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Introduction

Our goals here are to run Logistic SuSiE on differential expression results from TCGA. We want to assess:

  1. If the resulting enrichment results look good/interpretable across multiple/concatenated gene sets
  2. Assess sensitivity to a range of p-value thresholds
  3. 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')
}

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. ### Overview

pbmc_res_set_summary %>%
  filter(active_set, thresh==1e-4) %>%
  group_by(celltype, thresh, db, top_component) %>%
  select(geneSet, description) %>% chop(c(geneSet, description)) %>%
  knitr::kable()
Adding missing grouping variables: `celltype`, `thresh`, `db`, `top_component`
celltype thresh db top_component geneSet description
CD19+ B 1e-04 gobp L5 GO:0001775, GO:0002263, GO:0002366, GO:0045321 cell activation , cell activation involved in immune response , leukocyte activation involved in immune response, leukocyte activation
CD19+ B 1e-04 gobp L1 GO:0002376 immune system process
CD19+ B 1e-04 gobp L3 GO:0006119, GO:0042773, GO:0042775 oxidative phosphorylation , ATP synthesis coupled electron transport , mitochondrial ATP synthesis coupled electron transport
CD19+ B 1e-04 gobp L6 GO:0006397, GO:0016071, GO:0050684, GO:0008380, GO:0043484, GO:0000375, GO:0000377, GO:0000398, GO:0048024, GO:0000380 mRNA processing , mRNA metabolic process , regulation of mRNA processing , RNA splicing , regulation of RNA splicing , RNA splicing, via transesterification reactions , RNA splicing, via transesterification reactions with bulged adenosine as nucleophile, mRNA splicing, via spliceosome , regulation of mRNA splicing, via spliceosome , alternative mRNA splicing, via spliceosome
CD19+ B 1e-04 gobp L2 GO:0045047, GO:0072599, GO:0006613, GO:0006614 protein targeting to ER , establishment of protein localization to endoplasmic reticulum, cotranslational protein targeting to membrane , SRP-dependent cotranslational protein targeting to membrane
CD19+ B 1e-04 gobp_nr L1 GO:0002446, GO:0036230 neutrophil mediated immunity, granulocyte activation
CD19+ B 1e-04 gobp_nr L5 GO:0002764 immune response-regulating signaling pathway
CD19+ B 1e-04 gobp_nr L4 GO:0009123, GO:0009141 nucleoside monophosphate metabolic process, nucleoside triphosphate metabolic process
CD19+ B 1e-04 gobp_nr L2 GO:0070972 protein localization to endoplasmic reticulum
CD19+ B 1e-04 gomf L1 GO:0003723 RNA binding
CD19+ B 1e-04 gomf L3 GO:0000976, GO:0000977, GO:0000978, GO:0000987, GO:0001012, GO:0001067, GO:0003690, GO:0044212, GO:1990837 transcription regulatory region sequence-specific DNA binding , RNA polymerase II regulatory region sequence-specific DNA binding, RNA polymerase II proximal promoter sequence-specific DNA binding, proximal promoter sequence-specific DNA binding , RNA polymerase II regulatory region DNA binding , regulatory region nucleic acid binding , double-stranded DNA binding , transcription regulatory region DNA binding , sequence-specific double-stranded DNA binding
CD19+ B 1e-04 gomf L7 GO:0016651, GO:0016655, GO:0003954, GO:0008137, GO:0050136 oxidoreductase activity, acting on NAD(P)H , oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor, NADH dehydrogenase activity , NADH dehydrogenase (ubiquinone) activity , NADH dehydrogenase (quinone) activity
CD19+ B 1e-04 gomf L2 GO:0000981, GO:0003700 DNA-binding transcription factor activity, RNA polymerase II-specific, DNA-binding transcription factor activity
