diff --git a/nbs/99_manuscript/coefs_comp/20_00-gtex_whole_blood-UTY_KDM6A.ipynb b/nbs/99_manuscript/coefs_comp/20_00-gtex_whole_blood-UTY_KDM6A.ipynb
new file mode 100644
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+++ b/nbs/99_manuscript/coefs_comp/20_00-gtex_whole_blood-UTY_KDM6A.ipynb
@@ -0,0 +1,4634 @@
+{
+ "cells": [
+ {
+ "cell_type": "markdown",
+ "id": "b9c35e72-e087-4511-9899-5da25f3ff7ba",
+ "metadata": {
+ "papermill": {
+ "duration": 0.013796,
+ "end_time": "2023-11-20T08:55:56.439073",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:56.425277",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "source": [
+ "# Description"
+ ]
+ },
+ {
+ "cell_type": "markdown",
+ "id": "2422b873-5148-44ef-9884-0dd0fa8e69fa",
+ "metadata": {
+ "papermill": {
+ "duration": 0.013051,
+ "end_time": "2023-11-20T08:55:56.465902",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:56.452851",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "source": [
+ "This notebooks analyzes more closely the pattern between gene pair *UTY* / *KDM6A*. The analyses are focused on the Reviewer 2's comment:\n",
+ "\n",
+ "```\n",
+ "In Figure 4, while there is a visible difference between the correlation of male samples, the CCC values are still quite close. For example, this can be observed in Brain Cerebellum and Small Intestine Terminal Ileum. Please address this.\n",
+ "```"
+ ]
+ },
+ {
+ "cell_type": "markdown",
+ "id": "5d4ae4df-624d-4951-917c-880462cfb658",
+ "metadata": {
+ "papermill": {
+ "duration": 0.012554,
+ "end_time": "2023-11-20T08:55:56.490793",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:56.478239",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "source": [
+ "# Modules"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 1,
+ "id": "2dcd0e52-236a-44cd-9cd9-71cca1232338",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:55:56.512994Z",
+ "iopub.status.busy": "2023-11-20T08:55:56.512464Z",
+ "iopub.status.idle": "2023-11-20T08:55:57.280770Z",
+ "shell.execute_reply": "2023-11-20T08:55:57.280425Z"
+ },
+ "papermill": {
+ "duration": 0.778767,
+ "end_time": "2023-11-20T08:55:57.282390",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:56.503623",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [],
+ "source": [
+ "import pandas as pd\n",
+ "\n",
+ "from scipy.stats import pearsonr, spearmanr\n",
+ "import matplotlib.pyplot as plt\n",
+ "import seaborn as sns\n",
+ "import numpy as np\n",
+ "\n",
+ "from ccc import conf\n",
+ "from ccc.coef import ccc"
+ ]
+ },
+ {
+ "cell_type": "markdown",
+ "id": "e9ef3211-8d35-4b4b-be45-2de384b6fdee",
+ "metadata": {
+ "papermill": {
+ "duration": 0.010558,
+ "end_time": "2023-11-20T08:55:57.300232",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:57.289674",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "source": [
+ "# Settings"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 2,
+ "id": "3e9781c8-faf2-41ec-a5c3-ab84dec6a7fa",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:55:57.313597Z",
+ "iopub.status.busy": "2023-11-20T08:55:57.313511Z",
+ "iopub.status.idle": "2023-11-20T08:55:57.315760Z",
+ "shell.execute_reply": "2023-11-20T08:55:57.315469Z"
+ },
+ "papermill": {
+ "duration": 0.009823,
+ "end_time": "2023-11-20T08:55:57.316518",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:57.306695",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [],
+ "source": [
+ "# this gene pair was originally found with ccc on whole blood\n",
+ "# interesting: https://clincancerres.aacrjournals.org/content/26/21/5567.figures-only\n",
+ "gene0_id, gene1_id = \"ENSG00000147050.14\", \"ENSG00000183878.15\"\n",
+ "gene0_symbol, gene1_symbol = \"KDM6A\", \"UTY\""
+ ]
+ },
+ {
+ "cell_type": "markdown",
+ "id": "649a237d-595e-4bd7-a607-7c1773b36cb5",
+ "metadata": {
+ "papermill": {
+ "duration": 0.026613,
+ "end_time": "2023-11-20T08:55:57.349663",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:57.323050",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "source": [
+ "# Paths"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 3,
+ "id": "1ea8a834-34dd-480f-b85f-5706aa4db334",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:55:57.363287Z",
+ "iopub.status.busy": "2023-11-20T08:55:57.363162Z",
+ "iopub.status.idle": "2023-11-20T08:55:57.365443Z",
+ "shell.execute_reply": "2023-11-20T08:55:57.365163Z"
+ },
+ "papermill": {
+ "duration": 0.009932,
+ "end_time": "2023-11-20T08:55:57.366200",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:57.356268",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [],
+ "source": [
+ "TISSUE_DIR = conf.GTEX[\"DATA_DIR\"] / \"data_by_tissue\"\n",
+ "assert TISSUE_DIR.exists()"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 4,
+ "id": "f869a719-5302-4c5b-b496-0878617ea3d3",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:55:57.379862Z",
+ "iopub.status.busy": "2023-11-20T08:55:57.379650Z",
+ "iopub.status.idle": "2023-11-20T08:55:57.383787Z",
+ "shell.execute_reply": "2023-11-20T08:55:57.383383Z"
+ },
+ "papermill": {
+ "duration": 0.011846,
+ "end_time": "2023-11-20T08:55:57.384630",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:57.372784",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [
+ {
+ "data": {
+ "text/plain": [
+ "PosixPath('/opt/manuscript/content/images/coefs_comp/kdm6a_vs_uty')"
+ ]
+ },
+ "metadata": {},
+ "output_type": "display_data"
+ }
+ ],
+ "source": [
+ "OUTPUT_FIGURE_DIR = (\n",
+ " conf.MANUSCRIPT[\"FIGURES_DIR\"]\n",
+ " / \"coefs_comp\"\n",
+ " / f\"{gene0_symbol.lower()}_vs_{gene1_symbol.lower()}\"\n",
+ ")\n",
+ "OUTPUT_FIGURE_DIR.mkdir(parents=True, exist_ok=True)\n",
+ "display(OUTPUT_FIGURE_DIR)"
+ ]
+ },
+ {
+ "cell_type": "markdown",
+ "id": "35453032-07b1-4e68-9f65-f8ec0d0ebcd1",
+ "metadata": {
+ "papermill": {
+ "duration": 0.006516,
+ "end_time": "2023-11-20T08:55:57.397804",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:57.391288",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "source": [
+ "# Data"
+ ]
+ },
+ {
+ "cell_type": "markdown",
+ "id": "76b3390f-360a-45e8-b38d-f14f92823125",
+ "metadata": {
+ "papermill": {
+ "duration": 0.006556,
+ "end_time": "2023-11-20T08:55:57.410974",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:57.404418",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "source": [
+ "## GTEx metadata"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 5,
+ "id": "e2dffcd4-3280-4f2e-8e5b-1797c6333894",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:55:57.425110Z",
+ "iopub.status.busy": "2023-11-20T08:55:57.424812Z",
+ "iopub.status.idle": "2023-11-20T08:55:57.460560Z",
+ "shell.execute_reply": "2023-11-20T08:55:57.460088Z"
+ },
+ "papermill": {
+ "duration": 0.043947,
+ "end_time": "2023-11-20T08:55:57.461533",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:57.417586",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [],
+ "source": [
+ "gtex_metadata = pd.read_pickle(conf.GTEX[\"DATA_DIR\"] / \"gtex_v8-sample_metadata.pkl\")"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 6,
+ "id": "f762c76d-31b6-46e3-9660-3352112c9326",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:55:57.475718Z",
+ "iopub.status.busy": "2023-11-20T08:55:57.475409Z",
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+ "shell.execute_reply": "2023-11-20T08:55:57.478744Z"
+ },
+ "papermill": {
+ "duration": 0.011791,
+ "end_time": "2023-11-20T08:55:57.479973",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:57.468182",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [
+ {
+ "data": {
+ "text/plain": [
+ "(22951, 66)"
+ ]
+ },
+ "execution_count": 6,
+ "metadata": {},
+ "output_type": "execute_result"
+ }
+ ],
+ "source": [
+ "gtex_metadata.shape"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 7,
+ "id": "870baa0e-4f5b-44c7-b32d-f3763f74a2b7",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:55:57.494199Z",
+ "iopub.status.busy": "2023-11-20T08:55:57.493904Z",
+ "iopub.status.idle": "2023-11-20T08:55:57.515276Z",
+ "shell.execute_reply": "2023-11-20T08:55:57.514837Z"
+ },
+ "papermill": {
+ "duration": 0.029424,
+ "end_time": "2023-11-20T08:55:57.516109",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:57.486685",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [
+ {
+ "data": {
+ "text/html": [
+ "
