueHypergeometric) %>%
mutate_at(vars(celltype, db), factor) %>%
datatable(filter = 'top')
}
set_focussed_table = function(thresh=1e-3, filter_db=NULL, filter_celltype=NULL){
pbmc_res_set_summary %>%
filter(
case_when(
is.null(filter_db) ~ TRUE,
!is.null(filter_db) ~ db %in% filter_db
) &
thresh == 1e-3 &
in_cs & active_set &
case_when(
is.null(filter_celltype) ~ TRUE,
!is.null(filter_celltype) ~ celltype %in% filter_celltype
)
) %>%
dplyr::arrange(celltype, db, desc(pip)) %>%
select(celltype, db, geneSet, description, pip, top_component, oddsRatio, propSetInList, pValueHypergeometric) %>%
mutate_at(vars(celltype, geneSet, db), factor) %>%
datatable(filter = 'top')
}
#' takes a tibble
#' organize by database and component
#' report credible set, descriptions, pips, and hypergeometric pvalue
#' in one row, with cs ordered by pip
db_component_kable = function(tbl){
tbl %>%
filter(active_set, thresh==1e-4) %>%
group_by(db, celltype, top_component) %>%
arrange(db, celltype, top_component, desc(pip)) %>%
select(geneSet, description, pip, pValueHypergeometric) %>%
chop(c(geneSet, description, pip, pValueHypergeometric)) %>%
knitr::kable()
}Results/Explore enrichments
Our goal is to assess 1. The quality of the gene set enrichments we get from each celltype - do reported gene set enrichments seem celltype specific/celltype relevant? - how much “interesting” marginal enrichment do we fail to capture in the multivariate model - how sensitive are we to the choice of pvalue threshold
Results
Lets take a look at what enrichment we’re getting across cell-types.
CD19+ B
pbmc_res_set_summary %>%
filter(celltype == 'CD19+ B') %>%
filter(active_set, thresh==1e-4) %>%
db_component_kableAdding missing grouping variables: `db`, `celltype`, `top_component`| db | celltype | top_component | geneSet | description | pip | pValueHypergeometric |
|---|---|---|---|---|---|---|
| gobp | CD19+ B | L1 | GO:0002376 | immune system process | 0.9999575 | 2.526664e-269 |
| gobp | CD19+ B | L2 | GO:0045047, GO:0006613, GO:0072599, GO:0006614 | protein targeting to ER , cotranslational protein targeting to membrane , establishment of protein localization to endoplasmic reticulum, SRP-dependent cotranslational protein targeting to membrane | 0.96205208, 0.02165616, 0.01453688, 0.00410197 | 2.532661e-36, 1.984360e-34, 8.259486e-35, 9.432379e-33 |
| gobp | CD19+ B | L3 | GO:0042773, GO:0042775, GO:0006119 | ATP synthesis coupled electron transport , mitochondrial ATP synthesis coupled electron transport, oxidative phosphorylation | 0.62449631, 0.36002221, 0.01752387 | 1.605842e-25, 4.064871e-25, 2.075548e-29 |
| gobp | CD19+ B | L5 | GO:0001775, GO:0045321, GO:0002366, GO:0002263 | cell activation , leukocyte activation , leukocyte activation involved in immune response, cell activation involved in immune response | 0.9780541751, 0.0218972721, 0.0005957131, 0.0005770067 | 4.428372e-165, 7.685551e-152, 1.405750e-97, 8.244815e-98 |
| gobp | CD19+ B | L6 | GO:0008380, GO:0000377, GO:0000398, GO:0000375, GO:0006397, GO:0050684, GO:0043484, GO:0000380, GO:0048024, GO:0016071 | RNA splicing , RNA splicing, via transesterification reactions with bulged adenosine as nucleophile, mRNA splicing, via spliceosome , RNA splicing, via transesterification reactions , mRNA processing , regulation of mRNA processing , regulation of RNA splicing , alternative mRNA splicing, via spliceosome , regulation of mRNA splicing, via spliceosome , mRNA metabolic process | 0.822736133, 0.049644134, 0.049644134, 0.033005117, 0.017234053, 0.009417204, 0.007220671, 0.002939483, 0.001834918, 0.001051637 | 2.990867e-36, 3.387925e-28, 3.387925e-28, 6.887275e-28, 4.148046e-35, 6.486732e-18, 1.878944e-17, 7.772036e-12, 1.226187e-12, 1.879865e-61 |
| gobp_nr | CD19+ B | L1 | GO:0002446, GO:0036230 | neutrophil mediated immunity, granulocyte activation | 0.5151440, 0.4857358 | 4.775951e-71, 2.936426e-71 |
| gobp_nr | CD19+ B | L2 | GO:0070972 | protein localization to endoplasmic reticulum | 0.999958 | 7.382525e-33 |
| gobp_nr | CD19+ B | L4 | GO:0009123, GO:0009141 | nucleoside monophosphate metabolic process, nucleoside triphosphate metabolic process | 0.98449756, 0.01648675 | 7.371703e-40, 2.011998e-35 |