CD19+ B 1e-04 gomf L6 GO:0003735 structural constituent of ribosome
CD19+ B 1e-04 kegg L1 hsa00190, hsa05012 Oxidative phosphorylation, Parkinson disease
CD19+ B 1e-04 kegg L3 hsa03010 Ribosome
CD19+ B 1e-04 kegg L2 hsa04640 Hematopoietic cell lineage
CD19+ B 1e-04 reactome L8 R-HSA-109582, R-HSA-114608, R-HSA-76002 , R-HSA-76005 Hemostasis , Platelet degranulation , Platelet activation, signaling and aggregation, Response to elevated platelet cytosolic Ca2+
CD19+ B 1e-04 reactome L1 R-HSA-168256 Immune System
CD19+ B 1e-04 reactome L3 R-HSA-212436, R-HSA-73857 , R-HSA-74160 Generic Transcription Pathway , RNA Polymerase II Transcription, Gene expression (Transcription)
CD19+ B 1e-04 reactome L5 R-HSA-983168, R-HSA-983169 Antigen processing: Ubiquitination & Proteasome degradation, Class I MHC mediated antigen processing & presentation
CD19+ B 1e-04 reactome L7 R-HSA-72163 , R-HSA-72172 , R-HSA-72203 , R-HSA-109688, R-HSA-73856 mRNA Splicing - Major Pathway , mRNA Splicing , Processing of Capped Intron-Containing Pre-mRNA , Cleavage of Growing Transcript in the Termination Region, RNA Polymerase II Transcription Termination
CD19+ B 1e-04 reactome L6 R-HSA-983705 , R-HSA-351202 , R-HSA-69563 , R-HSA-69580 , R-HSA-69615 , R-HSA-69229 , R-HSA-75815 , R-HSA-1169091, R-HSA-1234174, R-HSA-1234176, R-HSA-1236978, R-HSA-169911 , R-HSA-174084 , R-HSA-174113 , R-HSA-174154 , R-HSA-174178 , R-HSA-174184 , R-HSA-176409 , R-HSA-179419 , R-HSA-180534 , R-HSA-180585 , R-HSA-211733 , R-HSA-2262749, R-HSA-349425 , R-HSA-350562 , R-HSA-450408 , R-HSA-5362768, R-HSA-5610780, R-HSA-68867 , R-HSA-69541 , R-HSA-69601 , R-HSA-69610 , R-HSA-69613 , R-HSA-8854050, R-HSA-9604323 Signaling by the B Cell Receptor (BCR) , Metabolism of polyamines , p53-Dependent G1 DNA Damage Response , p53-Dependent G1/S DNA damage checkpoint , G1/S DNA Damage Checkpoints , Ubiquitin-dependent degradation of Cyclin D1 , Ubiquitin-dependent degradation of Cyclin D , Activation of NF-kappaB in B cells , Regulation of Hypoxia-inducible Factor (HIF) by oxygen , Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha , Cross-presentation of soluble exogenous antigens (endosomes) , Regulation of Apoptosis , Autodegradation of Cdh1 by Cdh1:APC/C , SCF-beta-TrCP mediated degradation of Emi1 , APC/C:Cdc20 mediated degradation of Securin , APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1, Cdc20:Phospho-APC/C mediated degradation of Cyclin A , APC/C:Cdc20 mediated degradation of mitotic proteins , APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint , Vpu mediated degradation of CD4 , Vif-mediated degradation of APOBEC3G , Regulation of activated PAK-2p34 by proteasome mediated degradation , Cellular response to hypoxia , Autodegradation of the E3 ubiquitin ligase COP1 , Regulation of ornithine decarboxylase (ODC) , AUF1 (hnRNP D0) binds and destabilizes mRNA , Hh mutants that don’t undergo autocatalytic processing are degraded by ERAD , Degradation of GLI1 by the proteasome , Assembly of the pre-replicative complex , Stabilization of p53 , Ubiquitin Mediated Degradation of Phosphorylated Cdc25A , p53-Independent DNA Damage Response , p53-Independent G1/S DNA damage checkpoint , FBXL7 down-regulates AURKA during mitotic entry and in early mitosis , Negative regulation of NOTCH4 signaling
CD19+ B 1e-04 reactome L4 R-HSA-1428517, R-HSA-163200 , R-HSA-611105 The citric acid (TCA) cycle and respiratory electron transport , Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins., Respiratory electron transport