\n",
+ "\n",
+ "
\n",
+ " \n",
+ " \n",
+ " | \n",
+ " SUBJID | \n",
+ " SEX | \n",
+ " AGE | \n",
+ " DTHHRDY | \n",
+ " SMATSSCR | \n",
+ " SMCENTER | \n",
+ " SMPTHNTS | \n",
+ " SMRIN | \n",
+ " SMTS | \n",
+ " SMTSD | \n",
+ " ... | \n",
+ " SME1ANTI | \n",
+ " SMSPLTRD | \n",
+ " SMBSMMRT | \n",
+ " SME1SNSE | \n",
+ " SME1PCTS | \n",
+ " SMRRNART | \n",
+ " SME1MPRT | \n",
+ " SMNUM5CD | \n",
+ " SMDPMPRT | \n",
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\n",
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+ " SAMPID | \n",
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\n",
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+ " \n",
+ " GTEX-1117F-0003-SM-58Q7G | \n",
+ " GTEX-1117F | \n",
+ " Female | \n",
+ " 60-69 | \n",
+ " 4.0 | \n",
+ " NaN | \n",
+ " B1 | \n",
+ " NaN | \n",
+ " NaN | \n",
+ " Blood | \n",
+ " Whole Blood | \n",
+ " ... | \n",
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+ " NaN | \n",
+ " NaN | \n",
+ " NaN | \n",
+ " NaN | \n",
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+ " NaN | \n",
+ " NaN | \n",
+ " NaN | \n",
+ "
\n",
+ " \n",
+ " GTEX-1117F-0003-SM-5DWSB | \n",
+ " GTEX-1117F | \n",
+ " Female | \n",
+ " 60-69 | \n",
+ " 4.0 | \n",
+ " NaN | \n",
+ " B1 | \n",
+ " NaN | \n",
+ " NaN | \n",
+ " Blood | \n",
+ " Whole Blood | \n",
+ " ... | \n",
+ " NaN | \n",
+ " NaN | \n",
+ " NaN | \n",
+ " NaN | \n",
+ " NaN | \n",
+ " NaN | \n",
+ " NaN | \n",
+ " NaN | \n",
+ " NaN | \n",
+ " NaN | \n",
+ "
\n",
+ " \n",
+ " GTEX-1117F-0003-SM-6WBT7 | \n",
+ " GTEX-1117F | \n",
+ " Female | \n",
+ " 60-69 | \n",
+ " 4.0 | \n",
+ " NaN | \n",
+ " B1 | \n",
+ " NaN | \n",
+ " NaN | \n",
+ " Blood | \n",
+ " Whole Blood | \n",
+ " ... | \n",
+ " NaN | \n",
+ " NaN | \n",
+ " NaN | \n",
+ " NaN | \n",
+ " NaN | \n",
+ " NaN | \n",
+ " NaN | \n",
+ " NaN | \n",
+ " NaN | \n",
+ " NaN | \n",
+ "
\n",
+ " \n",
+ " GTEX-1117F-0011-R10a-SM-AHZ7F | \n",
+ " GTEX-1117F | \n",
+ " Female | \n",
+ " 60-69 | \n",
+ " 4.0 | \n",
+ " NaN | \n",
+ " B1, A1 | \n",
+ " NaN | \n",
+ " NaN | \n",
+ " Brain | \n",
+ " Brain - Frontal Cortex (BA9) | \n",
+ " ... | \n",
+ " NaN | \n",
+ " NaN | \n",
+ " NaN | \n",
+ " NaN | \n",
+ " NaN | \n",
+ " NaN | \n",
+ " NaN | \n",
+ " NaN | \n",
+ " NaN | \n",
+ " NaN | \n",
+ "
\n",
+ " \n",
+ " GTEX-1117F-0011-R10b-SM-CYKQ8 | \n",
+ " GTEX-1117F | \n",
+ " Female | \n",
+ " 60-69 | \n",
+ " 4.0 | \n",
+ " NaN | \n",
+ " B1, A1 | \n",
+ " NaN | \n",
+ " 7.2 | \n",
+ " Brain | \n",
+ " Brain - Frontal Cortex (BA9) | \n",
+ " ... | \n",
+ " NaN | \n",
+ " NaN | \n",
+ " NaN | \n",
+ " NaN | \n",
+ " NaN | \n",
+ " NaN | \n",
+ " NaN | \n",
+ " NaN | \n",
+ " NaN | \n",
+ " NaN | \n",
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+ "
5 rows × 66 columns
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+ "
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+ ],
+ "text/plain": [
+ " SUBJID SEX AGE DTHHRDY SMATSSCR \\\n",
+ "SAMPID \n",
+ "GTEX-1117F-0003-SM-58Q7G GTEX-1117F Female 60-69 4.0 NaN \n",
+ "GTEX-1117F-0003-SM-5DWSB GTEX-1117F Female 60-69 4.0 NaN \n",
+ "GTEX-1117F-0003-SM-6WBT7 GTEX-1117F Female 60-69 4.0 NaN \n",
+ "GTEX-1117F-0011-R10a-SM-AHZ7F GTEX-1117F Female 60-69 4.0 NaN \n",
+ "GTEX-1117F-0011-R10b-SM-CYKQ8 GTEX-1117F Female 60-69 4.0 NaN \n",
+ "\n",
+ " SMCENTER SMPTHNTS SMRIN SMTS \\\n",
+ "SAMPID \n",
+ "GTEX-1117F-0003-SM-58Q7G B1 NaN NaN Blood \n",
+ "GTEX-1117F-0003-SM-5DWSB B1 NaN NaN Blood \n",
+ "GTEX-1117F-0003-SM-6WBT7 B1 NaN NaN Blood \n",
+ "GTEX-1117F-0011-R10a-SM-AHZ7F B1, A1 NaN NaN Brain \n",
+ "GTEX-1117F-0011-R10b-SM-CYKQ8 B1, A1 NaN 7.2 Brain \n",
+ "\n",
+ " SMTSD ... SME1ANTI \\\n",
+ "SAMPID ... \n",
+ "GTEX-1117F-0003-SM-58Q7G Whole Blood ... NaN \n",
+ "GTEX-1117F-0003-SM-5DWSB Whole Blood ... NaN \n",
+ "GTEX-1117F-0003-SM-6WBT7 Whole Blood ... NaN \n",
+ "GTEX-1117F-0011-R10a-SM-AHZ7F Brain - Frontal Cortex (BA9) ... NaN \n",
+ "GTEX-1117F-0011-R10b-SM-CYKQ8 Brain - Frontal Cortex (BA9) ... NaN \n",
+ "\n",
+ " SMSPLTRD SMBSMMRT SME1SNSE SME1PCTS SMRRNART \\\n",
+ "SAMPID \n",
+ "GTEX-1117F-0003-SM-58Q7G NaN NaN NaN NaN NaN \n",
+ "GTEX-1117F-0003-SM-5DWSB NaN NaN NaN NaN NaN \n",
+ "GTEX-1117F-0003-SM-6WBT7 NaN NaN NaN NaN NaN \n",
+ "GTEX-1117F-0011-R10a-SM-AHZ7F NaN NaN NaN NaN NaN \n",
+ "GTEX-1117F-0011-R10b-SM-CYKQ8 NaN NaN NaN NaN NaN \n",
+ "\n",
+ " SME1MPRT SMNUM5CD SMDPMPRT SME2PCTS \n",
+ "SAMPID \n",
+ "GTEX-1117F-0003-SM-58Q7G NaN NaN NaN NaN \n",
+ "GTEX-1117F-0003-SM-5DWSB NaN NaN NaN NaN \n",
+ "GTEX-1117F-0003-SM-6WBT7 NaN NaN NaN NaN \n",
+ "GTEX-1117F-0011-R10a-SM-AHZ7F NaN NaN NaN NaN \n",
+ "GTEX-1117F-0011-R10b-SM-CYKQ8 NaN NaN NaN NaN \n",
+ "\n",
+ "[5 rows x 66 columns]"
+ ]
+ },
+ "execution_count": 7,
+ "metadata": {},
+ "output_type": "execute_result"
+ }
+ ],
+ "source": [
+ "gtex_metadata.head()"
+ ]
+ },
+ {
+ "cell_type": "markdown",
+ "id": "85a68693-1bae-4473-bd18-086caf5820eb",
+ "metadata": {
+ "papermill": {
+ "duration": 0.006772,
+ "end_time": "2023-11-20T08:55:57.529828",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:57.523056",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "source": [
+ "## Gene Ensembl ID -> Symbol mapping"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 8,
+ "id": "3cf14b08-658d-46bc-9581-c9afd70be177",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:55:57.544600Z",
+ "iopub.status.busy": "2023-11-20T08:55:57.544199Z",
+ "iopub.status.idle": "2023-11-20T08:55:57.562921Z",
+ "shell.execute_reply": "2023-11-20T08:55:57.562384Z"
+ },
+ "papermill": {
+ "duration": 0.027167,
+ "end_time": "2023-11-20T08:55:57.563910",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:57.536743",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [],
+ "source": [
+ "gene_map = pd.read_pickle(conf.GTEX[\"DATA_DIR\"] / \"gtex_gene_id_symbol_mappings.pkl\")"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 9,
+ "id": "a2564d82-f685-4bc4-8ab9-5c09988830ae",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:55:57.579072Z",
+ "iopub.status.busy": "2023-11-20T08:55:57.578653Z",
+ "iopub.status.idle": "2023-11-20T08:55:57.634878Z",
+ "shell.execute_reply": "2023-11-20T08:55:57.634425Z"
+ },
+ "papermill": {
+ "duration": 0.064994,
+ "end_time": "2023-11-20T08:55:57.635818",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:57.570824",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [],
+ "source": [
+ "gene_map = gene_map.set_index(\"gene_ens_id\")[\"gene_symbol\"].to_dict()"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 10,
+ "id": "ced72294-1843-427e-8dc0-3f57572fd9fd",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:55:57.650500Z",
+ "iopub.status.busy": "2023-11-20T08:55:57.650207Z",
+ "iopub.status.idle": "2023-11-20T08:55:57.652491Z",
+ "shell.execute_reply": "2023-11-20T08:55:57.652119Z"
+ },
+ "papermill": {
+ "duration": 0.010461,
+ "end_time": "2023-11-20T08:55:57.653268",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:57.642807",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [],
+ "source": [
+ "assert gene_map[\"ENSG00000145309.5\"] == \"CABS1\""
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 11,
+ "id": "e7d49359-73b7-4e13-b404-24bbcce77172",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:55:57.667993Z",
+ "iopub.status.busy": "2023-11-20T08:55:57.667737Z",
+ "iopub.status.idle": "2023-11-20T08:55:57.670315Z",
+ "shell.execute_reply": "2023-11-20T08:55:57.669870Z"
+ },
+ "papermill": {
+ "duration": 0.010763,
+ "end_time": "2023-11-20T08:55:57.671152",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:57.660389",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [],
+ "source": [
+ "assert gene_map[gene0_id] == gene0_symbol\n",
+ "assert gene_map[gene1_id] == gene1_symbol"
+ ]
+ },
+ {
+ "cell_type": "markdown",
+ "id": "80037782-e5d0-4bf3-a7bf-ee6cb22e064e",
+ "metadata": {
+ "papermill": {
+ "duration": 0.006923,
+ "end_time": "2023-11-20T08:55:57.685112",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:57.678189",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "source": [
+ "## Get male/females sample IDs"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 12,
+ "id": "5122cc00-b5da-4327-a0e3-d0d4829b1986",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:55:57.700015Z",
