{ "cells": [ { "cell_type": "code", "execution_count": 1, "metadata": {}, "outputs": [ { "data": { "text/html": [ "" ], "text/vnd.plotly.v1+html": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/html": [ "
" ], "text/plain": [ "" ] }, "execution_count": 1, "metadata": {}, "output_type": "execute_result" } ], "source": [ "# Initialize Notebook\n", "%run ../library/v1.1.4/init.ipy\n", "HTML('''
''')" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "# TSA vs Control (DATA analysis and visualization)\n", "---\n", "# Introduction\n", "This notebook contains an analyis of a user-submitted RNA-seq dataset. created using BioJupies. For more information on BioJupies, please visit http://biojupies.cloud.\n", "If the notebook is not correctly displayed on your browser, please visit our Notebook Troubleshooting Guide.\n", "### Table of Contents\n", "The notebook is divided into the following sections:\n", "
  1. Load Dataset - Loads and previews the input dataset in the notebook environment.
  2. PCA - Linear dimensionality reduction technique to visualize similarity between samples
  3. Library Size Analysis - Analysis of readcount distribution for the samples within the dataset
  4. Enrichr Links - Links to enrichment analysis results of the differentially expressed genes via Enrichr
  5. Gene Ontology Enrichment Analysis - Identifies Gene Ontology terms which are enriched in the differentially expressed genes
  6. Pathway Enrichment Analysis - Identifies biological pathways which are enriched in the differentially expressed genes
  7. Transcription Factor Enrichment Analysis - Identifies transcription factors whose targets are enriched in the differentially expressed genes
  8. Kinase Enrichment Analysis - Identifies protein kinases whose substrates are enriched in the differentially expressed genes
  9. miRNA Enrichment Analysis - Identifies miRNAs whose targets are enriched in the differentially expressed genes
  10. L1000CDS2 Query - Identifies small molecules which mimic or reverse a given differential gene expression signature
  11. L1000FWD Query - Projects signatures on a 2-dimensional visualization of the L1000 signature database
" ] }, { "cell_type": "markdown", "metadata": { "task": "load_dataset" }, "source": [ "---\n", "# Results\n", "## 1. Load Dataset\n", "Here we upload a user-submitted dataset." ] }, { "cell_type": "code", "execution_count": 2, "metadata": {}, "outputs": [ { "data": { "text/html": [ "\n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", "
I18R026a01_01_R1I18R026a02_01_R1I18R026a03_01_R1I18R026b01_01_R1I18R026b02_01_R1I18R026b03_01_R1
0610007P14Rik70980328763336283387
0610009B22Rik603033735126826467858254
0610009L18Rik000000
0610009O20Rik23037341
0610010F05Rik19268183342
" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" } ], "source": [ "# Load dataset\n", "dataset = load_dataset(source='upload', uid='ETafDguzb9O')\n", "\n", "# Preview expression data\n", "preview_data(dataset)" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "**Table 1 | RNA-seq expression data.** The table displays the first 5 rows of the quantified RNA-seq expression dataset. Rows represent genes, columns represent samples, and values show the number of mapped reads." ] }, { "cell_type": "code", "execution_count": 3, "metadata": {}, "outputs": [ { "data": { "text/html": [ "
\n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", " \n", "
Group
Sample
I18R026a01_01_R1Ctrl1
I18R026a02_01_R1Ctrl2
I18R026a03_01_R1Ctrl3
I18R026b01_01_R1TSA1
I18R026b02_01_R1TSA2
I18R026b03_01_R1TSA3
" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" } ], "source": [ "# Display metadata\n", "display_metadata(dataset)" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "**Table 2 | Sample metadata.** The table displays the metadata associated with the samples in the RNA-seq dataset. Rows represent RNA-seq samples, columns represent metadata categories." ] }, { "cell_type": "code", "execution_count": 4, "metadata": { "task": "generate_signature" }, "outputs": [], "source": [ "# Configure signatures\n", "dataset['signature_metadata'] = {\n", " 'Control vs Perturbation': {\n", " 'A': ['I18R026a01_01_R1', 'I18R026a02_01_R1', 'I18R026a03_01_R1'],\n", " 'B': ['I18R026b01_01_R1', 'I18R026b02_01_R1', 'I18R026b03_01_R1']\n", " }\n", "}\n", "\n", "# Generate signatures\n", "for label, groups in dataset['signature_metadata'].items():\n", " signatures[label] = generate_signature(group_A=groups['A'], group_B=groups['B'], method='limma', dataset=dataset)" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "---\n", " ## 2. PCA\n", "Principal Component Analysis (PCA) is a statistical technique used to identify global patterns in high-dimensional datasets. It is commonly used to explore the similarity of biological samples in RNA-seq datasets. To achieve this, gene expression values are transformed into Principal Components (PCs), a set of linearly uncorrelated features which represent the most relevant sources of variance in the data, and subsequently visualized using a scatter plot." ] }, { "cell_type": "code", "execution_count": 5, "metadata": { "task": "pca" }, "outputs": [ { "data": { "application/vnd.plotly.v1+json": { "config": { "linkText": "Export to plot.ly", "plotlyServerURL": "https://plot.ly", "showLink": false }, "data": [ { "hoverinfo": "text", "marker": { "color": "blue", "size": 15 }, "mode": "markers", "name": "Control", "text": [ "I18R026a01_01_R1
Group: Ctrl1
Sample Group: Control", "I18R026a02_01_R1
Group: Ctrl2
Sample Group: Control", "I18R026a03_01_R1
Group: Ctrl3
Sample Group: Control" ], "type": "scatter3d", "uid": "6c1b978a-7c43-468a-a299-1d0dfe540010", "x": [ 0.37624101772043345, -0.775754643091322, -0.21224215126433438 ], "y": [ -0.26319676662395025, -0.43089487808171756, 0.8543316251560578 ], "z": [ 0.7207111478456495, -0.05632890011068872, 0.09614273917289562 ] }, { "hoverinfo": "text", "marker": { "color": "red", "size": 15 }, "mode": "markers", "name": "Perturbation", "text": [ "I18R026b01_01_R1
Group: TSA1
Sample Group: Perturbation", "I18R026b02_01_R1
Group: TSA2
Sample Group: Perturbation", "I18R026b03_01_R1
Group: TSA3
Sample Group: Perturbation" ], "type": "scatter3d", "uid": "6394f6c9-59a9-4a48-bbf8-2e970a6de59e", "x": [ 0.16679883917721314, 0.016583460670572592, 0.4283734767874374 ], "y": [ -0.013932717820332927, -0.026906944056164, -0.11940031857389277 ], "z": [ -0.010473789605573797, -0.06944339160067921, -0.6806078057016035 ] } ], "layout": { "hovermode": "closest", "margin": { "b": 0, "l": 0, "r": 0, "t": 50 }, "scene": { "xaxis": { "title": { "text": "PC1(26.9% var. explained)" } }, "yaxis": { "title": { "text": "PC2(24.0% var. explained)" } }, "zaxis": { "title": { "text": "PC3(19.9% var. explained)" } } }, "title": { "text": "PCA Analysis | Scatter Plot
Colored by Sample Group" }, "width": 900 } }, "text/html": [ "
" ], "text/vnd.plotly.v1+html": [ "
" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/markdown": [ "** Figure 1 | Principal Component Analysis results. ** The figure displays an interactive, three-dimensional scatter plot of the first three Principal Components (PCs) of the data. Each point represents an RNA-seq sample. Samples with similar gene expression profiles are closer in the three-dimensional space. If provided, sample groups are indicated using different colors, allowing for easier interpretation of the results. If you are experiencing issues visualizing the plot, please visit our Troubleshooting guide" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" } ], "source": [ "# Run analysis\n", "results['pca'] = analyze(dataset=dataset, tool='pca', nr_genes=2500, normalization='logCPM', z_score=True, plot_type='interactive')\n", "\n", "# Display results\n", "plot(results['pca'])" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "---\n", " ## 3. Library Size Analysis\n", "In order to quantify gene expression in an RNA-seq dataset, reads generated from the sequencing step are mapped to a reference genome and subsequently aggregated into numeric gene counts. Due to experimental variations and random technical noise, samples in an RNA-seq datasets often have variable amounts of the total RNA. Library size analysis calculates and displays the total number of reads mapped for each sample in the RNA-seq dataset, facilitating the identification of outlying samples and the assessment of the overall quality of the data." ] }, { "cell_type": "code", "execution_count": 6, "metadata": { "task": "library_size_analysis" }, "outputs": [ { "data": { "application/vnd.plotly.v1+json": { "config": { "linkText": "Export to plot.ly", "plotlyServerURL": "https://plot.ly", "showLink": false }, "data": [ { "hoverinfo": "text", "marker": { "color": "rgb(0,119,177)" }, "orientation": "h", "text": [ "I18R026a02_01_R1
Group: Ctrl2
Sample Group: Control", "I18R026b02_01_R1
Group: TSA2
Sample Group: Perturbation", "I18R026a03_01_R1
Group: Ctrl3
Sample Group: Control", "I18R026b01_01_R1
Group: TSA1
Sample Group: Perturbation", "I18R026b03_01_R1
Group: TSA3
Sample Group: Perturbation", "I18R026a01_01_R1
Group: Ctrl1
Sample Group: Control" ], "type": "bar", "uid": "463747f0-1fff-4c08-889c-a2cbaf7bacd2", "x": [ 11.793168, 15.147413, 15.560041, 15.967028, 16.369704, 17.421066 ], "y": [ "I18R026a02_01_R1", "I18R026b02_01_R1", "I18R026a03_01_R1", "I18R026b01_01_R1", "I18R026b03_01_R1", "I18R026a01_01_R1" ] } ], "layout": { "margin": { "b": 50, "l": 100, "pad": 5, "r": 0, "t": 75 }, "title": { "text": "Library Size Analysis | Bar Plot
Million reads per sample" }, "xaxis": { "title": { "text": "Million Reads" } } } }, "text/html": [ "
" ], "text/vnd.plotly.v1+html": [ "
" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/markdown": [ "** Figure 2 | Library Size Analysis results. **The figure contains an interactive bar chart which displays the total number of reads mapped to each RNA-seq sample in the dataset. Additional information for each sample is available by hovering over the bars. If provided, sample groups are indicated using different colors, thus allowing for easier interpretation of the results. If you are experiencing issues visualizing the plot, please visit our Troubleshooting guide." ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" } ], "source": [ "# Run analysis\n", "results['library_size_analysis'] = analyze(dataset=dataset, tool='library_size_analysis', plot_type='interactive')\n", "\n", "# Display results\n", "plot(results['library_size_analysis'])" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "---\n", " ## 4. Enrichr Links\n", "Enrichment analysis is a statistical procedure used to identify biological terms which are over-represented in a given gene set. These include signaling pathways, molecular functions, diseases, and a wide variety of other biological terms obtained by integrating prior knowledge of gene function from multiple resources. Enrichr is a web-based application which allows to perform enrichment analysis using a large collection of gene-set libraries and various interactive approaches to display enrichment results." ] }, { "cell_type": "code", "execution_count": 7, "metadata": { "task": "enrichr" }, "outputs": [ { "data": { "text/markdown": [ "##### Control vs Perturbation Signature:\n", " * Upregulated: https://amp.pharm.mssm.edu/Enrichr/enrich?dataset=a308263d3f2e1789e3bd7d6420b7924f \n", " * Downregulated: https://amp.pharm.mssm.edu/Enrichr/enrich?dataset=4da4b3482c02067af4803fbd8c7d412c" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/markdown": [ "** Table 3 | Enrichr links. **The table displays links to Enrichr containing the results of enrichment analyses generated by analyzing the up-regulated and down-regulated genes from a differential expression analysis. By clicking on these links, users can interactively explore and download the enrichment results from the Enrichr website" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" } ], "source": [ "# Initialize results\n", "results['enrichr'] = {}\n", "\n", "# Loop through signatures\n", "for label, signature in signatures.items():\n", "\n", " # Run analysis\n", " results['enrichr'][label] = analyze(signature=signature, tool='enrichr', signature_label=label, geneset_size=500, sort_genes_by='logFC')\n", "\n", " # Display results\n", " plot(results['enrichr'][label])" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "---\n", " ## 5. Gene Ontology Enrichment Analysis\n", "Gene Ontology (GO) is a major bioinformatics initiative aimed at unifying the representation of gene attributes across all species. It contains a large collection of experimentally validated and predicted associations between genes and biological terms. This information can be leveraged by Enrichr to identify the biological processes, molecular functions and cellular components which are over-represented in the up-regulated and down-regulated genes identified by comparing two groups of samples." ] }, { "cell_type": "code", "execution_count": 8, "metadata": { "task": "go_enrichment" }, "outputs": [ { "data": { "application/vnd.plotly.v1+json": { "config": { "linkText": "Export to plot.ly", "plotlyServerURL": "https://plot.ly", "showLink": false }, "data": [ { "hoverinfo": "text", "hovertext": [ "regulation of spindle assembly (GO:0090169)