| gobp_nr | CD19+ B | L5 | GO:0002764 | immune response-regulating signaling pathway | 0.9961853 | 8.086259e-55 |
| gomf | CD19+ B | L1 | GO:0003723 | RNA binding | 0.999744 | 3.707404e-127 |
| gomf | CD19+ B | L2 | GO:0000981, GO:0003700 | DNA-binding transcription factor activity, RNA polymerase II-specific, DNA-binding transcription factor activity | 0.995003783, 0.005058241 | 1.942472e-16, 2.738455e-20 |
| gomf | CD19+ B | L3 | GO:0000977, GO:0001012, GO:0000987, GO:0000978, GO:0000976, GO:0003690, GO:1990837, GO:0001067, GO:0044212 | RNA polymerase II regulatory region sequence-specific DNA binding, RNA polymerase II regulatory region DNA binding , proximal promoter sequence-specific DNA binding , RNA polymerase II proximal promoter sequence-specific DNA binding, transcription regulatory region sequence-specific DNA binding , double-stranded DNA binding , sequence-specific double-stranded DNA binding , regulatory region nucleic acid binding , transcription regulatory region DNA binding | 0.4872513913, 0.4313993168, 0.0365953412, 0.0243679373, 0.0132413813, 0.0059278956, 0.0013679037, 0.0004652721, 0.0003557059 | 2.822624e-34, 2.658045e-34, 8.331683e-30, 2.661740e-29, 5.231202e-34, 8.306797e-44, 1.071864e-35, 1.990230e-36, 5.770724e-36 |
| gomf | CD19+ B | L6 | GO:0003735 | structural constituent of ribosome | 0.9953441 | 2.994289e-32 |
| gomf | CD19+ B | L7 | GO:0003954, GO:0008137, GO:0050136, GO:0016655, GO:0016651 | NADH dehydrogenase activity , NADH dehydrogenase (ubiquinone) activity , NADH dehydrogenase (quinone) activity , oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor, oxidoreductase activity, acting on NAD(P)H | 0.32595362, 0.21858318, 0.21858318, 0.17726552, 0.03879761 | 1.385073e-13, 3.413042e-13, 3.413042e-13, 1.315866e-14, 2.200053e-17 |
| kegg | CD19+ B | L1 | hsa00190, hsa05012 | Oxidative phosphorylation, Parkinson disease | 0.9979902, 0.0125303 | 5.027625e-29, 3.697096e-27 |
| kegg | CD19+ B | L2 | hsa04640 | Hematopoietic cell lineage | 0.9997951 | 8.551153e-21 |
| kegg | CD19+ B | L3 | hsa03010 | Ribosome | 1 | 3.24636e-30 |
| reactome | CD19+ B | L1 | R-HSA-168256 | Immune System | 1 | 7.929629e-180 |
| reactome | CD19+ B | L2 | R-HSA-156842 , R-HSA-156902 , R-HSA-192823 , R-HSA-2408557, R-HSA-72764 , R-HSA-72689 , R-HSA-1799339, R-HSA-72706 , R-HSA-156827 | Eukaryotic Translation Elongation , Peptide chain elongation , Viral mRNA Translation , Selenocysteine synthesis , Eukaryotic Translation Termination , Formation of a pool of free 40S subunits , SRP-dependent cotranslational protein targeting to membrane , GTP hydrolysis and joining of the 60S ribosomal subunit , L13a-mediated translational silencing of Ceruloplasmin expression | 0.760651464, 0.124389740, 0.067132923, 0.026006681, 0.017267678, 0.003305376, 0.003131980, 0.001226762, 0.001000830 | 7.985692e-32, 1.394445e-30, 1.394445e-30, 9.148401e-31, 9.148401e-31, 2.883586e-31, 2.254688e-34, 4.386878e-33, 1.096100e-32 |
| reactome | CD19+ B | L3 | R-HSA-74160 , R-HSA-212436, R-HSA-73857 | Gene expression (Transcription), Generic Transcription Pathway , RNA Polymerase II Transcription | 0.88567935, 0.07266257, 0.04183476 | 8.299766e-30, 2.296229e-21, 4.497082e-27 |
| reactome | CD19+ B | L4 | R-HSA-163200 , R-HSA-1428517, R-HSA-611105 | Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins., The citric acid (TCA) cycle and respiratory electron transport , Respiratory electron transport | 0.845323000, 0.149383366, 0.005965744 | 9.259886e-26, 5.557534e-29, 1.019708e-20 |
| reactome | CD19+ B | L5 | R-HSA-983168, R-HSA-983169 | Antigen processing: Ubiquitination & Proteasome degradation, Class I MHC mediated antigen processing & presentation | 0.997049696, 0.003118792 | 6.660057e-09, 4.421456e-14 |
