1 Procedure

AME (Analysis of Motif Enrichment; tool in MEME Suite) is used to do motif enrichment analysis. For a given motif set and a set of sequences, test whether a motif occurs significantly in the sequences.

Some windows were extracted and fed to AME to perform motif enrichment analysis (search in JASPAR 2016 vertebrates). Here top 0.1% windows that decrease the score most in positive sequences and top 0.1% windows that increase the score most in negative sequences and randomly selected windows in positive sequences were analyzed respectively.

Results of randomly selected windows can be found:

2 GO term analysis of hitted TF

Here JASPAR TFs is selected as the background protein list.

2.1 Overview

library(pander)
pandoc.table(tf.counts)
number.of.TFs dataset.name
45 e081_merged
49 e081_random_bed_0
31 e081_random_bed_1
35 e081_random_bed_2 
panderOptions('knitr.auto.asis', FALSE)
panderOptions('table.split.table', Inf)
for (i in names(go.results)){
  cat('\n')
  cat("## ", i, "\n")
  pander(go.results[[i]][['allRes']])
  cat('## Top GO term \n')
  for(j in 1 : 3){
    goid <- go.results[[i]][['allRes']][j, 1]
    cat('### Top ', i, ' GO:', goid, '\n')
    cat('Biological process: ', go.results[[i]][['allRes']][j, 2], '\n')
    tfid <- go.results[[i]][['allGO']][[goid]]
    tfid.in <- tfid[tfid %in% gene.lists[[i]]$V7]
    gene.list.sub <- gene.lists[[i]][match(tfid.in, gene.lists[[i]]$V7), c('V6', 'V7')]
    colnames(gene.list.sub) <- c('Motif.ID', 'TF.Name')
    pander(gene.list.sub)
    cat('\n')
  }
  cat('\n')
}

2.2 e081_merged

GO.ID Term Annotated Significant Expected classicFisher
GO:0045666 positive regulation of neuron differenti… 17 5 1.45 0.0097
GO:0006260 DNA replication 8 3 0.68 0.0234
GO:0030182 neuron differentiation 102 14 8.68 0.0265
GO:0045664 regulation of neuron differentiation 37 7 3.15 0.0270
GO:0019058 viral life cycle 9 3 0.77 0.0331
GO:0048708 astrocyte differentiation 9 3 0.77 0.0331
GO:0048519 negative regulation of biological proces… 219 24 18.63 0.0349
GO:0010720 positive regulation of cell development 31 6 2.64 0.0370
GO:0010470 regulation of gastrulation 4 2 0.34 0.0378
GO:0035855 megakaryocyte development 4 2 0.34 0.0378
GO:0060284 regulation of cell development 58 9 4.93 0.0411
GO:0006259 DNA metabolic process 24 5 2.04 0.0427
GO:0050769 positive regulation of neurogenesis 26 5 2.21 0.0583
GO:0051962 positive regulation of nervous system de… 26 5 2.21 0.0583
GO:0048699 generation of neurons 112 14 9.53 0.0584
GO:0006333 chromatin assembly or disassembly 5 2 0.43 0.0597
GO:0032924 activin receptor signaling pathway 5 2 0.43 0.0597
GO:0038092 nodal signaling pathway 5 2 0.43 0.0597
GO:0051302 regulation of cell division 5 2 0.43 0.0597
GO:0098751 bone cell development 5 2 0.43 0.0597
GO:0048523 negative regulation of cellular process 215 23 18.29 0.0599
GO:0009890 negative regulation of biosynthetic proc… 171 19 14.54 0.0740
GO:0010558 negative regulation of macromolecule bio… 171 19 14.54 0.0740
GO:0031327 negative regulation of cellular biosynth… 171 19 14.54 0.0740
GO:0045934 negative regulation of nucleobase-contai… 171 19 14.54 0.0740
GO:0051172 negative regulation of nitrogen compound… 171 19 14.54 0.0740
GO:0051253 negative regulation of RNA metabolic pro… 171 19 14.54 0.0740
GO:1902679 negative regulation of RNA biosynthetic … 171 19 14.54 0.0740
GO:1903507 negative regulation of nucleic acid-temp… 171 19 14.54 0.0740
GO:0022008 neurogenesis 116 14 9.87 0.0769
GO:0031324 negative regulation of cellular metaboli… 172 19 14.63 0.0785
GO:0007369 gastrulation 20 4 1.7 0.0792
GO:0061515 myeloid cell development 6 2 0.51 0.0848
GO:0000819 sister chromatid segregation 1 1 0.09 0.0851
GO:0001672 regulation of chromatin assembly or disa… 1 1 0.09 0.0851
GO:0001705 ectoderm formation 1 1 0.09 0.0851
GO:0001712 ectodermal cell fate commitment 1 1 0.09 0.0851
GO:0006349 regulation of gene expression by genetic… 1 1 0.09 0.0851
GO:0007059 chromosome segregation 1 1 0.09 0.0851
GO:0007062 sister chromatid cohesion 1 1 0.09 0.0851
GO:0007063 regulation of sister chromatid cohesion 1 1 0.09 0.0851
GO:0010216 maintenance of DNA methylation 1 1 0.09 0.0851
GO:0010623 programmed cell death involved in cell d… 1 1 0.09 0.0851
GO:0010668 ectodermal cell differentiation 1 1 0.09 0.0851
GO:0014707 branchiomeric skeletal muscle developmen… 1 1 0.09 0.0851
GO:0016584 nucleosome positioning 1 1 0.09 0.0851
GO:0030193 regulation of blood coagulation 1 1 0.09 0.0851
GO:0030194 positive regulation of blood coagulation 1 1 0.09 0.0851
GO:0030195 negative regulation of blood coagulation 1 1 0.09 0.0851
GO:0033044 regulation of chromosome organization 1 1 0.09 0.0851

