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Application of RcisTarget (an R package to analyze Transcription factor binding motif enrichment analysis) on Generation 3 Modules

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RcisTarget R Package: Transcription factor binding motif enrichment

Overview of RcisTarget R Package

RcisTarget identifies transcription factor binding motifs (TFBS) over-represented on a gene list. In a first step, RcisTarget selects DNA motifs that are significantly over-represented in the surroundings of the transcription start site (TSS) of the genes in the gene-set. This is achieved by using a database that contains genome-wide cross-species rankings for each motif. The motifs that are then annotated to TFs and those that have a high Normalized Enrichment Score (NES) are retained. Finally, for each motif and gene-set, RcisTarget predicts the candidate target genes (i.e. genes in the gene-set that are ranked above the leading edge). For additional details about RcisTarget package, please refer Reference Paper 1, R Package 1, and R Package 1 vignettes

Brief instructions about application of the RcisTarget R package on Generation 3 Modules

  1. The RcisTarget R script was applied on all 382 Generation 3 modules Reference Paper 2 using the default settings.

  2. The input data are *.txt files containing Gene Symbol column as mandatory.

  3. The output data (see table below) of this analysis is Motif_Enrichment_AUC_Histogram_Plot.pdf, Best_Enrichment_Motifs_NES_Plot.pdf, motifEnrichmentTable.csv, motifEnrichmentTable_wGenes.csv, Motif_data_table.html, and Network.html. For more details about the outputs (plots, data tables), refer the documentation link provided above.

    Note:

    • All the plots and csv files can be opened by a simple left click and viewed in RcisTarget Advanced Data Analysis column (see below), however, Motif_data_table.html and Network.html cannot be viewed by a simple left click. To view the interactive Motif data table and Network for the appropriate module, click on the link under each column provided below

    • Best_Enrichment_Motifs_NES_Plot.pdf and Network.html outputs are only the outputs of subset data (considering the top 3 best motif enrichments). This is because the size of the output files and limitation of storage space. However, it is worth noting it is possible to include all motifs while performing the analysis. This generates larger data files, requires more storage space and more computation

  4. In summary, from RcisTarget analysis, outputs were obtained for a total of 235 modules successfully, however, 147 modules failed to run (due to non-matching Gene Symbol identifier between the input file and motif database). Hence, no results will be found for these modules.