CD19+ B 1e-04 reactome L2 R-HSA-156827 , R-HSA-72689 , R-HSA-72706 , R-HSA-1799339, R-HSA-156842 , R-HSA-156902 , R-HSA-192823 , R-HSA-2408557, R-HSA-72764 L13a-mediated translational silencing of Ceruloplasmin expression, Formation of a pool of free 40S subunits , GTP hydrolysis and joining of the 60S ribosomal subunit , SRP-dependent cotranslational protein targeting to membrane , Eukaryotic Translation Elongation , Peptide chain elongation , Viral mRNA Translation , Selenocysteine synthesis , Eukaryotic Translation Termination
CD19+ B 1e-04 wikipathway_cancer L1 WP619 Type II interferon signaling (IFNG)
CD19+ B 1e-04 wikipathway L2 WP111 Electron Transport Chain (OXPHOS system in mitochondria)
CD19+ B 1e-04 wikipathway L1 WP477 Cytoplasmic Ribosomal Proteins
CD56+ NK 1e-04 gobp L1 GO:0002376 immune system process
CD56+ NK 1e-04 gobp L4 GO:0009123, GO:0009126, GO:0009161, GO:0009167, GO:0046034, GO:0006119, GO:0022900, GO:0022904, GO:0042773, GO:0042775 nucleoside monophosphate metabolic process , purine nucleoside monophosphate metabolic process , ribonucleoside monophosphate metabolic process , purine ribonucleoside monophosphate metabolic process , ATP metabolic process , oxidative phosphorylation , electron transport chain , respiratory electron transport chain , ATP synthesis coupled electron transport , mitochondrial ATP synthesis coupled electron transport
CD56+ NK 1e-04 gobp L5 GO:0006397, GO:0016071, GO:0008380, GO:0000375, GO:0000377, GO:0000398 mRNA processing , mRNA metabolic process , RNA splicing , RNA splicing, via transesterification reactions , RNA splicing, via transesterification reactions with bulged adenosine as nucleophile, mRNA splicing, via spliceosome
CD56+ NK 1e-04 gobp L2 GO:0045047, GO:0072599, GO:0006613, GO:0006614 protein targeting to ER , establishment of protein localization to endoplasmic reticulum, cotranslational protein targeting to membrane , SRP-dependent cotranslational protein targeting to membrane
CD56+ NK 1e-04 gobp_nr L1 GO:0002446, GO:0036230 neutrophil mediated immunity, granulocyte activation
CD56+ NK 1e-04 gobp_nr L2 GO:0006413 translational initiation
CD56+ NK 1e-04 gobp_nr L3 GO:0007159, GO:0042110 leukocyte cell-cell adhesion, T cell activation
CD56+ NK 1e-04 gobp_nr L4 GO:0009123, GO:0009141, GO:0009259 nucleoside monophosphate metabolic process, nucleoside triphosphate metabolic process , ribonucleotide metabolic process
CD56+ NK 1e-04 gobp_nr L5 GO:0042113 B cell activation
CD56+ NK 1e-04 gomf L3 GO:0000976, GO:0000977, GO:0000987, GO:0001012, GO:0001067, GO:0003690, GO:0043565, GO:0044212, GO:1990837 transcription regulatory region sequence-specific DNA binding , RNA polymerase II regulatory region sequence-specific DNA binding, proximal promoter sequence-specific DNA binding , RNA polymerase II regulatory region DNA binding , regulatory region nucleic acid binding , double-stranded DNA binding , sequence-specific DNA binding , transcription regulatory region DNA binding , sequence-specific double-stranded DNA binding
CD56+ NK 1e-04 gomf L2 GO:0000981, GO:0003700 DNA-binding transcription factor activity, RNA polymerase II-specific, DNA-binding transcription factor activity
CD56+ NK 1e-04 gomf L1 GO:0003735 structural constituent of ribosome
CD56+ NK 1e-04 kegg L1 hsa03010 Ribosome
CD56+ NK 1e-04 kegg L3 hsa04640 Hematopoietic cell lineage
CD56+ NK 1e-04 kegg L2 hsa05012 Parkinson disease
CD56+ NK 1e-04 reactome L1 R-HSA-168256 Immune System
