Last updated: 2023-06-30

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Knit directory: Cardiotoxicity/

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library(tidyverse)
library(gprofiler2)
library(readr)
library(BiocGenerics)
library(gridExtra)
library(VennDiagram)
library(kableExtra)
library(scales)
library(ggVennDiagram)
library(Cormotif)
library(RColorBrewer)
library(ggpubr)

Creation of the data set:

library(edgeR)
library(Cormotif)
library(RColorBrewer)
library(BiocParallel)
## read in count file##
design <- read.csv("data/data_outline.txt", row.names = 1)
mymatrix <- readRDS("data/filtermatrix_x.RDS")#should be 14084
x_counts <- mymatrix$counts

indv <- as.factor(rep(c(1,2,3,4,5,6), c(12,12,12,12,12,12)))
time <- rep((rep(c("3h", "24h"), c(6,6))), 6)
time <- ordered(time, levels =c("3h", "24h"))
group <- as.factor(rep((c("1","2","3","4","5","6","7","8","9","10","11","12")),6))
drug <- rep(c("Daunorubicin","Doxorubicin","Epirubicin","Mitoxantrone","Trastuzumab", "Vehicle"),12)
group1 <- interaction(drug,time)
label <- (interaction(substring(drug, 0, 2), indv, time))
colnames(x_counts) <- label
group_fac <- group1
groupid <- as.numeric(group_fac)
# saveRDS(x_counts,"output/x_counts.RDS")
compid <- data.frame(c1= c(1,2,3,4,5,7,8,9,10,11), c2 = c( 6,6,6,6,6,12,12,12,12,12))

y_TMM_cpm <- cpm(x_counts, log = TRUE)

colnames(y_TMM_cpm) <- label
y_TMM_cpm
set.seed(12345)
cormotif_initial <- cormotiffit(exprs = y_TMM_cpm,
                             groupid = groupid,
                             compid = compid,
                               K=1:8, max.iter = 500, runtype="logCPM")
gene_prob_tran <- cormotif_initial$bestmotif$p.post
rownames(gene_prob_tran) <- rownames(y_TMM_cpm)
motif_prob <- cormotif_initial$bestmotif$clustlike
rownames(motif_prob) <- rownames(y_TMM_cpm)
write.csv(motif_prob,"cormotif_probability_genelist.csv")

cormotif_initial was created after calling corMotif, then running the corMotifcustom.R script. The extra R script enabled me to generate a table containing the likelihood of each gene that belongs to the specific cluster.

After generating the Motifs from 1 to 8, the number of motifs that best fit the data was 4 using the BIC and AIC results below.

cormotif_initial <- readRDS("data/cormotif_initialall.RDS")
myColors <-  rev(c("#FFFFFF", "#E6E6E6" ,"#CCCCCC", "#B3B3B3", "#999999", "#808080", "#666666","#4C4C4C", "#333333", "#191919","#000000"))


plotIC(cormotif_initial)

plotMotif(cormotif_initial)

plot.new()
legend('bottomleft',fill=myColors, legend =rev(c("0", "0.1", "0.2", "0.3", "0.4",  "0.5", "0.6", "0.7", "0.8","0.9", "1")), box.col="white",title = "Probability\nlegend", horiz=FALSE,title.cex=.8)

Viewing the motifs, the following groups were named:

  • Motif 1: No Response (n=7409)

  • Motif 2: Top2 inhibitor response, Time-independent

    • (Time-independent response, n= 589)
  • Motif 3: Top2 inhibitor response, Early

    • (Early response, n= 487)
  • Motif 4: Top2 inhibitor response, Late

    • (Late response, n= 5596)
clust1 <- motif_prob %>%
  as.data.frame() %>%
  filter(V1>0.5) %>% 
  rownames
clust2 <- motif_prob %>%
  as.data.frame() %>%
  filter(V2>0.5) %>% 
  rownames
clust3 <- motif_prob %>%
  as.data.frame() %>%
  filter(V3>0.5) %>% 
  rownames
clust4 <- motif_prob %>%
  as.data.frame() %>%
  filter(V4>0.5) %>% 
  rownames
old_clust1  <- rownames(gene_prob_tran[(gene_prob_tran[,1] <0.45 &
                                          gene_prob_tran[,2] <0.45 &
                                          gene_prob_tran[,3] <0.45 &
                                          gene_prob_tran[,4] <0.45 &
                                          gene_prob_tran[,5] <0.45 &
                                          gene_prob_tran[,6] <0.45 &
                                          gene_prob_tran[,7] <0.45 &
                                          gene_prob_tran[,8] <0.45 &
                                          gene_prob_tran[,9] <0.45 &
                                         gene_prob_tran[,10] <0.45),])
length(intersect(old_clust1,clust1))##7358 out of 7362 oldclust1

old_clust2  <- rownames(gene_prob_tran[(gene_prob_tran[,1]> 0.10 &
                                         gene_prob_tran[,2] > 0.10 &
                                         gene_prob_tran[,3] > 0.10 &
                                         gene_prob_tran[,4] > 0.10 &
                                         # gene_prob_tran[,5] < 0.10 &
                                           gene_prob_tran[,6] > 0.10&
                                           gene_prob_tran[,7]> 0.10 &
                                           gene_prob_tran[,8]> 0.10 &
                                           gene_prob_tran[,9]> 0.10),])
# &                                      # gene_prob_tran[,10]< 0.10),])
                                                   
length(intersect(old_clust2,clust2))##251 out of 432 oldclust2

old_clust3 <- rownames(gene_prob_tran[(gene_prob_tran[,1]>0.55 &
                                           gene_prob_tran[,2] >0.55 &
                                           gene_prob_tran[,3] >0.55 &
                                           gene_prob_tran[,4] >0.25&
                                           gene_prob_tran[,5] <0.90 &
                                           gene_prob_tran[,6] <0.9 &
                                           gene_prob_tran[,7]<0.9&
                                           gene_prob_tran[,8]<0.9 &
                                          gene_prob_tran[,9]<0.9 &
                                           gene_prob_tran[,10]<0.90),])
length(intersect(old_clust3,clust3)) ##414 out of 481 oldclust3

old_clust4 <- rownames(gene_prob_tran[(gene_prob_tran[,1] <0.970 &
                                            gene_prob_tran[,2] <0.97 &
                                            gene_prob_tran[,3] <0.97 &
                                            gene_prob_tran[,4] <0.97 &
                                            gene_prob_tran[,5] <0.9&
                                            gene_prob_tran[,6] >0.55 &
                                            gene_prob_tran[,7] >0.55 &
                                            gene_prob_tran[,8] >0.55 &
                                            gene_prob_tran[,9] >0.05 &
                                            gene_prob_tran[,10] <0.9),])
length(intersect(old_clust4,clust4))##4675 out of 4850 oldclust4
backGL <- read.csv("data/backGL.txt")  ##14084
length(setdiff(backGL$ENTREZID,(union(clust1,union(clust2,union(clust3,clust4))))))
##63 genes not used overall  same as (14084-7504-528-444-5545)

Pie Chart of overall numbers

#make data frame
Set <- c("Early Response", "Time-Independent Response","Late Response", "No Response")
gene_num <- c(487,589,5596,7409)
fills <- c("#F8766D",  "#00BFC4","#7CAE00", "#C77CFF")

pie_chartdata <- data.frame(Set, gene_num, fills)
 
    pie(gene_num,labels =Set )       

##label computation
pie_chartdata <- pie_chartdata %>% 
   mutate(prop = gene_num / sum(pie_chartdata$gene_num) *100) %>%
  mutate(ypos = (prop)+ 0.5*prop )


pie_chartdata %>% 
  ggplot(.,aes(x="",y=gene_num, fill=Set))+
  geom_col(width =1) +
  coord_polar("y", pi/2)+
  theme_void()+
  ggtitle("Distribution of genes for each set")+
  geom_text(aes(label = paste0(Set," (",gene_num,")")),
                position = position_stack(vjust =.55)) +
  theme(legend.position="none") +
  theme(plot.title = element_text(size = rel(1.5), hjust = 0.5))

The genes belonging to each set were identified by the following:

motif 1- No Response set: 7504 (gene list made by filtering likelihood of gene belonging to cluster 1 <0.5)

motif 2- Time-independent Top2i response cluster: 528 (gene list made by filtering likelihood of gene belonging to cluster 2 <0.5)

motif 3- Early Top2i response cluster: 444 (gene list made by filtering likelihood of gene belonging to cluster 3 <0.5)

motif 4- Late Top2i response cluster: 5545 (gene list made by filtering likelihood of gene belonging to cluster 4 <0.5)

There was overlap between the previous sets and the new sets, so I moved on expecting similar responses in the GO analysis. I did subset out the genes not used overall from the background gene list (rowmeans>0 from log(cpm(count matrix))) ## GO and KEGG of each set

DEG_cormotif <- readRDS("data/DEG_cormotif.RDS")
list2env(DEG_cormotif,envir=.GlobalEnv)
<environment: R_GlobalEnv>
# motif_NR <- DEG_cormotif$motif_NR
# motif_TI <- DEG_cormotif$motif_TI
# motif_LR <- DEG_cormotif$motif_LR
# motif_ER <- DEG_cormotif$motif_ER
label_list <- readRDS("data/label_list.RDS")
list2env(label_list,envir=.GlobalEnv)
<environment: R_GlobalEnv>
label <- (interaction(substring(drug, 0, 2), indv, time))
 
backGL <- read.csv("data/backGL.txt")
#NRresp <- read_csv("data/cormotif_NRset.txt")