Module Analysis Result Table

Module ID Module Annotation Number of unique genes RcisTarget- Advanced Data Analysis RcisTarget- Motif Data Table RcisTarget- Network Analysis
M3.1 Cell cycle 106 No Result No Result No Result
M8.1 TBD 51 No Result No Result No Result
M8.2 Prostanoids 36 Link Link Link
M8.3 Type 1 Interferon 17 Link Link Link
M9.1 Cytotoxic lymphocytes 28 Link Link Link
M9.2 Erythrocytes 30 Link Link Link
M10.1 Interferon 21 Link Link Link
M10.2 Protein synthesis 19 Link Link Link
M10.3 Platelet 20 Link Link Link
M10.4 Neutrophil activation 13 No Result No Result No Result
M11.1 Protein synthesis 46 No Result No Result No Result
M11.2 TBD 39 Link Link Link
M11.3 Erythrocytes 24 Link Link Link
M11.4 TBD 26 Link Link Link
M12.1 Protein modification 111 Link Link Link
M12.2 Monocytes 44 Link Link Link
M12.3 Cell cycle 70 Link Link Link
M12.4 Gene transcription 62 Link Link Link
M12.5 Protein modification 91 Link Link Link
M12.6 T cells 33 Link Link Link
M12.7 Protein synthesis 35 No Result No Result No Result
M12.8 B cells 26 Link Link Link
M12.9 Protein phosphorylation 42 Link Link Link
M12.10 Inflammation 53 Link Link Link
M12.11 Erythrocytes 24 No Result No Result No Result
M12.12 Oxidative stress 31 No Result No Result No Result
M12.13 Oxidative phosphorylation 47 Link Link Link
M12.14 TBD 20 No Result No Result No Result
M12.15 Cell cycle 17 Link Link Link
M13.1 Inflammation 137 Link Link Link
M13.2 Gene transcription 92 Link Link Link
M13.3 TBD 100 Link Link Link
M13.4 Protein synthesis 119 Link Link Link
M13.5 Cell death 134 Link Link Link
M13.6 Gene transcription 127 Link Link Link
M13.7 TBD 98 Link Link Link
M13.8 TBD 55 No Result No Result No Result
M13.9 Gene transcription 99 Link Link Link
M13.10 Protein synthesis 91 No Result No Result No Result
M13.11 TBD 78 Link Link Link
M13.12 Inflammation 55 Link Link Link
M13.13 Gene transcription 58 No Result No Result No Result
M13.14 Proteolysis 72 Link Link Link
M13.15 Gene transcription 76 Link Link Link
M13.16 Cytokines/chemokines 39 Link Link Link
M13.17 Interferon 31 Link Link Link
M13.18 B cells 88 Link Link Link
M13.19 Protein phosphorylation 63 Link Link Link
M13.20 Cell cycle 47 No Result No Result No Result
M13.21 Cytotoxic lymphocytes 23 Link Link Link
M13.22 Neutrophils 65 Link Link Link
M13.23 TBD 79 Link Link Link
M13.24 TBD 70 Link Link Link
M13.25 Protein phosphorylation 79 Link Link Link
M13.26 Oxidative stress 40 Link Link Link
M13.27 B cells 33 Link Link Link
M13.28 Protein synthesis 29 No Result No Result No Result
M13.29 Protein modification 65 Link Link Link
M13.30 Erythrocytes 29 Link Link Link
M13.31 TBD 25 Link Link Link
M13.32 Cell cycle 30 Link Link Link
M14.1 Gene transcription 44 Link Link Link
M14.2 Protein synthesis 44 Link Link Link
M14.3 Protein modification 39 Link Link Link
M14.4 Gene transcription 38 Link Link Link
M14.5 Gene transcription 36 No Result No Result No Result
M14.6 TBD 31 No Result No Result No Result
M14.7 TBD 31 Link Link Link
M14.8 TBD 30 Link Link Link
M14.9 TBD 27 Link Link Link
M14.10 TBD 28 Link Link Link
M14.11 TBD 28 Link Link Link
M14.12 Cell cycle 26 Link Link Link
M14.13 Oxidative phosphorylation 26 Link Link Link
M14.14 Protein modification 27 Link Link Link
M14.15 Protein modification 25 Link Link Link
M14.16 TBD 26 Link Link Link
M14.17 Gene transcription 26 Link Link Link
M14.18 TBD 25 Link Link Link
M14.19 Inflammation 23 Link Link Link
M14.20 Gene transcription 24 Link Link Link
M14.21 TBD 23 Link Link Link
M14.22 TBD 23 Link Link Link
M14.23 Gene transcription 24 Link Link Link
M14.24 Inflammation 23 Link Link Link
M14.25 TBD 22 Link Link Link
M14.26 Inflammation 22 Link Link Link
M14.27 Protein synthesis 21 No Result No Result No Result
M14.28 Neutrophils 20 Link Link Link
M14.29 TBD 22 Link Link Link
M14.30 Oxidative phosphorylation 21 Link Link Link
M14.31 Cell cycle 22 Link Link Link
M14.32 TBD 22 Link Link Link
M14.33 Proteolysis 22 No Result No Result No Result
M14.34 Gene transcription 21 Link Link Link