CD56+ NK 1e-04 reactome L3 R-HSA-212436, R-HSA-73857 , R-HSA-74160 Generic Transcription Pathway , RNA Polymerase II Transcription, Gene expression (Transcription)
CD56+ NK 1e-04 reactome L5 R-HSA-157118 , R-HSA-8878171, R-HSA-8939236 Signaling by NOTCH , Transcriptional regulation by RUNX1 , RUNX1 regulates transcription of genes involved in differentiation of HSCs
CD56+ NK 1e-04 reactome L6 R-HSA-8951664, R-HSA-983168 , R-HSA-983169 Neddylation , Antigen processing: Ubiquitination & Proteasome degradation, Class I MHC mediated antigen processing & presentation
CD56+ NK 1e-04 reactome L4 R-HSA-1428517, R-HSA-163200 , R-HSA-611105 The citric acid (TCA) cycle and respiratory electron transport , Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins., Respiratory electron transport
CD56+ NK 1e-04 reactome L2 R-HSA-72689 , R-HSA-156842, R-HSA-156902, R-HSA-192823, R-HSA-72764 Formation of a pool of free 40S subunits, Eukaryotic Translation Elongation , Peptide chain elongation , Viral mRNA Translation , Eukaryotic Translation Termination
CD56+ NK 1e-04 wikipathway L2 WP111, WP623 Electron Transport Chain (OXPHOS system in mitochondria), Oxidative phosphorylation
CD56+ NK 1e-04 wikipathway L1 WP477 Cytoplasmic Ribosomal Proteins
T cell 1e-04 gobp L1 GO:0001775, GO:0045321 cell activation , leukocyte activation
T cell 1e-04 gobp L5 GO:0002376, GO:0006955 immune system process, immune response
T cell 1e-04 gobp L3 GO:0048518, GO:0048519, GO:0048522, GO:0006915, GO:0008219, GO:0010941, GO:0012501, GO:0042981, GO:0043067, GO:0097190, GO:0010942, GO:0043065, GO:0043068 positive regulation of biological process , negative regulation of biological process , positive regulation of cellular process , apoptotic process , cell death , regulation of cell death , programmed cell death , regulation of apoptotic process , regulation of programmed cell death , apoptotic signaling pathway , positive regulation of cell death , positive regulation of apoptotic process , positive regulation of programmed cell death
T cell 1e-04 gobp L2 GO:0006119, GO:0042773, GO:0042775 oxidative phosphorylation , ATP synthesis coupled electron transport , mitochondrial ATP synthesis coupled electron transport
T cell 1e-04 gobp L4 GO:0070972, GO:0045047, GO:0072599, GO:0006613, GO:0006614 protein localization to endoplasmic reticulum , protein targeting to ER , establishment of protein localization to endoplasmic reticulum, cotranslational protein targeting to membrane , SRP-dependent cotranslational protein targeting to membrane
T cell 1e-04 gobp_nr L1 GO:0002446, GO:0036230 neutrophil mediated immunity, granulocyte activation
T cell 1e-04 gobp_nr L2 GO:0042110 T cell activation
T cell 1e-04 gobp_nr L3 GO:0070972 protein localization to endoplasmic reticulum
T cell 1e-04 gomf L1 GO:0005515 protein binding
T cell 1e-04 kegg L1 hsa05010 Alzheimer disease
T cell 1e-04 reactome L1 R-HSA-6798695 Neutrophil degranulation
T cell 1e-04 reactome L2 R-HSA-156827, R-HSA-72613 , R-HSA-72689 , R-HSA-72706 , R-HSA-72737 , R-HSA-156902, R-HSA-192823 L13a-mediated translational silencing of Ceruloplasmin expression, Eukaryotic Translation Initiation , Formation of a pool of free 40S subunits , GTP hydrolysis and joining of the 60S ribosomal subunit , Cap-dependent Translation Initiation , Peptide chain elongation , Viral mRNA Translation
CD14+ Monocyte 1e-04 gobp L4 GO:0006810, GO:0006887, GO:0016192, GO:0045055, GO:0051234, GO:0002376, GO:0006955, GO:0042119 transport , exocytosis , vesicle-mediated transport , regulated exocytosis , establishment of localization, immune system process , immune response , neutrophil activation