No response motif genes

GO:BP

source term_id term_name intersection_size term_size p_value
GO:BP GO:0002181 cytoplasmic translation 117 156 1.507e-05
GO:BP GO:0042773 ATP synthesis coupled electron transport 68 82 1.507e-05
GO:BP GO:0042775 mitochondrial ATP synthesis coupled electron transport 68 82 1.507e-05
GO:BP GO:0019646 aerobic electron transport chain 63 74 1.507e-05
GO:BP GO:0009060 aerobic respiration 125 168 1.507e-05
GO:BP GO:0006119 oxidative phosphorylation 96 122 1.507e-05
GO:BP GO:0022904 respiratory electron transport chain 83 104 1.507e-05
GO:BP GO:0045333 cellular respiration 150 211 4.426e-05
GO:BP GO:1901566 organonitrogen compound biosynthetic process 872 1484 4.539e-04
GO:BP GO:0009100 glycoprotein metabolic process 209 316 7.784e-04
GO:BP GO:0006518 peptide metabolic process 469 771 1.771e-03
GO:BP GO:0043603 amide metabolic process 593 993 2.042e-03
GO:BP GO:0022900 electron transport chain 102 142 2.042e-03
GO:BP GO:0006412 translation 396 646 2.783e-03
GO:BP GO:0006486 protein glycosylation 129 187 2.783e-03
GO:BP GO:0043413 macromolecule glycosylation 129 187 2.783e-03
GO:BP GO:0070085 glycosylation 138 202 2.783e-03
GO:BP GO:0033108 mitochondrial respiratory chain complex assembly 71 94 2.799e-03
GO:BP GO:0015980 energy derivation by oxidation of organic compounds 189 288 3.008e-03
GO:BP GO:1901564 organonitrogen compound metabolic process 2733 4955 3.325e-03
GO:BP GO:0022613 ribonucleoprotein complex biogenesis 283 453 6.889e-03
GO:BP GO:0043043 peptide biosynthetic process 403 666 9.904e-03
GO:BP GO:0043604 amide biosynthetic process 464 775 1.033e-02
GO:BP GO:0019538 protein metabolic process 2342 4241 1.532e-02
GO:BP GO:0015986 proton motive force-driven ATP synthesis 51 66 1.576e-02
GO:BP GO:0009101 glycoprotein biosynthetic process 164 252 1.831e-02
GO:BP GO:0006487 protein N-linked glycosylation 50 65 2.164e-02
GO:BP GO:0006754 ATP biosynthetic process 64 87 2.244e-02
GO:BP GO:0010257 NADH dehydrogenase complex assembly 43 55 3.368e-02
GO:BP GO:0032981 mitochondrial respiratory chain complex I assembly 43 55 3.368e-02
GO:BP GO:0006091 generation of precursor metabolites and energy 230 369 3.697e-02
GO:BP GO:0042776 proton motive force-driven mitochondrial ATP synthesis 44 57 4.441e-02
GO:BP GO:0046034 ATP metabolic process 81 116 4.441e-02
GO:BP GO:0042254 ribosome biogenesis 190 301 4.978e-02
KEGG KEGG:05171 Coronavirus disease - COVID-19 122 162 7.225e-07
KEGG KEGG:03010 Ribosome 98 127 1.551e-06
KEGG KEGG:05208 Chemical carcinogenesis - reactive oxygen species 133 186 1.136e-05
KEGG KEGG:04510 Focal adhesion 127 177 1.198e-05
KEGG KEGG:00190 Oxidative phosphorylation 81 106 2.532e-05
KEGG KEGG:05012 Parkinson disease 153 226 1.368e-04
KEGG KEGG:04512 ECM-receptor interaction 55 69 1.368e-04
KEGG KEGG:04714 Thermogenesis 134 195 1.395e-04
KEGG KEGG:05020 Prion disease 148 220 2.532e-04
KEGG KEGG:05415 Diabetic cardiomyopathy 117 169 2.653e-04
KEGG KEGG:04141 Protein processing in endoplasmic reticulum 110 161 1.020e-03
KEGG KEGG:00531 Glycosaminoglycan degradation 16 16 1.020e-03
KEGG KEGG:05016 Huntington disease 165 256 2.083e-03
KEGG KEGG:05010 Alzheimer disease 197 315 5.425e-03
KEGG KEGG:00513 Various types of N-glycan biosynthesis 29 36 1.088e-02
KEGG KEGG:04932 Non-alcoholic fatty liver disease 88 131 1.088e-02
KEGG KEGG:04142 Lysosome 80 118 1.175e-02
KEGG KEGG:00510 N-Glycan biosynthesis 36 48 2.410e-02
KEGG KEGG:04810 Regulation of actin cytoskeleton 114 179 3.226e-02
KEGG KEGG:01200 Carbon metabolism 66 98 3.806e-02
KEGG KEGG:03040 Spliceosome 86 132 3.945e-02
KEGG KEGG:05022 Pathways of neurodegeneration - multiple diseases 230 385 4.301e-02

Late response Top2\(\beta\) inhibitor motif genes

GO:BP/KEGG

source term_id term_name intersection_size term_size p_value
GO:BP GO:0007059 chromosome segregation 200 369 2.598e-05
GO:BP GO:0000280 nuclear division 185 344 1.136e-04
GO:BP GO:0051301 cell division 286 570 1.287e-04
GO:BP GO:0007049 cell cycle 694 1529 2.325e-04
GO:BP GO:0006261 DNA-templated DNA replication 89 148 4.174e-04
GO:BP GO:0022402 cell cycle process 502 1086 6.439e-04
GO:BP GO:0098813 nuclear chromosome segregation 147 273 6.439e-04
GO:BP GO:0061982 meiosis I cell cycle process 54 81 6.439e-04
GO:BP GO:0007051 spindle organization 107 188 6.439e-04
GO:BP GO:0140014 mitotic nuclear division 137 251 6.439e-04
GO:BP GO:0048285 organelle fission 198 388 9.885e-04
GO:BP GO:0000070 mitotic sister chromatid segregation 102 179 9.885e-04
GO:BP GO:0007127 meiosis I 51 77 1.225e-03
GO:BP GO:0000278 mitotic cell cycle 387 827 2.041e-03
GO:BP GO:1903047 mitotic cell cycle process 329 694 2.774e-03
GO:BP GO:0006260 DNA replication 135 255 3.497e-03
GO:BP GO:0045132 meiotic chromosome segregation 43 64 3.592e-03
GO:BP GO:0140013 meiotic nuclear division 71 120 4.267e-03
GO:BP GO:0000226 microtubule cytoskeleton organization 266 552 4.267e-03
GO:BP GO:1903046 meiotic cell cycle process 78 135 5.053e-03
GO:BP GO:0007017 microtubule-based process 353 760 8.645e-03
GO:BP GO:2001251 negative regulation of chromosome organization 55 90 1.077e-02
GO:BP GO:0000819 sister chromatid segregation 115 217 1.132e-02
GO:BP GO:0045930 negative regulation of mitotic cell cycle 112 211 1.259e-02
GO:BP GO:0051716 cellular response to stimulus 2050 4953 1.303e-02
GO:BP GO:0032465 regulation of cytokinesis 49 79 1.380e-02
GO:BP GO:0070925 organelle assembly 375 817 1.380e-02
GO:BP GO:0051276 chromosome organization 258 543 1.380e-02
GO:BP GO:0008654 phospholipid biosynthetic process 122 234 1.380e-02
GO:BP GO:0045839 negative regulation of mitotic nuclear division 36 54 1.546e-02
GO:BP GO:0046474 glycerophospholipid biosynthetic process 101 189 1.675e-02
GO:BP GO:1902850 microtubule cytoskeleton organization involved in mitosis 86 157 1.761e-02
GO:BP GO:0050896 response to stimulus 2369 5770 1.761e-02
GO:BP GO:0045017 glycerolipid biosynthetic process 114 218 1.777e-02
GO:BP GO:0033046 negative regulation of sister chromatid segregation 32 47 1.794e-02
GO:BP GO:0033048 negative regulation of mitotic sister chromatid segregation 32 47 1.794e-02
GO:BP GO:2000816 negative regulation of mitotic sister chromatid separation 32 47 1.794e-02
GO:BP GO:0019692 deoxyribose phosphate metabolic process 26 36 1.798e-02
GO:BP GO:0009262 deoxyribonucleotide metabolic process 26 36 1.798e-02
GO:BP GO:0007093 mitotic cell cycle checkpoint signaling 77 139 2.123e-02
GO:BP GO:0051784 negative regulation of nuclear division 37 57 2.123e-02
GO:BP GO:0071173 spindle assembly checkpoint signaling 30 44 2.444e-02
GO:BP GO:0071174 mitotic spindle checkpoint signaling 30 44 2.444e-02
GO:BP GO:0007094 mitotic spindle assembly checkpoint signaling 30 44 2.444e-02
GO:BP GO:0000075 cell cycle checkpoint signaling 97 183 2.444e-02
GO:BP GO:0045841 negative regulation of mitotic metaphase/anaphase transition 31 46 2.546e-02
GO:BP GO:1905819 negative regulation of chromosome separation 32 48 2.570e-02
GO:BP GO:0051985 negative regulation of chromosome segregation 32 48 2.570e-02
GO:BP GO:0045786 negative regulation of cell cycle 166 338 2.570e-02
GO:BP GO:0006270 DNA replication initiation 25 35 2.570e-02
GO:BP GO:0009394 2’-deoxyribonucleotide metabolic process 25 35 2.570e-02
GO:BP GO:0033047 regulation of mitotic sister chromatid segregation 34 52 2.637e-02
GO:BP GO:0051304 chromosome separation 46 76 2.918e-02
GO:BP GO:0006996 organelle organization 1261 3000 3.028e-02
GO:BP GO:0071417 cellular response to organonitrogen compound 229 485 3.122e-02
GO:BP GO:0031577 spindle checkpoint signaling 30 45 3.655e-02
GO:BP GO:0021537 telencephalon development 104 201 3.660e-02
GO:BP GO:1902100 negative regulation of metaphase/anaphase transition of cell cycle 31 47 3.660e-02
GO:BP GO:0007052 mitotic spindle organization 71 129 3.660e-02
GO:BP GO:0045143 homologous chromosome segregation 24 34 4.009e-02
GO:BP GO:0090407 organophosphate biosynthetic process 237 506 4.009e-02
GO:BP GO:1905818 regulation of chromosome separation 43 71 4.021e-02
GO:BP GO:1901653 cellular response to peptide 142 287 4.048e-02
GO:BP GO:0051256 mitotic spindle midzone assembly 9 9 4.080e-02
GO:BP GO:0010889 regulation of sequestering of triglyceride 11 12 4.632e-02
GO:BP GO:0051255 spindle midzone assembly 11 12 4.632e-02
GO:BP GO:1901699 cellular response to nitrogen compound 241 517 4.632e-02
GO:BP GO:0010564 regulation of cell cycle process 287 626 4.989e-02
KEGG KEGG:03030 DNA replication 25 35 2.693e-02
KEGG KEGG:00230 Purine metabolism 56 97 2.693e-02