M14.35 TBD 20 Link Link Link
M14.36 TBD 20 Link Link Link
M14.37 TBD 19 Link Link Link
M14.38 TBD 17 Link Link Link
M14.39 Cell cycle 18 Link Link Link
M14.40 Cellular respiration 19 Link Link Link
M14.41 TBD 19 Link Link Link
M14.42 T cells 19 Link Link Link
M14.43 TBD 18 Link Link Link
M14.44 Protein synthesis 18 Link Link Link
M14.45 TBD 18 No Result No Result No Result
M14.46 TBD 18 Link Link Link
M14.47 Protein synthesis 18 No Result No Result No Result
M14.48 Inflammation 17 Link Link Link
M14.49 Gene transcription 18 No Result No Result No Result
M14.50 Inflammation 18 Link Link Link
M14.51 Oxidative stress 14 Link Link Link
M14.52 TBD 17 Link Link Link
M14.53 Erythrocytes 16 Link Link Link
M14.54 Cell cycle 18 No Result No Result No Result
M14.55 Gene transcription 17 Link Link Link
M14.56 TBD 17 Link Link Link
M14.57 Protein modification 16 Link Link Link
M14.58 Protein synthesis 17 No Result No Result No Result
M14.59 TBD 16 Link Link Link
M14.60 TBD 17 Link Link Link
M14.61 Protein modification 16 Link Link Link
M14.62 TBD 16 Link Link Link
M14.63 Oxidative phosphorylation 16 Link Link Link
M14.64 Cell cycle 16 Link Link Link
M14.65 Monocytes 15 Link Link Link
M14.66 Inflammation 16 Link Link Link
M14.67 Gene transcription 16 Link Link Link
M14.68 Protein synthesis 16 Link Link Link
M14.69 Gene transcription 15 Link Link Link
M14.70 TBD 15 Link Link Link
M14.71 Gene transcription 14 No Result No Result No Result
M14.72 TBD 15 Link Link Link
M14.73 TBD 15 Link Link Link
M14.74 TBD 14 Link Link Link
M14.75 Protein synthesis 15 No Result No Result No Result
M14.76 Leukocyte activation 15 Link Link Link
M14.77 Gene transcription 15 Link Link Link
M14.78 TBD 15 Link Link Link
M14.79 Protein synthesis 15 Link Link Link
M14.80 Protein synthesis 12 No Result No Result No Result
M14.81 Platelet 14 No Result No Result No Result
M14.82 Cytokines/chemokines 15 Link Link Link
M14.83 TBD 14 Link Link Link
M15.1 TBD 79 Link Link Link
M15.2 TBD 60 Link Link Link
M15.3 Gene transcription 57 No Result No Result No Result
M15.4 B cells 54 No Result No Result No Result
M15.5 Protein modification 53 Link Link Link
M15.6 Cell cycle 54 Link Link Link
M15.7 Monocytes 52 Link Link Link
M15.8 Gene transcription 51 No Result No Result No Result
M15.9 T cells 51 No Result No Result No Result
M15.10 Gene transcription 50 Link Link Link
M15.11 TBD 49 No Result No Result No Result
M15.12 TBD 48 Link Link Link
M15.13 TBD 48 Link Link Link
M15.14 TBD 47 No Result No Result No Result
M15.15 TBD 46 Link Link Link
M15.16 Antigen presentation 45 No Result No Result No Result
M15.17 TBD 44 No Result No Result No Result
M15.18 TBD 41 Link Link Link
M15.19 Gene transcription 43 No Result No Result No Result
M15.20 TBD 41 Link Link Link
M15.21 Gene transcription 42 Link Link Link
M15.22 TBD 42 Link Link Link
M15.23 Cell death 41 Link Link Link
M15.24 TBD 41 Link Link Link
M15.25 TBD 38 Link Link Link
M15.26 Neutrophils 38 Link Link Link
M15.27 Cell cycle 40 No Result No Result No Result
M15.28 Oxidative phosphorylation 37 No Result No Result No Result
M15.29 Cell death 35 No Result No Result No Result
M15.30 TBD 36 Link Link Link
M15.31 Protein modification 35 Link Link Link
M15.32 TBD 36 No Result No Result No Result
M15.33 T cells 35 No Result No Result No Result
M15.34 T cells 34 Link Link Link
M15.35 Neutrophils 33 Link Link Link
M15.36 Protein modification 34 Link Link Link
M15.37 Inflammation 33 Link Link Link
M15.38 T cells 32 No Result No Result No Result
M15.39 TBD 32 Link Link Link
M15.40 Gene transcription 31 No Result No Result No Result
M15.41 TBD 31 Link Link Link
M15.42 Gene transcription 30 Link Link Link
M15.43 TBD 30 Link Link Link
M15.44 Protein modification 28 No Result No Result No Result
M15.45 Platelet 29 Link Link Link
M15.46 TBD 27 Link Link Link
M15.47 Antigen presentation 28 Link Link Link
M15.48 TBD 27 No Result No Result No Result
M15.49 Cell death 27 No Result No Result No Result
M15.50 TBD 27 Link Link Link
M15.51 Protein synthesis 26 No Result No Result No Result