CD14+ Monocyte 1e-04 gobp L1 GO:0001775, GO:0045321 cell activation , leukocyte activation
CD14+ Monocyte 1e-04 gobp L5 GO:0050896, GO:0006950, GO:0048518, GO:0048519, GO:0048523, GO:0050790, GO:0051716, GO:0070887, GO:0048522, GO:0010033, GO:0006915, GO:0008219, GO:0010941, GO:0012501, GO:0042981, GO:0043066, GO:0043067, GO:0043069, GO:0060548, GO:0097190, GO:0010942, GO:0043065, GO:0043068, GO:2001233 response to stimulus , response to stress , positive regulation of biological process , negative regulation of biological process , negative regulation of cellular process , regulation of catalytic activity , cellular response to stimulus , cellular response to chemical stimulus , positive regulation of cellular process , response to organic substance , apoptotic process , cell death , regulation of cell death , programmed cell death , regulation of apoptotic process , negative regulation of apoptotic process , regulation of programmed cell death , negative regulation of programmed cell death, negative regulation of cell death , apoptotic signaling pathway , positive regulation of cell death , positive regulation of apoptotic process , positive regulation of programmed cell death, regulation of apoptotic signaling pathway
CD14+ Monocyte 1e-04 gobp L6 GO:0043603, GO:0043604, GO:0006412, GO:0006518, GO:0043043 cellular amide metabolic process, amide biosynthetic process , translation , peptide metabolic process , peptide biosynthetic process
CD14+ Monocyte 1e-04 gobp L3 GO:0006119, GO:0042773, GO:0042775 oxidative phosphorylation , ATP synthesis coupled electron transport , mitochondrial ATP synthesis coupled electron transport
CD14+ Monocyte 1e-04 gobp L7 GO:0006397, GO:0016071, GO:0008380, GO:0000375, GO:0000377, GO:0000398 mRNA processing , mRNA metabolic process , RNA splicing , RNA splicing, via transesterification reactions , RNA splicing, via transesterification reactions with bulged adenosine as nucleophile, mRNA splicing, via spliceosome
CD14+ Monocyte 1e-04 gobp L2 GO:0070972, GO:0045047, GO:0072599, GO:0006613, GO:0006614 protein localization to endoplasmic reticulum , protein targeting to ER , establishment of protein localization to endoplasmic reticulum, cotranslational protein targeting to membrane , SRP-dependent cotranslational protein targeting to membrane
CD14+ Monocyte 1e-04 gobp_nr L1 GO:0002446, GO:0036230 neutrophil mediated immunity, granulocyte activation
CD14+ Monocyte 1e-04 gobp_nr L4 GO:0002521, GO:0002694, GO:0042110, GO:1903706 leukocyte differentiation , regulation of leukocyte activation, T cell activation , regulation of hemopoiesis
CD14+ Monocyte 1e-04 gobp_nr L5 GO:0006397, GO:0008380, GO:1903311 mRNA processing , RNA splicing , regulation of mRNA metabolic process
CD14+ Monocyte 1e-04 gobp_nr L2 GO:0006413 translational initiation
CD14+ Monocyte 1e-04 gobp_nr L6 GO:0006605, GO:0070972, GO:0090150 protein targeting , protein localization to endoplasmic reticulum , establishment of protein localization to membrane
CD14+ Monocyte 1e-04 gobp_nr L3 GO:0009123, GO:0009141 nucleoside monophosphate metabolic process, nucleoside triphosphate metabolic process
CD14+ Monocyte 1e-04 gomf L1 GO:0003723 RNA binding
CD14+ Monocyte 1e-04 gomf L3 GO:0000976, GO:0000977, GO:0000978, GO:0000987, GO:0001012, GO:0043565, GO:0044212, GO:1990837 transcription regulatory region sequence-specific DNA binding , RNA polymerase II regulatory region sequence-specific DNA binding, RNA polymerase II proximal promoter sequence-specific DNA binding, proximal promoter sequence-specific DNA binding , RNA polymerase II regulatory region DNA binding , sequence-specific DNA binding , transcription regulatory region DNA binding , sequence-specific double-stranded DNA binding