| reactome | CD19+ B | L6 | R-HSA-180585 , R-HSA-1234176, R-HSA-211733 , R-HSA-69601 , R-HSA-69610 , R-HSA-69613 , R-HSA-69541 , R-HSA-69229 , R-HSA-75815 , R-HSA-180534 , R-HSA-169911 , R-HSA-349425 , R-HSA-9604323, R-HSA-8854050, R-HSA-1236978, R-HSA-174154 , R-HSA-1169091, R-HSA-174084 , R-HSA-1234174, R-HSA-2262749, R-HSA-983705 , R-HSA-174113 , R-HSA-450408 , R-HSA-69563 , R-HSA-69580 , R-HSA-174184 , R-HSA-351202 , R-HSA-68867 , R-HSA-176409 , R-HSA-350562 , R-HSA-69615 , R-HSA-5362768, R-HSA-174178 , R-HSA-179419 , R-HSA-5610780 | Vif-mediated degradation of APOBEC3G , Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha , Regulation of activated PAK-2p34 by proteasome mediated degradation , Ubiquitin Mediated Degradation of Phosphorylated Cdc25A , p53-Independent DNA Damage Response , p53-Independent G1/S DNA damage checkpoint , Stabilization of p53 , Ubiquitin-dependent degradation of Cyclin D1 , Ubiquitin-dependent degradation of Cyclin D , Vpu mediated degradation of CD4 , Regulation of Apoptosis , Autodegradation of the E3 ubiquitin ligase COP1 , Negative regulation of NOTCH4 signaling , FBXL7 down-regulates AURKA during mitotic entry and in early mitosis , Cross-presentation of soluble exogenous antigens (endosomes) , APC/C:Cdc20 mediated degradation of Securin , Activation of NF-kappaB in B cells , Autodegradation of Cdh1 by Cdh1:APC/C , Regulation of Hypoxia-inducible Factor (HIF) by oxygen , Cellular response to hypoxia , Signaling by the B Cell Receptor (BCR) , SCF-beta-TrCP mediated degradation of Emi1 , AUF1 (hnRNP D0) binds and destabilizes mRNA , p53-Dependent G1 DNA Damage Response , p53-Dependent G1/S DNA damage checkpoint , Cdc20:Phospho-APC/C mediated degradation of Cyclin A , Metabolism of polyamines , Assembly of the pre-replicative complex , APC/C:Cdc20 mediated degradation of mitotic proteins , Regulation of ornithine decarboxylase (ODC) , G1/S DNA Damage Checkpoints , Hh mutants that don’t undergo autocatalytic processing are degraded by ERAD , APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1, APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint , Degradation of GLI1 by the proteasome | 0.7490393108, 0.0319137209, 0.0256472437, 0.0242873384, 0.0242873384, 0.0242873384, 0.0225422403, 0.0120133659, 0.0120133659, 0.0119846233, 0.0108046763, 0.0101911528, 0.0071579856, 0.0070377887, 0.0040655484, 0.0038589122, 0.0037679238, 0.0036141487, 0.0030579708, 0.0030579708, 0.0028683640, 0.0024109404, 0.0017126798, 0.0015009738, 0.0015009738, 0.0013319088, 0.0013173159, 0.0012105047, 0.0011649631, 0.0010246799, 0.0009578296, 0.0009514080, 0.0008622334, 0.0007207196, 0.0006610228 | 2.433018e-13, 1.735945e-13, 7.193688e-12, 5.424345e-12, 5.424345e-12, 5.424345e-12, 1.741572e-12, 1.238520e-11, 1.238520e-11, 1.238520e-11, 5.424345e-12, 1.238520e-11, 8.907071e-12, 4.486919e-11, 3.832536e-11, 1.884699e-12, 9.112376e-15, 2.855537e-12, 1.201408e-13, 1.201408e-13, 6.637218e-26, 6.786237e-11, 3.945748e-12, 8.833851e-12, 8.833851e-12, 3.601389e-12, 3.634256e-14, 8.655424e-13, 2.266767e-12, 2.223514e-10, 1.211591e-11, 6.786237e-11, 1.005329e-11, 1.005329e-11, 1.369024e-10 |
| reactome | CD19+ B | L7 | R-HSA-72163 , R-HSA-72172 , R-HSA-109688, R-HSA-73856 , R-HSA-72203 | mRNA Splicing - Major Pathway , mRNA Splicing , Cleavage of Growing Transcript in the Termination Region, RNA Polymerase II Transcription Termination , Processing of Capped Intron-Containing Pre-mRNA | 0.5457887505, 0.4439546364, 0.0021482288, 0.0021482288, 0.0006461411 | 1.512823e-22, 6.075949e-23, 1.754344e-08, 1.754344e-08, 5.751685e-20 |
| reactome | CD19+ B | L8 | R-HSA-76005 , R-HSA-114608, R-HSA-76002 , R-HSA-109582 | Response to elevated platelet cytosolic Ca2+ , Platelet degranulation , Platelet activation, signaling and aggregation, Hemostasis | 0.7063848487, 0.2314322026, 0.0252623002, 0.0004075344 | 1.614308e-20, 3.964098e-19, 1.767108e-29, 2.862108e-43 |
| wikipathway | CD19+ B | L1 | WP477 | Cytoplasmic Ribosomal Proteins | 1 | 1.254966e-28 |
| wikipathway | CD19+ B | L2 | WP111 | Electron Transport Chain (OXPHOS system in mitochondria) | 0.9999189 | 4.726328e-27 |
| wikipathway_cancer | CD19+ B | L1 | WP619 | Type II interferon signaling (IFNG) | 0.9998636 | 2.260695e-11 |
CD56+ NK
pbmc_res_set_summary %>%
filter(celltype == 'CD56+ NK') %>%
filter(active_set, thresh==1e-4) %>%
db_component_kableAdding missing grouping variables: `db`, `celltype`, `top_component`| db | celltype | top_component | geneSet | description | pip | pValueHypergeometric |
|---|---|---|---|---|---|---|
| gobp | CD56+ NK | L1 | GO:0002376 | immune system process | 0.9999984 | 2.947781e-276 |