2.3 Top GO term

2.3.1 Top e081_merged GO: GO:0045666

Biological process: positive regulation of neuron differenti…

  Motif.ID TF.Name
12 MA0669.1 NEUROG2
21 MA0522.2 TCF3
20 MA0830.1 TCF4
28 MA0796.1 TGIF1
24 MA0797.1 TGIF2

2.3.2 Top e081_merged GO: GO:0006260

Biological process: DNA replication

  Motif.ID TF.Name
6 MA0670.1 NFIA
10 MA0161.1 NFIC
7 MA0671.1 NFIX

2.3.3 Top e081_merged GO: GO:0030182

Biological process: neuron differentiation

  Motif.ID TF.Name
39 MA0817.1 BHLHE23
37 MA0156.2 FEV
36 MA0824.1 ID4
29 MA0498.2 MEIS1
12 MA0669.1 NEUROG2
7 MA0671.1 NFIX
14 MA0826.1 OLIG1
8 MA0827.1 OLIG3
21 MA0522.2 TCF3
20 MA0830.1 TCF4
28 MA0796.1 TGIF1
24 MA0797.1 TGIF2
40 MA0698.1 ZBTB18

2.4 e081_random_bed_0

GO.ID Term Annotated Significant Expected classicFisher
GO:0019722 calcium-mediated signaling 5 5 0.49 7.0e-06
GO:0033173 calcineurin-NFAT signaling cascade 4 4 0.39 7.9e-05
GO:0048016 inositol phosphate-mediated signaling 4 4 0.39 7.9e-05
GO:0097720 calcineurin-mediated signaling 4 4 0.39 7.9e-05
GO:0019932 second-messenger-mediated signaling 7 5 0.69 0.00013
GO:1901342 regulation of vasculature development 11 5 1.08 0.00208
GO:0016525 negative regulation of angiogenesis 4 3 0.39 0.00325
GO:2000181 negative regulation of blood vessel morp… 4 3 0.39 0.00325
GO:0045765 regulation of angiogenesis 8 4 0.78 0.00414
GO:0000278 mitotic cell cycle 24 7 2.35 0.00495
GO:0001974 blood vessel remodeling 5 3 0.49 0.00758
GO:1901343 negative regulation of vasculature devel… 5 3 0.49 0.00758
GO:0045087 innate immune response 26 7 2.55 0.00810
GO:0003018 vascular process in circulatory system 2 2 0.2 0.00936
GO:0003275 apoptotic process involved in outflow tr… 2 2 0.2 0.00936
GO:0003278 apoptotic process involved in heart morp… 2 2 0.2 0.00936
GO:0030199 collagen fibril organization 2 2 0.2 0.00936
GO:0033152 immunoglobulin V(D)J recombination 2 2 0.2 0.00936
GO:0035150 regulation of tube size 2 2 0.2 0.00936
GO:0035456 response to interferon-beta 2 2 0.2 0.00936
GO:0035458 cellular response to interferon-beta 2 2 0.2 0.00936
GO:0050848 regulation of calcium-mediated signaling 2 2 0.2 0.00936
GO:0050880 regulation of blood vessel size 2 2 0.2 0.00936
GO:0061437 renal system vasculature development 2 2 0.2 0.00936
GO:0061440 kidney vasculature development 2 2 0.2 0.00936
GO:0072012 glomerulus vasculature development 2 2 0.2 0.00936
GO:0072109 glomerular mesangium development 2 2 0.2 0.00936
GO:0072203 cell proliferation involved in metanephr… 2 2 0.2 0.00936
GO:1902256 regulation of apoptotic process involved… 2 2 0.2 0.00936
GO:1902257 negative regulation of apoptotic process… 2 2 0.2 0.00936
GO:0007346 regulation of mitotic cell cycle 15 5 1.47 0.01003
GO:0038093 Fc receptor signaling pathway 10 4 0.98 0.01074
GO:0038095 Fc-epsilon receptor signaling pathway 10 4 0.98 0.01074
GO:0002220 innate immune response activating cell s… 6 3 0.59 0.01414
GO:0002223 stimulatory C-type lectin receptor signa… 6 3 0.59 0.01414
GO:0002684 positive regulation of immune system pro… 36 8 3.53 0.01571
GO:0006952 defense response 44 9 4.31 0.01778
GO:0045088 regulation of innate immune response 17 5 1.66 0.01781
GO:0021549 cerebellum development 12 4 1.18 0.02189
GO:0002053 positive regulation of mesenchymal cell … 7 3 0.69 0.02307
GO:0032944 regulation of mononuclear cell prolifera… 7 3 0.69 0.02307
GO:0034340 response to type I interferon 7 3 0.69 0.02307
GO:0050670 regulation of lymphocyte proliferation 7 3 0.69 0.02307
GO:0060337 type I interferon signaling pathway 7 3 0.69 0.02307
GO:0070663 regulation of leukocyte proliferation 7 3 0.69 0.02307
GO:0071357 cellular response to type I interferon 7 3 0.69 0.02307
GO:0002682 regulation of immune system process 54 10 5.29 0.02468
GO:0031347 regulation of defense response 25 6 2.45 0.02589
GO:0001946 lymphangiogenesis 3 2 0.29 0.02634
GO:0014904 myotube cell development 3 2 0.29 0.02634