+ "iopub.status.busy": "2023-11-20T08:55:57.699725Z",
+ "iopub.status.idle": "2023-11-20T08:55:57.707873Z",
+ "shell.execute_reply": "2023-11-20T08:55:57.707403Z"
+ },
+ "papermill": {
+ "duration": 0.016514,
+ "end_time": "2023-11-20T08:55:57.708660",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:57.692146",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [
+ {
+ "data": {
+ "text/plain": [
+ "count 22951\n",
+ "unique 2\n",
+ "top Male\n",
+ "freq 15046\n",
+ "Name: SEX, dtype: object"
+ ]
+ },
+ "execution_count": 12,
+ "metadata": {},
+ "output_type": "execute_result"
+ }
+ ],
+ "source": [
+ "gtex_metadata[\"SEX\"].describe()"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 13,
+ "id": "a31f26d7-91dc-468d-81b1-f6e563d7b88d",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:55:57.723690Z",
+ "iopub.status.busy": "2023-11-20T08:55:57.723392Z",
+ "iopub.status.idle": "2023-11-20T08:55:57.734583Z",
+ "shell.execute_reply": "2023-11-20T08:55:57.734034Z"
+ },
+ "papermill": {
+ "duration": 0.019757,
+ "end_time": "2023-11-20T08:55:57.735493",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:57.715736",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [],
+ "source": [
+ "male_samples = gtex_metadata[gtex_metadata[\"SEX\"] == \"Male\"].index.tolist()"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 14,
+ "id": "275350ae-f69f-4351-9a3e-0363a423487c",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:55:57.750681Z",
+ "iopub.status.busy": "2023-11-20T08:55:57.750313Z",
+ "iopub.status.idle": "2023-11-20T08:55:57.754061Z",
+ "shell.execute_reply": "2023-11-20T08:55:57.753594Z"
+ },
+ "papermill": {
+ "duration": 0.012315,
+ "end_time": "2023-11-20T08:55:57.754893",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:57.742578",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [
+ {
+ "data": {
+ "text/plain": [
+ "15046"
+ ]
+ },
+ "execution_count": 14,
+ "metadata": {},
+ "output_type": "execute_result"
+ }
+ ],
+ "source": [
+ "len(male_samples)"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 15,
+ "id": "7f9ddb05-4328-4a98-921d-16c3bdff1c67",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:55:57.769965Z",
+ "iopub.status.busy": "2023-11-20T08:55:57.769676Z",
+ "iopub.status.idle": "2023-11-20T08:55:57.773333Z",
+ "shell.execute_reply": "2023-11-20T08:55:57.772871Z"
+ },
+ "papermill": {
+ "duration": 0.012109,
+ "end_time": "2023-11-20T08:55:57.774177",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:57.762068",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [
+ {
+ "data": {
+ "text/plain": [
+ "['GTEX-111CU-0003-SM-58Q95',\n",
+ " 'GTEX-111CU-0003-SM-5DWTR',\n",
+ " 'GTEX-111CU-0003-SM-6WBUD',\n",
+ " 'GTEX-111CU-0126-SM-5GZWZ',\n",
+ " 'GTEX-111CU-0226-SM-5GZXC']"
+ ]
+ },
+ "execution_count": 15,
+ "metadata": {},
+ "output_type": "execute_result"
+ }
+ ],
+ "source": [
+ "male_samples[:5]"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 16,
+ "id": "dede5dad-0df7-40a1-8ea5-eab06fc3b9af",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:55:57.789526Z",
+ "iopub.status.busy": "2023-11-20T08:55:57.789169Z",
+ "iopub.status.idle": "2023-11-20T08:55:57.797293Z",
+ "shell.execute_reply": "2023-11-20T08:55:57.796743Z"
+ },
+ "papermill": {
+ "duration": 0.016816,
+ "end_time": "2023-11-20T08:55:57.798240",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:57.781424",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [],
+ "source": [
+ "female_samples = gtex_metadata[gtex_metadata[\"SEX\"] == \"Female\"].index.tolist()"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 17,
+ "id": "57609f27-8bb6-4377-827b-ae9d55537be1",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:55:57.813663Z",
+ "iopub.status.busy": "2023-11-20T08:55:57.813372Z",
+ "iopub.status.idle": "2023-11-20T08:55:57.817067Z",
+ "shell.execute_reply": "2023-11-20T08:55:57.816608Z"
+ },
+ "papermill": {
+ "duration": 0.012367,
+ "end_time": "2023-11-20T08:55:57.817919",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:57.805552",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [
+ {
+ "data": {
+ "text/plain": [
+ "7905"
+ ]
+ },
+ "execution_count": 17,
+ "metadata": {},
+ "output_type": "execute_result"
+ }
+ ],
+ "source": [
+ "len(female_samples)"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 18,
+ "id": "e8fea00b-9119-440b-b33a-fadbc2131210",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:55:57.833423Z",
+ "iopub.status.busy": "2023-11-20T08:55:57.833136Z",
+ "iopub.status.idle": "2023-11-20T08:55:57.836776Z",
+ "shell.execute_reply": "2023-11-20T08:55:57.836311Z"
+ },
+ "papermill": {
+ "duration": 0.012323,
+ "end_time": "2023-11-20T08:55:57.837601",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:57.825278",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [
+ {
+ "data": {
+ "text/plain": [
+ "['GTEX-1117F-0003-SM-58Q7G',\n",
+ " 'GTEX-1117F-0003-SM-5DWSB',\n",
+ " 'GTEX-1117F-0003-SM-6WBT7',\n",
+ " 'GTEX-1117F-0011-R10a-SM-AHZ7F',\n",
+ " 'GTEX-1117F-0011-R10b-SM-CYKQ8']"
+ ]
+ },
+ "execution_count": 18,
+ "metadata": {},
+ "output_type": "execute_result"
+ }
+ ],
+ "source": [
+ "female_samples[:5]"
+ ]
+ },
+ {
+ "cell_type": "markdown",
+ "id": "e5e52d3d-2d87-488a-ab48-d105b85fe46b",
+ "metadata": {
+ "papermill": {
+ "duration": 0.007277,
+ "end_time": "2023-11-20T08:55:57.852283",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:57.845006",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "source": [
+ "# Brain cerebellum"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 19,
+ "id": "137ce1ba-751a-4758-91dc-2ad1e2fb57d6",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:55:57.868126Z",
+ "iopub.status.busy": "2023-11-20T08:55:57.867764Z",
+ "iopub.status.idle": "2023-11-20T08:55:57.971907Z",
+ "shell.execute_reply": "2023-11-20T08:55:57.971473Z"
+ },
+ "papermill": {
+ "duration": 0.11334,
+ "end_time": "2023-11-20T08:55:57.973180",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:57.859840",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [],
+ "source": [
+ "brain_cerebellum = (\n",
+ " pd.read_pickle(TISSUE_DIR / \"gtex_v8_data_brain_cerebellum.pkl\")\n",
+ " .loc[[gene0_id, gene1_id]]\n",
+ " .T.rename_axis(\"sample_id\")\n",
+ ")"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 20,
+ "id": "6e2eb857-c33c-4a65-a401-db3ced529623",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:55:57.989734Z",
+ "iopub.status.busy": "2023-11-20T08:55:57.989634Z",
+ "iopub.status.idle": "2023-11-20T08:55:57.992488Z",
+ "shell.execute_reply": "2023-11-20T08:55:57.992134Z"
+ },
+ "papermill": {
+ "duration": 0.011606,
+ "end_time": "2023-11-20T08:55:57.993202",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:57.981596",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [
+ {
+ "data": {
+ "text/plain": [
+ "(241, 2)"
+ ]
+ },
+ "execution_count": 20,
+ "metadata": {},
+ "output_type": "execute_result"
+ }
+ ],
+ "source": [
+ "brain_cerebellum.shape"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 21,
+ "id": "61a489c4-de22-46ec-b795-8199d68123ae",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:55:58.008703Z",
+ "iopub.status.busy": "2023-11-20T08:55:58.008476Z",
+ "iopub.status.idle": "2023-11-20T08:55:58.012908Z",
+ "shell.execute_reply": "2023-11-20T08:55:58.012553Z"
+ },
+ "papermill": {
+ "duration": 0.012911,
+ "end_time": "2023-11-20T08:55:58.013590",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:58.000679",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [
+ {
+ "data": {
+ "text/html": [
+ "\n",
+ "\n",
+ "
\n",
+ " \n",
+ " \n",
+ " gene_ens_id | \n",
+ " ENSG00000147050.14 | \n",
+ " ENSG00000183878.15 | \n",
+ "
\n",
+ " \n",
+ " sample_id | \n",
+ " | \n",
+ " | \n",
+ "
\n",
+ " \n",
+ " \n",
+ " \n",
+ " GTEX-111FC-3326-SM-5GZYV | \n",
+ " 9.268 | \n",
+ " 6.988 | \n",
+ "
\n",
+ " \n",
+ " GTEX-1128S-2826-SM-5N9DI | \n",
+ " 12.930 | \n",
+ " 0.000 | \n",
+ "
\n",
+ " \n",
+ " GTEX-117XS-3126-SM-5GIDP | \n",
+ " 10.840 | \n",
+ " 7.389 | \n",
+ "
\n",
+ " \n",
+ " GTEX-1192X-3226-SM-5987D | \n",
+ " 10.780 | \n",
+ " 5.132 | \n",
+ "
\n",
+ " \n",
+ " GTEX-11DXW-1026-SM-5H11K | \n",
+ " 10.060 | \n",
+ " 7.823 | \n",
+ "
\n",
+ " \n",
+ "
\n",
+ "
"
+ ],
+ "text/plain": [
+ "gene_ens_id ENSG00000147050.14 ENSG00000183878.15\n",