M15.52 TBD 27 No Result No Result No Result
M15.53 Erythrocytes 25 Link Link Link
M15.54 TBD 26 No Result No Result No Result
M15.55 Protein phosphorylation 24 Link Link Link
M15.56 Cell adhesion 25 No Result No Result No Result
M15.57 TBD 26 Link Link Link
M15.58 Monocytes 22 No Result No Result No Result
M15.59 TBD 24 No Result No Result No Result
M15.60 TBD 25 No Result No Result No Result
M15.61 Monocytes 25 Link Link Link
M15.62 TBD 25 No Result No Result No Result
M15.63 TBD 22 Link Link Link
M15.64 Interferon 21 Link Link Link
M15.65 TBD 23 Link Link Link
M15.66 TBD 23 Link Link Link
M15.67 TBD 22 No Result No Result No Result
M15.68 TBD 23 No Result No Result No Result
M15.69 TBD 22 Link Link Link
M15.70 Protein modification 22 Link Link Link
M15.71 TBD 22 Link Link Link
M15.72 TBD 22 Link Link Link
M15.73 Cell cycle 22 No Result No Result No Result
M15.74 Erythrocytes 21 No Result No Result No Result
M15.75 TBD 20 Link Link Link
M15.76 TBD 21 Link Link Link
M15.77 TBD 21 No Result No Result No Result
M15.78 TBD 20 No Result No Result No Result
M15.79 Mitochondrial Stress/Proteasome 19 Link Link Link
M15.80 TBD 20 Link Link Link
M15.81 TBD 20 Link Link Link
M15.82 TBD 20 Link Link Link
M15.83 Gene transcription 20 No Result No Result No Result
M15.84 Cytokines/chemokines 20 No Result No Result No Result
M15.85 TBD 20 No Result No Result No Result
M15.86 Interferon 15 Link Link Link
M15.87 TBD 19 No Result No Result No Result
M15.88 TBD 19 No Result No Result No Result
M15.89 TBD 19 No Result No Result No Result
M15.90 TBD 16 Link Link Link
M15.91 TBD 17 Link Link Link
M15.92 Protein modification 18 No Result No Result No Result
M15.93 TBD 18 No Result No Result No Result
M15.94 TBD 18 Link Link Link
M15.95 TBD 18 No Result No Result No Result
M15.96 TBD 18 Link Link Link
M15.97 Cell death 17 No Result No Result No Result
M15.98 T cells 18 Link Link Link
M15.99 Protein modification 15 Link Link Link
M15.100 Erythrocytes 17 Link Link Link
M15.101 TBD 18 Link Link Link
M15.102 Prostanoids 15 Link Link Link
M15.103 TBD 17 Link Link Link
M15.104 TBD 17 Link Link Link
M15.105 Inflammation 16 Link Link Link
M15.106 TBD 17 Link Link Link
M15.107 TBD 17 Link Link Link
M15.108 TBD 17 Link Link Link
M15.109 Inflammation 17 No Result No Result No Result
M15.110 Cell cycle 16 Link Link Link
M15.111 TBD 17 No Result No Result No Result
M15.112 TBD 16 Link Link Link
M15.113 Inflammation 16 No Result No Result No Result
M15.114 TBD 16 No Result No Result No Result
M15.115 TBD 16 No Result No Result No Result
M15.116 TBD 16 No Result No Result No Result
M15.117 TBD 16 No Result No Result No Result
M15.118 Gene transcription 14 Link Link Link
M15.119 TBD 16 No Result No Result No Result
M15.120 TBD 16 No Result No Result No Result
M15.121 TBD 14 Link Link Link
M15.122 TBD 15 No Result No Result No Result
M15.123 TBD 15 Link Link Link
M15.124 TBD 15 Link Link Link
M15.125 TBD 15 Link Link Link
M15.126 Gene transcription 15 Link Link Link
M15.127 Interferon 14 No Result No Result No Result
M16.1 TBD 169 Link Link Link
M16.2 Protein synthesis 161 Link Link Link
M16.3 T cells 145 Link Link Link
M16.4 TBD 130 No Result No Result No Result
M16.5 TBD 123 Link Link Link
M16.6 Monocytes 119 No Result No Result No Result
M16.7 TBD 116 Link Link Link
M16.8 TBD 116 Link Link Link
M16.9 Protein modification 109 Link Link Link
M16.10 TBD 105 No Result No Result No Result
M16.11 Protein synthesis 102 No Result No Result No Result
M16.12 B cells 100 No Result No Result No Result
M16.13 Protein modification 94 No Result No Result No Result
M16.14 TBD 89 Link Link Link
M16.15 Cell death 86 No Result No Result No Result
M16.16 TBD 88 No Result No Result No Result
M16.17 Gene transcription 83 No Result No Result No Result
M16.18 TBD 82 No Result No Result No Result
M16.19 TBD 82 No Result No Result No Result
M16.20 TBD 81 No Result No Result No Result
M16.21 TBD 80 No Result No Result No Result
M16.22 TBD 76 No Result No Result No Result
M16.23 Cell cycle 76 Link Link Link