2.5 Top GO term

2.5.1 Top e081_random_bed_0 GO: GO:0019722

Biological process: calcium-mediated signaling

  Motif.ID TF.Name
1 MA0668.1 NEUROD2
17 MA0606.1 NFAT5
6 MA0624.1 NFATC1
5 MA0152.1 NFATC2
10 MA0625.1 NFATC3

2.5.2 Top e081_random_bed_0 GO: GO:0033173

Biological process: calcineurin-NFAT signaling cascade

  Motif.ID TF.Name
17 MA0606.1 NFAT5
6 MA0624.1 NFATC1
5 MA0152.1 NFATC2
10 MA0625.1 NFATC3

2.5.3 Top e081_random_bed_0 GO: GO:0048016

Biological process: inositol phosphate-mediated signaling

  Motif.ID TF.Name
17 MA0606.1 NFAT5
6 MA0624.1 NFATC1
5 MA0152.1 NFATC2
10 MA0625.1 NFATC3

2.6 e081_random_bed_1

GO.ID Term Annotated Significant Expected classicFisher
GO:0033173 calcineurin-NFAT signaling cascade 4 3 0.25 0.0008
GO:0048016 inositol phosphate-mediated signaling 4 3 0.25 0.0008
GO:0097720 calcineurin-mediated signaling 4 3 0.25 0.0008
GO:0019722 calcium-mediated signaling 5 3 0.31 0.0019
GO:0007638 mechanosensory behavior 2 2 0.12 0.0037
GO:0002220 innate immune response activating cell s… 6 3 0.37 0.0037
GO:0002223 stimulatory C-type lectin receptor signa… 6 3 0.37 0.0037
GO:0019932 second-messenger-mediated signaling 7 3 0.43 0.0062
GO:0014904 myotube cell development 3 2 0.19 0.0106
GO:0030890 positive regulation of B cell proliferat… 3 2 0.19 0.0106
GO:0045088 regulation of innate immune response 17 4 1.05 0.0156
GO:0002429 immune response-activating cell surface … 10 3 0.62 0.0188
GO:0038093 Fc receptor signaling pathway 10 3 0.62 0.0188
GO:0038095 Fc-epsilon receptor signaling pathway 10 3 0.62 0.0188
GO:0000768 syncytium formation by plasma membrane f… 4 2 0.25 0.0204
GO:0006949 syncytium formation 4 2 0.25 0.0204
GO:0030888 regulation of B cell proliferation 4 2 0.25 0.0204
GO:0032946 positive regulation of mononuclear cell … 4 2 0.25 0.0204
GO:0035855 megakaryocyte development 4 2 0.25 0.0204
GO:0050671 positive regulation of lymphocyte prolif… 4 2 0.25 0.0204
GO:0060142 regulation of syncytium formation by pla… 4 2 0.25 0.0204
GO:0070665 positive regulation of leukocyte prolife… 4 2 0.25 0.0204
GO:0042100 B cell proliferation 5 2 0.31 0.0327
GO:0098751 bone cell development 5 2 0.31 0.0327
GO:0050871 positive regulation of B cell activation 6 2 0.37 0.0473
GO:0061515 myeloid cell development 6 2 0.37 0.0473
GO:0002218 activation of innate immune response 14 3 0.87 0.0483
GO:0002758 innate immune response-activating signal… 14 3 0.87 0.0483
GO:0031349 positive regulation of defense response 14 3 0.87 0.0483
GO:0045089 positive regulation of innate immune res… 14 3 0.87 0.0483
GO:0002768 immune response-regulating cell surface … 15 3 0.93 0.0579
GO:0031347 regulation of defense response 25 4 1.55 0.0591
GO:0002684 positive regulation of immune system pro… 36 5 2.23 0.0596
GO:0001672 regulation of chromatin assembly or disa… 1 1 0.06 0.0619
GO:0001705 ectoderm formation 1 1 0.06 0.0619
GO:0001712 ectodermal cell fate commitment 1 1 0.06 0.0619
GO:0001937 negative regulation of endothelial cell … 1 1 0.06 0.0619
GO:0002115 store-operated calcium entry 1 1 0.06 0.0619
GO:0003337 mesenchymal to epithelial transition inv… 1 1 0.06 0.0619
GO:0003339 regulation of mesenchymal to epithelial … 1 1 0.06 0.0619
GO:0003340 negative regulation of mesenchymal to ep… 1 1 0.06 0.0619
GO:0010668 ectodermal cell differentiation 1 1 0.06 0.0619
GO:0010996 response to auditory stimulus 1 1 0.06 0.0619
GO:0021756 striatum development 1 1 0.06 0.0619
GO:0021757 caudate nucleus development 1 1 0.06 0.0619
GO:0021758 putamen development 1 1 0.06 0.0619
GO:0031223 auditory behavior 1 1 0.06 0.0619
GO:0033209 tumor necrosis factor-mediated signaling… 1 1 0.06 0.0619
GO:0034238 macrophage fusion 1 1 0.06 0.0619
GO:0034239 regulation of macrophage fusion 1 1 0.06 0.0619