| gobp | CD56+ NK | L2 | GO:0045047, GO:0072599, GO:0006614, GO:0006613 | protein targeting to ER , establishment of protein localization to endoplasmic reticulum, SRP-dependent cotranslational protein targeting to membrane , cotranslational protein targeting to membrane | 0.68278614, 0.20978513, 0.07123053, 0.03822676 | 9.495193e-34, 1.280004e-33, 1.085035e-31, 6.691900e-32 |
| gobp | CD56+ NK | L4 | GO:0006119, GO:0009123, GO:0042773, GO:0042775, GO:0009161, GO:0009126, GO:0009167, GO:0022900, GO:0022904, GO:0046034 | oxidative phosphorylation , nucleoside monophosphate metabolic process , ATP synthesis coupled electron transport , mitochondrial ATP synthesis coupled electron transport, ribonucleoside monophosphate metabolic process , purine nucleoside monophosphate metabolic process , purine ribonucleoside monophosphate metabolic process , electron transport chain , respiratory electron transport chain , ATP metabolic process | 0.9815754083, 0.0075172568, 0.0050461669, 0.0035658370, 0.0031462719, 0.0018470112, 0.0018470112, 0.0017166414, 0.0015391764, 0.0009472366 | 2.922476e-26, 3.203909e-41, 3.830697e-19, 8.794047e-19, 6.509045e-39, 2.429909e-37, 2.429909e-37, 8.544784e-26, 1.986936e-19, 5.926956e-33 |
| gobp | CD56+ NK | L5 | GO:0008380, GO:0006397, GO:0000375, GO:0000377, GO:0000398, GO:0016071 | RNA splicing , mRNA processing , RNA splicing, via transesterification reactions , RNA splicing, via transesterification reactions with bulged adenosine as nucleophile, mRNA splicing, via spliceosome , mRNA metabolic process | 0.59074452, 0.22252471, 0.05825611, 0.05441422, 0.05441422, 0.01452235 | 1.141014e-39, 2.284529e-42, 9.013714e-32, 1.546092e-31, 1.546092e-31, 3.470305e-72 |
| gobp_nr | CD56+ NK | L1 | GO:0036230, GO:0002446 | granulocyte activation , neutrophil mediated immunity | 0.6655074, 0.3354429 | 8.805074e-72, 8.544872e-71 |
| gobp_nr | CD56+ NK | L2 | GO:0006413 | translational initiation | 0.9954877 | 9.230939e-37 |
| gobp_nr | CD56+ NK | L3 | GO:0042110, GO:0007159 | T cell activation , leukocyte cell-cell adhesion | 0.985660130, 0.008171918 | 3.058385e-58, 4.198497e-42 |
| gobp_nr | CD56+ NK | L4 | GO:0009123, GO:0009141, GO:0009259 | nucleoside monophosphate metabolic process, nucleoside triphosphate metabolic process , ribonucleotide metabolic process | 0.981592710, 0.015904774, 0.001372449 | 5.279727e-40, 6.177407e-35, 6.209394e-41 |
| gobp_nr | CD56+ NK | L5 | GO:0042113 | B cell activation | 0.9972725 | 9.375193e-38 |
| gomf | CD56+ NK | L1 | GO:0003735 | structural constituent of ribosome | 1 | 1.182382e-44 |
| gomf | CD56+ NK | L2 | GO:0000981, GO:0003700 | DNA-binding transcription factor activity, RNA polymerase II-specific, DNA-binding transcription factor activity | 0.996770584, 0.003356549 | 3.240357e-18, 3.414777e-22 |
| gomf | CD56+ NK | L3 | GO:0000977, GO:0000976, GO:0001012, GO:1990837, GO:0003690, GO:0043565, GO:0000987, GO:0001067, GO:0044212 | RNA polymerase II regulatory region sequence-specific DNA binding, transcription regulatory region sequence-specific DNA binding , RNA polymerase II regulatory region DNA binding , sequence-specific double-stranded DNA binding , double-stranded DNA binding , sequence-specific DNA binding , proximal promoter sequence-specific DNA binding , regulatory region nucleic acid binding , transcription regulatory region DNA binding | 0.5246638008, 0.2816905881, 0.1760785081, 0.0110809288, 0.0067171732, 0.0006260858, 0.0003679068, 0.0002517074, 0.0002268130 | 6.617810e-37, 8.879108e-39, 2.222485e-36, 3.657740e-40, 6.115445e-47, 6.947558e-44, 1.156041e-28, 1.529375e-38, 4.443215e-38 |
| kegg | CD56+ NK | L1 | hsa03010 | Ribosome | 1 | 9.217956e-36 |
| kegg | CD56+ NK | L2 | hsa05012 | Parkinson disease | 0.9999978 | 2.585983e-32 |
| kegg | CD56+ NK | L3 | hsa04640 | Hematopoietic cell lineage | 0.9978541 | 4.769128e-19 |
| reactome | CD56+ NK | L1 | R-HSA-168256 | Immune System | 1 | 9.313458e-193 |
| reactome | CD56+ NK | L2 | R-HSA-156842, R-HSA-156902, R-HSA-192823, R-HSA-72764 , R-HSA-72689 | Eukaryotic Translation Elongation , Peptide chain elongation , Viral mRNA Translation , Eukaryotic Translation Termination , Formation of a pool of free 40S subunits | 0.864742537, 0.106897566, 0.027158260, 0.002413175, 0.001418708 | 6.208280e-34, 1.059151e-32, 1.059151e-32, 1.163653e-32, 2.528922e-34 |