Early Response Top2 inhibitor motif genes

GO:BP/KEGG

query significant p_value term_size query_size intersection_size precision recall term_id source term_name effective_domain_size source_order parents
query_1 TRUE 0.0000000 2684 428 2.16e+02 0.5046729 0.0804769 GO:0097659 GO:BP nucleic acid-templated transcription 13586 19768 GO:0010467, GO:0032774
query_1 TRUE 0.0000000 2683 428 2.16e+02 0.5046729 0.0805069 GO:0006351 GO:BP DNA-templated transcription 13586 2176 GO:0097659
query_1 TRUE 0.0000000 2714 428 2.16e+02 0.5046729 0.0795873 GO:0032774 GO:BP RNA biosynthetic process 13586 8240 GO:0009059, GO:0016070, GO:0034654
query_1 TRUE 0.0000000 1995 428 1.83e+02 0.4275701 0.0917293 GO:0006366 GO:BP transcription by RNA polymerase II 13586 2189 GO:0006351
query_1 TRUE 0.0000000 2576 428 2.09e+02 0.4883178 0.0811335 GO:1903506 GO:BP regulation of nucleic acid-templated transcription 13586 24157 GO:0097659, GO:2001141
query_1 TRUE 0.0000000 2574 428 2.09e+02 0.4883178 0.0811966 GO:0006355 GO:BP regulation of DNA-templated transcription 13586 2180 GO:0006351, GO:0010468, GO:1903506
query_1 TRUE 0.0000000 1914 428 1.78e+02 0.4158879 0.0929990 GO:0006357 GO:BP regulation of transcription by RNA polymerase II 13586 2182 GO:0006355, GO:0006366
query_1 TRUE 0.0000000 3080 428 2.30e+02 0.5373832 0.0746753 GO:0019219 GO:BP regulation of nucleobase-containing compound metabolic process 13586 5897 GO:0006139, GO:0031323, GO:0051171, GO:0080090
query_1 TRUE 0.0000000 2593 428 2.09e+02 0.4883178 0.0806016 GO:2001141 GO:BP regulation of RNA biosynthetic process 13586 27647 GO:0010556, GO:0031326, GO:0032774, GO:0051252
query_1 TRUE 0.0000000 2845 428 2.19e+02 0.5116822 0.0769772 GO:0051252 GO:BP regulation of RNA metabolic process 13586 14368 GO:0016070, GO:0019219, GO:0060255
query_1 TRUE 0.0000000 4048 428 2.59e+02 0.6051402 0.0639822 GO:0090304 GO:BP nucleic acid metabolic process 13586 19208 GO:0006139, GO:0043170
query_1 TRUE 0.0000000 3012 428 2.19e+02 0.5116822 0.0727092 GO:0010556 GO:BP regulation of macromolecule biosynthetic process 13586 4304 GO:0009059, GO:0009889, GO:0060255
query_1 TRUE 0.0000000 4174 428 2.63e+02 0.6144860 0.0630091 GO:0031323 GO:BP regulation of cellular metabolic process 13586 7510 GO:0019222, GO:0044237, GO:0050794
query_1 TRUE 0.0000000 3600 428 2.41e+02 0.5630841 0.0669444 GO:0016070 GO:BP RNA metabolic process 13586 5221 GO:0090304
query_1 TRUE 0.0000000 3070 428 2.19e+02 0.5116822 0.0713355 GO:0034654 GO:BP nucleobase-containing compound biosynthetic process 13586 9171 GO:0006139, GO:0018130, GO:0019438, GO:0044271, GO:1901362
query_1 TRUE 0.0000000 3080 428 2.19e+02 0.5116822 0.0711039 GO:0031326 GO:BP regulation of cellular biosynthetic process 13586 7513 GO:0009889, GO:0031323, GO:0044249
query_1 TRUE 0.0000000 3133 428 2.20e+02 0.5140187 0.0702202 GO:0019438 GO:BP aromatic compound biosynthetic process 13586 6097 GO:0006725, GO:0044249
query_1 TRUE 0.0000000 3132 428 2.20e+02 0.5140187 0.0702427 GO:0018130 GO:BP heterocycle biosynthetic process 13586 5504 GO:0044249, GO:0046483
query_1 TRUE 0.0000000 3169 428 2.20e+02 0.5140187 0.0694225 GO:0009889 GO:BP regulation of biosynthetic process 13586 3827 GO:0009058, GO:0019222
query_1 TRUE 0.0000000 3237 428 2.21e+02 0.5163551 0.0682731 GO:1901362 GO:BP organic cyclic compound biosynthetic process 13586 22388 GO:1901360, GO:1901576
query_1 TRUE 0.0000000 4292 428 2.60e+02 0.6074766 0.0605778 GO:0051171 GO:BP regulation of nitrogen compound metabolic process 13586 14316 GO:0006807, GO:0019222
query_1 TRUE 0.0000000 4417 428 2.64e+02 0.6168224 0.0597691 GO:0080090 GO:BP regulation of primary metabolic process 13586 18790 GO:0019222, GO:0044238
query_1 TRUE 0.0000000 3580 428 2.33e+02 0.5443925 0.0650838 GO:0010468 GO:BP regulation of gene expression 13586 4251 GO:0010467, GO:0060255
query_1 TRUE 0.0000000 3730 428 2.36e+02 0.5514019 0.0632708 GO:0009059 GO:BP macromolecule biosynthetic process 13586 3311 GO:0043170, GO:1901576
query_1 TRUE 0.0000000 4455 428 2.62e+02 0.6121495 0.0588103 GO:0006139 GO:BP nucleobase-containing compound metabolic process 13586 2028 GO:0006725, GO:0034641, GO:0044238, GO:0046483, GO:1901360
query_1 TRUE 0.0000000 4617 428 2.66e+02 0.6214953 0.0576132 GO:0060255 GO:BP regulation of macromolecule metabolic process 13586 15305 GO:0019222, GO:0043170
query_1 TRUE 0.0000000 4570 428 2.63e+02 0.6144860 0.0575492 GO:0046483 GO:BP heterocycle metabolic process 13586 12897 GO:0044237
query_1 TRUE 0.0000000 4596 428 2.63e+02 0.6144860 0.0572237 GO:0006725 GO:BP cellular aromatic compound metabolic process 13586 2484 GO:0044237
query_1 TRUE 0.0000000 3750 428 2.31e+02 0.5397196 0.0616000 GO:0044271 GO:BP cellular nitrogen compound biosynthetic process 13586 11584 GO:0034641, GO:0044249
query_1 TRUE 0.0000000 4747 428 2.65e+02 0.6191589 0.0558247 GO:1901360 GO:BP organic cyclic compound metabolic process 13586 22386 GO:0071704
query_1 TRUE 0.0000000 5017 428 2.73e+02 0.6378505 0.0544150 GO:0019222 GO:BP regulation of metabolic process 13586 5900 GO:0008152, GO:0050789
query_1 TRUE 0.0000000 4587 428 2.58e+02 0.6028037 0.0562459 GO:0010467 GO:BP gene expression 13586 4250 GO:0043170
query_1 TRUE 0.0000000 4245 428 2.45e+02 0.5724299 0.0577150 GO:0044249 GO:BP cellular biosynthetic process 13586 11577 GO:0009058, GO:0044237
query_1 TRUE 0.0000000 4946 428 2.67e+02 0.6238318 0.0539830 GO:0034641 GO:BP cellular nitrogen compound metabolic process 13586 9164 GO:0006807, GO:0044237
query_1 TRUE 0.0000000 4539 428 2.49e+02 0.5817757 0.0548579 GO:1901576 GO:BP organic substance biosynthetic process 13586 22571 GO:0009058, GO:0071704
query_1 TRUE 0.0000000 4590 428 2.49e+02 0.5817757 0.0542484 GO:0009058 GO:BP biosynthetic process 13586 3310 GO:0008152
query_1 TRUE 0.0000000 7069 428 3.22e+02 0.7523364 0.0455510 GO:0043170 GO:BP macromolecule metabolic process 13586 11154 GO:0071704
query_1 TRUE 0.0000000 6996 428 3.14e+02 0.7336449 0.0448828 GO:0044237 GO:BP cellular metabolic process 13586 11571 GO:0008152, GO:0009987
query_1 TRUE 0.0000000 7552 428 3.29e+02 0.7686916 0.0435646 GO:0050794 GO:BP regulation of cellular process 13586 14008 GO:0009987, GO:0050789
query_1 TRUE 0.0000000 1315 428 1.05e+02 0.2453271 0.0798479 GO:1903508 GO:BP positive regulation of nucleic acid-templated transcription 13586 24159 GO:0097659, GO:1902680, GO:1903506
query_1 TRUE 0.0000000 1315 428 1.05e+02 0.2453271 0.0798479 GO:0045893 GO:BP positive regulation of DNA-templated transcription 13586 12393 GO:0006351, GO:0006355, GO:1903508
query_1 TRUE 0.0000000 1441 428 1.11e+02 0.2593458 0.0770298 GO:0051254 GO:BP positive regulation of RNA metabolic process 13586 14370 GO:0010604, GO:0016070, GO:0045935, GO:0051252