2.7 Top GO term

2.7.1 Top e081_random_bed_1 GO: GO:0033173

Biological process: calcineurin-NFAT signaling cascade

  Motif.ID TF.Name
2 MA0624.1 NFATC1
10 MA0152.1 NFATC2
7 MA0625.1 NFATC3

2.7.2 Top e081_random_bed_1 GO: GO:0048016

Biological process: inositol phosphate-mediated signaling

  Motif.ID TF.Name
2 MA0624.1 NFATC1
10 MA0152.1 NFATC2
7 MA0625.1 NFATC3

2.7.3 Top e081_random_bed_1 GO: GO:0097720

Biological process: calcineurin-mediated signaling

  Motif.ID TF.Name
2 MA0624.1 NFATC1
10 MA0152.1 NFATC2
7 MA0625.1 NFATC3

2.8 e081_random_bed_2

GO.ID Term Annotated Significant Expected classicFisher
GO:0019722 calcium-mediated signaling 5 5 0.35 1.1e-06
GO:0033173 calcineurin-NFAT signaling cascade 4 4 0.28 1.9e-05
GO:0048016 inositol phosphate-mediated signaling 4 4 0.28 1.9e-05
GO:0097720 calcineurin-mediated signaling 4 4 0.28 1.9e-05
GO:0019932 second-messenger-mediated signaling 7 5 0.49 2.2e-05
GO:0038093 Fc receptor signaling pathway 10 4 0.7 0.0030
GO:0038095 Fc-epsilon receptor signaling pathway 10 4 0.7 0.0030
GO:0050848 regulation of calcium-mediated signaling 2 2 0.14 0.0047
GO:0002220 innate immune response activating cell s… 6 3 0.42 0.0052
GO:0002223 stimulatory C-type lectin receptor signa… 6 3 0.42 0.0052
GO:0014904 myotube cell development 3 2 0.21 0.0134
GO:0033144 negative regulation of intracellular ste… 3 2 0.21 0.0134
GO:0002768 immune response-regulating cell surface … 15 4 1.04 0.0150
GO:0055001 muscle cell development 9 3 0.63 0.0191
GO:0055002 striated muscle cell development 9 3 0.63 0.0191
GO:0016525 negative regulation of angiogenesis 4 2 0.28 0.0257
GO:0033143 regulation of intracellular steroid horm… 4 2 0.28 0.0257
GO:2000181 negative regulation of blood vessel morp… 4 2 0.28 0.0257
GO:0002429 immune response-activating cell surface … 10 3 0.7 0.0260
GO:0002684 positive regulation of immune system pro… 36 6 2.51 0.0290
GO:0002764 immune response-regulating signaling pat… 19 4 1.32 0.0350
GO:0001974 blood vessel remodeling 5 2 0.35 0.0410
GO:0060218 hematopoietic stem cell differentiation 5 2 0.35 0.0410
GO:0098751 bone cell development 5 2 0.35 0.0410
GO:1901343 negative regulation of vasculature devel… 5 2 0.35 0.0410
GO:0021549 cerebellum development 12 3 0.84 0.0434