P-value: 0.0037
FDR: 1.0
Z-score: 6.15
Combined score: 34.4
4 Genes: SENP6, VPS4B, CHMP1A, CHMP2B
", "ubiquitin-dependent protein catabolic process (GO:0006511)
P-value: 0.0026
FDR: 0.93
Z-score: 2.11
Combined score: 12.6
18 Genes: PSMD10, VPS4B, ADRM1, CUL1, UBE4A, FBXO22, RNF5
ANAPC10, SPSB2, CDC23, KCTD10, PLAA, ERCC8, BTRC
FBXO8, FBXO7, FBXL4, NFE2L2
", "positive regulation of sodium ion transmembrane transporter activity (GO:2000651)
P-value: 0.0022
FDR: 0.87
Z-score: 10.9
Combined score: 66.7
3 Genes: CHORDC1, WNK3, GLRX
", "axonal transport (GO:0098930)
P-value: 0.0022
FDR: 0.92
Z-score: 5.41
Combined score: 33.2
5 Genes: BLOC1S4, BLOC1S5, FMR1, TMEM108, MAPT
", "histone acetylation (GO:0016573)
P-value: 0.0021
FDR: 0.98
Z-score: 3.89
Combined score: 23.9
7 Genes: NAA50, DR1, ING3, MORF4L2, RUVBL1, HAT1, POLE3
", "ER to Golgi vesicle-mediated transport (GO:0006888)
P-value: 0.0021
FDR: 1.0
Z-score: 2.65
Combined score: 16.4
12 Genes: COPB2, MCFD2, TFG, COG5, LMAN2, COL7A1, VTI1A
RANGRF, SEC22A, NRBP1, CTSC, ERGIC1
", "macroautophagy (GO:0016236)
P-value: 0.0019
FDR: 1.0
Z-score: 3.24
Combined score: 20.4
9 Genes: MTMR3, MTMR14, VPS4B, CHMP2B, ATG10, PLAA, ATG4B
ATG12, ATG5
", "ESCRT complex disassembly (GO:1904896)
P-value: 0.0016
FDR: 1.0
Z-score: 12.0
Combined score: 77.0
3 Genes: VPS4B, CHMP1A, CHMP2B
", "ESCRT III complex disassembly (GO:1904903)
P-value: 0.0016
FDR: 1.0
Z-score: 12.0
Combined score: 77.0
3 Genes: VPS4B, CHMP1A, CHMP2B
", "metaphase plate congression (GO:0051310)
P-value: 0.00084
FDR: 0.72
Z-score: 5.33
Combined score: 37.7
6 Genes: CDC23, VPS4B, PINX1, CHMP1A, CHMP2B, PIBF1
", "peptidyl-lysine monomethylation (GO:0018026)
P-value: 0.00079
FDR: 0.81
Z-score: 15.0
Combined score: 1.07e+02
3 Genes: SETD3, SETD6, SMYD2
", "mitotic metaphase plate congression (GO:0007080)
P-value: 0.00075
FDR: 0.95
Z-score: 5.45
Combined score: 39.3
6 Genes: CDC23, VPS4B, PINX1, CHMP1A, CHMP2B, PIBF1
", "autophagy of mitochondrion (GO:0000422)
P-value: 0.00051
FDR: 0.86
Z-score: 5.85
Combined score: 44.4
6 Genes: ATG4C, ATG4B, FBXO7, ATG12, ATG5, ATG4D
", "mitochondrion disassembly (GO:0061726)
P-value: 0.00038
FDR: 0.98
Z-score: 6.15
Combined score: 48.4
6 Genes: ATG4C, ATG4B, FBXO7, ATG12, ATG5, ATG4D
", "autophagy of nucleus (GO:0044804)
P-value: 0.00011
FDR: 0.55
Z-score: 10.0
Combined score: 91.3
5 Genes: ATG4C, ATG4B, ATG12, ATG4D, ATG5
" ], "marker": { "color": "#FA8072" }, "name": "Upregulated", "orientation": "h", "showlegend": false, "type": "bar", "uid": "15fb418d-cddc-43dc-843b-f5754b08b813", "x": [ 2.4285237576063854, 2.592162919153194, 2.6563377699160555, 2.6664643380763478, 2.673092693047238, 2.6873007384829686, 2.7250796713311045, 2.786541210804128, 2.786541210804128, 3.0737761193569337, 3.101305250360028, 3.1267867149202098, 3.2952303650789125, 3.416212318931749, 3.9636202529264817 ], "xaxis": "x", "y": [ "regulation of spindle assembly (GO:0090169)", "ubiquitin-dependent protein catabolic process (GO:0006511)", "positive regulation of sodium ion transmembrane transporter activity (GO:2000651)", "axonal transport (GO:0098930)", "histone acetylation (GO:0016573)", "ER to Golgi vesicle-mediated transport (GO:0006888)", "macroautophagy (GO:0016236)", "ESCRT complex disassembly (GO:1904896)", "ESCRT III complex disassembly (GO:1904903)", "metaphase plate congression (GO:0051310)", "peptidyl-lysine monomethylation (GO:0018026)", "mitotic metaphase plate congression (GO:0007080)", "autophagy of mitochondrion (GO:0000422)", "mitochondrion disassembly (GO:0061726)", "autophagy of nucleus (GO:0044804)" ], "yaxis": "y" }, { "hoverinfo": "none", "mode": "text", "showlegend": false, "text": [ "regulation of spindle assembly (GO:0090169)", "ubiquitin-dependent protein catabolic process (GO:0006511)", "positive regulation of sodium ion transmembrane transporter activity (GO:2000651)", "axonal transport (GO:0098930)", "histone acetylation (GO:0016573)", "ER to Golgi vesicle-mediated transport (GO:0006888)", "macroautophagy (GO:0016236)", "ESCRT complex disassembly (GO:1904896)", "ESCRT III complex disassembly (GO:1904903)", "metaphase plate congression (GO:0051310)", "peptidyl-lysine monomethylation (GO:0018026)", "mitotic metaphase plate congression (GO:0007080)", "autophagy of mitochondrion (GO:0000422)", "mitochondrion disassembly (GO:0061726)", "autophagy of nucleus (GO:0044804)" ], "textfont": { "color": "black" }, "textposition": "middle right", "type": "scatter", "uid": "246394b3-caac-4a1c-b5b5-779434a8e202", "x": [ 0.07927240505852963, 0.07927240505852963, 0.07927240505852963, 0.07927240505852963, 0.07927240505852963, 0.07927240505852963, 0.07927240505852963, 0.07927240505852963, 0.07927240505852963, 0.07927240505852963, 0.07927240505852963, 0.07927240505852963, 0.07927240505852963, 0.07927240505852963, 0.07927240505852963 ], "xaxis": "x", "y": [ "regulation of spindle assembly (GO:0090169)", "ubiquitin-dependent protein catabolic process (GO:0006511)", "positive regulation of sodium ion transmembrane transporter activity (GO:2000651)", "axonal transport (GO:0098930)", "histone acetylation (GO:0016573)", "ER to Golgi vesicle-mediated transport (GO:0006888)", "macroautophagy (GO:0016236)", "ESCRT complex disassembly (GO:1904896)", "ESCRT III complex disassembly (GO:1904903)", "metaphase plate congression (GO:0051310)", "peptidyl-lysine monomethylation (GO:0018026)", "mitotic metaphase plate congression (GO:0007080)", "autophagy of mitochondrion (GO:0000422)", "mitochondrion disassembly (GO:0061726)", "autophagy of nucleus (GO:0044804)" ], "yaxis": "y" }, { "hoverinfo": "text", "hovertext": [ "nuclear envelope disassembly (GO:0051081)
P-value: 0.0011
FDR: 0.36
Z-score: 5.11
Combined score: 34.9
6 Genes: NEK9, NUP205, SEH1L, NUP85, NUP62, PRKCA
", "neuron projection morphogenesis (GO:0048812)
P-value: 0.00088
FDR: 0.32
Z-score: 2.93
Combined score: 20.6
12 Genes: APP, BRSK2, DBNL, SLC9A6, FLRT3, DVL1, APBB1
CTNNA2, MAPK8IP2, S100B, LLGL1, MAP4K4
", "mitotic nuclear envelope disassembly (GO:0007077)
P-value: 0.00084
FDR: 0.33
Z-score: 5.33
Combined score: 37.7
6 Genes: NEK9, NUP205, SEH1L, NUP85, NUP62, PRKCA
", "protein phosphorylation (GO:0006468)
P-value: 0.00084
FDR: 0.36
Z-score: 2.04
Combined score: 14.4
24 Genes: CDKL2, APP, BRSK2, MAST1, EIF2AK3, DYRK1A, DCLK2
PRKCA, OXSR1, MAPK14, HIPK2, IGF1R, SMAD7, CCNA2
PINK1, LATS2, TAOK3, AKT2, PDK3, MAP3K7, CSNK1G2
MAP3K12, MAP4K4, CDK5R1
", "regulation of insulin secretion (GO:0050796)
P-value: 0.00084
FDR: 0.39
Z-score: 3.64
Combined score: 25.8
9 Genes: BRSK2, MARCKS, CACNA1A, IRS2, PRKCA, KCNA5, TM7SF3
SYT7, ARNTL
", "tRNA aminoacylation for mitochondrial protein translation (GO:0070127)
P-value: 0.00079
FDR: 0.4
Z-score: 15.0
Combined score: 1.07e+02
3 Genes: DARS2, YARS2, WARS2
", "gene expression (GO:0010467)
P-value: 0.00075
FDR: 0.42
Z-score: 2.14
Combined score: 15.4
22 Genes: UPF2, GTF3C2, NUP205, SEH1L, THRB, GTF3C6, GATB
DDX54, NOL9, CASC3, SMG7, GSPT2, YARS2, MRPS5
MRPL4, HNRNPUL1, NUP85, MED20, NUP62, DROSHA, SRSF4
EIF4G1
", "negative regulation of STAT cascade (GO:1904893)
P-value: 0.00058
FDR: 0.37
Z-score: 5.71
Combined score: 42.6
6 Genes: LEPROT, FLRT3, HGS, CAV1, SOCS6, SOCS5
", "negative regulation of protein kinase activity (GO:0006469)
P-value: 0.00044
FDR: 0.32
Z-score: 3.64
Combined score: 28.1
10 Genes: CDKN1B, FLRT3, CAV1, DVL1, ITGB1BP1, ADARB1, TRIB1
SOCS6, PPM1E, IGF1R
", "regulation of protein secretion (GO:0050708)
P-value: 0.00038
FDR: 0.32
Z-score: 3.7
Combined score: 29.2
10 Genes: MARCKS, TGFB3, CACNA1A, PRKCA, STXBP5, KCNA5, MYH10
LLGL1, SYT7, ARNTL
", "positive regulation of glycogen metabolic process (GO:0070875)
P-value: 0.00032
FDR: 0.32
Z-score: 11.4
Combined score: 92.1
4 Genes: EPM2AIP1, AKT2, IRS2, SORBS1
", "regulation of cellular response to stress (GO:0080135)
P-value: 0.0003
FDR: 0.38
Z-score: 3.81
Combined score: 30.9
10 Genes: DNAJC2, NUP205, PINK1, SEH1L, NUP85, NUP62, HSF1
MCL1, EIF4G1, ARNTL
", "positive regulation of glycogen biosynthetic process (GO:0045725)
P-value: 0.00023
FDR: 0.39
Z-score: 12.3
Combined score: 1.03e+02
4 Genes: EPM2AIP1, AKT2, IRS2, SORBS1
", "peptidyl-serine modification (GO:0018209)
P-value: 0.00011
FDR: 0.27
Z-score: 3.27
Combined score: 30.0
14 Genes: MAST1, DYRK1A, EIF2AK3, DCLK2, PRKCA, MAPK14, HIPK2
PINK1, LATS2, AKT2, PDK3, CSNK1G2, MAP3K12, CDK5R1
", "peptidyl-serine phosphorylation (GO:0018105)
P-value: 1.8e-05
FDR: 0.094
Z-score: 3.84
Combined score: 41.8
14 Genes: MAST1, DYRK1A, EIF2AK3, DCLK2, PRKCA, MAPK14, HIPK2
PINK1, LATS2, AKT2, PDK3, CSNK1G2, MAP3K12, CDK5R1
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P-value: 0.0088
FDR: 0.67
Z-score: 13.3
Combined score: 63.2
2 Genes: FMR1, MCRS1
", "histone methyltransferase activity (H3-K36 specific) (GO:0046975)
P-value: 0.0088
FDR: 0.72
Z-score: 13.3
Combined score: 63.2
2 Genes: SETD3, SMYD2
", "H4 histone acetyltransferase activity (GO:0010485)
P-value: 0.0081
FDR: 0.72
Z-score: 7.06
Combined score: 34.0
3 Genes: NAA50, MCRS1, HAT1
", "poly(U) RNA binding (GO:0008266)
P-value: 0.0068
FDR: 0.65
Z-score: 7.5
Combined score: 37.4
3 Genes: FMR1, MCRS1, PATL1
", "damaged DNA binding (GO:0003684)
P-value: 0.0062
FDR: 0.65
Z-score: 4.26
Combined score: 21.6
5 Genes: PNKP, ERCC1, APEX1, GTF2H3, APTX
", "phosphatidylinositol-3-phosphatase activity (GO:0004438)
P-value: 0.0046
FDR: 0.53
Z-score: 8.57
Combined score: 46.1
3 Genes: MTMR1, MTMR3, MTMR14
", "phosphatidylinositol monophosphate phosphatase activity (GO:0052744)
P-value: 0.0046
FDR: 0.59
Z-score: 8.57
Combined score: 46.1
3 Genes: MTMR1, MTMR3, MTMR14
", "pyrophosphatase activity (GO:0016462)
P-value: 0.0038
FDR: 0.55
Z-score: 4.76
Combined score: 26.5
5 Genes: ENTPD5, NUDT6, DCPS, NUDT14, ITPA
", "protein methyltransferase activity (GO:0008276)
P-value: 0.0038
FDR: 0.62
Z-score: 4.76
Combined score: 26.5
5 Genes: METTL22, SETD3, SETD6, SMYD2, WDR77
", "phosphatidylinositol-3,5-bisphosphate 3-phosphatase activity (GO:0052629)
P-value: 0.0029
FDR: 0.55
Z-score: 10.0
Combined score: 58.5
3 Genes: MTMR1, MTMR3, MTMR14
", "lysine N-methyltransferase activity (GO:0016278)
P-value: 0.002
FDR: 0.45
Z-score: 7.27
Combined score: 45.3
4 Genes: METTL22, SETD3, SETD6, SMYD2
", "poly(G) binding (GO:0034046)
P-value: 0.0005
FDR: 0.15
Z-score: 17.1
Combined score: 1.3e+02
3 Genes: FMR1, MCRS1, PATL1
", "phosphatidylinositol-3,5-bisphosphate phosphatase activity (GO:0106018)
P-value: 0.00042
FDR: 0.16
Z-score: 10.7
Combined score: 82.9
4 Genes: FIG4, MTMR1, MTMR3, MTMR14
", "cysteine-type endopeptidase activity (GO:0004197)
P-value: 0.00021
FDR: 0.12
Z-score: 4.39
Combined score: 37.3
9 Genes: USP8, USP14, USP7, ATG4C, ATG4B, CTSF, CTSS
CTSC, ATG4D
", "cysteine-type peptidase activity (GO:0008234)
P-value: 3.7e-05
FDR: 0.043
Z-score: 5.45
Combined score: 55.7
9 Genes: USP8, USP14, USP7, ATG4C, ATG4B, CTSF, CTSS
CTSC, ATG4D
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P-value: 0.011
FDR: 0.88
Z-score: 1.81
Combined score: 8.1
18 Genes: BRSK2, MAST1, TWF1, DARS2, NOL9, OXSR1, YARS2
SYN1, RHOBTB2, PINK1, LATS2, PPIP5K2, AKT2, LANCL2
PDK3, MYH10, EIF4G1, MAP4K4
", "repressing transcription factor binding (GO:0070491)
P-value: 0.011
FDR: 0.91
Z-score: 3.7
Combined score: 16.7
5 Genes: TCERG1, HDAC5, PRDM5, DMAP1, ARNTL
", "RNA polymerase II transcription cofactor activity (GO:0001104)
P-value: 0.0054
FDR: 0.48
Z-score: 3.29
Combined score: 17.2
7 Genes: TCERG1, MED14, URI1, PHF12, SOX12, MED17, HIPK2
", "tRNA binding (GO:0000049)
P-value: 0.0027
FDR: 0.26
Z-score: 5.13
Combined score: 30.3
5 Genes: YRDC, NAT10, DARS2, NSUN6, YARS2
", "protein kinase inhibitor activity (GO:0004860)
P-value: 0.0015
FDR: 0.16
Z-score: 4.12
Combined score: 26.7
7 Genes: CDKN1B, TAOK3, FLRT3, TRIB1, SOCS6, NCK1, SOCS5
", "protein kinase activity (GO:0004672)
P-value: 0.0013
FDR: 0.15
Z-score: 1.95
Combined score: 13.0
25 Genes: BRSK2, MAST1, PPM1D, IGF1R, AKT2, PDK3, MAP3K7
MAP4K4, CDKL2, SRPK3, MMD, DYRK1A, EIF2AK3, DCLK2
PRKCA, OXSR1, MAPK14, HIPK2, CCNA2, PINK1, LATS2
TAOK3, CSNK1G2, MAP3K12, CDK5R1
", "adenyl ribonucleotide binding (GO:0032559)
P-value: 0.00073
FDR: 0.093
Z-score: 2.43
Combined score: 17.5
17 Genes: BRSK2, MAST1, TWF1, DARS2, NOL9, OXSR1, YARS2
SYN1, PINK1, LATS2, PPIP5K2, AKT2, LANCL2, PDK3
MYH10, MAP4K4, EIF4G1
", "kinase inhibitor activity (GO:0019210)
P-value: 0.00072
FDR: 0.1
Z-score: 4.67
Combined score: 33.8
7 Genes: CDKN1B, TAOK3, FLRT3, TRIB1, SOCS6, NCK1, SOCS5
", "peptidase activator activity (GO:0016504)
P-value: 0.00055
FDR: 0.091
Z-score: 10.0