+ "sample_id \n",
+ "GTEX-111FC-3326-SM-5GZYV 9.268 6.988\n",
+ "GTEX-1128S-2826-SM-5N9DI 12.930 0.000\n",
+ "GTEX-117XS-3126-SM-5GIDP 10.840 7.389\n",
+ "GTEX-1192X-3226-SM-5987D 10.780 5.132\n",
+ "GTEX-11DXW-1026-SM-5H11K 10.060 7.823"
+ ]
+ },
+ "execution_count": 21,
+ "metadata": {},
+ "output_type": "execute_result"
+ }
+ ],
+ "source": [
+ "brain_cerebellum.head()"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 22,
+ "id": "23a5e80d-afbf-4780-b84d-ba4553421f8b",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:55:58.029435Z",
+ "iopub.status.busy": "2023-11-20T08:55:58.029164Z",
+ "iopub.status.idle": "2023-11-20T08:55:58.034801Z",
+ "shell.execute_reply": "2023-11-20T08:55:58.034365Z"
+ },
+ "papermill": {
+ "duration": 0.014433,
+ "end_time": "2023-11-20T08:55:58.035617",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:58.021184",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [],
+ "source": [
+ "brain_cerebellum_males = brain_cerebellum.loc[\n",
+ " brain_cerebellum.index.intersection(male_samples)\n",
+ "]"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 23,
+ "id": "38730891-f083-4c34-8530-30f511003abc",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:55:58.051552Z",
+ "iopub.status.busy": "2023-11-20T08:55:58.051264Z",
+ "iopub.status.idle": "2023-11-20T08:55:58.054819Z",
+ "shell.execute_reply": "2023-11-20T08:55:58.054358Z"
+ },
+ "papermill": {
+ "duration": 0.012427,
+ "end_time": "2023-11-20T08:55:58.055626",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:58.043199",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [
+ {
+ "data": {
+ "text/plain": [
+ "(174, 2)"
+ ]
+ },
+ "execution_count": 23,
+ "metadata": {},
+ "output_type": "execute_result"
+ }
+ ],
+ "source": [
+ "brain_cerebellum_males.shape"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 24,
+ "id": "2081927d-7970-4805-891c-c8bc76a2351f",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:55:58.071750Z",
+ "iopub.status.busy": "2023-11-20T08:55:58.071458Z",
+ "iopub.status.idle": "2023-11-20T08:55:58.076640Z",
+ "shell.execute_reply": "2023-11-20T08:55:58.076155Z"
+ },
+ "papermill": {
+ "duration": 0.014105,
+ "end_time": "2023-11-20T08:55:58.077423",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:58.063318",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [],
+ "source": [
+ "brain_cerebellum_females = brain_cerebellum.loc[\n",
+ " brain_cerebellum.index.intersection(female_samples)\n",
+ "]"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 25,
+ "id": "23e75a4b-0c77-470d-9a7b-4d07909be735",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:55:58.097064Z",
+ "iopub.status.busy": "2023-11-20T08:55:58.096854Z",
+ "iopub.status.idle": "2023-11-20T08:55:58.105749Z",
+ "shell.execute_reply": "2023-11-20T08:55:58.105289Z"
+ },
+ "papermill": {
+ "duration": 0.021495,
+ "end_time": "2023-11-20T08:55:58.106610",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:58.085115",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [
+ {
+ "data": {
+ "text/plain": [
+ "(67, 2)"
+ ]
+ },
+ "execution_count": 25,
+ "metadata": {},
+ "output_type": "execute_result"
+ }
+ ],
+ "source": [
+ "brain_cerebellum_females.shape"
+ ]
+ },
+ {
+ "cell_type": "markdown",
+ "id": "47ed8fc3-e037-405a-bd25-010665c91132",
+ "metadata": {
+ "papermill": {
+ "duration": 0.007803,
+ "end_time": "2023-11-20T08:55:58.122565",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:58.114762",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "source": [
+ "# Small intestine (terminal ileum)"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 26,
+ "id": "695487c0-35c7-4a5e-b91c-4e8ee47b0295",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:55:58.139576Z",
+ "iopub.status.busy": "2023-11-20T08:55:58.139132Z",
+ "iopub.status.idle": "2023-11-20T08:55:58.230646Z",
+ "shell.execute_reply": "2023-11-20T08:55:58.230353Z"
+ },
+ "papermill": {
+ "duration": 0.100976,
+ "end_time": "2023-11-20T08:55:58.231502",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:58.130526",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [],
+ "source": [
+ "small_intestine = (\n",
+ " pd.read_pickle(TISSUE_DIR / \"gtex_v8_data_small_intestine_terminal_ileum.pkl\")\n",
+ " .loc[[gene0_id, gene1_id]]\n",
+ " .T.rename_axis(\"sample_id\")\n",
+ ")"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 27,
+ "id": "a84a00a6-b51f-4a79-b056-0f515f526c95",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:55:58.247529Z",
+ "iopub.status.busy": "2023-11-20T08:55:58.247442Z",
+ "iopub.status.idle": "2023-11-20T08:55:58.250183Z",
+ "shell.execute_reply": "2023-11-20T08:55:58.249901Z"
+ },
+ "papermill": {
+ "duration": 0.011604,
+ "end_time": "2023-11-20T08:55:58.250884",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:58.239280",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [
+ {
+ "data": {
+ "text/plain": [
+ "(187, 2)"
+ ]
+ },
+ "execution_count": 27,
+ "metadata": {},
+ "output_type": "execute_result"
+ }
+ ],
+ "source": [
+ "small_intestine.shape"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 28,
+ "id": "d9ef287c-3f2a-46da-99a8-2b6688379fc8",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:55:58.267183Z",
+ "iopub.status.busy": "2023-11-20T08:55:58.267093Z",
+ "iopub.status.idle": "2023-11-20T08:55:58.271467Z",
+ "shell.execute_reply": "2023-11-20T08:55:58.271146Z"
+ },
+ "papermill": {
+ "duration": 0.013258,
+ "end_time": "2023-11-20T08:55:58.272186",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:58.258928",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [
+ {
+ "data": {
+ "text/html": [
+ "\n",
+ "\n",
+ "
\n",
+ " \n",
+ " \n",
+ " gene_ens_id | \n",
+ " ENSG00000147050.14 | \n",
+ " ENSG00000183878.15 | \n",
+ "
\n",
+ " \n",
+ " sample_id | \n",
+ " | \n",
+ " | \n",
+ "
\n",
+ " \n",
+ " \n",
+ " \n",
+ " GTEX-111CU-1326-SM-5NQ8L | \n",
+ " 7.586 | \n",
+ " 4.0370 | \n",
+ "
\n",
+ " \n",
+ " GTEX-111YS-1426-SM-5GID8 | \n",
+ " 13.500 | \n",
+ " 3.3700 | \n",
+ "
\n",
+ " \n",
+ " GTEX-1122O-1326-SM-5H11F | \n",
+ " 21.680 | \n",
+ " 0.0309 | \n",
+ "
\n",
+ " \n",
+ " GTEX-117YX-0326-SM-5GICL | \n",
+ " 8.964 | \n",
+ " 5.2350 | \n",
+ "
\n",
+ " \n",
+ " GTEX-1192X-2526-SM-59868 | \n",
+ " 10.010 | \n",
+ " 6.3990 | \n",
+ "
\n",
+ " \n",
+ "
\n",
+ "
"
+ ],
+ "text/plain": [
+ "gene_ens_id ENSG00000147050.14 ENSG00000183878.15\n",
+ "sample_id \n",
+ "GTEX-111CU-1326-SM-5NQ8L 7.586 4.0370\n",
+ "GTEX-111YS-1426-SM-5GID8 13.500 3.3700\n",
+ "GTEX-1122O-1326-SM-5H11F 21.680 0.0309\n",
+ "GTEX-117YX-0326-SM-5GICL 8.964 5.2350\n",
+ "GTEX-1192X-2526-SM-59868 10.010 6.3990"
+ ]
+ },
+ "execution_count": 28,
+ "metadata": {},
+ "output_type": "execute_result"
+ }
+ ],
+ "source": [
+ "small_intestine.head()"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 29,
+ "id": "e485ed5e-6d56-4432-8fcb-dd2956dbe605",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:55:58.288638Z",
+ "iopub.status.busy": "2023-11-20T08:55:58.288544Z",
+ "iopub.status.idle": "2023-11-20T08:55:58.293896Z",
+ "shell.execute_reply": "2023-11-20T08:55:58.293520Z"
+ },
+ "papermill": {
+ "duration": 0.014431,
+ "end_time": "2023-11-20T08:55:58.294649",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:58.280218",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [],
+ "source": [
+ "small_intestine_males = small_intestine.loc[\n",
+ " small_intestine.index.intersection(male_samples)\n",
+ "]"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 30,
+ "id": "558a0a54-558a-4af6-baec-4dd1189909cc",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:55:58.311601Z",
+ "iopub.status.busy": "2023-11-20T08:55:58.311263Z",
+ "iopub.status.idle": "2023-11-20T08:55:58.314724Z",
+ "shell.execute_reply": "2023-11-20T08:55:58.314331Z"
+ },
+ "papermill": {
+ "duration": 0.01288,
+ "end_time": "2023-11-20T08:55:58.315541",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:58.302661",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [
+ {
+ "data": {
+ "text/plain": [
+ "(120, 2)"
+ ]
+ },
+ "execution_count": 30,
+ "metadata": {},
+ "output_type": "execute_result"
+ }
+ ],
+ "source": [
+ "small_intestine_males.shape"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 31,
+ "id": "5094eb5e-7d8d-408f-9e7e-3f73fa8e91ed",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:55:58.332677Z",