query_1 TRUE 0.0000000 1322 428 1.05e+02 0.2453271 0.0794251 GO:1902680 GO:BP positive regulation of RNA biosynthetic process 13586 23482 GO:0010557, GO:0031328, GO:0032774, GO:0051254, GO:2001141
query_1 TRUE 0.0000000 1602 428 1.16e+02 0.2710280 0.0724095 GO:0045935 GO:BP positive regulation of nucleobase-containing compound metabolic process 13586 12431 GO:0006139, GO:0019219, GO:0031325, GO:0051173
query_1 TRUE 0.0000000 7441 428 3.21e+02 0.7500000 0.0431394 GO:0006807 GO:BP nitrogen compound metabolic process 13586 2543 GO:0008152
query_1 TRUE 0.0000000 1015 428 8.60e+01 0.2009346 0.0847291 GO:0045892 GO:BP negative regulation of DNA-templated transcription 13586 12392 GO:0006351, GO:0006355, GO:1903507
query_1 TRUE 0.0000000 7806 428 3.29e+02 0.7686916 0.0421471 GO:0044238 GO:BP primary metabolic process 13586 11572 GO:0008152
query_1 TRUE 0.0000000 1017 428 8.60e+01 0.2009346 0.0845624 GO:1903507 GO:BP negative regulation of nucleic acid-templated transcription 13586 24158 GO:0097659, GO:1902679, GO:1903506
query_1 TRUE 0.0000000 1026 428 8.60e+01 0.2009346 0.0838207 GO:1902679 GO:BP negative regulation of RNA biosynthetic process 13586 23481 GO:0010558, GO:0031327, GO:0032774, GO:0051253, GO:2001141
query_1 TRUE 0.0000000 1507 428 1.09e+02 0.2546729 0.0723291 GO:0010557 GO:BP positive regulation of macromolecule biosynthetic process 13586 4305 GO:0009059, GO:0009891, GO:0010556, GO:0010604
query_1 TRUE 0.0000000 8061 428 3.35e+02 0.7827103 0.0415581 GO:0050789 GO:BP regulation of biological process 13586 14004 GO:0008150, GO:0065007
query_1 TRUE 0.0000000 1119 428 9.00e+01 0.2102804 0.0804290 GO:0051253 GO:BP negative regulation of RNA metabolic process 13586 14369 GO:0010605, GO:0016070, GO:0045934, GO:0051252
query_1 TRUE 0.0000000 1209 428 9.40e+01 0.2196262 0.0777502 GO:0045934 GO:BP negative regulation of nucleobase-containing compound metabolic process 13586 12430 GO:0006139, GO:0019219, GO:0031324, GO:0051172
query_1 TRUE 0.0000000 8320 428 3.40e+02 0.7943925 0.0408654 GO:0065007 GO:BP biological regulation 13586 16811 GO:0008150
query_1 TRUE 0.0000000 1564 428 1.09e+02 0.2546729 0.0696931 GO:0031328 GO:BP positive regulation of cellular biosynthetic process 13586 7515 GO:0009891, GO:0031325, GO:0031326, GO:0044249
query_1 TRUE 0.0000000 937 428 7.90e+01 0.1845794 0.0843116 GO:0045944 GO:BP positive regulation of transcription by RNA polymerase II 13586 12439 GO:0006357, GO:0006366, GO:0045893
query_1 TRUE 0.0000000 1735 428 1.16e+02 0.2710280 0.0668588 GO:0031324 GO:BP negative regulation of cellular metabolic process 13586 7511 GO:0009892, GO:0031323, GO:0044237, GO:0048523
query_1 TRUE 0.0000000 8169 428 3.34e+02 0.7803738 0.0408863 GO:0071704 GO:BP organic substance metabolic process 13586 17822 GO:0008152
query_1 TRUE 0.0000000 1604 428 1.09e+02 0.2546729 0.0679551 GO:0009891 GO:BP positive regulation of biosynthetic process 13586 3829 GO:0009058, GO:0009889, GO:0009893
query_1 TRUE 0.0000000 1214 428 9.10e+01 0.2126168 0.0749588 GO:0010558 GO:BP negative regulation of macromolecule biosynthetic process 13586 4306 GO:0009059, GO:0009890, GO:0010556, GO:0010605
query_1 TRUE 0.0000000 1239 428 9.10e+01 0.2126168 0.0734463 GO:0031327 GO:BP negative regulation of cellular biosynthetic process 13586 7514 GO:0009890, GO:0031324, GO:0031326, GO:0044249
query_1 TRUE 0.0000000 2412 428 1.40e+02 0.3271028 0.0580431 GO:0051173 GO:BP positive regulation of nitrogen compound metabolic process 13586 14318 GO:0006807, GO:0009893, GO:0051171
query_1 TRUE 0.0000000 740 428 6.50e+01 0.1518692 0.0878378 GO:0000122 GO:BP negative regulation of transcription by RNA polymerase II 13586 51 GO:0006357, GO:0006366, GO:0045892
query_1 TRUE 0.0000000 1280 428 9.10e+01 0.2126168 0.0710938 GO:0009890 GO:BP negative regulation of biosynthetic process 13586 3828 GO:0009058, GO:0009889, GO:0009892
query_1 TRUE 0.0000000 2646 428 1.47e+02 0.3434579 0.0555556 GO:0010604 GO:BP positive regulation of macromolecule metabolic process 13586 4347 GO:0009893, GO:0043170, GO:0060255
query_1 TRUE 0.0000000 2270 428 1.31e+02 0.3060748 0.0577093 GO:0031325 GO:BP positive regulation of cellular metabolic process 13586 7512 GO:0009893, GO:0031323, GO:0044237, GO:0048522
query_1 TRUE 0.0000000 8518 428 3.36e+02 0.7850467 0.0394459 GO:0008152 GO:BP metabolic process 13586 3197 GO:0008150
query_1 TRUE 0.0000000 2293 428 1.29e+02 0.3014019 0.0562582 GO:0009892 GO:BP negative regulation of metabolic process 13586 3830 GO:0008152, GO:0019222, GO:0048519
query_1 TRUE 0.0000000 1849 428 1.11e+02 0.2593458 0.0600324 GO:0051172 GO:BP negative regulation of nitrogen compound metabolic process 13586 14317 GO:0006807, GO:0009892, GO:0051171
query_1 TRUE 0.0000000 2135 428 1.22e+02 0.2850467 0.0571429 GO:0010605 GO:BP negative regulation of macromolecule metabolic process 13586 4348 GO:0009892, GO:0043170, GO:0060255
query_1 TRUE 0.0000000 2880 428 1.49e+02 0.3481308 0.0517361 GO:0009893 GO:BP positive regulation of metabolic process 13586 3831 GO:0008152, GO:0019222, GO:0048518
query_1 TRUE 0.0000000 3625 428 1.75e+02 0.4088785 0.0482759 GO:0048523 GO:BP negative regulation of cellular process 13586 13544 GO:0009987, GO:0048519, GO:0050794
query_1 TRUE 0.0000000 4045 428 1.86e+02 0.4345794 0.0459827 GO:0048519 GO:BP negative regulation of biological process 13586 13540 GO:0008150, GO:0050789
query_1 TRUE 0.0000001 551 428 4.60e+01 0.1074766 0.0834846 GO:0006325 GO:BP chromatin organization 13586 2169 GO:0016043
query_1 TRUE 0.0000002 378 428 3.60e+01 0.0841121 0.0952381 GO:0006338 GO:BP chromatin remodeling 13586 2173 GO:0006325
query_1 TRUE 0.0000397 4099 428 1.76e+02 0.4112150 0.0429373 GO:0048522 GO:BP positive regulation of cellular process 13586 13543 GO:0009987, GO:0048518, GO:0050794
query_1 TRUE 0.0001518 433 428 3.30e+01 0.0771028 0.0762125 GO:0016570 GO:BP histone modification 13586 5382 GO:0036211
query_1 TRUE 0.0001867 4579 428 1.89e+02 0.4415888 0.0412754 GO:0048518 GO:BP positive regulation of biological process 13586 13539 GO:0008150, GO:0050789
query_1 TRUE 0.0015558 1835 428 8.80e+01 0.2056075 0.0479564 GO:0050793 GO:BP regulation of developmental process 13586 14007 GO:0032502, GO:0050789
query_1 TRUE 0.0044985 117 428 1.30e+01 0.0303738 0.1111111 GO:0016571 GO:BP histone methylation 13586 5383 GO:0006479, GO:0016570
query_1 TRUE 0.0057725 104 428 1.20e+01 0.0280374 0.1153846 GO:0018022 GO:BP peptidyl-lysine methylation 13586 5461 GO:0006479, GO:0018205
query_1 TRUE 0.0059120 89 428 1.10e+01 0.0257009 0.1235955 GO:0034968 GO:BP histone lysine methylation 13586 9215 GO:0016571, GO:0018022