| reactome | CD56+ NK | L3 | R-HSA-212436, R-HSA-74160 , R-HSA-73857 | Generic Transcription Pathway , Gene expression (Transcription), RNA Polymerase II Transcription | 0.68127740, 0.29679295, 0.02222635 | 1.321222e-30, 3.097765e-41, 2.085936e-37 |
| reactome | CD56+ NK | L4 | R-HSA-163200 , R-HSA-1428517, R-HSA-611105 | Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins., The citric acid (TCA) cycle and respiratory electron transport , Respiratory electron transport | 0.993324533, 0.006034017, 0.001575567 | 1.782486e-25, 1.148730e-26, 7.189017e-19 |
| reactome | CD56+ NK | L5 | R-HSA-8878171, R-HSA-157118 , R-HSA-8939236 | Transcriptional regulation by RUNX1 , Signaling by NOTCH , RUNX1 regulates transcription of genes involved in differentiation of HSCs | 0.97128181, 0.04393861, 0.01998012 | 4.649106e-25, 1.638239e-27, 2.982359e-17 |
| reactome | CD56+ NK | L6 | R-HSA-983168 , R-HSA-983169 , R-HSA-8951664 | Antigen processing: Ubiquitination & Proteasome degradation, Class I MHC mediated antigen processing & presentation , Neddylation | 0.8808248324, 0.1189949639, 0.0009720837 | 4.596003e-14, 1.163224e-19, 1.837871e-09 |
| wikipathway | CD56+ NK | L1 | WP477 | Cytoplasmic Ribosomal Proteins | 1 | 3.731258e-31 |
| wikipathway | CD56+ NK | L2 | WP111, WP623 | Electron Transport Chain (OXPHOS system in mitochondria), Oxidative phosphorylation | 0.99086202, 0.01897664 | 3.364560e-24, 3.188613e-17 |
T cell
pbmc_res_set_summary %>%
filter(celltype == 'T cell') %>%
filter(active_set, thresh==1e-4) %>%
db_component_kableAdding missing grouping variables: `db`, `celltype`, `top_component`| db | celltype | top_component | geneSet | description | pip | pValueHypergeometric |
|---|---|---|---|---|---|---|
| gobp | T cell | L1 | GO:0001775, GO:0045321 | cell activation , leukocyte activation | 0.998243491, 0.002864201 | 1.098801e-248, 2.328201e-226 |
| gobp | T cell | L2 | GO:0006119, GO:0042773, GO:0042775 | oxidative phosphorylation , ATP synthesis coupled electron transport , mitochondrial ATP synthesis coupled electron transport | 0.998867321, 0.002306692, 0.002090733 | 1.891240e-33, 9.259766e-25, 2.100714e-24 |
| gobp | T cell | L3 | GO:0010941, GO:0008219, GO:0043067, GO:0042981, GO:0012501, GO:0006915, GO:0097190, GO:0048518, GO:0010942, GO:0048522, GO:0048519, GO:0043068, GO:0043065 | regulation of cell death , cell death , regulation of programmed cell death , regulation of apoptotic process , programmed cell death , apoptotic process , apoptotic signaling pathway , positive regulation of biological process , positive regulation of cell death , positive regulation of cellular process , negative regulation of biological process , positive regulation of programmed cell death, positive regulation of apoptotic process | 0.404035437, 0.367067203, 0.059812581, 0.059590178, 0.042848010, 0.038547811, 0.020693460, 0.009702335, 0.006246010, 0.006037632, 0.005468877, 0.002090144, 0.001933994 | 2.138535e-192, 7.032734e-238, 3.661703e-176, 1.383501e-174, 1.127119e-219, 4.508930e-213, 1.876837e-89, 0.000000e+00, 7.689401e-95, 0.000000e+00, 0.000000e+00, 3.313749e-84, 5.541783e-83 |
| gobp | T cell | L4 | GO:0045047, GO:0006614, GO:0072599, GO:0070972, GO:0006613 | protein targeting to ER , SRP-dependent cotranslational protein targeting to membrane , establishment of protein localization to endoplasmic reticulum, protein localization to endoplasmic reticulum , cotranslational protein targeting to membrane | 0.42251775, 0.37005939, 0.13809458, 0.04385614, 0.03174252 | 6.738692e-29, 2.697911e-27, 1.069848e-28, 2.389817e-33, 4.015516e-26 |
| gobp | T cell | L5 | GO:0002376, GO:0006955 | immune system process, immune response | 0.998468901, 0.002881243 | 0.000000e+00, 2.059792e-293 |
| gobp_nr | T cell | L1 | GO:0036230, GO:0002446 | granulocyte activation , neutrophil mediated immunity | 0.7324297, 0.2703360 | 8.893801e-111, 9.709562e-110 |
| gobp_nr | T cell | L2 | GO:0042110 | T cell activation | 0.9999906 | 2.423836e-82 |
| gobp_nr | T cell | L3 | GO:0070972 | protein localization to endoplasmic reticulum | 0.9998559 | 7.082395e-33 |