CD14+ Monocyte 1e-04 gomf L6 GO:0050839, GO:0045296 cell adhesion molecule binding, cadherin binding
CD14+ Monocyte 1e-04 gomf L5 GO:0016651, GO:0016655, GO:0003954, GO:0008137, GO:0050136 oxidoreductase activity, acting on NAD(P)H , oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor, NADH dehydrogenase activity , NADH dehydrogenase (ubiquinone) activity , NADH dehydrogenase (quinone) activity
CD14+ Monocyte 1e-04 gomf L2 GO:0000981, GO:0003700 DNA-binding transcription factor activity, RNA polymerase II-specific, DNA-binding transcription factor activity
CD14+ Monocyte 1e-04 gomf L4 GO:0003735 structural constituent of ribosome
CD14+ Monocyte 1e-04 kegg L1 hsa03010 Ribosome
CD14+ Monocyte 1e-04 kegg L2 hsa05012 Parkinson disease
CD14+ Monocyte 1e-04 reactome L1 R-HSA-6798695 Neutrophil degranulation
CD14+ Monocyte 1e-04 reactome L6 R-HSA-198933 Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
CD14+ Monocyte 1e-04 reactome L5 R-HSA-72163, R-HSA-72172, R-HSA-72203 mRNA Splicing - Major Pathway , mRNA Splicing , Processing of Capped Intron-Containing Pre-mRNA
CD14+ Monocyte 1e-04 reactome L2 R-HSA-72766 Translation
CD14+ Monocyte 1e-04 reactome L3 R-HSA-163200, R-HSA-611105 Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins., Respiratory electron transport
CD14+ Monocyte 1e-04 reactome L7 R-HSA-379726 Mitochondrial tRNA aminoacylation
CD14+ Monocyte 1e-04 wikipathway L2 WP111 Electron Transport Chain (OXPHOS system in mitochondria)
CD14+ Monocyte 1e-04 wikipathway L1 WP477 Cytoplasmic Ribosomal Proteins
CD34+ 1e-04 gobp L1 GO:0001775, GO:0045321 cell activation , leukocyte activation
CD34+ 1e-04 gobp L3 GO:0006119, GO:0042773, GO:0042775 oxidative phosphorylation , ATP synthesis coupled electron transport , mitochondrial ATP synthesis coupled electron transport
CD34+ 1e-04 gobp L4 GO:0016032, GO:0044403, GO:0044419 viral process , symbiont process , interspecies interaction between organisms
CD34+ 1e-04 gobp L2 GO:0045047, GO:0072599, GO:0006613, GO:0006614 protein targeting to ER , establishment of protein localization to endoplasmic reticulum, cotranslational protein targeting to membrane , SRP-dependent cotranslational protein targeting to membrane
CD34+ 1e-04 gobp_nr L1 GO:0002446, GO:0036230 neutrophil mediated immunity, granulocyte activation
CD34+ 1e-04 gobp_nr L2 GO:0006413 translational initiation
CD34+ 1e-04 gomf L2 GO:0005515 protein binding
CD34+ 1e-04 gomf L1 GO:0003735 structural constituent of ribosome
CD34+ 1e-04 kegg L1 hsa00190, hsa05012 Oxidative phosphorylation, Parkinson disease
CD34+ 1e-04 kegg L2 hsa03010 Ribosome
CD34+ 1e-04 reactome L2 R-HSA-168249 , R-HSA-6798695 Innate Immune System , Neutrophil degranulation
CD34+ 1e-04 reactome L4 R-HSA-198933 Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
CD34+ 1e-04 reactome L3 R-HSA-163200, R-HSA-611105 Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins., Respiratory electron transport
CD34+ 1e-04 reactome L1 R-HSA-156842, R-HSA-156902, R-HSA-72764 Eukaryotic Translation Elongation , Peptide chain elongation , Eukaryotic Translation Termination
CD34+ 1e-04 wikipathway L2 WP111 Electron Transport Chain (OXPHOS system in mitochondria)
CD34+ 1e-04 wikipathway L1 WP477 Cytoplasmic Ribosomal Proteins 
knitr::knit_exit()