+ "iopub.status.busy": "2023-11-20T08:55:58.332302Z",
+ "iopub.status.idle": "2023-11-20T08:55:58.337054Z",
+ "shell.execute_reply": "2023-11-20T08:55:58.336655Z"
+ },
+ "papermill": {
+ "duration": 0.01416,
+ "end_time": "2023-11-20T08:55:58.337830",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:58.323670",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [],
+ "source": [
+ "small_intestine_females = small_intestine.loc[\n",
+ " small_intestine.index.intersection(female_samples)\n",
+ "]"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 32,
+ "id": "81168021-bd56-45f8-9acc-0d6e5a1c7ba5",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:55:58.354948Z",
+ "iopub.status.busy": "2023-11-20T08:55:58.354661Z",
+ "iopub.status.idle": "2023-11-20T08:55:58.358062Z",
+ "shell.execute_reply": "2023-11-20T08:55:58.357659Z"
+ },
+ "papermill": {
+ "duration": 0.012847,
+ "end_time": "2023-11-20T08:55:58.358878",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:58.346031",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [
+ {
+ "data": {
+ "text/plain": [
+ "(67, 2)"
+ ]
+ },
+ "execution_count": 32,
+ "metadata": {},
+ "output_type": "execute_result"
+ }
+ ],
+ "source": [
+ "small_intestine_females.shape"
+ ]
+ },
+ {
+ "cell_type": "markdown",
+ "id": "67e48d49-8a28-45b1-b8bd-0fd85db559b6",
+ "metadata": {
+ "papermill": {
+ "duration": 0.008076,
+ "end_time": "2023-11-20T08:55:58.375169",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:58.367093",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "source": [
+ "# Compute correlation"
+ ]
+ },
+ {
+ "cell_type": "markdown",
+ "id": "cfabd8a6-ac3b-4ba0-963e-689236871151",
+ "metadata": {
+ "papermill": {
+ "duration": 0.008133,
+ "end_time": "2023-11-20T08:55:58.391481",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:58.383348",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "source": [
+ "## Brain cerebellum"
+ ]
+ },
+ {
+ "cell_type": "markdown",
+ "id": "44e81899-ebee-4625-ba7f-7ce82dc25eca",
+ "metadata": {
+ "papermill": {
+ "duration": 0.008075,
+ "end_time": "2023-11-20T08:55:58.407755",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:58.399680",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "source": [
+ "### CCC"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 33,
+ "id": "0adc0cb7-6a22-49be-aafc-894aebb42dde",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:55:58.424934Z",
+ "iopub.status.busy": "2023-11-20T08:55:58.424612Z",
+ "iopub.status.idle": "2023-11-20T08:55:59.027926Z",
+ "shell.execute_reply": "2023-11-20T08:55:59.027542Z"
+ },
+ "papermill": {
+ "duration": 0.613147,
+ "end_time": "2023-11-20T08:55:59.029090",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:58.415943",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [
+ {
+ "data": {
+ "text/plain": [
+ "(0.3674627535203262, 0.000999000999000999)"
+ ]
+ },
+ "execution_count": 33,
+ "metadata": {},
+ "output_type": "execute_result"
+ }
+ ],
+ "source": [
+ "ccc(brain_cerebellum_males, pvalue_n_perms=1000)"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 34,
+ "id": "2d8d145a-f9bd-42eb-89ae-beee42621083",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:55:59.049822Z",
+ "iopub.status.busy": "2023-11-20T08:55:59.049738Z",
+ "iopub.status.idle": "2023-11-20T08:55:59.386803Z",
+ "shell.execute_reply": "2023-11-20T08:55:59.386444Z"
+ },
+ "papermill": {
+ "duration": 0.349521,
+ "end_time": "2023-11-20T08:55:59.388102",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:59.038581",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [
+ {
+ "data": {
+ "text/plain": [
+ "(0.10427807486631016, 0.015984015984015984)"
+ ]
+ },
+ "execution_count": 34,
+ "metadata": {},
+ "output_type": "execute_result"
+ }
+ ],
+ "source": [
+ "ccc(brain_cerebellum_females, pvalue_n_perms=1000)"
+ ]
+ },
+ {
+ "cell_type": "markdown",
+ "id": "439a1bce-e610-47b8-aa63-d49c5402c727",
+ "metadata": {
+ "papermill": {
+ "duration": 0.015606,
+ "end_time": "2023-11-20T08:55:59.419596",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:59.403990",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "source": [
+ "### Pearson"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 35,
+ "id": "d7ef4ad5-afbe-4365-9d90-3fecd0f382cc",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:55:59.453572Z",
+ "iopub.status.busy": "2023-11-20T08:55:59.453491Z",
+ "iopub.status.idle": "2023-11-20T08:55:59.456801Z",
+ "shell.execute_reply": "2023-11-20T08:55:59.456505Z"
+ },
+ "papermill": {
+ "duration": 0.022649,
+ "end_time": "2023-11-20T08:55:59.458058",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:59.435409",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [
+ {
+ "data": {
+ "text/plain": [
+ "(0.8570928082720543, 2.0135444417639445e-51)"
+ ]
+ },
+ "execution_count": 35,
+ "metadata": {},
+ "output_type": "execute_result"
+ }
+ ],
+ "source": [
+ "pearsonr(brain_cerebellum_males.iloc[:, 0], brain_cerebellum_males.iloc[:, 1])"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 36,
+ "id": "4b4bb182-418b-4ef6-997d-0a7569a794c4",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:55:59.483075Z",
+ "iopub.status.busy": "2023-11-20T08:55:59.482995Z",
+ "iopub.status.idle": "2023-11-20T08:55:59.486455Z",
+ "shell.execute_reply": "2023-11-20T08:55:59.486022Z"
+ },
+ "papermill": {
+ "duration": 0.01374,
+ "end_time": "2023-11-20T08:55:59.487298",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:59.473558",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [
+ {
+ "data": {
+ "text/plain": [
+ "(0.21500691975584293, 0.08058770847518525)"
+ ]
+ },
+ "execution_count": 36,
+ "metadata": {},
+ "output_type": "execute_result"
+ }
+ ],
+ "source": [
+ "pearsonr(brain_cerebellum_females.iloc[:, 0], brain_cerebellum_females.iloc[:, 1])"
+ ]
+ },
+ {
+ "cell_type": "markdown",
+ "id": "105fd413-62ed-4fcf-baf6-35adfd5de8c6",
+ "metadata": {
+ "papermill": {
+ "duration": 0.008299,
+ "end_time": "2023-11-20T08:55:59.504020",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:59.495721",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "source": [
+ "### Spearman"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 37,
+ "id": "e5712802-eb2c-4779-987f-ccd4817c6070",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:55:59.521582Z",
+ "iopub.status.busy": "2023-11-20T08:55:59.521432Z",
+ "iopub.status.idle": "2023-11-20T08:55:59.526539Z",
+ "shell.execute_reply": "2023-11-20T08:55:59.526078Z"
+ },
+ "papermill": {
+ "duration": 0.014912,
+ "end_time": "2023-11-20T08:55:59.527335",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:59.512423",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [
+ {
+ "data": {
+ "text/plain": [
+ "SpearmanrResult(correlation=0.7909406514931421, pvalue=1.5562774794999233e-38)"
+ ]
+ },
+ "execution_count": 37,
+ "metadata": {},
+ "output_type": "execute_result"
+ }
+ ],
+ "source": [
+ "spearmanr(brain_cerebellum_males.iloc[:, 0], brain_cerebellum_males.iloc[:, 1])"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 38,
+ "id": "290b1ebf-91cc-4032-a0d8-fa147d39aaeb",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:55:59.545195Z",
+ "iopub.status.busy": "2023-11-20T08:55:59.544867Z",
+ "iopub.status.idle": "2023-11-20T08:55:59.549626Z",
+ "shell.execute_reply": "2023-11-20T08:55:59.549230Z"
+ },
+ "papermill": {
+ "duration": 0.014564,
+ "end_time": "2023-11-20T08:55:59.550412",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:59.535848",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [
+ {
+ "data": {
+ "text/plain": [
+ "SpearmanrResult(correlation=0.2225445085313031, pvalue=0.07028065513936946)"
+ ]
+ },
+ "execution_count": 38,
+ "metadata": {},
+ "output_type": "execute_result"
+ }
+ ],
+ "source": [
+ "spearmanr(brain_cerebellum_females.iloc[:, 0], brain_cerebellum_females.iloc[:, 1])"
+ ]
+ },
+ {
+ "cell_type": "markdown",
+ "id": "a1d1d5c7-dbc0-440a-8eec-31aa252868e6",
+ "metadata": {
+ "papermill": {
+ "duration": 0.008566,
+ "end_time": "2023-11-20T08:55:59.567627",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:59.559061",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "source": [
+ "## Small intestine (terminal ileum)"
+ ]
+ },
+ {
+ "cell_type": "markdown",
+ "id": "6fc2d04e-39fb-4d55-919b-3f2f830386a0",