| gomf | T cell | L1 | GO:0005515 | protein binding | 1 | 0 |
| kegg | T cell | L1 | hsa05010 | Alzheimer disease | 0.9999993 | 1.469698e-43 |
| reactome | T cell | L1 | R-HSA-6798695 | Neutrophil degranulation | 1 | 4.546436e-106 |
| reactome | T cell | L2 | R-HSA-72706 , R-HSA-156827, R-HSA-72689 , R-HSA-72613 , R-HSA-72737 , R-HSA-192823, R-HSA-156902 | GTP hydrolysis and joining of the 60S ribosomal subunit , L13a-mediated translational silencing of Ceruloplasmin expression, Formation of a pool of free 40S subunits , Eukaryotic Translation Initiation , Cap-dependent Translation Initiation , Viral mRNA Translation , Peptide chain elongation | 0.586005479, 0.400596683, 0.009180040, 0.004668524, 0.004668524, 0.003496445, 0.003174071 | 4.807983e-34, 1.097988e-33, 4.127765e-30, 2.515433e-32, 2.515433e-32, 6.804717e-29, 6.804717e-29 |
CD14+ Monocyte
pbmc_res_set_summary %>%
filter(celltype == 'CD14+ Monocyte') %>%
filter(active_set, thresh==1e-4) %>%
db_component_kableAdding missing grouping variables: `db`, `celltype`, `top_component`| db | celltype | top_component | geneSet | description | pip | pValueHypergeometric |
|---|---|---|---|---|---|---|
| gobp | CD14+ Monocyte | L1 | GO:0045321, GO:0001775 | leukocyte activation, cell activation | 0.9139560, 0.0861039 | 1.266041e-152, 4.878344e-159 |
| gobp | CD14+ Monocyte | L2 | GO:0045047, GO:0006614, GO:0006613, GO:0072599, GO:0070972 | protein targeting to ER , SRP-dependent cotranslational protein targeting to membrane , cotranslational protein targeting to membrane , establishment of protein localization to endoplasmic reticulum, protein localization to endoplasmic reticulum | 0.8615391988, 0.0574691370, 0.0477713854, 0.0336165786, 0.0004015912 | 6.375283e-36, 1.173258e-33, 6.348075e-34, 1.637199e-34, 6.297308e-36 |
| gobp | CD14+ Monocyte | L3 | GO:0006119, GO:0042773, GO:0042775 | oxidative phosphorylation , ATP synthesis coupled electron transport , mitochondrial ATP synthesis coupled electron transport | 0.9990484928, 0.0006152697, 0.0004379516 | 1.775985e-31, 7.453047e-24, 1.881893e-23 |
| gobp | CD14+ Monocyte | L4 | GO:0016192, GO:0002376, GO:0006955, GO:0045055, GO:0006810, GO:0042119, GO:0006887, GO:0051234 | vesicle-mediated transport , immune system process , immune response , regulated exocytosis , transport , neutrophil activation , exocytosis , establishment of localization | 0.9851433899, 0.0210152324, 0.0059841488, 0.0010584611, 0.0009289568, 0.0008104012, 0.0007570762, 0.0007478103 | 2.927115e-145, 3.659065e-228, 8.733808e-175, 1.874116e-97, 3.322971e-280, 8.790244e-89, 1.301435e-98, 1.576263e-285 |
| gobp | CD14+ Monocyte | L5 | GO:0006915, GO:0012501, GO:0043067, GO:0042981, GO:0010941, GO:0008219, GO:0097190, GO:0006950, GO:0010942, GO:0050790, GO:0048518, GO:0010033, GO:0070887, GO:2001233, GO:0043065, GO:0043068, GO:0043069, GO:0043066, GO:0051716, GO:0048522, GO:0060548, GO:0050896, GO:0048523, GO:0048519 | apoptotic process , programmed cell death , regulation of programmed cell death , regulation of apoptotic process , regulation of cell death , cell death , apoptotic signaling pathway , response to stress , positive regulation of cell death , regulation of catalytic activity , positive regulation of biological process , response to organic substance , cellular response to chemical stimulus , regulation of apoptotic signaling pathway , positive regulation of apoptotic process , positive regulation of programmed cell death, negative regulation of programmed cell death, negative regulation of apoptotic process , cellular response to stimulus , positive regulation of cellular process , negative regulation of cell death , response to stimulus , negative regulation of cellular process , negative regulation of biological process | 2.720176e-01, 1.948576e-01, 1.940882e-01, 1.583264e-01, 1.008376e-01, 5.132999e-02, 2.549188e-03, 9.307323e-04, 6.576479e-04, 5.735087e-04, 5.459875e-04, 4.811908e-04, 4.506495e-04, 3.491954e-04, 3.298411e-04, 2.900530e-04, 1.817724e-04, 1.476441e-04, 1.365127e-04, 1.359366e-04, 1.228290e-04, 1.125502e-04, 7.493961e-05, 6.920531e-05 | 4.451786e-113, 8.301835e-116, 7.895560e-95, 1.189669e-93, 3.999854e-100, 1.272117e-119, 1.841090e-46, 1.495543e-192, 1.854200e-49, 1.361590e-109, 1.578429e-290, 7.322372e-153, 5.666552e-149, 3.085467e-32, 1.847719e-44, 1.848623e-44, 2.655090e-54, 1.185635e-52, 7.682074e-311, 9.343174e-247, 5.466768e-57, 0.000000e+00, 3.391448e-204, 2.249264e-243 |