GO:0007417 central nervous system development 97 11 6.75 0.0465
GO:0021695 cerebellar cortex development 6 2 0.42 0.0588
GO:0021781 glial cell fate commitment 6 2 0.42 0.0588
GO:0048745 smooth muscle tissue development 6 2 0.42 0.0588
GO:0051155 positive regulation of striated muscle c… 6 2 0.42 0.0588
GO:0061515 myeloid cell development 6 2 0.42 0.0588
GO:0002682 regulation of immune system process 54 7 3.76 0.0644
GO:0002218 activation of innate immune response 14 3 0.97 0.0653
GO:0002758 innate immune response-activating signal… 14 3 0.97 0.0653
GO:0031349 positive regulation of defense response 14 3 0.97 0.0653
GO:0045089 positive regulation of innate immune res… 14 3 0.97 0.0653
GO:0001672 regulation of chromatin assembly or disa… 1 1 0.07 0.0696
GO:0001783 B cell apoptotic process 1 1 0.07 0.0696
GO:0002115 store-operated calcium entry 1 1 0.07 0.0696
GO:0002327 immature B cell differentiation 1 1 0.07 0.0696
GO:0002329 pre-B cell differentiation 1 1 0.07 0.0696
GO:0002902 regulation of B cell apoptotic process 1 1 0.07 0.0696
GO:0002903 negative regulation of B cell apoptotic … 1 1 0.07 0.0696
GO:0007095 mitotic G2 DNA damage checkpoint 1 1 0.07 0.0696
GO:0008354 germ cell migration 1 1 0.07 0.0696
GO:0010972 negative regulation of G2/M transition o… 1 1 0.07 0.0696
GO:0010996 response to auditory stimulus 1 1 0.07 0.0696
GO:0021529 spinal cord oligodendrocyte cell differe… 1 1 0.07 0.0696
GO:0021530 spinal cord oligodendrocyte cell fate sp… 1 1 0.07 0.0696

2.9 Top GO term

2.9.1 Top e081_random_bed_2 GO: GO:0019722

Biological process: calcium-mediated signaling

  Motif.ID TF.Name
2 MA0668.1 NEUROD2
11 MA0606.1 NFAT5
5 MA0624.1 NFATC1
6 MA0152.1 NFATC2
9 MA0625.1 NFATC3

2.9.2 Top e081_random_bed_2 GO: GO:0033173

Biological process: calcineurin-NFAT signaling cascade

  Motif.ID TF.Name
11 MA0606.1 NFAT5
5 MA0624.1 NFATC1
6 MA0152.1 NFATC2
9 MA0625.1 NFATC3

2.9.3 Top e081_random_bed_2 GO: GO:0048016

Biological process: inositol phosphate-mediated signaling

  Motif.ID TF.Name
11 MA0606.1 NFAT5
5 MA0624.1 NFATC1
6 MA0152.1 NFATC2
9 MA0625.1 NFATC3

2.10 Summary

The top 1% of the positive windows in E081 and Noonan hit in enriched in neuron development process.