Combined score: 75.0
4 Genes: PINK1, CAV1, PSME3, EBAG9
", "RNA binding (GO:0003723)
P-value: 0.00048
FDR: 0.091
Z-score: 1.59
Combined score: 12.1
55 Genes: RBM27, TCERG1, CCDC47, WDR3, NAT10, NUCKS1, ADARB1
CASC3, SMG7, TFB1M, YARS2, IPO5, CCAR1, MRPL4
RIMS1, LUC7L, KIF1C, SNRNP35, RBM33, ZC3H10, SCAF11
WDR75, DDX54, DARS2, NSUN6, IMP4, MRPS5, CKAP4
DNAJC2, HNRNPUL1, NFX1, SRSF4, NAF1, EIF4E2, ANP32A
USP10, MEPCE, NOL8, GSPT2, EXOSC6, ZMAT3, EXOSC9
DROSHA, LTA4H, MYH10, RDX, GATB, MEX3C, TDRD3
YRDC, CCDC9, TRMT6, CEBPZ, PRPF31, EIF4G1
", "ATP binding (GO:0005524)
P-value: 0.00026
FDR: 0.06
Z-score: 2.66
Combined score: 21.9
17 Genes: BRSK2, MAST1, TWF1, DARS2, NOL9, OXSR1, YARS2
SYN1, PINK1, LATS2, PPIP5K2, AKT2, LANCL2, PDK3
MYH10, MAP4K4, EIF4G1
", "kinase binding (GO:0019900)
P-value: 0.00016
FDR: 0.045
Z-score: 2.29
Combined score: 20.1
24 Genes: SLC12A2, NEK9, SHC2, CDKN1B, FBXW5, MAPKAP1, CAV1
CADPS, HTT, KCNA5, MAPK8IP2, SYN1, RHOBTB2, TTC28
GOLGA2, CCNA2, SV2A, TRAF6, DVL1, HSF1, CEP250
LLGL1, MAP3K12, CDK5R1
", "insulin receptor binding (GO:0005158)
P-value: 8.3e-05
FDR: 0.032
Z-score: 10.5
Combined score: 98.9
5 Genes: SNX1, IRS2, PTPN11, SORBS1, IGF1R
", "protein serine/threonine kinase activity (GO:0004674)
P-value: 6.1e-05
FDR: 0.035
Z-score: 2.49
Combined score: 24.2
23 Genes: CDKL2, SRPK3, BRSK2, CDKN1B, MAST1, EIF2AK3, DYRK1A
DCLK2, PRKCA, OXSR1, PPM1D, MAPK14, HIPK2, PINK1
LATS2, TAOK3, AKT2, PDK3, MNAT1, MAP3K7, CSNK1G2
MAP4K4, MAP3K12
", "protein kinase binding (GO:0019901)
P-value: 5.8e-05
FDR: 0.067
Z-score: 2.26
Combined score: 22.0
28 Genes: HDAC5, SHC2, CDKN1B, PRKCSH, MAPKAP1, KCNA5, PPM1D
RHOBTB2, IGF1R, GOLGA2, SV2A, DVL1, HSF1, CEP250
SLC12A2, NEK9, FBXW5, CAV1, CADPS, MAPK8IP2, SYN1
CCNA2, PINK1, TRAF6, TRIB1, LLGL1, MAP3K12, CDK5R1
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P-value: 0.042
FDR: 1.0
Z-score: 2.63
Combined score: 8.37
5 Genes: MCFD2, LMAN2, COL7A1, VTI1A, CTSC
", "chromosome, telomeric region (GO:0000781)
P-value: 0.038
FDR: 1.0
Z-score: 2.24
Combined score: 7.35
7 Genes: ORC1, ERCC1, APEX1, NSMCE2, HAT1, PINX1, NHP2
", "coated vesicle (GO:0030135)
P-value: 0.034
FDR: 1.0
Z-score: 2.78
Combined score: 9.38
5 Genes: CCDC115, LMAN2, COL7A1, VTI1A, CTSC
", "MLL1 complex (GO:0071339)
P-value: 0.032
FDR: 1.0
Z-score: 4.29
Combined score: 14.7
3 Genes: INO80C, MCRS1, RUVBL1
", "MLL1/2 complex (GO:0044665)
P-value: 0.032
FDR: 1.0
Z-score: 4.29
Combined score: 14.7
3 Genes: INO80C, MCRS1, RUVBL1
", "preribosome, small subunit precursor (GO:0030688)
P-value: 0.025
FDR: 1.0
Z-score: 8.0
Combined score: 29.6
2 Genes: LTV1, NOB1
", "N-terminal protein acetyltransferase complex (GO:0031414)
P-value: 0.025
FDR: 1.0
Z-score: 8.0
Combined score: 29.6
2 Genes: NAA50, NAA35
", "Swr1 complex (GO:0000812)
P-value: 0.02
FDR: 1.0
Z-score: 8.89
Combined score: 34.8
2 Genes: ING3, RUVBL1
", "cullin-RING ubiquitin ligase complex (GO:0031461)
P-value: 0.016
FDR: 1.0
Z-score: 2.2
Combined score: 9.03
10 Genes: SPSB2, CDC23, KCTD10, FBXO25, FBXO4, CUL1, ERCC8
BTRC, FBXO7, ANAPC10
", "nucleolus (GO:0005730)
P-value: 0.012
FDR: 0.89
Z-score: 1.6
Combined score: 7.06
27 Genes: SETD3, DDX25, PNKP, FMR1, PINX1, MRPS31, ORC1
SURF6, DTD1, ZC3H15, PCGF5, PNO1, PARP2, MCRS1
DDX52, GNL2, MIF4GD, APTX, UTP18, PUM3, GNL3
METTL22, KLF6, APEX1, MORF4L2, ANP32B, KDM7A
", "nuclear chromosome part (GO:0044454)
P-value: 0.01
FDR: 0.93
Z-score: 1.83
Combined score: 8.36
18 Genes: CENPT, INO80C, KLHDC3, SETD3, MCRS1, GINS4, PINX1
APTX, SYCE2, ING3, ORC1, APEX1, ERCC1, RUVBL1
HAT1, POLE3, NHP2, TAF5
", "Ino80 complex (GO:0031011)
P-value: 0.0056
FDR: 0.63
Z-score: 8.0
Combined score: 41.4
3 Genes: INO80C, MCRS1, RUVBL1
", "endoplasmic reticulum-Golgi intermediate compartment (GO:0005793)
P-value: 0.0028
FDR: 0.42
Z-score: 3.33
Combined score: 19.6
8 Genes: ERP44, MCFD2, CCDC115, LMAN2, COL7A1, CTSC, ERGIC1
NUCB2
", "SCF ubiquitin ligase complex (GO:0019005)
P-value: 0.0024
FDR: 0.54
Z-score: 4.36
Combined score: 26.3
6 Genes: SPSB2, FBXO25, FBXO4, CUL1, BTRC, FBXO7
", "INO80-type complex (GO:0097346)
P-value: 0.002
FDR: 0.88
Z-score: 7.27
Combined score: 45.3
4 Genes: INO80C, ING3, MCRS1, RUVBL1
" ], "marker": { "color": "#FA8072" }, "name": "Upregulated", "orientation": "h", "showlegend": false, "type": "bar", "uid": "d8b0c2b7-04d8-4897-86bf-a5e53934f294", "x": [ 1.3808207287732666, 1.4241973696701369, 1.466965985925766, 1.4945389064528258, 1.4945389064528258, 1.6094942765704183, 1.6094942765704183, 1.699241560472231, 1.783427512994717, 1.9222337726118823, 1.9813250910623919, 2.2481034067689922, 2.5531354343073733, 2.6135469929010737, 2.7047076375442405 ], "xaxis": "x", "y": [ "COPII-coated ER to Golgi transport vesicle (GO:0030134)", "chromosome, telomeric region (GO:0000781)", "coated vesicle (GO:0030135)", "MLL1 complex (GO:0071339)", "MLL1/2 complex (GO:0044665)", "preribosome, small subunit precursor (GO:0030688)", "N-terminal protein acetyltransferase complex (GO:0031414)", "Swr1 complex (GO:0000812)", "cullin-RING ubiquitin ligase complex (GO:0031461)", "nucleolus (GO:0005730)", "nuclear chromosome part (GO:0044454)", "Ino80 complex (GO:0031011)", "endoplasmic reticulum-Golgi intermediate compartment (GO:0005793)", "SCF ubiquitin ligase complex (GO:0019005)", "INO80-type complex (GO:0097346)" ], "yaxis": "y" }, { "hoverinfo": "none", "mode": "text", "showlegend": false, "text": [ "COPII-coated ER to Golgi transport vesicle (GO:0030134)", "chromosome, telomeric region (GO:0000781)", "coated vesicle (GO:0030135)", "MLL1 complex (GO:0071339)", "MLL1/2 complex (GO:0044665)", "preribosome, small subunit precursor (GO:0030688)", "N-terminal protein acetyltransferase complex (GO:0031414)", "Swr1 complex (GO:0000812)", "cullin-RING ubiquitin ligase complex (GO:0031461)", "nucleolus (GO:0005730)", "nuclear chromosome part (GO:0044454)", "Ino80 complex (GO:0031011)", "endoplasmic reticulum-Golgi intermediate compartment (GO:0005793)", "SCF ubiquitin ligase complex (GO:0019005)", "INO80-type complex (GO:0097346)" ], "textfont": { "color": "black" }, "textposition": "middle right", "type": "scatter", "uid": "777dc215-36e8-44c1-84de-f2f0c36c5204", "x": [ 0.05409415275088481, 0.05409415275088481, 0.05409415275088481, 0.05409415275088481, 0.05409415275088481, 0.05409415275088481, 0.05409415275088481, 0.05409415275088481, 0.05409415275088481, 0.05409415275088481, 0.05409415275088481, 0.05409415275088481, 0.05409415275088481, 0.05409415275088481, 0.05409415275088481 ], "xaxis": "x", "y": [ "COPII-coated ER to Golgi transport vesicle (GO:0030134)", "chromosome, telomeric region (GO:0000781)", "coated vesicle (GO:0030135)", "MLL1 complex (GO:0071339)", "MLL1/2 complex (GO:0044665)", "preribosome, small subunit precursor (GO:0030688)", "N-terminal protein acetyltransferase complex (GO:0031414)", "Swr1 complex (GO:0000812)", "cullin-RING ubiquitin ligase complex (GO:0031461)", "nucleolus (GO:0005730)", "nuclear chromosome part (GO:0044454)", "Ino80 complex (GO:0031011)", "endoplasmic reticulum-Golgi intermediate compartment (GO:0005793)", "SCF ubiquitin ligase complex (GO:0019005)", "INO80-type complex (GO:0097346)" ], "yaxis": "y" }, { "hoverinfo": "text", "hovertext": [ "centriolar satellite (GO:0034451)
P-value: 0.026
FDR: 0.73
Z-score: 4.62
Combined score: 16.8
3 Genes: C2CD3, CEP290, SSX2IP
", "lipid droplet (GO:0005811)
P-value: 0.023
FDR: 0.74
Z-score: 3.08
Combined score: 11.6
5 Genes: NSDHL, TRAF6, CAV1, LSS, CKAP4
", "RNA polymerase III transcription factor complex (GO:0090576)
P-value: 0.016
FDR: 0.54
Z-score: 10.0
Combined score: 41.5
2 Genes: GTF3C2, GTF3C6
", "microtubule minus-end (GO:0036449)
P-value: 0.016
FDR: 0.59
Z-score: 10.0
Combined score: 41.5
2 Genes: NIN, CAMSAP2
", "core mediator complex (GO:0070847)
P-value: 0.016
FDR: 0.64
Z-score: 10.0
Combined score: 41.5
2 Genes: MED14, MED17
", "Cul4-RING E3 ubiquitin ligase complex (GO:0080008)
P-value: 0.013
FDR: 0.59
Z-score: 4.32
Combined score: 18.7
4 Genes: CDKN1B, FBXW5, DCAF12L1, DDB2
", "RNA polymerase II transcription factor complex (GO:0090575)
P-value: 0.012
FDR: 0.61
Z-score: 2.43
Combined score: 10.7
9 Genes: TLE3, MED14, THRB, TAF13, ERCC5, MNAT1, E2F6
MED17, HIPK2
", "transcription factor TFIIIC complex (GO:0000127)
P-value: 0.0088
FDR: 0.49
Z-score: 13.3
Combined score: 63.2
2 Genes: GTF3C2, GTF3C6
", "nucleolus (GO:0005730)
P-value: 0.0067
FDR: 0.43
Z-score: 1.65
Combined score: 8.29
28 Genes: FEN1, WDR3, GEMIN2, PRDM5, NAT10, NOL8, XPC
NUCKS1, NOL9, ADARB1, PPM1E, EXOSC6, EXOSC9, PDK3
SNRNP35, PDHA1, TRIM41, SCAF11, TAF13, WDR75, MAD2L1BP
DDX54, IMP4, NIN, CDKN2AIPNL, NFX1, MOB2, WDFY3
", "spindle pole (GO:0000922)
P-value: 0.0057
FDR: 0.43
Z-score: 2.96
Combined score: 15.3
8 Genes: GOLGA2, NIN, LATS2, FBF1, NUP62, HSF1, EML1
CDC14A
", "mitotic spindle (GO:0072686)
P-value: 0.0013
FDR: 0.11
Z-score: 3.76
Combined score: 25.1
8 Genes: GOLGA2, ATAT1, NIN, HECW2, NUP62, HSF1, EML1
CDC14A
", "endoplasmic reticulum-Golgi intermediate compartment membrane (GO:0033116)
P-value: 0.0012
FDR: 0.13
Z-score: 5.0
Combined score: 33.7
6 Genes: GOLGA2, TBC1D20, GOSR2, GORASP1, TMED3, YKT6
", "nuclear body (GO:0016604)
P-value: 0.00096
FDR: 0.14
Z-score: 1.87
Combined score: 13.0
29 Genes: MDC1, HDAC5, ZCCHC12, THRB, GTF3C6, GEMIN2, PRDM5
EHMT1, ARRB1, YARS2, CDC14A, HSF1, NELFA, RREB1
BRD2, TRIM41, WTAP, SCAF11, TINF2, DYRK1A, MAPK14
CKAP4, HIPK2, THAP7, AAGAB, SRSF4, PRPF31, WDFY3
ITGB1BP1
", "nucleoplasm part (GO:0044451)
P-value: 0.00027
FDR: 0.06
Z-score: 2.25
Combined score: 18.6
23 Genes: MDC1, URI1, TRIM41, THRB, GTF3C6, SCAF11, TAF13
GEMIN2, TINF2, PRDM5, EHMT1, ARRB1, YARS2, CDC14A
MED17, HIPK2, MED14, KANSL2, ITGB1BP1, ERCC5, NELFA
MNAT1, RREB1
", "axon (GO:0030424)
P-value: 0.00024
FDR: 0.11
Z-score: 3.38
Combined score: 28.2
12 Genes: APP, MTMR2, PINK1, DYRK1A, KIF1C, HTT, KCNA6
CTNNA2, CPT1C, LLGL1, IGF1R, CDK5R1
" ], "marker": { "color": "#87CEFA" }, "name": "Downregulated", "orientation": "h", "showlegend": false, "type": "bar", "uid": "a52558ed-e1c4-4264-ba4d-5cdcf41a7dee", "x": [ 1.5790657644871438, 1.635096240969572, 1.801207848533266, 1.801207848533266, 1.801207848533266, 1.8768468338652915, 1.9124530810898408, 2.0578722091422117, 2.1754023157796483, 2.241213870233918, 2.890129056555879, 2.9231569462020475, 3.015793241917603, 3.57287528199221, 3.619101453535678 ], "xaxis": "x2", "y": [ "centriolar satellite (GO:0034451)", "lipid droplet (GO:0005811)", "RNA polymerase III transcription factor complex (GO:0090576)", "microtubule minus-end (GO:0036449)", "core mediator complex (GO:0070847)", "Cul4-RING E3 ubiquitin ligase complex (GO:0080008)", "RNA polymerase II transcription factor complex (GO:0090575)", "transcription factor TFIIIC complex (GO:0000127)", "nucleolus (GO:0005730)", "spindle pole (GO:0000922)", "mitotic spindle (GO:0072686)", "endoplasmic reticulum-Golgi intermediate compartment membrane (GO:0033116)", "nuclear body (GO:0016604)", "nucleoplasm part (GO:0044451)", "axon (GO:0030424)" ], "yaxis": "y2" }, { "hoverinfo": "none", "mode": "text", "showlegend": false, "text": [ "centriolar satellite (GO:0034451)", "lipid droplet (GO:0005811)", "RNA polymerase III transcription factor complex (GO:0090576)", "microtubule minus-end (GO:0036449)", "core mediator complex (GO:0070847)", "Cul4-RING E3 ubiquitin ligase complex (GO:0080008)", "RNA polymerase II transcription factor complex (GO:0090575)", "transcription factor TFIIIC complex (GO:0000127)", "nucleolus (GO:0005730)", "spindle pole (GO:0000922)", "mitotic spindle (GO:0072686)", "endoplasmic reticulum-Golgi intermediate compartment membrane (GO:0033116)", "nuclear body (GO:0016604)", "*nucleoplasm part (GO:0044451)", "axon (GO:0030424)" ], "textfont": { "color": "black" }, "textposition": "middle right", "type": "scatter", "uid": "bf1f6c67-f9bc-440f-80b2-a93cff68c897", "x": [ 0.07238202907071356, 0.07238202907071356, 0.07238202907071356, 0.07238202907071356, 0.07238202907071356, 0.07238202907071356, 0.07238202907071356, 0.07238202907071356, 0.07238202907071356, 0.07238202907071356, 0.07238202907071356, 0.07238202907071356, 0.07238202907071356, 0.07238202907071356, 0.07238202907071356 ], "xaxis": "x2", "y": [ "centriolar satellite (GO:0034451)", "lipid droplet (GO:0005811)", "RNA polymerase III transcription factor complex (GO:0090576)", "microtubule minus-end (GO:0036449)", "core mediator complex (GO:0070847)", "Cul4-RING E3 ubiquitin ligase complex (GO:0080008)", "RNA polymerase II transcription factor complex (GO:0090575)", "transcription factor TFIIIC complex (GO:0000127)", "nucleolus (GO:0005730)", "spindle pole (GO:0000922)", "mitotic spindle (GO:0072686)", "endoplasmic reticulum-Golgi intermediate compartment membrane (GO:0033116)", "nuclear body (GO:0016604)", "nucleoplasm part (GO:0044451)", "axon (GO:0030424)" ], "yaxis": "y2" } ], "layout": { "annotations": [ { "showarrow": false, "text": "Up-regulated in Perturbation", "x": 0.25, "xanchor": "center", "xref": "paper", "y": 1.06, "yref": "paper" }, { "showarrow": false, "text": "Down-regulated in Perturbation", "x": 0.75, "xanchor": "center", "xref": "paper", "y": 1.06, "yref": "paper" } ], "height": 400, "hovermode": "closest", "margin": { "b": 35, "l": 0, "r": 0, "t": 65 }, "title": { "text": "Control vs Perturbation | Gene Ontology Cellular Component (2018 version)" }, "xaxis": { "anchor": "y", "domain": [ 0, 0.49 ], "title": { "text": "-log10P" } }, "xaxis2": { "anchor": "y2", "domain": [ 0.51, 1 ], "title": { "text": "-log10P" } }, "yaxis": { "anchor": "x", "domain": [ 0.0, 1.0 ], "showticklabels": false }, "yaxis2": { "anchor": "x2", "domain": [ 0.0, 1.0 ], "showticklabels": false } } }, "text/html": [ "