+ "metadata": {
+ "papermill": {
+ "duration": 0.008572,
+ "end_time": "2023-11-20T08:55:59.584887",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:59.576315",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "source": [
+ "### CCC"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 39,
+ "id": "ebe913d2-d02e-4515-9742-a9303f527395",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:55:59.603192Z",
+ "iopub.status.busy": "2023-11-20T08:55:59.602834Z",
+ "iopub.status.idle": "2023-11-20T08:56:00.192183Z",
+ "shell.execute_reply": "2023-11-20T08:56:00.191803Z"
+ },
+ "papermill": {
+ "duration": 0.599662,
+ "end_time": "2023-11-20T08:56:00.193244",
+ "exception": false,
+ "start_time": "2023-11-20T08:55:59.593582",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [
+ {
+ "data": {
+ "text/plain": [
+ "(0.13137865911237015, 0.000999000999000999)"
+ ]
+ },
+ "execution_count": 39,
+ "metadata": {},
+ "output_type": "execute_result"
+ }
+ ],
+ "source": [
+ "ccc(small_intestine_males, pvalue_n_perms=1000)"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 40,
+ "id": "f173bde0-9cf2-47fa-af40-739845d16247",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:56:00.214571Z",
+ "iopub.status.busy": "2023-11-20T08:56:00.214489Z",
+ "iopub.status.idle": "2023-11-20T08:56:00.557902Z",
+ "shell.execute_reply": "2023-11-20T08:56:00.557502Z"
+ },
+ "papermill": {
+ "duration": 0.355935,
+ "end_time": "2023-11-20T08:56:00.559121",
+ "exception": false,
+ "start_time": "2023-11-20T08:56:00.203186",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [
+ {
+ "data": {
+ "text/plain": [
+ "(0.04191990815775257, 0.35264735264735264)"
+ ]
+ },
+ "execution_count": 40,
+ "metadata": {},
+ "output_type": "execute_result"
+ }
+ ],
+ "source": [
+ "ccc(small_intestine_females, pvalue_n_perms=1000)"
+ ]
+ },
+ {
+ "cell_type": "markdown",
+ "id": "867e5576-5224-46fe-ab7a-0366b8019b7b",
+ "metadata": {
+ "papermill": {
+ "duration": 0.016368,
+ "end_time": "2023-11-20T08:56:00.592088",
+ "exception": false,
+ "start_time": "2023-11-20T08:56:00.575720",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "source": [
+ "### Pearson"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 41,
+ "id": "75f54397-bfb4-467d-b329-fb159d87ba77",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:56:00.625863Z",
+ "iopub.status.busy": "2023-11-20T08:56:00.625776Z",
+ "iopub.status.idle": "2023-11-20T08:56:00.629256Z",
+ "shell.execute_reply": "2023-11-20T08:56:00.628844Z"
+ },
+ "papermill": {
+ "duration": 0.021756,
+ "end_time": "2023-11-20T08:56:00.630532",
+ "exception": false,
+ "start_time": "2023-11-20T08:56:00.608776",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [
+ {
+ "data": {
+ "text/plain": [
+ "(0.5401927091270222, 1.918887071018949e-10)"
+ ]
+ },
+ "execution_count": 41,
+ "metadata": {},
+ "output_type": "execute_result"
+ }
+ ],
+ "source": [
+ "pearsonr(small_intestine_males.iloc[:, 0], small_intestine_males.iloc[:, 1])"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 42,
+ "id": "181af358-ac4a-400e-bc46-5213cf866c50",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:56:00.658608Z",
+ "iopub.status.busy": "2023-11-20T08:56:00.658303Z",
+ "iopub.status.idle": "2023-11-20T08:56:00.662418Z",
+ "shell.execute_reply": "2023-11-20T08:56:00.662026Z"
+ },
+ "papermill": {
+ "duration": 0.015931,
+ "end_time": "2023-11-20T08:56:00.663236",
+ "exception": false,
+ "start_time": "2023-11-20T08:56:00.647305",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [
+ {
+ "data": {
+ "text/plain": [
+ "(-0.12377555020943821, 0.3183161563369864)"
+ ]
+ },
+ "execution_count": 42,
+ "metadata": {},
+ "output_type": "execute_result"
+ }
+ ],
+ "source": [
+ "pearsonr(small_intestine_females.iloc[:, 0], small_intestine_females.iloc[:, 1])"
+ ]
+ },
+ {
+ "cell_type": "markdown",
+ "id": "f21bd584-c23b-4026-8caa-fcec19f7752e",
+ "metadata": {
+ "papermill": {
+ "duration": 0.008623,
+ "end_time": "2023-11-20T08:56:00.680667",
+ "exception": false,
+ "start_time": "2023-11-20T08:56:00.672044",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "source": [
+ "### Spearman"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 43,
+ "id": "f3eef972-8259-4a03-8b1e-24cb05cf7c57",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:56:00.699282Z",
+ "iopub.status.busy": "2023-11-20T08:56:00.698900Z",
+ "iopub.status.idle": "2023-11-20T08:56:00.703998Z",
+ "shell.execute_reply": "2023-11-20T08:56:00.703548Z"
+ },
+ "papermill": {
+ "duration": 0.015248,
+ "end_time": "2023-11-20T08:56:00.704802",
+ "exception": false,
+ "start_time": "2023-11-20T08:56:00.689554",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [
+ {
+ "data": {
+ "text/plain": [
+ "SpearmanrResult(correlation=0.46555777415724725, pvalue=8.417733469299811e-08)"
+ ]
+ },
+ "execution_count": 43,
+ "metadata": {},
+ "output_type": "execute_result"
+ }
+ ],
+ "source": [
+ "spearmanr(small_intestine_males.iloc[:, 0], small_intestine_males.iloc[:, 1])"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 44,
+ "id": "9dfdbf5a-fca2-4a80-a8af-fe5fa3887c66",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:56:00.723658Z",
+ "iopub.status.busy": "2023-11-20T08:56:00.723226Z",
+ "iopub.status.idle": "2023-11-20T08:56:00.727952Z",
+ "shell.execute_reply": "2023-11-20T08:56:00.727552Z"
+ },
+ "papermill": {
+ "duration": 0.014948,
+ "end_time": "2023-11-20T08:56:00.728742",
+ "exception": false,
+ "start_time": "2023-11-20T08:56:00.713794",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [
+ {
+ "data": {
+ "text/plain": [
+ "SpearmanrResult(correlation=0.1041356321278035, pvalue=0.40167737622824995)"
+ ]
+ },
+ "execution_count": 44,
+ "metadata": {},
+ "output_type": "execute_result"
+ }
+ ],
+ "source": [
+ "spearmanr(small_intestine_females.iloc[:, 0], small_intestine_females.iloc[:, 1])"
+ ]
+ },
+ {
+ "cell_type": "markdown",
+ "id": "ecd455af-8f12-484d-9338-140f69aedb75",
+ "metadata": {
+ "papermill": {
+ "duration": 0.008966,
+ "end_time": "2023-11-20T08:56:00.746800",
+ "exception": false,
+ "start_time": "2023-11-20T08:56:00.737834",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "source": [
+ "# Compute correlation on all tissues, males only"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 45,
+ "id": "8b86aa69-c53b-4906-b8fd-fa97b9f90462",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:56:00.765779Z",
+ "iopub.status.busy": "2023-11-20T08:56:00.765437Z",
+ "iopub.status.idle": "2023-11-20T08:56:05.764878Z",
+ "shell.execute_reply": "2023-11-20T08:56:05.764531Z"
+ },
+ "papermill": {
+ "duration": 5.01057,
+ "end_time": "2023-11-20T08:56:05.766475",
+ "exception": false,
+ "start_time": "2023-11-20T08:56:00.755905",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [],
+ "source": [
+ "res_all_males = pd.DataFrame(\n",
+ " {\n",
+ " f.stem.split(\"_data_\")[1]: {\n",
+ " \"ccc\": ccc(data[gene0_id], data[gene1_id]),\n",
+ " \"pearson\": pearsonr(data[gene0_id], data[gene1_id])[0],\n",
+ " \"spearman\": spearmanr(data[gene0_id], data[gene1_id])[0],\n",
+ " }\n",
+ " for f in TISSUE_DIR.glob(\"*.pkl\")\n",
+ " if (\n",
+ " data := pd.read_pickle(f)\n",
+ " .T[[gene0_id, gene1_id]]\n",
+ " .reindex(male_samples)\n",
+ " .dropna()\n",
+ " )\n",
+ " is not None\n",
+ " and data.shape[0] > 10\n",
+ " }\n",
+ ").T.abs()"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 46,
+ "id": "93b8e40d-a049-4272-81b0-6c4f45fa1df6",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:56:05.801558Z",
+ "iopub.status.busy": "2023-11-20T08:56:05.801475Z",
+ "iopub.status.idle": "2023-11-20T08:56:05.804294Z",
+ "shell.execute_reply": "2023-11-20T08:56:05.804009Z"
+ },
+ "papermill": {
+ "duration": 0.021576,
+ "end_time": "2023-11-20T08:56:05.805494",
+ "exception": false,
+ "start_time": "2023-11-20T08:56:05.783918",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [
+ {
+ "data": {
+ "text/plain": [
+ "(47, 3)"
+ ]
+ },
+ "execution_count": 46,
+ "metadata": {},
+ "output_type": "execute_result"
+ }
+ ],
+ "source": [
+ "res_all_males.shape"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 47,
+ "id": "52c86cee-59b3-41a7-ac71-8a000d9c472f",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:56:05.840469Z",
+ "iopub.status.busy": "2023-11-20T08:56:05.840392Z",