query_1 TRUE 0.0066377 4 428 3.00e+00 0.0070093 0.7500000 GO:0097676 GO:BP histone H3-K36 dimethylation 13586 19769 GO:0010452, GO:0018027
query_1 TRUE 0.0077228 785 428 4.40e+01 0.1028037 0.0560510 GO:0006974 GO:BP DNA damage response 13586 2659 GO:0033554
query_1 TRUE 0.0088927 336 428 2.40e+01 0.0560748 0.0714286 GO:0018205 GO:BP peptidyl-lysine modification 13586 5568 GO:0018193
query_1 TRUE 0.0097655 18 428 5.00e+00 0.0116822 0.2777778 GO:0006607 GO:BP NLS-bearing protein import into nucleus 13586 2378 GO:0006606
query_1 TRUE 0.0117205 850 428 4.60e+01 0.1074766 0.0541176 GO:0060429 GO:BP epithelium development 13586 15465 GO:0009888
query_1 TRUE 0.0145341 665 428 3.80e+01 0.0887850 0.0571429 GO:0016071 GO:BP mRNA metabolic process 13586 5222 GO:0016070
query_1 TRUE 0.0146171 884 428 4.70e+01 0.1098131 0.0531674 GO:0072359 GO:BP circulatory system development 13586 18343 GO:0048731
query_1 TRUE 0.0149450 5 428 3.00e+00 0.0070093 0.6000000 GO:0010452 GO:BP histone H3-K36 methylation 13586 4237 GO:0034968
query_1 TRUE 0.0154985 227 428 1.80e+01 0.0420561 0.0792952 GO:0030522 GO:BP intracellular receptor signaling pathway 13586 7201 GO:0007165
query_1 TRUE 0.0168245 153 428 1.40e+01 0.0327103 0.0915033 GO:0040029 GO:BP epigenetic regulation of gene expression 13586 10481 GO:0006338, GO:0010468
query_1 TRUE 0.0178521 11336 428 3.82e+02 0.8925234 0.0336980 GO:0009987 GO:BP cellular process 13586 3889 GO:0008150
query_1 TRUE 0.0245270 178 428 1.50e+01 0.0350467 0.0842697 GO:0090596 GO:BP sensory organ morphogenesis 13586 19390 GO:0007423, GO:0009887
query_1 TRUE 0.0245270 1425 428 6.70e+01 0.1565421 0.0470175 GO:0009888 GO:BP tissue development 13586 3826 GO:0048856
query_1 TRUE 0.0251445 160 428 1.40e+01 0.0327103 0.0875000 GO:0006479 GO:BP protein methylation 13586 2267 GO:0008213, GO:0043414
query_1 TRUE 0.0251445 160 428 1.40e+01 0.0327103 0.0875000 GO:0008213 GO:BP protein alkylation 13586 3212 GO:0036211
query_1 TRUE 0.0253959 279 428 2.00e+01 0.0467290 0.0716846 GO:1903706 GO:BP regulation of hemopoiesis 13586 24346 GO:0002682, GO:0030097, GO:0060284, GO:2000026
query_1 TRUE 0.0260534 199 428 1.60e+01 0.0373832 0.0804020 GO:1902105 GO:BP regulation of leukocyte differentiation 13586 23039 GO:0002521, GO:1903706
query_1 TRUE 0.0262717 6 428 3.00e+00 0.0070093 0.5000000 GO:0086023 GO:BP adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process 13586 18890 GO:0071880, GO:0086103
query_1 TRUE 0.0287928 504 428 3.00e+01 0.0700935 0.0595238 GO:0048729 GO:BP tissue morphogenesis 13586 13726 GO:0009653, GO:0009888
query_1 TRUE 0.0304015 506 428 3.00e+01 0.0700935 0.0592885 GO:0007507 GO:BP heart development 13586 3064 GO:0048513, GO:0072359
query_1 TRUE 0.0321858 165 428 1.40e+01 0.0327103 0.0848485 GO:0007623 GO:BP circadian rhythm 13586 3152 GO:0048511
query_1 TRUE 0.0345089 534 428 3.10e+01 0.0724299 0.0580524 GO:0043009 GO:BP chordate embryonic development 13586 11060 GO:0009792
query_1 TRUE 0.0347034 49 428 7.00e+00 0.0163551 0.1428571 GO:1902275 GO:BP regulation of chromatin organization 13586 23191 GO:0006325, GO:0051128
query_1 TRUE 0.0369747 149 428 1.30e+01 0.0303738 0.0872483 GO:0019827 GO:BP stem cell population maintenance 13586 6381 GO:0032501, GO:0098727
query_1 TRUE 0.0408860 7 428 3.00e+00 0.0070093 0.4285714 GO:1900246 GO:BP positive regulation of RIG-I signaling pathway 13586 21445 GO:0039529, GO:0039535, GO:0062208
query_1 TRUE 0.0408860 151 428 1.30e+01 0.0303738 0.0860927 GO:0098727 GO:BP maintenance of cell number 13586 19907 GO:0032502
query_1 TRUE 0.0408860 2 428 2.00e+00 0.0046729 1.0000000 GO:0032242 GO:BP regulation of nucleoside transport 13586 7848 GO:0015858, GO:0032239
query_1 TRUE 0.0408860 2 428 2.00e+00 0.0046729 1.0000000 GO:1901898 GO:BP negative regulation of relaxation of cardiac muscle 13586 22853 GO:0055119, GO:1901078, GO:1901897
query_1 TRUE 0.0411487 15 428 4.00e+00 0.0093458 0.2666667 GO:0032239 GO:BP regulation of nucleobase-containing compound transport 13586 7845 GO:0015931, GO:0051049
query_1 TRUE 0.0449089 38 428 6.00e+00 0.0140187 0.1578947 GO:2001222 GO:BP regulation of neuron migration 13586 27702 GO:0001764, GO:0030334
query_1 TRUE 0.0490935 155 428 1.30e+01 0.0303738 0.0838710 GO:0045165 GO:BP cell fate commitment 13586 11997 GO:0030154, GO:0048869
query_1 TRUE 0.0490935 118 428 1.10e+01 0.0257009 0.0932203 GO:1903708 GO:BP positive regulation of hemopoiesis 13586 24348 GO:0002684, GO:0010720, GO:0030097, GO:0051240, GO:1903706
query_1 TRUE 0.0490935 118 428 1.10e+01 0.0257009 0.0932203 GO:1902107 GO:BP positive regulation of leukocyte differentiation 13586 23041 GO:0002521, GO:1902105, GO:1903708
query_1 TRUE 0.0000000 415 428 4.50e+01 0.1051402 0.1084337 KEGG:05168 KEGG Herpes simplex virus 1 infection 13586 442 KEGG:00000
source term_id term_name intersection_size term_size p_value
GO:BP GO:0097659 nucleic acid-templated transcription 216 2684 4.831e-44
GO:BP GO:0006351 DNA-templated transcription 216 2683 4.831e-44
GO:BP GO:0032774 RNA biosynthetic process 216 2714 2.189e-43
GO:BP GO:0006366 transcription by RNA polymerase II 183 1995 2.249e-43
GO:BP GO:1903506 regulation of nucleic acid-templated transcription 209 2576 4.789e-43
GO:BP GO:0006355 regulation of DNA-templated transcription 209 2574 4.789e-43
GO:BP GO:0006357 regulation of transcription by RNA polymerase II 178 1914 5.740e-43
GO:BP GO:0019219 regulation of nucleobase-containing compound metabolic process 230 3080 5.740e-43
GO:BP GO:2001141 regulation of RNA biosynthetic process 209 2593 9.534e-43
GO:BP GO:0051252 regulation of RNA metabolic process 219 2845 2.793e-42
GO:BP GO:0090304 nucleic acid metabolic process 259 4048 3.333e-38
GO:BP GO:0010556 regulation of macromolecule biosynthetic process 219 3012 3.797e-38
GO:BP GO:0031323 regulation of cellular metabolic process 263 4174 5.752e-38
GO:BP GO:0016070 RNA metabolic process 241 3600 1.603e-37
GO:BP GO:0034654 nucleobase-containing compound biosynthetic process 219 3070 7.321e-37
GO:BP GO:0031326 regulation of cellular biosynthetic process 219 3080 1.177e-36
GO:BP GO:0019438 aromatic compound biosynthetic process 220 3133 4.702e-36
GO:BP GO:0018130 heterocycle biosynthetic process 220 3132 4.702e-36
GO:BP GO:0009889 regulation of biosynthetic process 220 3169 2.937e-35
GO:BP GO:1901362 organic cyclic compound biosynthetic process 221 3237 2.510e-34
GO:BP GO:0051171 regulation of nitrogen compound metabolic process 260 4292 3.891e-34
GO:BP GO:0080090 regulation of primary metabolic process 264 4417 6.045e-34
GO:BP GO:0010468 regulation of gene expression 233 3580 1.125e-33
GO:BP GO:0009059 macromolecule biosynthetic process 236 3730 2.901e-32
GO:BP GO:0006139 nucleobase-containing compound metabolic process 262 4455 3.237e-32