" ], "text/vnd.plotly.v1+html": [ "
" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/html": [ " Download" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/html": [ "" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/markdown": [ "** Figure 3 | Gene Ontology Enrichment Analysis Results. **The figure contains interactive bar charts displaying the results of the Gene Ontology enrichment analysis generated using Enrichr. The x axis indicates the -log10(P-value) for each term. Significant terms are highlighted in bold. Additional information about enrichment results is available by hovering over each bar. If you are experiencing issues visualizing the plot, please visit our Troubleshooting guide." ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" } ], "source": [ "# Initialize results\n", "results['go_enrichment'] = {}\n", "\n", "# Loop through results\n", "for label, enrichr_results in results['enrichr'].items():\n", "\n", " # Run analysis\n", " results['go_enrichment'][label] = analyze(enrichr_results=enrichr_results['results'], tool='go_enrichment', signature_label=label, plot_type='interactive', go_version=2018, sort_results_by='pvalue')\n", "\n", " # Display results\n", " plot(results['go_enrichment'][label])" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "---\n", " ## 6. Pathway Enrichment Analysis\n", "Biological pathways are sequences of interactions between biochemical compounds which play a key role in determining cellular behavior. Databases such as KEGG, Reactome and WikiPathways contain a large number of associations between such pathways and genes. This information can be leveraged by Enrichr to identify the biological pathways which are over-represented in the up-regulated and down-regulated genes identified by comparing two groups of samples." ] }, { "cell_type": "code", "execution_count": 9, "metadata": { "task": "pathway_enrichment" }, "outputs": [ { "data": { "application/vnd.plotly.v1+json": { "config": { "linkText": "Export to plot.ly", "plotlyServerURL": "https://plot.ly", "showLink": false }, "data": [ { "hoverinfo": "text", "hovertext": [ "p53 signaling pathway_Homo sapiens_hsa04115
P-value: 0.094
FDR: 1.0
Z-score: 2.32
Combined score: 5.48
4 Genes: SESN3, SESN1, IGF1, GADD45G
", "Lysosome_Homo sapiens_hsa04142
P-value: 0.088
FDR: 1.0
Z-score: 1.95
Combined score: 4.73
6 Genes: ACP2, CTSF, GLA, CTSS, CTSC, AP1M1
", "Porphyrin and chlorophyll metabolism_Homo sapiens_hsa00860
P-value: 0.087
FDR: 1.0
Z-score: 2.86
Combined score: 6.97
3 Genes: ALAD, UROD, UROS
", "Shigellosis_Homo sapiens_hsa05131
P-value: 0.08
FDR: 1.0
Z-score: 2.46
Combined score: 6.23
4 Genes: MAPK9, ELMO1, BTRC, ATG5
", "RNA transport_Homo sapiens_hsa03013
P-value: 0.068
FDR: 1.0
Z-score: 1.86
Combined score: 5.01
8 Genes: EIF2B2, FMR1, POP4, AAAS, EIF2B1, RPP25L, SNUPN
NUP37
", "Apoptosis_Homo sapiens_hsa04210
P-value: 0.062
FDR: 1.0
Z-score: 2.0
Combined score: 5.56
7 Genes: MAPK9, PARP2, CTSF, FOS, CTSS, CTSC, GADD45G
", "Base excision repair_Homo sapiens_hsa03410
P-value: 0.049
FDR: 1.0
Z-score: 3.64
Combined score: 11.0
3 Genes: PARP2, APEX1, POLE3
", "Glycosphingolipid biosynthesis - globo series_Homo sapiens_hsa00603
P-value: 0.047
FDR: 1.0
Z-score: 5.71
Combined score: 17.5
2 Genes: FUT1, GLA
", "Propanoate metabolism_Homo sapiens_hsa00640
P-value: 0.045
FDR: 1.0
Z-score: 3.75
Combined score: 11.6
3 Genes: LDHB, MUT, ACAT1
", "Herpes simplex infection_Homo sapiens_hsa05168
P-value: 0.043
FDR: 1.0
Z-score: 1.95
Combined score: 6.11
9 Genes: IFNAR2, MAPK9, USP7, TRAF3, EEF1D, MCRS1, CUL1
FOS, TAF5
", "Ubiquitin mediated proteolysis_Homo sapiens_hsa04120
P-value: 0.022
FDR: 1.0
Z-score: 2.34
Combined score: 8.92
8 Genes: HERC4, CDC23, FBXO4, CUL1, UBE4A, ERCC8, BTRC
ANAPC10
", "Ribosome biogenesis in eukaryotes_Homo sapiens_hsa03008
P-value: 0.0069
FDR: 0.51
Z-score: 3.15
Combined score: 15.6
7 Genes: NOB1, POP4, NHP2, GNL2, UTP18, RPP25L, GNL3
", "Nucleotide excision repair_Homo sapiens_hsa03420
P-value: 0.0062
FDR: 0.6
Z-score: 4.26
Combined score: 21.6
5 Genes: ERCC1, POLE3, ERCC8, RAD23A, GTF2H3
", "Protein processing in endoplasmic reticulum_Homo sapiens_hsa04141
P-value: 0.0036
FDR: 0.52
Z-score: 2.6
Combined score: 14.7
11 Genes: MAPK9, MAN1A2, LMAN2, CUL1, PLAA, RAD23A, SIL1
HSPBP1, RNF5, DDOST, NFE2L2
", "Regulation of autophagy_Homo sapiens_hsa04140
P-value: 0.00038
FDR: 0.11
Z-score: 6.15
Combined score: 48.4
6 Genes: ATG10, ATG4C, ATG4B, ATG12, ATG5, ATG4D
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P-value: 0.036
FDR: 0.66
Z-score: 2.74
Combined score: 9.11
5 Genes: SHC2, CDKN1B, TGFB3, AKT2, PTPN11
", "Prolactin signaling pathway_Homo sapiens_hsa04917
P-value: 0.034
FDR: 0.71
Z-score: 2.78
Combined score: 9.38
5 Genes: SHC2, AKT2, SOCS6, MAPK14, SOCS5
", "Nucleotide excision repair_Homo sapiens_hsa03420
P-value: 0.03
FDR: 0.67
Z-score: 3.4
Combined score: 12.0
4 Genes: XPC, ERCC5, MNAT1, DDB2
", "RNA transport_Homo sapiens_hsa03013
P-value: 0.029
FDR: 0.71
Z-score: 2.09
Combined score: 7.39
9 Genes: UPF2, NUP205, SEH1L, NUP85, GEMIN2, NUP62, CASC3
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P-value: 0.029
FDR: 0.78
Z-score: 2.9
Combined score: 10.3
5 Genes: GK, ACSL6, SORBS1, CPT1C, RXRG
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P-value: 0.028
FDR: 0.81
Z-score: 2.94
Combined score: 10.6
5 Genes: FCER1G, AKT2, PLA2G4B, PRKCA, MAPK14
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P-value: 0.024
FDR: 0.79
Z-score: 2.7
Combined score: 10.0
6 Genes: WDR3, NAT10, WDR75, DROSHA, IMP4, SPATA5
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P-value: 0.022
FDR: 0.8
Z-score: 2.76
Combined score: 10.5
6 Genes: SHC2, CDKN1B, AKT2, PRKCA, ELK1, NCK1
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P-value: 0.018
FDR: 0.76
Z-score: 3.28
Combined score: 13.2
5 Genes: SHC2, AKT2, PLA2G4B, PRKCA, MAPK14
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P-value: 0.017
FDR: 0.83
Z-score: 3.33
Combined score: 13.6
5 Genes: PLCB4, PLA2G4B, CACNA1A, PRKCA, IGF1R
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P-value: 0.015
FDR: 0.87
Z-score: 2.72
Combined score: 11.5
7 Genes: PDHA1, CDKN1B, ANGPT1, AKT2, PRKCA, EIF4E2, IGF1R
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P-value: 0.011
FDR: 0.84
Z-score: 2.86
Combined score: 12.8
7 Genes: ITPKB, MTMR2, PLCB4, PPIP5K2, PRKCA, PIP4K2C, CDS2
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P-value: 0.0096
FDR: 0.94
Z-score: 2.71
Combined score: 12.6
8 Genes: MED14, THRB, PLCB4, AKT2, PRKCA, RXRG, PFKP
MED17
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P-value: 0.0081
FDR: 1.0
Z-score: 3.43
Combined score: 16.5
6 Genes: AKT2, ACSL6, IRS2, PTPN11, CPT1C, RXRG
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P-value: 8.1e-05
FDR: 0.024
Z-score: 2.82
Combined score: 26.6
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FDR: 1.0
Z-score: 2.61
Combined score: 5.82
3 Genes: EIF2B2, EEF1D, EIF2B1
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FDR: 1.0
Z-score: 1.81
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7 Genes: MAPK9, PRKCB, BDNF, FOS, MAPT, MAP3K4, STK3
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FDR: 1.0
Z-score: 3.0
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FDR: 1.0
Z-score: 2.5
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4 Genes: SESN3, SESN1, IGF1, GADD45G
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FDR: 1.0
Z-score: 1.9
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FDR: 1.0
Z-score: 5.0
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2 Genes: FOS, NFE2L2
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FDR: 1.0
Z-score: 3.43
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FDR: 1.0
Z-score: 6.15
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2 Genes: SLC33A1, FUT1
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FDR: 1.0
Z-score: 6.15
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2 Genes: PRKCB, FOS
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P-value: 0.03
FDR: 1.0
Z-score: 3.4
Combined score: 12.0
4 Genes: CREM, FOS, TRNAU1AP, NFE2L2
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P-value: 0.028
FDR: 1.0
Z-score: 3.48
Combined score: 12.5
4 Genes: CREM, FOS, TRNAU1AP, NFE2L2
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P-value: 0.0081
FDR: 0.89
Z-score: 7.06
Combined score: 34.0
3 Genes: PRKCB, FMR1, FOS
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P-value: 0.0071
FDR: 1.0
Z-score: 5.16
Combined score: 25.5
4 Genes: GSTT2, CYBA, FOS, NFE2L2
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P-value: 0.0012
FDR: 0.25
Z-score: 13.3
Combined score: 90.1
3 Genes: ALAD, UROD, UROS
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P-value: 0.0012
FDR: 0.51
Z-score: 13.3
Combined score: 90.1
3 Genes: ALAD, UROD, UROS
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FDR: 0.47
Z-score: 2.32
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FDR: 0.37
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FDR: 0.43
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FDR: 0.54
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FDR: 0.56
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FDR: 0.41
Z-score: 4.35
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5 Genes: SHC2, CDKN1B, PRKCA, ELK1, NCK1
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P-value: 0.0054
FDR: 0.48
Z-score: 2.6
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FDR: 0.49
Z-score: 2.1
Combined score: 11.4
16 Genes: ACTR3, CDKN1B, ANGPT1, TGFB3, PRKCA, SEMA3F, IGF1R
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FDR: 0.15
Z-score: 3.06
Combined score: 21.1
11 Genes: SHC2, MARCKS, SORT1, TRAF6, IRS2, PTPN11, MAPK14
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FDR: 0.16
Z-score: 3.0
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12 Genes: SHC2, AKT2, IRS2, PRKCA, PTPN11, SORBS1, MAPK14
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FDR: 0.015
Z-score: 1.98
Combined score: 20.4
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P-value: 0.012
FDR: 1.0
Z-score: 11.4
Combined score: 50.5
2 Genes: PARP2, APEX1
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P-value: 0.0089
FDR: 0.97
Z-score: 4.85
Combined score: 22.9
4 Genes: MCFD2, LMAN2, COL7A1, CTSC
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P-value: 0.0088
FDR: 1.0
Z-score: 13.3
Combined score: 63.2
2 Genes: RUVBL1, NHP2
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P-value: 0.0081
FDR: 1.0
Z-score: 7.06
Combined score: 34.0
3 Genes: ALAD, UROD, UROS
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P-value: 0.0077
FDR: 1.0
Z-score: 2.47
Combined score: 12.0
10 Genes: COPB2, MCFD2, TFG, COG5, MAN1A2, LMAN2, COL7A1
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P-value: 0.0074
FDR: 1.0
Z-score: 2.48
Combined score: 12.2
10 Genes: CDS1, FIG4, MTMR1, PTDSS2, MTMR3, ABHD4, MTMR14
GDE1, GDPD1, TAZ
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P-value: 0.007
FDR: 1.0
Z-score: 3.53
Combined score: 17.5
6 Genes: MCFD2, TFG, LMAN2, COL7A1, SEC22A, CTSC
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P-value: 0.0058
FDR: 1.0
Z-score: 2.16
Combined score: 11.1
14 Genes: TSTA3, COPB2, MCFD2, CMAS, COG5, DDOST, TFG
MAN1A2, LMAN2, COL7A1, NUDT14, SEC22A, CTSC, ARF5
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P-value: 0.0057
FDR: 1.0
Z-score: 2.75
Combined score: 14.2
9 Genes: COPB2, MCFD2, TFG, COG5, LMAN2, COL7A1, SEC22A
CTSC, ARF5
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P-value: 0.0038
FDR: 0.97
Z-score: 4.0
Combined score: 22.3
6 Genes: FIG4, MTMR1, MTMR3, MTMR14, GDE1, GDPD1
", "Heme biosynthesis_Homo sapiens_R-HSA-189451
P-value: 0.0022
FDR: 0.68
Z-score: 10.9
Combined score: 66.7
3 Genes: ALAD, UROD, UROS
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P-value: 0.001
FDR: 0.39
Z-score: 3.9
Combined score: 26.9
8 Genes: INO80C, PARP2, MCRS1, ERCC1, RUVBL1, RAD23A, GTF2H3
COPS8
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P-value: 0.00038
FDR: 0.19
Z-score: 3.7
Combined score: 29.2
10 Genes: INO80C, USP7, PARP2, MCRS1, ERCC1, RUVBL1, ERCC8