+ "iopub.status.idle": "2023-11-20T08:56:05.844909Z",
+ "shell.execute_reply": "2023-11-20T08:56:05.844558Z"
+ },
+ "papermill": {
+ "duration": 0.023309,
+ "end_time": "2023-11-20T08:56:05.846180",
+ "exception": false,
+ "start_time": "2023-11-20T08:56:05.822871",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [
+ {
+ "data": {
+ "text/html": [
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\n",
+ " \n",
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\n",
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+ "metadata": {},
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\n",
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+ " 0.843063 | \n",
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\n",
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\n",
+ " \n",
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+ " 0.434682 | \n",
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+ " 0.791284 | \n",
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+ " 0.461364 | \n",
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\n",
+ " \n",
+ " heart_atrial_appendage | \n",
+ " 0.487768 | \n",
+ " 0.835058 | \n",
+ " 0.833513 | \n",
+ "
\n",
+ " \n",
+ " spleen | \n",
+ " 0.506982 | \n",
+ " 0.807828 | \n",
+ " 0.858734 | \n",
+ "
\n",
+ " \n",
+ " skin_not_sun_exposed_suprapubic | \n",
+ " 0.528096 | \n",
+ " 0.855796 | \n",
+ " 0.859677 | \n",
+ "
\n",
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+ " 0.536427 | \n",
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+ " 0.941653 | \n",
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+ " 0.609338 | \n",
+ " 0.928625 | \n",
+ " 0.946419 | \n",
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\n",
+ " \n",
+ " heart_left_ventricle | \n",
+ " 0.632231 | \n",
+ " 0.924407 | \n",
+ " 0.923212 | \n",
+ "
\n",
+ " \n",
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+ " 0.639569 | \n",
+ " 0.904160 | \n",
+ " 0.922021 | \n",
+ "
\n",
+ " \n",
+ " kidney_cortex | \n",
+ " 0.664256 | \n",
+ " 0.933545 | \n",
+ " 0.927273 | \n",
+ "
\n",
+ " \n",
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+ " 0.707989 | \n",
+ " 0.924438 | \n",
+ " 0.923254 | \n",
+ "
\n",
+ " \n",
+ " breast_mammary_tissue | \n",
+ " 0.719490 | \n",
+ " 0.913081 | \n",
+ " 0.937118 | \n",
+ "
\n",
+ " \n",
+ "
\n",
+ "
"
+ ],
+ "text/plain": [
+ " ccc pearson spearman\n",
+ "small_intestine_terminal_ileum 0.131379 0.540193 0.465558\n",
+ "stomach 0.186605 0.546008 0.631823\n",
+ "liver 0.189274 0.619830 0.618370\n",
+ "muscle_skeletal 0.205450 0.648536 0.658019\n",
+ "testis 0.206704 0.692661 0.690990\n",
+ "pituitary 0.217599 0.629830 0.643730\n",
+ "colon_transverse 0.237485 0.704703 0.691430\n",
+ "thyroid 0.255240 0.675918 0.697297\n",
+ "adrenal_gland 0.261443 0.657966 0.682019\n",
+ "colon_sigmoid 0.301971 0.784019 0.769884\n",
+ "nerve_tibial 0.323745 0.819943 0.772638\n",
+ "artery_tibial 0.336675 0.782014 0.776460\n",
+ "prostate 0.347597 0.804046 0.799923\n",
+ "cells_ebvtransformed_lymphocytes 0.362883 0.875265 0.827843\n",
+ "brain_cerebellum 0.367463 0.857093 0.790941\n",
+ "adipose_subcutaneous 0.380501 0.826960 0.807961\n",
+ "lung 0.383148 0.777688 0.767171\n",
+ "skin_sun_exposed_lower_leg 0.397742 0.806817 0.799174\n",
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+ " \n",
+ " skin_not_sun_exposed_suprapubic | \n",
+ " 0.528096 | \n",
+ " 0.855796 | \n",
+ " 0.859677 | \n",
+ "
\n",
+ " \n",
+ " brain_cerebellar_hemisphere | \n",
+ " 0.410069 | \n",
+ " 0.881902 | \n",
+ " 0.862051 | \n",
+ "
\n",
+ " \n",
+ " adipose_visceral_omentum | \n",
+ " 0.427460 | \n",
+ " 0.877532 | \n",
+ " 0.863902 | \n",
+ "
\n",
+ " \n",
+ " pancreas | \n",
+ " 0.461364 | \n",
+ " 0.896896 | \n",
+ " 0.871488 | \n",
+ "
\n",
+ " \n",
+ " brain_anterior_cingulate_cortex_ba24 | \n",
+ " 0.426146 | \n",
+ " 0.835251 | \n",
+ " 0.874480 | \n",
+ "
\n",
+ " \n",
+ " brain_frontal_cortex_ba9 | \n",
+ " 0.432036 | \n",
+ " 0.854144 | \n",
+ " 0.876284 | \n",
+ "
\n",
+ " \n",
+ " brain_cortex | \n",
+ " 0.443814 | \n",
+ " 0.884841 | \n",
+ " 0.889380 | \n",
+ "
\n",
+ " \n",
+ " brain_caudate_basal_ganglia | \n",
+ " 0.536427 | \n",
+ " 0.862235 | \n",
+ " 0.894522 | \n",
+ "
\n",
+ " \n",
+ " bladder | \n",
+ " 0.623077 | \n",
+ " 0.947606 | \n",
+ " 0.898901 | \n",
+ "
\n",
+ " \n",
+ " brain_amygdala | \n",
+ " 0.540782 | \n",
+ " 0.880306 | \n",
+ " 0.914251 | \n",
+ "
\n",
+ " \n",
+ " brain_hippocampus | \n",
+ " 0.599705 | \n",
+ " 0.899903 | \n",
+ " 0.916020 | \n",
+ "
\n",
+ " \n",
+ " brain_substantia_nigra | \n",
+ " 0.639569 | \n",
+ " 0.904160 | \n",
+ " 0.922021 | \n",
+ "
\n",
+ " \n",
+ " heart_left_ventricle | \n",
+ " 0.632231 | \n",
+ " 0.924407 | \n",
+ " 0.923212 | \n",
+ "
\n",
+ " \n",
+ " brain_spinal_cord_cervical_c1 | \n",
+ " 0.707989 | \n",
+ " 0.924438 | \n",
+ " 0.923254 | \n",
+ "
\n",
+ " \n",
+ " kidney_cortex | \n",
+ " 0.664256 | \n",
+ " 0.933545 | \n",
+ " 0.927273 | \n",
+ "
\n",
+ " \n",
+ " brain_putamen_basal_ganglia | \n",
+ " 0.550023 | \n",
+ " 0.915380 | \n",
+ " 0.929241 | \n",
+ "
\n",
+ " \n",
+ " whole_blood | \n",
+ " 0.614561 | \n",
+ " 0.911354 | \n",
+ " 0.929595 | \n",
+ "
\n",
+ " \n",
+ " breast_mammary_tissue | \n",
+ " 0.719490 | \n",
+ " 0.913081 | \n",
+ " 0.937118 | \n",
+ "
\n",
+ " \n",
+ " brain_nucleus_accumbens_basal_ganglia | \n",
+ " 0.606569 | \n",
+ " 0.920563 | \n",
+ " 0.941653 | \n",
+ "
\n",
+ " \n",
+ " brain_hypothalamus | \n",
+ " 0.609338 | \n",
+ " 0.928625 | \n",
+ " 0.946419 | \n",
+ "
\n",
+ " \n",
+ "
\n",
+ "
"
+ ],
+ "text/plain": [
+ " ccc pearson spearman\n",
+ "small_intestine_terminal_ileum 0.131379 0.540193 0.465558\n",
+ "liver 0.189274 0.619830 0.618370\n",
+ "stomach 0.186605 0.546008 0.631823\n",
+ "pituitary 0.217599 0.629830 0.643730\n",
+ "muscle_skeletal 0.205450 0.648536 0.658019\n",
+ "adrenal_gland 0.261443 0.657966 0.682019\n",
+ "testis 0.206704 0.692661 0.690990\n",
+ "colon_transverse 0.237485 0.704703 0.691430\n",
+ "thyroid 0.255240 0.675918 0.697297\n",
+ "lung 0.383148 0.777688 0.767171\n",
+ "colon_sigmoid 0.301971 0.784019 0.769884\n",
+ "nerve_tibial 0.323745 0.819943 0.772638\n",
+ "artery_tibial 0.336675 0.782014 0.776460\n",
+ "brain_cerebellum 0.367463 0.857093 0.790941\n",
+ "cells_cultured_fibroblasts 0.434682 0.772410 0.791284\n",
+ "skin_sun_exposed_lower_leg 0.397742 0.806817 0.799174\n",
+ "prostate 0.347597 0.804046 0.799923\n",
+ "artery_coronary 0.410458 0.861073 0.801901\n",
+ "minor_salivary_gland 0.420246 0.805288 0.804937\n",
+ "adipose_subcutaneous 0.380501 0.826960 0.807961\n",
+ "artery_aorta 0.428166 0.814962 0.810471\n",
+ "cells_ebvtransformed_lymphocytes 0.362883 0.875265 0.827843\n",
+ "heart_atrial_appendage 0.487768 0.835058 0.833513\n",
+ "esophagus_gastroesophageal_junction 0.419401 0.849706 0.843063\n",
+ "esophagus_muscularis 0.406628 0.859394 0.849154\n",
+ "esophagus_mucosa 0.403310 0.843500 0.850711\n",
+ "spleen 0.506982 0.807828 0.858734\n",
+ "skin_not_sun_exposed_suprapubic 0.528096 0.855796 0.859677\n",
+ "brain_cerebellar_hemisphere 0.410069 0.881902 0.862051\n",
+ "adipose_visceral_omentum 0.427460 0.877532 0.863902\n",
+ "pancreas 0.461364 0.896896 0.871488\n",
+ "brain_anterior_cingulate_cortex_ba24 0.426146 0.835251 0.874480\n",
+ "brain_frontal_cortex_ba9 0.432036 0.854144 0.876284\n",
+ "brain_cortex 0.443814 0.884841 0.889380\n",
+ "brain_caudate_basal_ganglia 0.536427 0.862235 0.894522\n",
+ "bladder 0.623077 0.947606 0.898901\n",
+ "brain_amygdala 0.540782 0.880306 0.914251\n",
+ "brain_hippocampus 0.599705 0.899903 0.916020\n",
+ "brain_substantia_nigra 0.639569 0.904160 0.922021\n",
+ "heart_left_ventricle 0.632231 0.924407 0.923212\n",
+ "brain_spinal_cord_cervical_c1 0.707989 0.924438 0.923254\n",
+ "kidney_cortex 0.664256 0.933545 0.927273\n",
+ "brain_putamen_basal_ganglia 0.550023 0.915380 0.929241\n",
+ "whole_blood 0.614561 0.911354 0.929595\n",
+ "breast_mammary_tissue 0.719490 0.913081 0.937118\n",
+ "brain_nucleus_accumbens_basal_ganglia 0.606569 0.920563 0.941653\n",
+ "brain_hypothalamus 0.609338 0.928625 0.946419"
+ ]
+ },
+ "execution_count": 50,
+ "metadata": {},
+ "output_type": "execute_result"
+ }
+ ],
+ "source": [
+ "res_all_males.sort_values(\"spearman\")"
+ ]
+ },
+ {
+ "cell_type": "markdown",
+ "id": "cccf7fd4-329c-49e0-b6a7-3f449d78a73c",