| gobp | CD14+ Monocyte | L6 | GO:0006518, GO:0006412, GO:0043043, GO:0043603, GO:0043604 | peptide metabolic process , translation , peptide biosynthetic process , cellular amide metabolic process, amide biosynthetic process | 0.790995030, 0.119614037, 0.082857945, 0.002543295, 0.001245957 | 4.678462e-78, 1.088274e-65, 4.547896e-66, 2.326686e-80, 8.359365e-66 |
| gobp | CD14+ Monocyte | L7 | GO:0008380, GO:0000375, GO:0000377, GO:0000398, GO:0006397, GO:0016071 | RNA splicing , RNA splicing, via transesterification reactions , RNA splicing, via transesterification reactions with bulged adenosine as nucleophile, mRNA splicing, via spliceosome , mRNA processing , mRNA metabolic process | 0.422448316, 0.196794593, 0.178759471, 0.178759471, 0.021244858, 0.001609996 | 9.748365e-38, 7.437684e-32, 1.388978e-31, 1.388978e-31, 7.467478e-38, 2.423046e-69 |
| gobp_nr | CD14+ Monocyte | L1 | GO:0036230, GO:0002446 | granulocyte activation , neutrophil mediated immunity | 0.97592803, 0.02469514 | 2.402996e-86, 1.745099e-83 |
| gobp_nr | CD14+ Monocyte | L2 | GO:0006413 | translational initiation | 0.999994 | 1.131814e-41 |
| gobp_nr | CD14+ Monocyte | L3 | GO:0009123, GO:0009141 | nucleoside monophosphate metabolic process, nucleoside triphosphate metabolic process | 0.98835280, 0.01259324 | 5.790725e-44, 5.147747e-40 |
| gobp_nr | CD14+ Monocyte | L4 | GO:0002521, GO:0042110, GO:0002694, GO:1903706 | leukocyte differentiation , T cell activation , regulation of leukocyte activation, regulation of hemopoiesis | 0.619222289, 0.358464783, 0.007935017, 0.004456591 | 9.454964e-48, 2.311611e-47, 1.222276e-45, 1.243755e-35 |
| gobp_nr | CD14+ Monocyte | L5 | GO:0008380, GO:0006397, GO:1903311 | RNA splicing , mRNA processing , regulation of mRNA metabolic process | 0.876773133, 0.089632405, 0.004303895 | 3.387665e-36, 3.352465e-36, 9.733062e-24 |
| gobp_nr | CD14+ Monocyte | L6 | GO:0090150, GO:0070972, GO:0006605 | establishment of protein localization to membrane, protein localization to endoplasmic reticulum , protein targeting | 0.756201036, 0.243465201, 0.004950252 | 9.080340e-44, 4.739729e-35, 6.381780e-43 |
| gomf | CD14+ Monocyte | L1 | GO:0003723 | RNA binding | 0.9999998 | 1.173386e-141 |
| gomf | CD14+ Monocyte | L2 | GO:0000981, GO:0003700 | DNA-binding transcription factor activity, RNA polymerase II-specific, DNA-binding transcription factor activity | 0.9998274825, 0.0002279895 | 1.396985e-15, 1.312394e-20 |
| gomf | CD14+ Monocyte | L3 | GO:0001012, GO:0000977, GO:0000987, GO:0000978, GO:0000976, GO:1990837, GO:0043565, GO:0044212 | RNA polymerase II regulatory region DNA binding , RNA polymerase II regulatory region sequence-specific DNA binding, proximal promoter sequence-specific DNA binding , RNA polymerase II proximal promoter sequence-specific DNA binding, transcription regulatory region sequence-specific DNA binding , sequence-specific double-stranded DNA binding , sequence-specific DNA binding , transcription regulatory region DNA binding | 0.6603205658, 0.2924363216, 0.0360620592, 0.0077244907, 0.0030829257, 0.0007025284, 0.0003868975, 0.0001017222 | 1.246290e-37, 4.365922e-37, 2.762407e-33, 3.447619e-32, 2.150387e-36, 1.010515e-38, 5.047518e-44, 3.418838e-38 |
| gomf | CD14+ Monocyte | L4 | GO:0003735 | structural constituent of ribosome | 1 | 4.918061e-44 |
| gomf | CD14+ Monocyte | L5 | GO:0016655, GO:0008137, GO:0050136, GO:0003954, GO:0016651 | oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor, NADH dehydrogenase (ubiquinone) activity , NADH dehydrogenase (quinone) activity , NADH dehydrogenase activity , oxidoreductase activity, acting on NAD(P)H | 0.8270835588, 0.0778621792, 0.0778621792, 0.0178702201, 0.0003469471 | 2.846509e-17, 9.084810e-15, 9.084810e-15, 5.476813e-14, 1.127698e-15 |
| gomf | CD14+ Monocyte | L6 | GO:0045296, GO:0050839 | cadherin binding , cell adhesion molecule binding | 0.7890801, 0.1881604 | 4.054477e-37, 1.113159e-41 |