RAD23A, COPS8, GTF2H3
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P-value: 0.00033
FDR: 0.25
Z-score: 6.32
Combined score: 50.6
6 Genes: INO80C, PARP2, MCRS1, RUVBL1, RAD23A, COPS8
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P-value: 4.2e-05
FDR: 0.064
Z-score: 5.37
Combined score: 54.2
9 Genes: MTMR3, MTMR14, CHMP2B, ATG10, ATG4C, ATG4B, ATG12
ATG4D, ATG5
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P-value: 0.0021
FDR: 0.19
Z-score: 3.48
Combined score: 21.4
8 Genes: APP, TRAF6, LY96, ECSIT, MAPK14, S100B, ELK1
MAP3K7
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P-value: 0.0021
FDR: 0.2
Z-score: 3.48
Combined score: 21.4
8 Genes: APP, TRAF6, LY96, ECSIT, MAPK14, S100B, ELK1
MAP3K7
", "Activated TLR4 signalling_Homo sapiens_R-HSA-166054
P-value: 0.002
FDR: 0.24
Z-score: 3.21
Combined score: 20.0
9 Genes: APP, TRAF6, LY96, PTPN11, ECSIT, MAPK14, S100B
ELK1, MAP3K7
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P-value: 0.0016
FDR: 0.21
Z-score: 4.71
Combined score: 30.2
6 Genes: NEK9, NUP205, SEH1L, NUP85, NUP62, PRKCA
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P-value: 0.0015
FDR: 0.2
Z-score: 5.88
Combined score: 38.4
5 Genes: NEK9, NUP205, SEH1L, NUP85, NUP62
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P-value: 0.00084
FDR: 0.13
Z-score: 5.33
Combined score: 37.7
6 Genes: NUP205, PHC2, SEH1L, NUP85, SCMH1, NUP62
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P-value: 0.00079
FDR: 0.13
Z-score: 15.0
Combined score: 1.07e+02
3 Genes: ANP32A, TNFSF13, PRKCA
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P-value: 0.00061
FDR: 0.12
Z-score: 1.52
Combined score: 11.3
62 Genes: MDC1, CDKN1B, THRB, WDR3, GEMIN2, NAT10, EHMT1
ADARB1, CASC3, SMG7, USP39, YARS2, MED17, CCAR1
MED14, PSMD2, AKT2, NUP62, NELFA, SNRNP35, UPF2
WDR75, DARS2, PRKCA, IMP4, QTRTD1, DDB2, CCNA2
HNRNPUL1, PSME3, MED20, TMEM219, SRSF4, GTF3C2, NUP205
SEH1L, ANP32A, GTF3C6, MAPKAP1, NOL9, GSPT2, EXOSC6
NUP85, EXOSC9, TCEB3, DROSHA, RXRG, WTAP, TAF13
MBD2, GSR, TNFSF13, MAPK14, HIPK2, SMAD7, WARS2
TRMT6, PRPF31, MNAT1, TRIM33, EIF4G1, CDK5R1
", "ER to Golgi Anterograde Transport_Homo sapiens_R-HSA-199977
P-value: 0.00046
FDR: 0.1
Z-score: 3.36
Combined score: 25.8
11 Genes: GOLGA2, SEC24B, TBC1D20, GORASP1, GOSR2, DCTN4, TMED3
SPTB, YKT6, SEC31A, SEC22C
", "Post-translational protein modification_Homo sapiens_R-HSA-597592
P-value: 0.00031
FDR: 0.08
Z-score: 2.07
Combined score: 16.7
27 Genes: MDC1, NUP205, L3MBTL2, SEH1L, PRKCSH, DCTN4, GOSR2
SEL1L, XPC, GOLGA2, GMPPB, NUP85, RAD21, NUP62
SCMH1, TMED3, YKT6, SEC31A, EDEM3, PHC2, SEC24B
DOHH, SPTB, SUMF1, TBC1D20, GORASP1, SEC22C
", "Regulation of mRNA stability by proteins that bind AU-rich elements_Homo sapiens_R-HSA-450531
P-value: 0.0003
FDR: 0.091
Z-score: 4.19
Combined score: 34.0
9 Genes: EXOSC6, ANP32A, PSMD2, PSME3, EXOSC9, TNFSF13, PRKCA
MAPK14, EIF4G1
", "COPII (Coat Protein 2) Mediated Vesicle Transport_Homo sapiens_R-HSA-204005
P-value: 0.00029
FDR: 0.11
Z-score: 4.71
Combined score: 38.4
8 Genes: GOLGA2, SEC24B, TBC1D20, GORASP1, GOSR2, YKT6, SEC22C
SEC31A
", "SUMOylation_Homo sapiens_R-HSA-2990846
P-value: 0.00022
FDR: 0.11
Z-score: 3.96
Combined score: 33.4
10 Genes: MDC1, NUP205, PHC2, L3MBTL2, SEH1L, NUP85, RAD21
SCMH1, NUP62, XPC
", "SUMO E3 ligases SUMOylate target proteins_Homo sapiens_R-HSA-3108232
P-value: 0.00014
FDR: 0.11
Z-score: 4.17
Combined score: 36.9
10 Genes: MDC1, NUP205, PHC2, L3MBTL2, SEH1L, NUP85, RAD21
SCMH1, NUP62, XPC
", "SUMOylation of DNA damage response and repair proteins_Homo sapiens_R-HSA-3108214
P-value: 0.0001
FDR: 0.16
Z-score: 4.8
Combined score: 44.1
9 Genes: MDC1, NUP205, PHC2, SEH1L, NUP85, RAD21, SCMH1
NUP62, XPC
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" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/html": [ " Download" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/html": [ "" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/markdown": [ "** Figure 4 | Pathway Enrichment Analysis Results.** The figure contains interactive bar charts displaying the results of the pathway enrichment analysis generated using Enrichr. The x axis indicates the -log10(P-value) for each term. Significant terms are highlighted in bold. Additional information about enrichment results is available by hovering over each bar. If you are experiencing issues visualizing the plot, please visit our Troubleshooting guide." ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" } ], "source": [ "# Initialize results\n", "results['pathway_enrichment'] = {}\n", "\n", "# Loop through results\n", "for label, enrichr_results in results['enrichr'].items():\n", "\n", " # Run analysis\n", " results['pathway_enrichment'][label] = analyze(enrichr_results=enrichr_results['results'], tool='pathway_enrichment', signature_label=label, plot_type='interactive', sort_results_by='pvalue')\n", "\n", " # Display results\n", " plot(results['pathway_enrichment'][label])" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "---\n", " ## 7. Transcription Factor Enrichment Analysis\n", "Transcription Factors (TFs) are proteins involved in the transcriptional regulation of gene expression. Databases such as ChEA and ENCODE contain a large number of associations between TFs and their transcriptional targets. This information can be leveraged by Enrichr to identify the transcription factors whose targets are over-represented in the up-regulated and down-regulated genes identified by comparing two groups of samples." ] }, { "cell_type": "code", "execution_count": 10, "metadata": { "task": "tf_enrichment" }, "outputs": [ { "data": { "text/html": [ "" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/html": [ "" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/markdown": [ "### A. ChEA (experimentally validated targets)" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/html": [ "
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RankTranscription FactorP-valueFDRTarget
1CREM*1.311906e-118.461796e-09214 downregulated targets
2JARID1A*8.938109e-105.765080e-07100 upregulated targets
3FOXO3*5.330393e-091.719052e-0692 upregulated targets
4GABP*6.585503e-071.061912e-04105 upregulated targets
5CREB1*4.682606e-071.510141e-0498 downregulated targets
6SFPI1*3.327097e-067.153258e-0494 downregulated targets
7E2F1*1.262246e-051.356915e-03144 upregulated targets
8KDM6A*1.188731e-051.533463e-0329 upregulated targets
9MYC*3.978855e-053.207952e-03120 upregulated targets
10SRF*3.960133e-053.648980e-0367 upregulated targets
11ASH2L*5.739836e-054.113549e-03117 upregulated targets
12VDR*1.346904e-047.897755e-0383 upregulated targets
13CEBPB*2.691147e-041.335223e-0222 upregulated targets
14EKLF*3.226797e-041.486631e-0251 upregulated targets
15ERG*3.986936e-041.512690e-0273 upregulated targets
16E2F4*3.891674e-041.568831e-02103 upregulated targets
17MITF*2.612402e-042.106249e-02175 downregulated targets
18ZFX*1.758903e-042.268985e-02112 downregulated targets
19NUCKS1*4.292184e-043.076065e-0229 downregulated targets
20BCL3*4.929676e-043.179641e-0238 downregulated targets
21KDM2B*6.221066e-043.647807e-0273 downregulated targets
22SIN3B9.330137e-045.014949e-02137 downregulated targets
23HOXC91.863824e-036.678702e-0271 upregulated targets
24MECOM2.000629e-037.590623e-0269 downregulated targets
25RUNX11.677377e-037.727915e-02156 downregulated targets
26GFI1B2.673467e-039.579925e-0266 downregulated targets
27MYCN2.989466e-039.641027e-0277 upregulated targets
28HNF4A2.878380e-039.771341e-02181 downregulated targets
29DMRT13.775589e-031.014690e-0171 downregulated targets
30RARB3.663383e-031.027340e-0169 downregulated targets
31FOXA13.663383e-031.074037e-0169 downregulated targets
32CLOCK3.345587e-031.078952e-0120 downregulated targets
33MEIS13.575024e-031.098043e-0153 downregulated targets
34SRY4.502396e-031.161618e-0199 downregulated targets
35DCP1A5.311817e-031.268934e-0131 downregulated targets
36CRX5.602497e-031.290575e-0128 downregulated targets
37ETS14.657952e-031.430657e-0157 upregulated targets
38PRDM56.578320e-031.463109e-0139 downregulated targets
39FLI15.191252e-031.521981e-0169 upregulated targets
40NANOG7.232857e-031.555064e-0133 downregulated targets
41RING1B8.091708e-031.683597e-0167 downregulated targets
42NELFA8.091708e-032.007366e-0167 upregulated targets
43KDM5B1.002696e-022.021060e-01114 downregulated targets
44SPI17.838466e-032.022324e-0166 upregulated targets
45TCF31.411156e-022.528322e-0148 downregulated targets
46WT11.334100e-022.530867e-01106 downregulated targets
47SIN3A1.468184e-022.559401e-0142 downregulated targets
48TAL11.390231e-022.561996e-0162 downregulated targets
49CCND11.586557e-022.692971e-0169 downregulated targets
50CHD11.174309e-022.705105e-0166 upregulated targets
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RankTranscription FactorP-valueFDRTarget
1HCFC1*2.628926e-132.145204e-10104 upregulated targets
2GATA1*1.427568e-112.912238e-09132 upregulated targets
3POLR2A*1.314807e-113.576275e-09189 upregulated targets
4USF2*1.073250e-109.730802e-0997 upregulated targets
5SIN3A*1.073250e-101.094715e-0897 upregulated targets
6GABPA*1.073250e-101.251103e-0897 upregulated targets
7FLI1*1.072629e-101.750531e-08101 upregulated targets
8TBP*2.406402e-101.963624e-0896 upregulated targets
9MYC*5.325321e-103.621219e-0895 upregulated targets
10ZMIZ1*5.325321e-103.950420e-0895 upregulated targets
11MAX*2.506572e-091.363575e-0793 upregulated targets
12IRF1*4.278559e-092.182065e-07170 upregulated targets
13KAT2A*5.330393e-092.558589e-0792 upregulated targets
14SRF*1.923548e-088.261130e-0777 upregulated targets
15MYOG*2.169900e-091.770638e-06144 downregulated targets
16NRF1*9.519704e-083.107231e-0688 upregulated targets
17NELFE*1.890910e-075.510653e-0687 upregulated targets
18CREB1*2.939223e-077.994687e-0682 upregulated targets
19USF1*2.314958e-089.445030e-0690 downregulated targets
20E2F4*3.703965e-079.749791e-0686 upregulated targets
21POLR2AphosphoS5*4.565893e-071.164303e-0568 upregulated targets
22MXI1*7.154318e-071.667978e-0585 upregulated targets
23EP300*7.154318e-071.717036e-0585 upregulated targets
24FOS*9.119717e-071.860422e-05145 upregulated targets
25SIX5*1.258018e-062.503762e-0579 upregulated targets
26NFYB*1.362485e-062.526790e-0584 upregulated targets
27RFX5*1.362485e-062.585552e-0584 upregulated targets
28TBL1XR1*1.362485e-062.647113e-0584 upregulated targets
29UBTF*1.890910e-073.857457e-0587 downregulated targets
30MAZ*2.558074e-064.348726e-0583 upregulated targets
31REST*4.734439e-066.898754e-0582 upregulated targets
32RCOR1*4.734439e-067.024186e-0582 upregulated targets
33ZC3H11A*4.734439e-067.154263e-0582 upregulated targets
34TAL1*4.734439e-067.289249e-0582 upregulated targets
35MAFK*4.734439e-067.429427e-0582 upregulated targets
36CTCF*4.734439e-067.575102e-0582 upregulated targets
37JUN*8.636804e-061.084251e-0481 upregulated targets
38ZNF143*8.636804e-061.101192e-0481 upregulated targets
39ELK1*8.636804e-061.118672e-0481 upregulated targets
40ATF1*8.636804e-061.136715e-0481 upregulated targets
41BCL3*8.374818e-061.138975e-0472 upregulated targets
42ELF1*8.286601e-061.146079e-0454 upregulated targets
43CEBPB*1.290130e-051.571263e-04102 upregulated targets
44PML*1.279257e-051.581626e-0454 upregulated targets
45TRIM28*1.552822e-051.810147e-0480 upregulated targets
46NFATC1*1.849136e-051.959603e-0465 upregulated targets
47TCF3*2.059075e-052.154109e-0461 upregulated targets
48POLR2AphosphoS2*2.751247e-052.467053e-0479 upregulated targets
49BRCA1*2.751247e-052.551157e-0479 upregulated targets
50CHD2*2.751247e-052.672640e-0479 upregulated targets
" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/html": [ "" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/html": [ "" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/markdown": [ "### C. ARCHS4 (coexpressed genes)" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/html": [ "
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RankTranscription FactorP-valueFDRTarget
1ZNF664*0.0000020.00353323 downregulated targets
2VPS72*0.0000230.01949221 upregulated targets
3ZNF205*0.0000230.01949221 downregulated targets
4GATAD2B*0.0000700.02004220 downregulated targets
5SLC2A4RG*0.0000700.02405020 downregulated targets
6DZIP1*0.0002040.02709419 downregulated targets
7AHCTF1*0.0002040.02935119 downregulated targets
8MBD3*0.0000700.03006320 downregulated targets
9FIZ1*0.0002040.03202019 downregulated targets
10ATMIN*0.0005670.03371218 downregulated targets
11DUS3L*0.0005670.03491618 downregulated targets
12TFDP1*0.0002040.03522219 downregulated targets
13ZNF768*0.0005670.03620918 downregulated targets
14ZNF598*0.0005670.03760218 downregulated targets
15MLX*0.0000230.03898421 upregulated targets
16FOXK1*0.0005670.03910618 downregulated targets
17SOX12*0.0002040.03913519 downregulated targets
18HSF1*0.0000700.04008420 downregulated targets
19ZNF787*0.0005670.04073518 downregulated targets