+ "metadata": {
+ "papermill": {
+ "duration": 0.010108,
+ "end_time": "2023-11-20T08:56:05.968664",
+ "exception": false,
+ "start_time": "2023-11-20T08:56:05.958556",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "source": [
+ "# Plot of male samples"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 51,
+ "id": "37979e0a-5a5d-40d7-8071-1ecc54a11c06",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:56:05.989605Z",
+ "iopub.status.busy": "2023-11-20T08:56:05.989454Z",
+ "iopub.status.idle": "2023-11-20T08:56:05.993475Z",
+ "shell.execute_reply": "2023-11-20T08:56:05.993079Z"
+ },
+ "papermill": {
+ "duration": 0.015537,
+ "end_time": "2023-11-20T08:56:05.994253",
+ "exception": false,
+ "start_time": "2023-11-20T08:56:05.978716",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [],
+ "source": [
+ "def get_tissue_file(name):\n",
+ " \"\"\"\n",
+ " Given a part of a tissue name, it returns a file path to the\n",
+ " expression data for that tissue in GTEx. It fails if more than\n",
+ " one files are found.\n",
+ "\n",
+ " Args:\n",
+ " name: a string with the tissue name (or a part of it).\n",
+ "\n",
+ " Returns:\n",
+ " A Path object pointing to the gene expression file for the\n",
+ " given tissue.\n",
+ " \"\"\"\n",
+ " tissue_files = []\n",
+ " for f in TISSUE_DIR.glob(\"*.pkl\"):\n",
+ " if name in f.name:\n",
+ " tissue_files.append(f)\n",
+ "\n",
+ " assert len(tissue_files) == 1\n",
+ " return tissue_files[0]"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 52,
+ "id": "08d2da77-49d4-471b-9e6c-c1d27fc5b13b",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:56:06.015399Z",
+ "iopub.status.busy": "2023-11-20T08:56:06.015248Z",
+ "iopub.status.idle": "2023-11-20T08:56:06.018280Z",
+ "shell.execute_reply": "2023-11-20T08:56:06.017885Z"
+ },
+ "papermill": {
+ "duration": 0.014842,
+ "end_time": "2023-11-20T08:56:06.019182",
+ "exception": false,
+ "start_time": "2023-11-20T08:56:06.004340",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [],
+ "source": [
+ "# testing\n",
+ "_tmp = get_tissue_file(\"whole_blood\")\n",
+ "assert _tmp.exists()"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 53,
+ "id": "0d04139a-2fd5-4f09-81c7-8f7b6b87d478",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:56:06.040472Z",
+ "iopub.status.busy": "2023-11-20T08:56:06.040325Z",
+ "iopub.status.idle": "2023-11-20T08:56:06.043073Z",
+ "shell.execute_reply": "2023-11-20T08:56:06.042681Z"
+ },
+ "papermill": {
+ "duration": 0.014423,
+ "end_time": "2023-11-20T08:56:06.043873",
+ "exception": false,
+ "start_time": "2023-11-20T08:56:06.029450",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [],
+ "source": [
+ "def simplify_tissue_name(tissue_name):\n",
+ " return f\"{tissue_name[0].upper()}{tissue_name[1:].replace('_', ' ')}\""
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 54,
+ "id": "5e0026f0-e25f-4058-bba8-810887f523f5",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:56:06.065222Z",
+ "iopub.status.busy": "2023-11-20T08:56:06.064825Z",
+ "iopub.status.idle": "2023-11-20T08:56:06.067504Z",
+ "shell.execute_reply": "2023-11-20T08:56:06.067101Z"
+ },
+ "papermill": {
+ "duration": 0.014174,
+ "end_time": "2023-11-20T08:56:06.068318",
+ "exception": false,
+ "start_time": "2023-11-20T08:56:06.054144",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [],
+ "source": [
+ "assert simplify_tissue_name(\"whole_blood\") == \"Whole blood\"\n",
+ "assert simplify_tissue_name(\"uterus\") == \"Uterus\""
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 55,
+ "id": "30becd4a-14ad-467d-b462-54429c61008a",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:56:06.089570Z",
+ "iopub.status.busy": "2023-11-20T08:56:06.089169Z",
+ "iopub.status.idle": "2023-11-20T08:56:06.099591Z",
+ "shell.execute_reply": "2023-11-20T08:56:06.099184Z"
+ },
+ "papermill": {
+ "duration": 0.021749,
+ "end_time": "2023-11-20T08:56:06.100320",
+ "exception": false,
+ "start_time": "2023-11-20T08:56:06.078571",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [],
+ "source": [
+ "def plot_gene_pair(\n",
+ " tissue_name,\n",
+ " gene0,\n",
+ " gene1,\n",
+ " hue=None,\n",
+ " kind=\"hex\",\n",
+ " ylim=None,\n",
+ " bins=\"log\",\n",
+ " samples=None,\n",
+ " filename_suffix=\"\",\n",
+ "):\n",
+ " \"\"\"\n",
+ " It plots (joint plot) a gene pair from the given tissue. It saves the plot\n",
+ " for the manuscript.\n",
+ " \"\"\"\n",
+ " # merge gene expression with metadata\n",
+ " tissue_file = get_tissue_file(tissue_name)\n",
+ " if samples is not None:\n",
+ " tissue_data = (\n",
+ " pd.read_pickle(tissue_file).T[[gene0, gene1]].reindex(samples).dropna()\n",
+ " )\n",
+ " else:\n",
+ " tissue_data = pd.read_pickle(tissue_file).T[[gene0, gene1]]\n",
+ "\n",
+ " tissue_data = pd.merge(\n",
+ " tissue_data,\n",
+ " gtex_metadata,\n",
+ " how=\"inner\",\n",
+ " left_index=True,\n",
+ " right_index=True,\n",
+ " validate=\"one_to_one\",\n",
+ " )\n",
+ "\n",
+ " # get gene symbols\n",
+ " gene0_symbol, gene1_symbol = gene_map[gene0], gene_map[gene1]\n",
+ " display((gene0_symbol, gene1_symbol))\n",
+ "\n",
+ " # compute correlations for this gene pair\n",
+ " _clustermatch = ccc(tissue_data[gene0], tissue_data[gene1])\n",
+ " _pearson = pearsonr(tissue_data[gene0], tissue_data[gene1])[0]\n",
+ " _spearman = spearmanr(tissue_data[gene0], tissue_data[gene1])[0]\n",
+ "\n",
+ " _title = f\"{simplify_tissue_name(tissue_name)}\\n$c={_clustermatch:.2f}$ $p={_pearson:.2f}$ $s={_spearman:.2f}$\"\n",
+ "\n",
+ " other_args = {\n",
+ " \"kind\": kind, # if hue is None else \"scatter\",\n",
+ " \"rasterized\": True,\n",
+ " }\n",
+ " if hue is None:\n",
+ " other_args[\"hue_order\"] = None\n",
+ " else:\n",
+ " other_args[\"hue_order\"] = [\"Male\", \"Female\"]\n",
+ "\n",
+ " with sns.plotting_context(\"paper\", font_scale=1.5):\n",
+ " p = sns.jointplot(\n",
+ " data=tissue_data,\n",
+ " x=gene0,\n",
+ " y=gene1,\n",
+ " hue=hue,\n",
+ " **other_args,\n",
+ " # ylim=(0, 500),\n",
+ " )\n",
+ "\n",
+ " # if samples is not None:\n",
+ " # p.ax_joint.legend_.remove()\n",
+ "\n",
+ " if ylim is not None:\n",
+ " p.ax_joint.set_ylim(ylim)\n",
+ "\n",
+ " gene_x_id = p.ax_joint.get_xlabel()\n",
+ " gene_x_symbol = gene_map[gene_x_id]\n",
+ " p.ax_joint.set_xlabel(f\"{gene_x_symbol}\", fontstyle=\"italic\")\n",
+ "\n",
+ " gene_y_id = p.ax_joint.get_ylabel()\n",
+ " gene_y_symbol = gene_map[gene_y_id]\n",
+ " p.ax_joint.set_ylabel(f\"{gene_y_symbol}\", fontstyle=\"italic\")\n",
+ "\n",
+ " p.fig.suptitle(_title)\n",
+ "\n",
+ " # save\n",
+ " output_file = (\n",
+ " OUTPUT_FIGURE_DIR\n",
+ " / f\"gtex_{tissue_name}-{gene_x_symbol}_vs_{gene_y_symbol}{filename_suffix}.svg\"\n",
+ " )\n",
+ " display(output_file)\n",
+ "\n",
+ " plt.savefig(\n",
+ " output_file,\n",
+ " bbox_inches=\"tight\",\n",
+ " dpi=300,\n",
+ " facecolor=\"white\",\n",
+ " )\n",
+ "\n",
+ " return tissue_data"
+ ]
+ },
+ {
+ "cell_type": "markdown",
+ "id": "a1203a1b-9192-43ee-8715-476aa7048ce6",
+ "metadata": {
+ "papermill": {
+ "duration": 0.010275,
+ "end_time": "2023-11-20T08:56:06.120691",
+ "exception": false,
+ "start_time": "2023-11-20T08:56:06.110416",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "source": [
+ "## Brain cerebellum (males)"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": 56,
+ "id": "ad7a21de-2d8e-423e-8044-38d6f3b43808",
+ "metadata": {
+ "execution": {
+ "iopub.execute_input": "2023-11-20T08:56:06.141871Z",
+ "iopub.status.busy": "2023-11-20T08:56:06.141469Z",
+ "iopub.status.idle": "2023-11-20T08:56:06.815437Z",
+ "shell.execute_reply": "2023-11-20T08:56:06.815120Z"
+ },
+ "papermill": {
+ "duration": 0.686272,
+ "end_time": "2023-11-20T08:56:06.817129",
+ "exception": false,
+ "start_time": "2023-11-20T08:56:06.130857",
+ "status": "completed"
+ },
+ "tags": []
+ },
+ "outputs": [
+ {
+ "data": {
+ "text/plain": [
+ "('KDM6A', 'UTY')"
+ ]
+ },
+ "metadata": {},
+ "output_type": "display_data"
+ },
+ {
+ "data": {
+ "text/plain": [
+ "PosixPath('/opt/manuscript/content/images/coefs_comp/kdm6a_vs_uty/gtex_brain_cerebellum-KDM6A_vs_UTY-all.svg')"
+ ]
+ },
+ "metadata": {},
+ "output_type": "display_data"
+ },
+ {
+ "data": {
+ "image/png": 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\n",
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