| kegg | CD14+ Monocyte | L1 | hsa03010 | Ribosome | 1 | 7.453734e-35 |
| kegg | CD14+ Monocyte | L2 | hsa05012 | Parkinson disease | 0.9999021 | 2.609968e-33 |
| reactome | CD14+ Monocyte | L1 | R-HSA-6798695 | Neutrophil degranulation | 0.9999954 | 3.105498e-81 |
| reactome | CD14+ Monocyte | L2 | R-HSA-72766 | Translation | 1 | 5.172352e-59 |
| reactome | CD14+ Monocyte | L3 | R-HSA-163200, R-HSA-611105 | Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins., Respiratory electron transport | 0.9996110591, 0.0008392269 | 1.294295e-30, 2.557783e-24 |
| reactome | CD14+ Monocyte | L5 | R-HSA-72172, R-HSA-72163, R-HSA-72203 | mRNA Splicing , mRNA Splicing - Major Pathway , Processing of Capped Intron-Containing Pre-mRNA | 0.67495558, 0.30641144, 0.01826453 | 2.542532e-25, 3.287091e-24, 2.103706e-25 |
| reactome | CD14+ Monocyte | L6 | R-HSA-198933 | Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell | 0.9974877 | 5.102985e-21 |
| reactome | CD14+ Monocyte | L7 | R-HSA-379726 | Mitochondrial tRNA aminoacylation | 0.9972986 | 0.6931782 |
| wikipathway | CD14+ Monocyte | L1 | WP477 | Cytoplasmic Ribosomal Proteins | 1 | 1.207268e-29 |
| wikipathway | CD14+ Monocyte | L2 | WP111 | Electron Transport Chain (OXPHOS system in mitochondria) | 0.9998312 | 9.058329e-28 |
CD34+
pbmc_res_set_summary %>%
filter(celltype == 'CD34+') %>%
filter(active_set, thresh==1e-4) %>%
db_component_kableAdding missing grouping variables: `db`, `celltype`, `top_component`| db | celltype | top_component | geneSet | description | pip | pValueHypergeometric |
|---|---|---|---|---|---|---|
| gobp | CD34+ | L1 | GO:0001775, GO:0045321 | cell activation , leukocyte activation | 0.9870540, 0.0137773 | 2.633476e-189, 3.972660e-173 |
| gobp | CD34+ | L2 | GO:0006613, GO:0006614, GO:0045047, GO:0072599 | cotranslational protein targeting to membrane , SRP-dependent cotranslational protein targeting to membrane , protein targeting to ER , establishment of protein localization to endoplasmic reticulum | 0.813781011, 0.153626340, 0.029062966, 0.008527809 | 7.184084e-30, 2.122256e-28, 4.082612e-30, 6.229293e-30 |
| gobp | CD34+ | L3 | GO:0006119, GO:0042773, GO:0042775 | oxidative phosphorylation , ATP synthesis coupled electron transport , mitochondrial ATP synthesis coupled electron transport | 0.998941297, 0.002197687, 0.002040038 | 4.557019e-31, 6.681278e-22, 1.502267e-21 |
| gobp | CD34+ | L4 | GO:0044419, GO:0016032, GO:0044403 | interspecies interaction between organisms, viral process , symbiont process | 0.4203517, 0.3833143, 0.1952495 | 2.033013e-99, 3.869982e-91, 3.235558e-95 |
| gobp_nr | CD34+ | L1 | GO:0002446, GO:0036230 | neutrophil mediated immunity, granulocyte activation | 0.6078439, 0.3946596 | 1.592450e-76, 1.318184e-76 |
| gobp_nr | CD34+ | L2 | GO:0006413 | translational initiation | 0.9996608 | 1.64713e-38 |
| gomf | CD34+ | L1 | GO:0003735 | structural constituent of ribosome | 1 | 4.128375e-42 |
| gomf | CD34+ | L2 | GO:0005515 | protein binding | 1 | 0 |
| kegg | CD34+ | L1 | hsa00190, hsa05012 | Oxidative phosphorylation, Parkinson disease | 0.9921759, 0.0333608 | 4.886096e-32, 6.352523e-33 |
| kegg | CD34+ | L2 | hsa03010 | Ribosome | 1 | 5.679335e-34 |
| reactome | CD34+ | L1 | R-HSA-72764 , R-HSA-156902, R-HSA-156842 | Eukaryotic Translation Termination, Peptide chain elongation , Eukaryotic Translation Elongation | 0.993056233, 0.006377217, 0.004060368 | 2.275039e-33, 7.764526e-32, 5.500776e-33 |
| reactome | CD34+ | L2 | R-HSA-6798695, R-HSA-168249 | Neutrophil degranulation, Innate Immune System | 0.98627161, 0.01669373 | 1.517922e-75, 6.465420e-123 |
| reactome | CD34+ | L3 | R-HSA-163200, R-HSA-611105 | Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins., Respiratory electron transport | 0.997732525, 0.003758523 | 8.425069e-32, 2.834000e-25 |
| reactome | CD34+ | L4 | R-HSA-198933 | Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell | 0.9999503 | 1.147541e-26 |
| wikipathway | CD34+ | L1 | WP477 | Cytoplasmic Ribosomal Proteins | 1 | 1.328872e-30 |
| wikipathway | CD34+ | L2 | WP111 | Electron Transport Chain (OXPHOS system in mitochondria) | 0.9999971 | 1.517475e-31 |
knitr::knit_exit()