20FOXJ3*0.0005670.04250618 downregulated targets
21KLF16*0.0002040.04402719 downregulated targets
22ZBTB2*0.0005670.04443918 downregulated targets
23ZNF740*0.0005670.04655518 downregulated targets
24WIZ*0.0005670.04888218 downregulated targets
25ATF40.0002040.05031719 downregulated targets
26FOXG10.0005670.05145518 downregulated targets
27INSM10.0005670.05431418 downregulated targets
28SNAPC40.0005670.05750918 downregulated targets
29SUZ120.0014880.05967817 downregulated targets
30CHD10.0014880.06109917 downregulated targets
31ERF0.0005670.06110318 downregulated targets
32SETDB10.0014880.06258917 downregulated targets
33CENPB0.0014880.06415417 downregulated targets
34MAZ0.0005670.06517718 downregulated targets
35BAZ2A0.0014880.06579917 downregulated targets
36HMG20B0.0014880.06753117 downregulated targets
37BRD90.0014880.06935617 downregulated targets
38SREBF10.0005670.06983218 downregulated targets
39ZFP910.0014880.07128217 downregulated targets
40ZFHX20.0014880.07331917 downregulated targets
41MLLT10.0014880.07547517 downregulated targets
42ZSCAN180.0014880.07776217 downregulated targets
43MAFK0.0014880.08019317 downregulated targets
44MYT10.0014880.08277917 downregulated targets
45ZNF2820.0014880.08553917 downregulated targets
46REPIN10.0036860.08588016 downregulated targets
47MTA10.0036860.08705616 downregulated targets
48CSDC20.0036860.08826516 downregulated targets
49MECP20.0036860.08950916 downregulated targets
50DVL30.0036860.09078716 downregulated targets
" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/html": [ " Download" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/html": [ "" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/markdown": [ "** Table 4 | Transcription Factor Enrichment Analysis Results. **The figure contains scrollable tables displaying the results of the Transcription Factor (TF) enrichment analysis generated using Enrichr. Every row represents a TF; significant TFs are highlighted in bold. A and B display results generated using ChEA and ENCODE libraries, indicating TFs whose experimentally validated targets are enriched. C displays results generated using the ARCHS4 library, indicating TFs whose top coexpressed genes (according to the ARCHS4 dataset) are enriched." ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" } ], "source": [ "# Initialize results\n", "results['tf_enrichment'] = {}\n", "\n", "# Loop through results\n", "for label, enrichr_results in results['enrichr'].items():\n", "\n", " # Run analysis\n", " results['tf_enrichment'][label] = analyze(enrichr_results=enrichr_results['results'], tool='tf_enrichment', signature_label=label)\n", "\n", " # Display results\n", " plot(results['tf_enrichment'][label])" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "---\n", " ## 8. Kinase Enrichment Analysis\n", "Protein kinases are enzymes that modify other proteins by chemically adding phosphate groups. Databases such as KEA contain a large number of associations between kinases and their substrates. This information can be leveraged by Enrichr to identify the protein kinases whose substrates are over-represented in the up-regulated and down-regulated genes identified by comparing two groups of samples." ] }, { "cell_type": "code", "execution_count": 11, "metadata": { "task": "kinase_enrichment" }, "outputs": [ { "data": { "text/html": [ "" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/html": [ "" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/markdown": [ "### A. KEA (experimentally validated targets)" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/html": [ "
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RankKinaseP-valueFDRSubstrate
1GSK3B0.0008350.17863326 downregulated substrates
2ABL10.0024520.2624148 downregulated substrates
3SIK20.0018400.2625412 downregulated substrates
4CDK20.0007800.33393127 downregulated substrates
5MAPK90.0172500.8203188 downregulated substrates
6NEK90.0963190.8413151 downregulated substrates
7MAP3K70.0199870.8554652 downregulated substrates
8MAP2K30.0963190.8588421 downregulated substrates
9MAPK100.0163190.8730797 downregulated substrates
10MAPK80.0265290.87342411 downregulated substrates
11PINK10.0963190.8771151 downregulated substrates
12NEK70.0250000.8916611 downregulated substrates
13PIK3CA0.0963190.8961831 downregulated substrates
14PDGFRB0.0733240.8966482 downregulated substrates
15CSNK2A10.1052250.90072311 downregulated substrates
16CDC70.0963190.9160981 downregulated substrates
17STK390.0731440.9207531 downregulated substrates
18ATM0.1097970.9214347 downregulated substrates
19NTRK10.0963190.9369191 downregulated substrates
20CSNK2A20.1217700.9475919 downregulated substrates
21PRPF4B0.0731440.9486541 downregulated substrates
22ROCK20.1201100.9519822 downregulated substrates
23MTOR0.0133710.9537826 downregulated substrates
24ZAP700.0245760.9562182 downregulated substrates
25MAP3K80.0806360.9586742 downregulated substrates
26NTRK30.0963190.9587081 downregulated substrates
27BMPR20.1189150.9602971 downregulated substrates
28PRKDC0.0830470.9606578 downregulated substrates
29DYRK1B0.0158050.9663582 downregulated substrates
30CHEK10.0566480.9698097 downregulated substrates
31PRKCZ0.1291600.9698353 downregulated substrates
32LYN0.0545610.9730085 downregulated substrates
33ICK0.0731440.9783001 downregulated substrates
34ERBB30.1189150.9787641 downregulated substrates
35BLK0.0963190.9815341 downregulated substrates
36ADRBK10.1284890.9820242 downregulated substrates
37PAK20.0528330.9831482 downregulated substrates
38SGK10.0903750.9918064 downregulated substrates
39CAMK10.0881620.9929852 downregulated substrates
40MAP3K40.0036201.0000002 upregulated substrates
41RPS6KB10.0098861.0000004 upregulated substrates
42UHMK10.0120521.0000002 downregulated substrates
43CHEK20.0189681.0000003 upregulated substrates
44TTBK10.0250001.0000001 upregulated substrates
45STK30.0295471.0000002 upregulated substrates
46PKN10.0405501.0000002 downregulated substrates
47SGK4940.0405501.0000002 downregulated substrates
48SGK2230.0405501.0000002 downregulated substrates
49PDK10.0487061.0000003 downregulated substrates
50RIPK40.0493761.0000001 upregulated substrates
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RankKinaseP-valueFDRSubstrate
1SCYL1*0.0000230.01126121 downregulated substrates
2GSK3B*0.0000700.01736820 downregulated substrates
3TLK2*0.0002040.02034819 downregulated substrates
4FASTK*0.0005670.02172418 downregulated substrates
5ADCK2*0.0005670.02353418 downregulated substrates
6TNIK*0.0002040.02543619 downregulated substrates
7UHMK1*0.0005670.02567318 downregulated substrates
8MAP2K2*0.0005670.02824118 downregulated substrates
9MAP2K1*0.0005670.03137918 downregulated substrates
10CDK16*0.0002040.03391419 downregulated substrates
11MARK4*0.0005670.03530118 downregulated substrates
12DAPK3*0.0005670.04034418 downregulated substrates
13RPS6KB2*0.0014880.04632917 downregulated substrates
14CDC42BPB*0.0005670.04706818 downregulated substrates
15RPS6KA4*0.0014880.04941817 downregulated substrates
16CDC42BPA0.0014880.05294817 downregulated substrates
17MTOR0.0036860.06330216 downregulated substrates
18WNK10.0036860.06556316 downregulated substrates
19STK160.0036860.06799116 downregulated substrates
20SBK10.0036860.07060616 downregulated substrates
21CHUK0.0036860.07343016 downregulated substrates
22TAOK20.0036860.07649016 downregulated substrates
23SLK0.0036860.07981516 downregulated substrates
24MAP3K90.0036860.08344316 downregulated substrates
25MAP3K40.0036860.08741716 downregulated substrates
26MAPK110.0036860.09178816 downregulated substrates
27GSK3A0.0036860.09661916 downregulated substrates
28BCKDK0.0085920.09951015 downregulated substrates
29WNK20.0085920.10188015 downregulated substrates
30CDK11B0.0036860.10198616 downregulated substrates
31BMP2K0.0085920.10436515 downregulated substrates
32YES10.0085920.10697415 downregulated substrates
33PKN10.0036860.10798616 downregulated substrates
34LMTK20.0085920.10971715 downregulated substrates
35IRAK10.0085920.11260415 downregulated substrates
36TAOK10.0085920.11564715 downregulated substrates
37PAK20.0085920.11886015 downregulated substrates
38MAP3K70.0085920.12225615 downregulated substrates
39CDK120.0085920.12585115 downregulated substrates
40DCLK20.0085920.12966515 downregulated substrates
41DCLK10.0085920.13371715 downregulated substrates
42AKT30.0085920.13803115 downregulated substrates
43AKT20.0085920.14263215 downregulated substrates
44EIF2AK10.0188020.16720114 downregulated substrates
45PTK20.0188020.17024114 downregulated substrates
46EPHB20.0188020.17339414 downregulated substrates
47EPHA20.0188020.17666514 downregulated substrates
48MINK10.0188020.18006314 downregulated substrates
49NEK90.0188020.18359314 downregulated substrates
50CDK130.0188020.18726514 downregulated substrates
" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/html": [ " Download" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/html": [ "" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/markdown": [ "** Table 5 | Kinase Enrichment Analysis Results. **The figure contains browsable tables displaying the results of the Protein Kinase (PK) enrichment analysis generated using Enrichr. Every row represents a PK; significant PKs are highlighted in bold. A displays results generated using KEA, indicating PKs whose experimentally validated substrates are enriched. C displays results generated using the ARCHS4 library, indicating PKs whose top coexpressed genes (according to the ARCHS4 dataset) are enriched." ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" } ], "source": [ "# Initialize results\n", "results['kinase_enrichment'] = {}\n", "\n", "# Loop through results\n", "for label, enrichr_results in results['enrichr'].items():\n", "\n", " # Run analysis\n", " results['kinase_enrichment'][label] = analyze(enrichr_results=enrichr_results['results'], tool='kinase_enrichment', signature_label=label)\n", "\n", " # Display results\n", " plot(results['kinase_enrichment'][label])" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "---\n", " ## 9. miRNA Enrichment Analysis\n", "microRNAs (miRNAs) are small non-coding RNA molecules which play a key role in the post-transcriptional regulation of gene expression. Databases such as TargetScan and MiRTarBase contain a large number of associations between miRNAs and their targets. This information can be leveraged by Enrichr to identify the miRNAs whose targets are over-represented in the up-regulated and down-regulated genes identified by comparing two groups of samples." ] }, { "cell_type": "code", "execution_count": 12, "metadata": { "task": "mirna_enrichment" }, "outputs": [ { "data": { "text/html": [ "" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/html": [ "" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/markdown": [ "### A. TargetScan (experimentally validated targets)" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/html": [ "
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RankmiRNAP-valueFDRTarget
1mmu-miR-193*0.0000070.00100573 downregulated targets
2mmu-miR-375*0.0000030.00109875 downregulated targets
3mmu-miR-193b*0.0000070.00125773 downregulated targets
4mmu-miR-5116*0.0000070.00148270 downregulated targets
5mmu-miR-130a*0.0000260.00163775 downregulated targets
6mmu-miR-301b*0.0000260.00180175 downregulated targets
7mmu-miR-721*0.0000260.00200175 downregulated targets
8mmu-miR-880*0.0000030.00207979 downregulated targets
9mmu-miR-767*0.0000180.00208373 downregulated targets
10mmu-miR-301a*0.0000260.00225175 downregulated targets
11mmu-miR-130b*0.0000260.00257275 downregulated targets
12hsa-miR-423-3p*0.0000620.00280430 downregulated targets
13mmu-miR-669i*0.0000610.00298670 downregulated targets
14mmu-miR-669j*0.0000610.00321670 downregulated targets
15mmu-miR-3087*0.0000580.00332774 downregulated targets
16mmu-miR-100*0.0001140.00431118 downregulated targets
17mmu-miR-99b*0.0001140.00456418 downregulated targets
18mmu-miR-99a*0.0001140.00484918 downregulated targets
19mmu-miR-142-3p*0.0001610.00524556 downregulated targets
20mmu-miR-1982.2*0.0001460.00525170 downregulated targets
21mmu-miR-154*0.0001610.00550454 downregulated targets
22mmu-miR-448-3p*0.0002530.00786574 downregulated targets
23mmu-miR-1306-5p*0.0002800.00795565 downregulated targets
24mmu-miR-3102*0.0002750.00815473 downregulated targets
25mmu-miR-3102-3p.2*0.0003040.00830870 downregulated targets
26mmu-miR-191*0.0004120.01082230 downregulated targets
27mmu-miR-468*0.0004530.01146369 downregulated targets
28mmu-miR-202-5p*0.0004850.01184270 downregulated targets
29mmu-miR-363-3p*0.0008490.01288765 downregulated targets
30mmu-miR-92b*0.0008490.01318065 downregulated targets
31mmu-miR-215*0.0006890.01344755 downregulated targets
32mmu-miR-367*0.0008490.01348665 downregulated targets
33mmu-miR-378b*0.0007250.01375664 downregulated targets
34mmu-miR-25*0.0008490.01380765 downregulated targets