GO:BP GO:0060255 regulation of macromolecule metabolic process 266 4617 2.141e-31
GO:BP GO:0046483 heterocycle metabolic process 263 4570 1.083e-30
GO:BP GO:0006725 cellular aromatic compound metabolic process 263 4596 3.013e-30
GO:BP GO:0044271 cellular nitrogen compound biosynthetic process 231 3750 2.354e-29
GO:BP GO:1901360 organic cyclic compound metabolic process 265 4747 1.106e-28
GO:BP GO:0019222 regulation of metabolic process 273 5017 3.556e-28
GO:BP GO:0010467 gene expression 258 4587 6.001e-28
GO:BP GO:0044249 cellular biosynthetic process 245 4245 1.931e-27
GO:BP GO:0034641 cellular nitrogen compound metabolic process 267 4946 1.932e-26
GO:BP GO:1901576 organic substance biosynthetic process 249 4539 1.734e-24
GO:BP GO:0009058 biosynthetic process 249 4590 1.070e-23
GO:BP GO:0043170 macromolecule metabolic process 322 7069 1.384e-21
GO:BP GO:0044237 cellular metabolic process 314 6996 5.668e-19
GO:BP GO:0050794 regulation of cellular process 329 7552 1.274e-18
GO:BP GO:1903508 positive regulation of nucleic acid-templated transcription 105 1315 7.760e-18
GO:BP GO:0045893 positive regulation of DNA-templated transcription 105 1315 7.760e-18
GO:BP GO:0051254 positive regulation of RNA metabolic process 111 1441 7.808e-18
GO:BP GO:1902680 positive regulation of RNA biosynthetic process 105 1322 1.100e-17
GO:BP GO:0045935 positive regulation of nucleobase-containing compound metabolic process 116 1602 1.150e-16
GO:BP GO:0006807 nitrogen compound metabolic process 321 7441 1.263e-16
GO:BP GO:0045892 negative regulation of DNA-templated transcription 86 1015 9.336e-16
GO:BP GO:0044238 primary metabolic process 329 7806 1.011e-15
GO:BP GO:1903507 negative regulation of nucleic acid-templated transcription 86 1017 1.011e-15
GO:BP GO:1902679 negative regulation of RNA biosynthetic process 86 1026 1.712e-15
GO:BP GO:0010557 positive regulation of macromolecule biosynthetic process 109 1507 1.770e-15
GO:BP GO:0050789 regulation of biological process 335 8061 2.536e-15
GO:BP GO:0051253 negative regulation of RNA metabolic process 90 1119 3.409e-15
GO:BP GO:0045934 negative regulation of nucleobase-containing compound metabolic process 94 1209 5.154e-15
GO:BP GO:0065007 biological regulation 340 8320 1.640e-14
GO:BP GO:0031328 positive regulation of cellular biosynthetic process 109 1564 2.373e-14
GO:BP GO:0045944 positive regulation of transcription by RNA polymerase II 79 937 2.887e-14
GO:BP GO:0031324 negative regulation of cellular metabolic process 116 1735 4.001e-14
GO:BP GO:0071704 organic substance metabolic process 334 8169 8.304e-14
GO:BP GO:0009891 positive regulation of biosynthetic process 109 1604 1.326e-13
GO:BP GO:0010558 negative regulation of macromolecule biosynthetic process 91 1214 1.594e-13
GO:BP GO:0031327 negative regulation of cellular biosynthetic process 91 1239 5.461e-13
GO:BP GO:0051173 positive regulation of nitrogen compound metabolic process 140 2412 1.626e-12
GO:BP GO:0000122 negative regulation of transcription by RNA polymerase II 65 740 2.417e-12
GO:BP GO:0009890 negative regulation of biosynthetic process 91 1280 3.689e-12
GO:BP GO:0010604 positive regulation of macromolecule metabolic process 147 2646 9.659e-12
GO:BP GO:0031325 positive regulation of cellular metabolic process 131 2270 2.536e-11
GO:BP GO:0008152 metabolic process 336 8518 4.520e-11
GO:BP GO:0009892 negative regulation of metabolic process 129 2293 2.638e-10
GO:BP GO:0051172 negative regulation of nitrogen compound metabolic process 111 1849 2.688e-10
GO:BP GO:0010605 negative regulation of macromolecule metabolic process 122 2135 4.514e-10
GO:BP GO:0009893 positive regulation of metabolic process 149 2880 1.795e-09
GO:BP GO:0048523 negative regulation of cellular process 175 3625 4.157e-09
GO:BP GO:0048519 negative regulation of biological process 186 4045 4.792e-08
GO:BP GO:0006325 chromatin organization 46 551 8.684e-08
GO:BP GO:0006338 chromatin remodeling 36 378 1.915e-07
GO:BP GO:0048522 positive regulation of cellular process 176 4099 3.968e-05
GO:BP GO:0016570 histone modification 33 433 1.518e-04
GO:BP GO:0048518 positive regulation of biological process 189 4579 1.867e-04
GO:BP GO:0050793 regulation of developmental process 88 1835 1.556e-03
GO:BP GO:0016571 histone methylation 13 117 4.499e-03
GO:BP GO:0018022 peptidyl-lysine methylation 12 104 5.773e-03
GO:BP GO:0034968 histone lysine methylation 11 89 5.912e-03
GO:BP GO:0097676 histone H3-K36 dimethylation 3 4 6.638e-03
GO:BP GO:0006974 DNA damage response 44 785 7.723e-03
GO:BP GO:0018205 peptidyl-lysine modification 24 336 8.893e-03
GO:BP GO:0006607 NLS-bearing protein import into nucleus 5 18 9.766e-03
GO:BP GO:0060429 epithelium development 46 850 1.172e-02
GO:BP GO:0016071 mRNA metabolic process 38 665 1.453e-02
GO:BP GO:0072359 circulatory system development 47 884 1.462e-02
GO:BP GO:0010452 histone H3-K36 methylation 3 5 1.495e-02
GO:BP GO:0030522 intracellular receptor signaling pathway 18 227 1.550e-02
GO:BP GO:0040029 epigenetic regulation of gene expression 14 153 1.682e-02
GO:BP GO:0009987 cellular process 382 11336 1.785e-02
GO:BP GO:0090596 sensory organ morphogenesis 15 178 2.453e-02
GO:BP GO:0009888 tissue development 67 1425 2.453e-02
GO:BP GO:0006479 protein methylation 14 160 2.514e-02
GO:BP GO:0008213 protein alkylation 14 160 2.514e-02
GO:BP GO:1903706 regulation of hemopoiesis 20 279 2.540e-02
GO:BP GO:1902105 regulation of leukocyte differentiation 16 199 2.605e-02
GO:BP GO:0086023 adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process 3 6 2.627e-02
GO:BP GO:0048729 tissue morphogenesis 30 504 2.879e-02
GO:BP GO:0007507 heart development 30 506 3.040e-02
GO:BP GO:0007623 circadian rhythm 14 165 3.219e-02
GO:BP GO:0043009 chordate embryonic development 31 534 3.451e-02
GO:BP GO:1902275 regulation of chromatin organization 7 49 3.470e-02
GO:BP GO:0019827 stem cell population maintenance 13 149 3.697e-02
GO:BP GO:1900246 positive regulation of RIG-I signaling pathway 3 7 4.089e-02
GO:BP GO:0098727 maintenance of cell number 13 151 4.089e-02
GO:BP GO:0032242 regulation of nucleoside transport 2 2 4.089e-02
GO:BP GO:1901898 negative regulation of relaxation of cardiac muscle 2 2 4.089e-02
GO:BP GO:0032239 regulation of nucleobase-containing compound transport 4 15 4.115e-02
GO:BP GO:2001222 regulation of neuron migration 6 38 4.491e-02
GO:BP GO:0045165 cell fate commitment 13 155 4.909e-02
GO:BP GO:1903708 positive regulation of hemopoiesis 11 118 4.909e-02
GO:BP GO:1902107 positive regulation of leukocyte differentiation 11 118 4.909e-02
KEGG KEGG:05168 Herpes simplex virus 1 infection 45 415 6.666e-11