M16.24 T cells 72 Link Link Link
M16.25 TBD 74 No Result No Result No Result
M16.26 TBD 72 Link Link Link
M16.27 TBD 69 Link Link Link
M16.28 TBD 67 No Result No Result No Result
M16.29 TBD 62 Link Link Link
M16.30 Complement 61 No Result No Result No Result
M16.31 TBD 62 No Result No Result No Result
M16.32 TBD 59 Link Link Link
M16.33 TBD 59 No Result No Result No Result
M16.34 Gene transcription 56 No Result No Result No Result
M16.35 TBD 55 No Result No Result No Result
M16.36 Gene transcription 54 Link Link Link
M16.37 TBD 48 No Result No Result No Result
M16.38 TBD 52 No Result No Result No Result
M16.39 TBD 52 No Result No Result No Result
M16.40 Monocytes 51 No Result No Result No Result
M16.41 TBD 48 No Result No Result No Result
M16.42 TBD 50 No Result No Result No Result
M16.43 Gene transcription 48 No Result No Result No Result
M16.44 Protein synthesis 48 Link Link Link
M16.45 TBD 47 Link Link Link
M16.46 TBD 48 No Result No Result No Result
M16.47 TNF 47 No Result No Result No Result
M16.48 TBD 47 No Result No Result No Result
M16.49 Inflammation 45 No Result No Result No Result
M16.50 Protein modification 45 No Result No Result No Result
M16.51 Protein synthesis 43 No Result No Result No Result
M16.52 Lymphocyte 43 Link Link Link
M16.53 TBD 42 No Result No Result No Result
M16.54 TBD 40 Link Link Link
M16.55 TBD 40 No Result No Result No Result
M16.56 Protein synthesis 38 No Result No Result No Result
M16.57 B cells 38 No Result No Result No Result
M16.58 TBD 39 No Result No Result No Result
M16.59 TBD 38 No Result No Result No Result
M16.60 Cell cycle 36 Link Link Link
M16.61 TBD 36 Link Link Link
M16.62 TBD 35 No Result No Result No Result
M16.63 TBD 35 Link Link Link
M16.64 Platelet/Prostaglandin 33 Link Link Link
M16.65 TGF-beta 34 Link Link Link
M16.66 TBD 34 No Result No Result No Result
M16.67 TBD 33 No Result No Result No Result
M16.68 Protein synthesis 33 Link Link Link
M16.69 Lipid metabolism 32 Link Link Link
M16.70 TBD 29 Link Link Link
M16.71 TBD 31 Link Link Link
M16.72 TBD 30 Link Link Link
M16.73 Protein synthesis 30 Link Link Link
M16.74 TBD 29 No Result No Result No Result
M16.75 Cell death 30 No Result No Result No Result
M16.76 TBD 25 Link Link Link
M16.77 Antigen presentation 28 No Result No Result No Result
M16.78 B cells 28 No Result No Result No Result
M16.79 Protein synthesis 27 Link Link Link
M16.80 Cytokines/chemokines 27 No Result No Result No Result
M16.81 TBD 27 No Result No Result No Result
M16.82 Gene transcription 25 No Result No Result No Result
M16.83 Cell adhesion 26 Link Link Link
M16.84 Protein phosphorylation 25 Link Link Link
M16.85 TBD 24 Link Link Link
M16.86 Oxidative stress 25 No Result No Result No Result
M16.87 TBD 23 No Result No Result No Result
M16.88 Erythrocytes 23 No Result No Result No Result
M16.89 TBD 23 No Result No Result No Result
M16.90 TBD 22 No Result No Result No Result
M16.91 TBD 21 Link Link Link
M16.92 Cell cycle 22 Link Link Link
M16.93 TBD 22 No Result No Result No Result
M16.94 TBD 21 No Result No Result No Result
M16.95 B cells 21 No Result No Result No Result
M16.96 Erythrocytes 19 Link Link Link
M16.97 Cell death 20 Link Link Link
M16.98 TBD 18 No Result No Result No Result
M16.99 Protein modification 17 Link Link Link
M16.100 TBD 18 No Result No Result No Result
M16.101 TBD 17 Link Link Link
M16.102 TBD 17 Link Link Link
M16.103 TBD 17 No Result No Result No Result
M16.104 Cell cycle 17 No Result No Result No Result
M16.105 TBD 17 No Result No Result No Result
M16.106 TBD 15 No Result No Result No Result
M16.107 Oxidative stress 16 No Result No Result No Result
M16.108 TBD 16 No Result No Result No Result
M16.109 Platelet 15 Link Link Link
M16.110 TBD 15 No Result No Result No Result
M16.111 TBD 15 Link Link Link

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Application of RcisTarget (an R package to analyze Transcription factor binding motif enrichment analysis) on Generation 3 Modules

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