35mmu-miR-192*0.0006890.01384355 downregulated targets
36mmu-miR-32*0.0008490.01414465 downregulated targets
37hsa-miR-621*0.0007870.01415046 downregulated targets
38hsa-miR-4665-3p*0.0006880.01423620 downregulated targets
39mmu-miR-5118*0.0006300.01434253 downregulated targets
40mmu-miR-707*0.0006100.01437266 downregulated targets
41mmu-miR-183*0.0008230.01441369 downregulated targets
42mmu-miR-1933-5p*0.0007810.01442164 downregulated targets
43mmu-miR-3102-5p.2*0.0006790.01449268 downregulated targets
44mmu-miR-92a*0.0008490.01449865 downregulated targets
45hsa-miR-4305*0.0006630.01461860 downregulated targets
46mmu-miR-1967*0.0009910.01470860 downregulated targets
47mmu-miR-3093-3p*0.0010610.01541671 downregulated targets
48mmu-miR-3967*0.0011420.01560567 downregulated targets
49mmu-miR-5121*0.0011050.01571871 downregulated targets
50hsa-miR-3681*0.0011400.01588862 downregulated targets
" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/html": [ "" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/html": [ "" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/markdown": [ "### B. miRTarBase (experimentally validated targets)" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/html": [ "
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RankmiRNAP-valueFDRTarget
1hsa-miR-193b-3p0.0002170.17557439 downregulated targets
2mmu-miR-17-5p0.0005390.19399422 downregulated targets
3mmu-miR-149-5p0.0006780.19961822 downregulated targets
4hsa-miR-1226-3p0.0006220.20140515 downregulated targets
5hsa-miR-6727-5p0.0000630.2029195 downregulated targets
6hsa-miR-181b-5p0.0005140.20802921 downregulated targets
7hsa-miR-96-3p0.0004700.2177747 downregulated targets
8hsa-miR-92a-3p0.0002030.21880357 downregulated targets
9mmu-miR-136-5p0.0008850.22048117 downregulated targets
10hsa-miR-200a-3p0.0004230.22838012 downregulated targets
11hsa-miR-6836-3p0.0008560.23124114 downregulated targets
12hsa-miR-141-3p0.0010670.24684311 downregulated targets
13mmu-miR-15a-5p0.0001580.25554827 downregulated targets
14hsa-miR-93-5p0.0004080.26457450 downregulated targets
15hsa-miR-106b-5p0.0012500.26993644 downregulated targets
16hsa-miR-548as-3p0.0014020.28400112 downregulated targets
17hsa-miR-548aa0.0020540.35034112 downregulated targets
18hsa-miR-548ap-3p0.0019610.35306412 downregulated targets
19hsa-miR-548t-3p0.0019610.37383312 downregulated targets
20hsa-miR-103a-3p0.0024110.39057522 downregulated targets
21mmu-miR-340-5p0.0028780.42381326 downregulated targets
22hsa-miR-20a-5p0.0045590.43443441 downregulated targets
23hsa-miR-4668-5p0.0028300.43659320 downregulated targets
24hsa-miR-142-3p0.0043390.43932619 downregulated targets
25hsa-miR-6771-3p0.0047760.44212714 downregulated targets
26hsa-miR-196b-5p0.0045290.44466310 downregulated targets
27hsa-miR-548c-3p0.0031850.44867424 downregulated targets
28hsa-miR-548k0.0043210.45158110 downregulated targets
29hsa-miR-7159-3p0.0057510.4544637 downregulated targets
30hsa-miR-1070.0038070.45684416 downregulated targets
31hsa-miR-296-3p0.0056570.45823114 downregulated targets
32hsa-miR-17-5p0.0054230.46235544 downregulated targets
33mmu-miR-503-5p0.0055840.4638704 downregulated targets
34hsa-miR-80540.0043210.46663310 downregulated targets
35hsa-miR-125a-3p0.0052030.46830816 downregulated targets
36hsa-miR-148a-5p0.0053960.4725087 downregulated targets
37hsa-miR-155-5p0.0040870.47297636 downregulated targets
38hsa-miR-1260b0.0038010.47372415 downregulated targets
39hsa-miR-60820.0036840.4775093 downregulated targets
40hsa-miR-548av-5p0.0043210.48272410 downregulated targets
41hsa-miR-28-3p0.0067670.4872485 downregulated targets
42hsa-miR-4703-3p0.0073850.4883155 downregulated targets
43hsa-miR-320a0.0066650.49075025 downregulated targets
44hsa-miR-181c-5p0.0065730.49525415 downregulated targets
45hsa-miR-16-5p0.0036730.49581256 downregulated targets
46hsa-miR-42740.0073850.4984885 downregulated targets
47hsa-miR-181a-5p0.0064620.49849424 downregulated targets
48hsa-miR-548at-3p0.0073480.5065177 downregulated targets
49hsa-miR-548ay-3p0.0073480.5175287 downregulated targets
50hsa-miR-42800.0080550.5219866 downregulated targets
" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/html": [ " Download" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/html": [ "" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/markdown": [ "** Table 6 | miRNA Enrichment Analysis Results. **The figure contains browsable tables displaying the results of the miRNA enrichment analysis generated using Enrichr. Every row represents a miRNA; significant miRNAs are highlighted in bold. A. displays results generated using the TargetScan library, B. displays results generated using the miRTarBase library." ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" } ], "source": [ "# Initialize results\n", "results['mirna_enrichment'] = {}\n", "\n", "# Loop through results\n", "for label, enrichr_results in results['enrichr'].items():\n", "\n", " # Run analysis\n", " results['mirna_enrichment'][label] = analyze(enrichr_results=enrichr_results['results'], tool='mirna_enrichment', signature_label=label)\n", "\n", " # Display results\n", " plot(results['mirna_enrichment'][label])" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "---\n", " ## 10. L1000CDS2 Query\n", "L1000CDS2 is a web-based tool for querying gene expression signatures against signatures created from human cell lines treated with over 20,000 small molecules and drugs for the LINCS project. It is commonly used to identify small molecules which mimic or reverse the effects of a gene expression signature generated from a differential gene expression analysis." ] }, { "cell_type": "code", "execution_count": 13, "metadata": { "task": "l1000cds2" }, "outputs": [ { "data": { "text/markdown": [ "\n", "### Control vs Perturbation signature:" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/markdown": [ " **L1000CDS2 Links:**" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/markdown": [ " *Mimic Signature Query Results*: http://amp.pharm.mssm.edu/L1000CDS2/#/result/5da6c757840d050700fb170c" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/markdown": [ " *Reverse Signature Query Results*: http://amp.pharm.mssm.edu/L1000CDS2/#/result/5da6c757840d050700fb170e" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "application/vnd.plotly.v1+json": { "config": { "linkText": "Export to plot.ly", "plotlyServerURL": "https://plot.ly", "showLink": false }, "data": [ { "hoverinfo": "text", "hovertext": [ "selumetinib", "daunorubicin", "radicicol", "\"\"\"N-((1H-naphtho[2,3-d]imidazol-2-yl)methyl)-2-morpholino-9-(thiophen-3-yl)-9H-purin-6-amine\"\"\"", "curcumin", "vorinostat", "trichostatin A" ], "marker": { "color": "#FF7F50" }, "name": "Mimic", "orientation": "h", "type": "bar", "uid": "d7a75e86-5c9b-444b-bba3-95b320f1347d", "x": [ 1, 1, 1, 3, 3, 9, 16 ], "xaxis": "x", "y": [ "selumetinib", "daunorubicin", "radicicol", "\"\"\"N-((1H-naphtho[2,3-d]imidazol-2-yl)methyl)-2-morpholino-9-(thiophen-3-yl)-9H-purin-6-amine\"\"\"", "curcumin", "vorinostat", "trichostatin A" ], "yaxis": "y" }, { "hoverinfo": "none", "mode": "text", "showlegend": false, "text": [ "selumetinib", "daunorubicin", "radicicol", "\"\"\"N-((1H-naphtho[2,3-d]imidazol-2-yl)methyl)-2-morpholino-9-(thiophen-3-yl)-9H-purin-6-amine\"\"\"", "curcumin", "vorinostat", "trichostatin A" ], "textfont": { "color": "black" }, "textposition": "middle right", "type": "scatter", "uid": "e1ceaf64-03ac-4b7b-9dd5-ac64c5260713", "x": [ 0.32, 0.32, 0.32, 0.32, 0.32, 0.32, 0.32 ], "xaxis": "x", "y": [ "selumetinib", "daunorubicin", "radicicol", "\"\"\"N-((1H-naphtho[2,3-d]imidazol-2-yl)methyl)-2-morpholino-9-(thiophen-3-yl)-9H-purin-6-amine\"\"\"", "curcumin", "vorinostat", "trichostatin A" ], "yaxis": "y" }, { "hoverinfo": "text", "hovertext": [ "IMD 0354", "Digitoxigenin", "torin-1", "KU-0063794", "GSK-1059615", "Ingenol 3, 20-dibenzoate", "Emetine Dihydrochloride Hydrate (74)" ], "marker": { "color": "#9370DB" }, "name": "Reverse", "orientation": "h", "type": "bar", "uid": "8c0cc203-bc65-4726-90ac-dd66e201c9d1", "x": [ 1, 1, 1, 2, 2, 2, 6 ], "xaxis": "x2", "y": [ "IMD 0354", "Digitoxigenin", "torin-1", "KU-0063794", "GSK-1059615", "Ingenol 3, 20-dibenzoate", "Emetine Dihydrochloride Hydrate (74)" ], "yaxis": "y2" }, { "hoverinfo": "none", "mode": "text", "showlegend": false, "text": [ "IMD 0354", "Digitoxigenin", "torin-1", "KU-0063794", "GSK-1059615", "Ingenol 3, 20-dibenzoate", "Emetine Dihydrochloride Hydrate (74)" ], "textfont": { "color": "black" }, "textposition": "middle right", "type": "scatter", "uid": "5e4c5c77-700b-4426-ad9b-e90703cc5a46", "x": [ 0.12, 0.12, 0.12, 0.12, 0.12, 0.12, 0.12 ], "xaxis": "x2", "y": [ "IMD 0354", "Digitoxigenin", "torin-1", "KU-0063794", "GSK-1059615", "Ingenol 3, 20-dibenzoate", "Emetine Dihydrochloride Hydrate (74)" ], "yaxis": "y2" } ], "layout": { "height": 300, "hovermode": "closest", "margin": { "b": 45, "l": 10, "pad": 5, "r": 0, "t": 95 }, "title": { "text": "L1000CDS2 | Small Molecule Query
Top small molecules" }, "xaxis": { "anchor": "y", "domain": [ 0, 0.5 ], "title": { "text": "
Count" } }, "xaxis2": { "anchor": "y2", "domain": [ 0.5, 1 ], "title": { "text": "
Count" } }, "yaxis": { "anchor": "x", "domain": [ 0.0, 1.0 ], "showticklabels": false }, "yaxis2": { "anchor": "x2", "domain": [ 0.0, 1.0 ], "showticklabels": false } } }, "text/html": [ "
" ], "text/vnd.plotly.v1+html": [ "
" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/html": [ " Download" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/html": [ "" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/markdown": [ "** Figure 5 | L1000CDS2 Query results. **The figure contains an interactive bar chart displaying the top small molecules identified by the L1000CDS2 query. The left panel displays the small molecules which mimic the observed gene expression signature, while the right panel displays the small molecules which reverse it. Links to the L1000CDS2 web server are additionally provided, allowing users to interactively explore the analysis results. If you are experiencing issues visualizing the plot, please visit our Troubleshooting guide." ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" } ], "source": [ "# Initialize results\n", "results['l1000cds2'] = {}\n", "\n", "# Loop through signatures\n", "for label, signature in signatures.items():\n", "\n", " # Run analysis\n", " results['l1000cds2'][label] = analyze(signature=signature, tool='l1000cds2', signature_label=label, plot_type='interactive')\n", "\n", " # Display results\n", " plot(results['l1000cds2'][label])" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "---\n", " ## 11. L1000FWD Query\n", "L1000FWD is a web-based tool for querying gene expression signatures against signatures created from human cell lines treated with over 20,000 small molecules and drugs for the LINCS project." ] }, { "cell_type": "code", "execution_count": 14, "metadata": { "task": "l1000fwd" }, "outputs": [ { "data": { "text/html": [ "\n", " \n", " " ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/markdown": [ "** Similar Signatures: **" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/html": [ "
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Signature IDP-valueFDRZ-scoreCombined Score
1CPC008_HCC515_6H:BRD-K10846167-001-01-6:100.0021981-1.6799794.465262
2CPC009_A549_6H:BRD-K26304855-001-01-5:100.0177561-1.6904372.959364
3CPC009_PC3_6H:BRD-A68009927-001-02-3:100.0182711-1.7325863.011632
4CPC009_PC3_6H:BRD-K83670234-001-01-1:100.0200091-1.7113902.907280
5CPC010_HCC515_6H:BRD-K70578146-001-03-4:100.0239511-1.7067502.766099
6CPC008_HCC515_6H:BRD-K07259155-001-05-2:100.0244711-1.7004342.740005
7CPC006_SW620_6H:BRD-K69840642-001-01-4:100.0295451-1.6561992.533180
8CPC014_HEPG2_6H:BRD-K75081836-001-01-3:100.0319281-1.7129662.562313
9CRCGN001_HA1E_24H:BRD-A76941896-003-04-6:10.20.0354371-1.7665482.562459
10CPC014_SKB_24H:BRD-K64800655-001-01-7:100.0360711-1.7522792.528270
11HOG003_A549_6H:BRD-K22503835-001-06-0:100.0373631-1.8018652.572260
12CPC009_HCC515_6H:BRD-K81814927-001-01-9:100.0414111-1.7325162.395862
13CPC009_HEPG2_6H:BRD-K81814927-001-01-9:100.0415061-1.6729232.311795
14CPC014_A549_6H:BRD-K74733595-001-02-9:100.0415061-1.7156482.370837
15CPC010_HA1E_6H:BRD-K70578146-001-03-4:100.0521251-1.6985262.179137
16CPC009_HCC515_6H:BRD-K79222491-001-01-5:100.0535661-1.6677022.119840
17CPC012_HT29_6H:BRD-A59985574-003-01-9:100.0539311-1.7380702.204149
18CPC008_HCC515_6H:BRD-K53780220-001-01-0:100.0700011-1.6646421.922491
19CPC009_A549_6H:BRD-K83670234-001-01-1:100.0710831-1.6919171.942715
20CPC013_HT29_6H:BRD-K17210248-003-01-7:100.0755991-1.7140891.922325
21NMH001_NPC_24H:BRD-K09416995-001-32-4:100.0839531-1.8173041.955351
22CPC009_HCC515_6H:BRD-K26304855-001-01-5:100.0839531-1.6725161.799564
23CPC006_HEPG2_6H:BRD-K00615600-001-06-1:250.0855241-1.6662581.779416