Time-independent Top2inhibitor motif genes

GO:BP/KEGG

source term_id term_name intersection_size term_size p_value
GO:BP GO:0006357 regulation of transcription by RNA polymerase II 179 1914 1.167e-29
GO:BP GO:0006366 transcription by RNA polymerase II 181 1995 1.181e-28
GO:BP GO:0006355 regulation of DNA-templated transcription 204 2574 2.150e-25
GO:BP GO:1903506 regulation of nucleic acid-templated transcription 204 2576 2.150e-25
GO:BP GO:0051252 regulation of RNA metabolic process 217 2845 2.150e-25
GO:BP GO:2001141 regulation of RNA biosynthetic process 204 2593 3.638e-25
GO:BP GO:0097659 nucleic acid-templated transcription 206 2684 3.793e-24
GO:BP GO:0006351 DNA-templated transcription 206 2683 3.793e-24
GO:BP GO:0032774 RNA biosynthetic process 206 2714 1.542e-23
GO:BP GO:0019219 regulation of nucleobase-containing compound metabolic process 222 3080 6.127e-23
GO:BP GO:0010556 regulation of macromolecule biosynthetic process 213 3012 1.591e-20
GO:BP GO:0090304 nucleic acid metabolic process 258 4048 5.317e-20
GO:BP GO:0031326 regulation of cellular biosynthetic process 214 3080 1.030e-19
GO:BP GO:0009889 regulation of biosynthetic process 218 3169 1.059e-19
GO:BP GO:0034654 nucleobase-containing compound biosynthetic process 213 3070 1.467e-19
GO:BP GO:0019438 aromatic compound biosynthetic process 215 3133 2.990e-19
GO:BP GO:0018130 heterocycle biosynthetic process 215 3132 2.990e-19
GO:BP GO:0016070 RNA metabolic process 236 3600 3.111e-19
GO:BP GO:0010468 regulation of gene expression 235 3580 3.256e-19
GO:BP GO:1901362 organic cyclic compound biosynthetic process 217 3237 3.041e-18
GO:BP GO:0051171 regulation of nitrogen compound metabolic process 260 4292 4.120e-17
GO:BP GO:0080090 regulation of primary metabolic process 264 4417 1.085e-16
GO:BP GO:0060255 regulation of macromolecule metabolic process 272 4617 1.317e-16
GO:BP GO:0031323 regulation of cellular metabolic process 253 4174 1.876e-16
GO:BP GO:0006139 nucleobase-containing compound metabolic process 262 4455 1.666e-15
GO:BP GO:0046483 heterocycle metabolic process 265 4570 6.283e-15
GO:BP GO:0006725 cellular aromatic compound metabolic process 265 4596 1.371e-14
GO:BP GO:0019222 regulation of metabolic process 282 5017 1.456e-14
GO:BP GO:1901360 organic cyclic compound metabolic process 268 4747 1.373e-13
GO:BP GO:0009059 macromolecule biosynthetic process 224 3730 3.408e-13
GO:BP GO:0051253 negative regulation of RNA metabolic process 98 1119 3.408e-13
GO:BP GO:0044271 cellular nitrogen compound biosynthetic process 224 3750 6.248e-13
GO:BP GO:0000122 negative regulation of transcription by RNA polymerase II 74 740 1.914e-12
GO:BP GO:0045892 negative regulation of DNA-templated transcription 90 1015 2.605e-12
GO:BP GO:1903507 negative regulation of nucleic acid-templated transcription 90 1017 2.846e-12
GO:BP GO:1902679 negative regulation of RNA biosynthetic process 90 1026 4.674e-12
GO:BP GO:0010467 gene expression 256 4587 5.204e-12
GO:BP GO:0045934 negative regulation of nucleobase-containing compound metabolic process 100 1209 5.404e-12
GO:BP GO:0034641 cellular nitrogen compound metabolic process 270 4946 7.415e-12
GO:BP GO:0045944 positive regulation of transcription by RNA polymerase II 80 937 5.876e-10
GO:BP GO:0031327 negative regulation of cellular biosynthetic process 96 1239 8.602e-10
GO:BP GO:0044249 cellular biosynthetic process 234 4245 8.602e-10
GO:BP GO:0010558 negative regulation of macromolecule biosynthetic process 94 1214 1.521e-09
GO:BP GO:0009890 negative regulation of biosynthetic process 97 1280 2.241e-09
GO:BP GO:0043170 macromolecule metabolic process 341 7069 5.242e-09
GO:BP GO:0050789 regulation of biological process 375 8061 1.411e-08
GO:BP GO:1901576 organic substance biosynthetic process 241 4539 1.699e-08
GO:BP GO:0009058 biosynthetic process 243 4590 1.743e-08
GO:BP GO:1903508 positive regulation of nucleic acid-templated transcription 96 1315 2.052e-08
GO:BP GO:0045893 positive regulation of DNA-templated transcription 96 1315 2.052e-08
GO:BP GO:1902680 positive regulation of RNA biosynthetic process 96 1322 2.687e-08
GO:BP GO:0050794 regulation of cellular process 354 7552 6.948e-08
GO:BP GO:0031324 negative regulation of cellular metabolic process 115 1735 8.154e-08
GO:BP GO:0051254 positive regulation of RNA metabolic process 100 1441 1.216e-07
GO:BP GO:0065007 biological regulation 379 8320 2.560e-07
GO:BP GO:0010557 positive regulation of macromolecule biosynthetic process 101 1507 6.184e-07
GO:BP GO:0051173 positive regulation of nitrogen compound metabolic process 143 2412 8.103e-07
GO:BP GO:0031328 positive regulation of cellular biosynthetic process 103 1564 1.034e-06
GO:BP GO:0051172 negative regulation of nitrogen compound metabolic process 116 1849 1.530e-06
GO:BP GO:0045935 positive regulation of nucleobase-containing compound metabolic process 104 1602 1.778e-06
GO:BP GO:0010604 positive regulation of macromolecule metabolic process 152 2646 1.826e-06
GO:BP GO:0009891 positive regulation of biosynthetic process 104 1604 1.837e-06
GO:BP GO:0010605 negative regulation of macromolecule metabolic process 128 2135 3.184e-06
GO:BP GO:0009893 positive regulation of metabolic process 160 2880 6.139e-06
GO:BP GO:0009892 negative regulation of metabolic process 134 2293 6.139e-06
GO:BP GO:0031325 positive regulation of cellular metabolic process 133 2270 6.139e-06
GO:BP GO:0006807 nitrogen compound metabolic process 340 7441 1.121e-05
GO:BP GO:0044238 primary metabolic process 350 7806 5.451e-05
GO:BP GO:0071704 organic substance metabolic process 362 8169 8.965e-05
GO:BP GO:0044237 cellular metabolic process 319 6996 8.965e-05
GO:BP GO:0003007 heart morphogenesis 24 216 1.824e-04
GO:BP GO:0009952 anterior/posterior pattern specification 17 127 4.487e-04
GO:BP GO:0045595 regulation of cell differentiation 72 1137 7.662e-04
GO:BP GO:0048523 negative regulation of cellular process 181 3625 9.101e-04
GO:BP GO:0048645 animal organ formation 10 51 1.259e-03
GO:BP GO:0045596 negative regulation of cell differentiation 37 482 2.670e-03
GO:BP GO:0140467 integrated stress response signaling 8 35 2.670e-03
GO:BP GO:0060411 cardiac septum morphogenesis 11 67 2.686e-03
GO:BP GO:0007389 pattern specification process 27 306 2.869e-03
GO:BP GO:0008152 metabolic process 366 8518 3.170e-03
GO:BP GO:0045597 positive regulation of cell differentiation 44 620 3.172e-03
GO:BP GO:0060537 muscle tissue development 29 343 3.172e-03
GO:BP GO:0014706 striated muscle tissue development 21 210 3.236e-03
GO:BP GO:0048738 cardiac muscle tissue development 20 198 4.167e-03
GO:BP GO:0060914 heart formation 7 29 5.075e-03
GO:BP GO:0048518 positive regulation of biological process 214 4579 7.246e-03
GO:BP GO:0003002 regionalization 24 273 7.258e-03
GO:BP GO:2000026 regulation of multicellular organismal development 62 1014 7.566e-03
GO:BP GO:0035914 skeletal muscle cell differentiation 9 52 7.737e-03
GO:BP GO:0051094 positive regulation of developmental process 59 957 8.730e-03
GO:BP GO:0048519 negative regulation of biological process 191 4045 1.183e-02
GO:BP GO:0035880 embryonic nail plate morphogenesis 3 4 1.183e-02
GO:BP GO:0021546 rhombomere development 3 4 1.183e-02
GO:BP GO:0003151 outflow tract morphogenesis 10 68 1.281e-02
GO:BP GO:0051093 negative regulation of developmental process 44 665 1.334e-02
GO:BP GO:0007049 cell cycle 84 1529 1.667e-02
GO:BP GO:0043009 chordate embryonic development 37 534 1.700e-02
GO:BP GO:0051239 regulation of multicellular organismal process 106 2035 1.822e-02
GO:BP GO:0050793 regulation of developmental process 97 1835 2.051e-02
GO:BP GO:0001756 somitogenesis 8 48 2.121e-02
GO:BP GO:0030336 negative regulation of cell migration 20 227 2.191e-02
GO:BP GO:0048522 positive regulation of cellular process 191 4099 2.296e-02
GO:BP GO:0051726 regulation of cell cycle 57 956 2.316e-02
GO:BP GO:0060284 regulation of cell development 40 605 2.365e-02
GO:BP GO:0051241 negative regulation of multicellular organismal process 47 748 2.370e-02
GO:BP GO:0045598 regulation of fat cell differentiation 12 102 2.370e-02
GO:BP GO:0035282 segmentation 10 75 2.530e-02
GO:BP GO:0048483 autonomic nervous system development 6 28 2.601e-02
GO:BP GO:0009792 embryo development ending in birth or egg hatching 37 551 2.744e-02
GO:BP GO:0002294 CD4-positive, alpha-beta T cell differentiation involved in immune response 7 40 3.146e-02
GO:BP GO:0060412 ventricular septum morphogenesis 7 40 3.146e-02
GO:BP GO:0002293 alpha-beta T cell differentiation involved in immune response 7 40 3.146e-02
GO:BP GO:0002287 alpha-beta T cell activation involved in immune response 7 40 3.146e-02
GO:BP GO:0042093 T-helper cell differentiation 7 40 3.146e-02
GO:BP GO:2000146 negative regulation of cell motility 20 236 3.158e-02
GO:BP GO:0055017 cardiac muscle tissue growth 9 65 3.329e-02
GO:BP GO:0045444 fat cell differentiation 17 187 3.493e-02
GO:BP GO:0048486 parasympathetic nervous system development 4 12 3.493e-02
GO:BP GO:0060429 epithelium development 51 850 3.493e-02
GO:BP GO:0048729 tissue morphogenesis 34 504 3.788e-02
GO:BP GO:0003206 cardiac chamber morphogenesis 12 109 3.788e-02
GO:BP GO:0007517 muscle organ development 22 277 3.929e-02
GO:BP GO:0002292 T cell differentiation involved in immune response 7 42 3.951e-02
GO:BP GO:0007507 heart development 34 506 3.952e-02
GO:BP GO:0060562 epithelial tube morphogenesis 22 278 4.020e-02
GO:BP GO:0048568 embryonic organ development 24 316 4.247e-02
GO:BP GO:1900744 regulation of p38MAPK cascade 6 32 4.660e-02
GO:BP GO:0060840 artery development 10 83 4.660e-02
GO:BP GO:0042127 regulation of cell population proliferation 64 1147 4.660e-02
GO:BP GO:0003281 ventricular septum development 9 69 4.660e-02
GO:BP GO:1902893 regulation of miRNA transcription 8 56 4.670e-02
GO:BP GO:0040013 negative regulation of locomotion 21 265 4.839e-02
GO:BP GO:0060038 cardiac muscle cell proliferation 7 44 4.861e-02
GO:BP GO:0010628 positive regulation of gene expression 47 783 4.922e-02
GO:BP GO:0030278 regulation of ossification 10 84 4.925e-02
GO:BP GO:0014855 striated muscle cell proliferation 8 57 4.953e-02
GO:BP GO:0045667 regulation of osteoblast differentiation 11 99 4.953e-02
GO:BP GO:0061614 miRNA transcription 8 57 4.953e-02
GO:BP GO:0040007 growth 45 742 4.953e-02
KEGG KEGG:05168 Herpes simplex virus 1 infection 47 415 3.765e-09
KEGG KEGG:04115 p53 signaling pathway 11 65 3.175e-03
KEGG KEGG:05217 Basal cell carcinoma 9 49 5.764e-03
KEGG KEGG:05224 Breast cancer 14 117 5.917e-03
KEGG KEGG:05225 Hepatocellular carcinoma 16 145 5.917e-03
KEGG KEGG:05226 Gastric cancer 13 117 1.757e-02
KEGG KEGG:05202 Transcriptional misregulation in cancer 13 128 3.526e-02

long GO:BP frame

long go KEGG frame

Example of genes from each cluster

Motif_NR

<environment: R_GlobalEnv>
[1] 72

Log-Fold Change of Motif_NR

lfc_nums <- readRDS("data/toplistall.RDS")
lfc_nums %>% 
  dplyr::filter(ENTREZID %in% motif_NR) %>% 
  mutate(absFC=abs(logFC)) %>% 
  mutate(id = as.factor(id)) %>%
  mutate(time=factor(time, levels=c("3_hours","24_hours"))) %>%
  ggplot(., aes(x=id,y=absFC))+
  geom_boxplot(aes(fill=id))+
  scale_fill_manual(values=drug_pal_fact)+
  guides(fill=guide_legend(title = "Treatment"))+
  facet_wrap(~time)+
  theme_bw()+
  xlab(" ")+
  ylab("|Log Fold Change|")+
  theme_bw()+
  ggtitle("|Log Fold| for all genes in NR set")+
  theme(plot.title = element_text(size = rel(1.5), hjust = 0.5),
        axis.title = element_text(size = 15, color = "black"),
        axis.line = element_line(linewidth = 1.5),
        strip.background = element_rect(fill = "#C77CFF"),
        axis.text.x = element_text(size = 8, color = "white", angle = 15),
        strip.text.x = element_text(size = 12, color = "black", face = "bold"))

Motif_TI

Log-Fold Change of TI response

lfc_nums %>% 
  dplyr::filter(ENTREZID %in% motif_TI) %>% 
  mutate(absFC=abs(logFC)) %>% 
  mutate(id = as.factor(id)) %>%
  mutate(time=factor(time, levels=c("3_hours","24_hours"))) %>%
  ggplot(., aes(x=id,y=absFC))+
  geom_boxplot(aes(fill=id))+
  scale_fill_manual(values=drug_pal_fact)+
  guides(fill=guide_legend(title = "Treatment"))+
  facet_wrap(~time)+
  theme_bw()+
  xlab("")+
  ylab("|Log Fold Change|")+
  theme_bw()+
  ggtitle("|Log Fold| for genes in TI response set")+
  theme(plot.title = element_text(size = rel(1.5), hjust = 0.5),
        axis.title = element_text(size = 15, color = "black"),
        axis.line = element_line(linewidth = 1.5),
        strip.background = element_rect(fill = "#00BFC4"),
        axis.text = element_text(size = 8, color = "white", angle = 10),    
        strip.text.x = element_text(size = 12, color = "black", face = "bold"))

Motif_LR

Log-Fold Change of Late Response

lfc_nums %>% 
  dplyr::filter(ENTREZID %in% motif_LR) %>% 
  mutate(absFC=abs(logFC)) %>% 
  mutate(id = as.factor(id)) %>%
  mutate(time=factor(time, levels=c("3_hours","24_hours"))) %>%
  ggplot(., aes(x=id,y=absFC))+
  geom_boxplot(aes(fill=id))+
  scale_fill_manual(values=drug_pal_fact)+
  guides(fill=guide_legend(title = "Treatment"))+
  facet_wrap(~time)+
  theme_bw()+
  xlab("")+
  ylab("|Log Fold Change|")+
  theme_bw()+
  ggtitle("|Log Fold| for genes in LR set")+
  theme(plot.title = element_text(size = rel(1.5), hjust = 0.5),
        axis.title = element_text(size = 15, color = "black"),
        axis.line = element_line(linewidth = 1.5),
        strip.background = element_rect(fill = "#7CAE00"),
        axis.text = element_text(size = 8, color = "white", angle = 10),     
        strip.text.x = element_text(size = 12, color = "black", face = "bold"))

Motif_ER

Log-Fold Change of Early Response

lfc_nums %>% 
  dplyr::filter(ENTREZID %in% motif_ER) %>% 
  mutate(absFC=abs(logFC)) %>% 
  mutate(id = as.factor(id)) %>%
  mutate(time=factor(time, levels=c("3_hours","24_hours"))) %>%
  ggplot(., aes(x=id,y=absFC))+
  geom_boxplot(aes(fill=id))+
  scale_fill_manual(values=drug_pal_fact)+
  guides(fill=guide_legend(title = "Treatment"))+
  facet_wrap(~time)+
  theme_bw()+
  xlab("")+
  ylab("|Log Fold Change|")+
  theme_bw()+
  ggtitle("|Log Fold| for genes in ER set")+
  theme(plot.title = element_text(size = rel(1.5), hjust = 0.5),
        axis.title = element_text(size = 15, color = "black"),
        axis.line = element_line(linewidth = 1.5),
        strip.background = element_rect(fill = "#F8766D"),
        axis.text = element_text(size = 8, color = "white", angle = 10),   
        strip.text.x = element_text(size = 12, color = "black", face = "bold"))


sessionInfo()
R version 4.2.2 (2022-10-31 ucrt)
Platform: x86_64-w64-mingw32/x64 (64-bit)
Running under: Windows 10 x64 (build 19045)

Matrix products: default

locale:
[1] LC_COLLATE=English_United States.utf8 
[2] LC_CTYPE=English_United States.utf8   
[3] LC_MONETARY=English_United States.utf8
[4] LC_NUMERIC=C                          
[5] LC_TIME=English_United States.utf8    

attached base packages:
[1] grid      stats     graphics  grDevices utils     datasets  methods  
[8] base     

other attached packages:
 [1] biomaRt_2.52.0      ggpubr_0.6.0        RColorBrewer_1.1-3 
 [4] Cormotif_1.42.0     limma_3.52.4        affy_1.74.0        
 [7] Biobase_2.56.0      ggVennDiagram_1.2.2 scales_1.2.1       
[10] kableExtra_1.3.4    VennDiagram_1.7.3   futile.logger_1.4.3
[13] gridExtra_2.3       BiocGenerics_0.42.0 gprofiler2_0.2.2   
[16] lubridate_1.9.2     forcats_1.0.0       stringr_1.5.0      
[19] dplyr_1.1.2         purrr_1.0.1         readr_2.1.4        
[22] tidyr_1.3.0         tibble_3.2.1        ggplot2_3.4.2      
[25] tidyverse_2.0.0     workflowr_1.7.0    

loaded via a namespace (and not attached):
  [1] colorspace_2.1-0       ggsignif_0.6.4         ellipsis_0.3.2        
  [4] rprojroot_2.0.3        XVector_0.36.0         fs_1.6.2              
  [7] rstudioapi_0.14        farver_2.1.1           affyio_1.66.0         
 [10] bit64_4.0.5            AnnotationDbi_1.58.0   fansi_1.0.4           
 [13] xml2_1.3.4             cachem_1.0.8           knitr_1.43            
 [16] jsonlite_1.8.5         broom_1.0.5            dbplyr_2.3.2          
 [19] png_0.1-8              shiny_1.7.4            BiocManager_1.30.21   
 [22] compiler_4.2.2         httr_1.4.6             backports_1.4.1       
 [25] fastmap_1.1.1          lazyeval_0.2.2         cli_3.6.1             
 [28] later_1.3.1            formatR_1.14           prettyunits_1.1.1     
 [31] htmltools_0.5.5        tools_4.2.2            GenomeInfoDbData_1.2.8
 [34] gtable_0.3.3           glue_1.6.2             rappdirs_0.3.3        
 [37] Rcpp_1.0.10            carData_3.0-5          jquerylib_0.1.4       
 [40] Biostrings_2.64.1      vctrs_0.6.3            svglite_2.1.1         
 [43] preprocessCore_1.58.0  crosstalk_1.2.0        xfun_0.39             
 [46] ps_1.7.5               rvest_1.0.3            timechange_0.2.0      
 [49] mime_0.12              lifecycle_1.0.3        rstatix_0.7.2         
 [52] XML_3.99-0.14          getPass_0.2-2          zlibbioc_1.42.0       
 [55] hms_1.1.3              promises_1.2.0.1       lambda.r_1.2.4        
 [58] curl_5.0.1             yaml_2.3.7             memoise_2.0.1         
 [61] sass_0.4.6             stringi_1.7.12         RSQLite_2.3.1         
 [64] highr_0.10             S4Vectors_0.34.0       filelock_1.0.2        
 [67] GenomeInfoDb_1.32.4    bitops_1.0-7           rlang_1.1.1           
 [70] pkgconfig_2.0.3        systemfonts_1.0.4      evaluate_0.21         
 [73] htmlwidgets_1.6.2      labeling_0.4.2         bit_4.0.5             
 [76] processx_3.8.1         tidyselect_1.2.0       magrittr_2.0.3        
 [79] R6_2.5.1               IRanges_2.30.1         generics_0.1.3        
 [82] DBI_1.1.3              pillar_1.9.0           whisker_0.4.1         
 [85] withr_2.5.0            RCurl_1.98-1.12        KEGGREST_1.36.3       
 [88] abind_1.4-5            crayon_1.5.2           car_3.1-2             
 [91] futile.options_1.0.1   utf8_1.2.3             BiocFileCache_2.4.0   
 [94] plotly_4.10.2          RVenn_1.1.0            tzdb_0.4.0            
 [97] rmarkdown_2.22         progress_1.2.2         data.table_1.14.8     
[100] blob_1.2.4             callr_3.7.3            git2r_0.32.0          
[103] digest_0.6.31          webshot_0.5.4          xtable_1.8-4          
[106] httpuv_1.6.11          stats4_4.2.2           munsell_0.5.0         
[109] viridisLite_0.4.2      bslib_0.5.0