24CPC006_A549_24H:BRD-K17561142-003-16-8:100.0883391-1.6954221.786718
25CPC015_MCF7_24H:BRD-K66874953-004-01-3:100.0894691-1.7746101.860371
26MUC.CP006_MCF7_6H:BRD-A39646320-001-01-3:1.11110.0977051-1.8460861.864703
27CPC006_PC3_6H:BRD-K28360340-001-01-8:100.1024131-1.6444451.627413
28CPC014_HT29_6H:BRD-A18497530-001-05-3:100.1073801-1.7775991.722632
29CPC015_MCF7_24H:BRD-K36198571-001-01-2:100.1078971-1.7773151.718649
30CPC013_PC3_24H:BRD-K68202742-001-05-8:100.1094041-1.7253791.658031
31CPC006_SW480_6H:BRD-K41895714-001-02-2:100.1140031-1.6405711.547195
32CPC008_HEPG2_6H:BRD-K10846167-001-01-6:100.1187181-1.6683991.544078
33CPC008_A549_6H:BRD-K70917163-001-04-0:100.1235471-1.6700181.516658
34CPC017_HT29_6H:BRD-K11927976-050-01-1:100.1270171-1.7681261.584488
35CPC014_SKB_24H:BRD-A39646320-001-01-3:100.1312311-1.6901981.490695
36CPC017_A375_6H:BRD-K43389675-001-01-3:100.1318491-1.7448971.535375
37LJP002_BT20_24H:BRD-K43389698-001-03-2:100.1369821-1.7896121.545038
38CPC014_PC3_6H:BRD-A11702965-001-01-6:100.1448701-1.7549891.472472
39MUC.CP005_MCF7_6H:BRD-A19037878-001-02-3:100.1457861-1.8240731.525444
40CPC013_A375_6H:BRD-K17743125-001-03-5:100.1457861-1.6948851.417406
41CPC009_A549_6H:BRD-K79222491-001-01-5:100.1504851-1.6905071.390453
42CPC010_HCC515_6H:BRD-K85853281-001-03-9:100.1660271-1.6704351.302640
43CPC009_HA1E_6H:BRD-K81814927-001-01-9:100.1782131-1.6821561.260037
44CPC009_HA1E_6H:BRD-A19037878:100.1922211-1.6367251.172220
45CPC006_HEPG2_6H:BRD-K69840642-001-01-4:100.2038801-1.6389041.131870
46CPC014_ASC_24H:BRD-K85493820-001-01-6:100.2069921-1.6739691.145073
47CPC020_HA1E_6H:BRD-K52522949-001-01-7:100.2083181-1.7685881.204892
48CPC014_SKB_24H:BRD-M16762496-001-01-9:100.2173251-1.7011371.127666
49CPC013_HEPG2_6H:BRD-K79090631-001-15-7:100.2218931-1.6836611.100872
50CPC003_HA1E_24H:BRD-A19037878:100.2334931-1.5977491.009340
" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/html": [ " Download" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/html": [ "" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/markdown": [ "** Opposite Signatures: **" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/html": [ "
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Signature IDP-valueFDRZ-scoreCombined Score
1PCLB003_PC3_24H:BRD-K78431006-001-05-2:100.03419411.609172-2.359126
2CPC019_HT29_6H:BRD-K45895591-001-05-9:100.04532411.695337-2.277974
3CPC006_HT29_24H:BRD-K73261812-001-01-1:100.05318011.879589-2.395071
4CPC018_A375_6H:BRD-A29082194-001-02-4:100.05863911.691290-2.083347
5CPC017_HEPG2_6H:BRD-K59469039-001-03-1:100.06675311.695415-1.993011
6CPC020_PC3_6H:BRD-K41775742-001-01-4:100.07556211.698815-1.905551
7CPC006_HCC515_24H:BRD-K94325918-001-03-8:100.07676311.837837-2.048905
8CPC002_PC3_6H:BRD-A42649439-001-02-8:100.08150711.822523-1.984370
9CPC010_HT29_6H:BRD-A24643465-001-05-3:100.08423511.793576-1.927215
10CPC006_A375_6H:BRD-K01868942-001-02-1:1600.09027711.777060-1.856004
11CPC006_HCC515_24H:BRD-K66792149-001-01-8:11.10.09216311.828512-1.893319
12CPC015_PHH_24H:BRD-K61401890-001-04-6:100.10241311.675793-1.658437
13CPC020_VCAP_24H:BRD-K06750613-001-01-6:100.10524311.638499-1.602137
14CPC006_SW620_6H:BRD-A81541225-001-02-7:100.11400311.788334-1.686547
15CPC020_HT29_6H:BRD-A75144621-001-02-8:100.12192311.693733-1.547927
16CPC019_MCF7_24H:BRD-K06405410-001-01-2:100.12849011.672496-1.490411
17CPC007_A375_24H:BRD-K32501161-003-07-0:100.12849011.783422-1.589260
18CPC013_HA1E_6H:BRD-K92428232-001-01-5:100.13048011.739151-1.538202
19CPC002_PC3_24H:BRD-K32501161-300-04-7:100.13698211.811962-1.564334
20CPC014_HA1E_6H:BRD-A06929388-001-01-1:100.13698211.692248-1.460980
21CPC017_A549_24H:BRD-K05151076-001-01-8:100.13784611.640598-1.411911
22CPC004_MCF7_6H:BRD-K39987650-001-15-9:100.13937411.841805-1.576250
23CPC016_SKB_24H:BRD-K80348542-001-01-4:100.14046611.672216-1.425443
24CPC006_VCAP_6H:BRD-K68065987-300-03-4:100.15238311.801192-1.471689
25CPC014_MCF7_6H:BRD-A55756846-001-16-2:100.15429411.702506-1.381843
26CPC006_NCIH1836_6H:BRD-K09635314-001-02-6:800.15621711.791317-1.444288
27CPC014_MCF7_6H:BRD-K52751261-001-01-2:100.15934611.743495-1.390715
28CPC004_HEPG2_6H:BRD-K80431395-001-02-4:100.16010311.806998-1.437648
29LJP001_MDAMB231_24H:BRD-K72636697-001-01-5:100.16240511.607030-1.268590
30CPC020_A375_6H:BRD-K73819439-001-02-7:100.16756611.704780-1.322591
31CPC009_HT29_6H:BRD-K84762162-019-01-3:100.16965511.811062-1.395302
32CPC003_PC3_24H:BRD-K17705806-003-01-0:100.17798711.788197-1.340454
33CPC004_MCF7_6H:BRD-A68930007-001-03-1:100.18237311.817765-1.343401
34CPC005_A375_24H:BRD-A45333398-001-01-7:100.18237311.786420-1.320236
35CPD002_MCF7_24H:BRD-K39987650-001-18-3:100.18447111.641689-1.205119
36CPC001_VCAP_6H:BRD-A39747742-001-03-5:100.19948611.816669-1.271827
37CPC020_MCF7_24H:BRD-A09472452-015-19-2:100.21280011.658897-1.114826
38LJP001_MDAMB231_6H:BRD-K85606544-001-04-2:20.21348011.590517-1.066671
39CPC006_H1299_6H:BRD-K04853698-003-01-4:100.22597611.817754-1.174155
40CPC012_A549_24H:BRD-A41250203-001-01-2:100.23322511.740829-1.100596
41CPC005_A375_24H:BRD-A63998256-001-02-3:100.24295111.785246-1.096999
42HOG003_A549_24H:BRD-K78126613-001-16-0:100.25300911.649837-0.984730
43CPC001_VCAP_24H:BRD-K02283807-003-01-4:100.25552611.830922-1.084941
44CPC014_VCAP_24H:BRD-K97764662-001-09-0:100.26313311.702771-0.987308
45LJP002_MDAMB231_24H:BRD-K19220233-001-02-3:20.26825011.608145-0.918991
46CPC006_SNUC5_6H:BRD-U94846492-000-01-1:100.27340211.777769-1.001238
47CPC001_PC3_24H:BRD-K74305673-001-01-3:100.27340211.812350-1.020714
48CPC018_A549_24H:BRD-K73395020-001-01-5:100.29698711.664211-0.877475
49HOG003_A549_24H:BRD-K06792661-001-01-9:3.33330.32659611.608445-0.781687
50CPC010_MCF7_24H:BRD-K99582188-001-04-0:100.33205811.704768-0.816220
" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/html": [ " Download" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/html": [ "" ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" }, { "data": { "text/html": [ "Full results available at: https://amp.pharm.mssm.edu/l1000fwd/vanilla/result/5da6c75af6128a00219c8189." ], "text/plain": [ "" ] }, "metadata": {}, "output_type": "display_data" } ], "source": [ "# Initialize results\n", "results['l1000fwd'] = {}\n", "\n", "# Loop through signatures\n", "for label, signature in signatures.items():\n", "\n", " # Run analysis\n", " results['l1000fwd'][label] = analyze(signature=signature, tool='l1000fwd', signature_label=label)\n", "\n", " # Display results\n", " plot(results['l1000fwd'][label])" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "---\n", "# Methods\n", "### Data \n", "##### Data Source\n", "Dataset was user-submitted, compressed in an HDF5 data package, and uploaded to Google Cloud.\n", "\n", "##### Data Normalization\n", "##### logCPM\n", "Raw counts were normalized to log10-Counts Per Million (logCPM) by dividing each column by the total sum of its counts, multiplying it by 106, followed by the application of a log10-transform.\n", "\n", "\n", "### Signature Generation\n", "The gene expression signature was generated by comparing gene expression levels between the control group and the experimental group using the limma R package (Ritchie et al., Nucleic Acids Research 2015), available on Bioconductor: http://bioconductor.org/packages/release/bioc/html/limma.html.\n", "\n", "### PCA\n", "Principal Component Analysis was performed using the PCA function from in the sklearn Python module. Prior to performing PCA, the raw gene counts were normalized using the logCPM method, filtered by selecting the 2500 genes with most variable expression, and finally transformed using the Z-score method.\n", "\n", "### Library Size Analysis\n", "Read counts were calculated by performing the sum for each column in the raw gene count matrix. Total counts were subsequently divided by 106 and displayed as million reads.\n", "\n", "### Enrichr Links\n", "The up-regulated and down-regulated gene sets were generated by extracting the 500 genes with the respectively highest and lowest values from the gene expression signature. The gene sets were subsequently submitted to Enrichr (Kuleshov et al., 2016), which is freely available at http://amp.pharm.mssm.edu/Enrichr/, using the gene set upload API. For more information on the methods used to generate the signature, see the Differential Gene Expression section.\n", "\n", "### Gene Ontology Enrichment Analysis\n", "Enrichment results were generated by analyzing the up-regulated and down-regulated gene sets using Enrichr. The following libraries were used for the analysis: GO_Biological_Process_2018, GO_Molecular_Function_2018, GO_Cellular_Component_2018. Significant terms are determined by using a cut-off of p-value<0.1 after applying Benjamini-Hochberg correction. For more information on the methods used to perform the enrichment analysis, see the Enrichr section.\n", "\n", "### Pathway Enrichment Analysis\n", "Enrichment results were generated by analyzing the up-regulated and down-regulated gene sets using Enrichr. The following libraries were used for the analysis: KEGG_2016, Reactome_2016, WikiPathways_2016. Significant terms are determined by using a cut-off of p-value<0.1 after applying Benjamini-Hochberg correction. For more information on the methods used to perform the enrichment analysis, see the Enrichr section.\n", "\n", "### Transcription Factor Enrichment Analysis\n", "Enrichment results were generated by analyzing the up-regulated and down-regulated gene sets using Enrichr. The following libraries were used for the analysis: ChEA_2016, ENCODE_TF_ChIP-seq_2015, ARCHS4_TFs_Coexp. Significant results are determined by using a cut-off of p-value<0.1 after applying Benjamini-Hochberg correction. For more information on the methods used to perform the enrichment analysis, see the Enrichr section.\n", "\n", "### Kinase Enrichment Analysis\n", "Enrichment results were generated by analyzing the up-regulated and down-regulated gene sets using Enrichr. The following libraries were used for the analysis: KEA_2015, ARCHS4_Kinases_Coexp. Significant results are determined by using a cut-off of p-value<0.1 after applying Benjamini-Hochberg correction. For more information on the methods used to perform the enrichment analysis, see the Enrichr section.\n", "\n", "### miRNA Enrichment Analysis\n", "Enrichment results were generated by analyzing the up-regulated and down-regulated gene sets using Enrichr. The following libraries were used for the analysis: TargetScan_microRNA_2017, miRTarBase_2017. Significant results are determined by using a cut-off of p-value<0.1 after applying Benjamini-Hochberg correction. For more information on the methods used to perform the enrichment analysis, see the Enrichr section.\n", "\n", "### L1000CDS2 Query\n", "The L1000CDS2 analysis (Duan et al., 2016) was performed by submitting the top 2000 genes in the gene expression signature to the L1000CDS2 signature search API. For more information on the methods used to generate the signature, see the Differential Gene Expression section.\n", "\n", "### L1000FWD Query\n", "The L1000FWD analysis (Wang et al., 2018) was performed by submitting the top 2000 genes in the gene expression signature to the L1000FWD signature search API. For more information on the methods used to generate the signature, see the Differential Gene Expression section." ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "---\n", "## References\n", "Duan, Q., Reid, S.P., Clark, N.R., Wang, Z., Fernandez, N.F., Rouillard, A.D., Readhead, B., Tritsch, S.R., Hodos, R., Hafner, M., et al. (2016). L1000CDS2: LINCS L1000 characteristic direction signatures search engine. Npj Systems Biology and Applications 2. doi: https://doi.org/10.1038/npjsba.2016.15

Kuleshov, M.V., Jones, M.R., Rouillard, A.D., Fernandez, N.F., Duan, Q., Wang, Z., Koplev, S., Jenkins, S.L., Jagodnik, K.M., Lachmann, A., et al. (2016). Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Research 44, W90ÐW97. doi: https://dx.doi.org/10.1093/nar/gkw377

Pearson, K. (1901). LIII. On lines and planes of closest fit to systems of points in space. The London, Edinburgh, and Dublin Philosophical Magazine and Journal of Science 2, 559Ð572. doi: https://doi.org/10.1080/14786440109462720

Ritchie, M.E., Phipson, B., Wu, D., Hu, Y., Law, C.W., Shi, W., and Smyth, G.K. (2015). limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Research 43, e47–e47. doi: https://doi.org/10.1093/nar/gkv007

Wang, Z., Lachmann, A., Keenan, A.B., and Ma’ayan, A. (2018). L1000FWD: fireworks visualization of drug-induced transcriptomic signatures. Bioinformatics. doi: https://doi.org/10.1093/bioinformatics/bty060
" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "---\n", "
BioJupies is being developed by the Ma'ayan Lab at the Icahn School of Medicine at Mount Sinai
and is an open source project available on GitHub.
" ] } ], "metadata": {}, "nbformat": 4, "nbformat_minor": 2 }