From 371ce9ded8e87f2ea7b6926a4e9f281a6d0a94da Mon Sep 17 00:00:00 2001
From: daveringelberg <141670222+daveringelberg@users.noreply.github.com>
Date: Wed, 26 Aug 2026 13:54:50 +0200
Subject: [PATCH 1/3] Add signature reversal tutorial section
---
enrichment.ipynb | 87 ++++++++++++++++++++++++++++++++++++++++++++++++
1 file changed, 87 insertions(+)
diff --git a/enrichment.ipynb b/enrichment.ipynb
index c91aa24..ec69731 100644
--- a/enrichment.ipynb
+++ b/enrichment.ipynb
@@ -697,6 +697,93 @@
"fig.show()"
]
},
+ {
+ "cell_type": "markdown",
+ "metadata": {},
+ "source": [
+ "## Signature reversal"
+ ]
+ },
+ {
+ "cell_type": "markdown",
+ "metadata": {},
+ "source": [
+ "`Enrichment.signature_reversal` ranks perturbations by how strongly their gene-level effects oppose an up/down query signature.\n",
+ "The method expects signed perturbation effects relative to matched controls rather than raw expression."
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": null,
+ "metadata": {},
+ "outputs": [],
+ "source": [
+ "cell_adata = pt.dt.distance_example()\n",
+ "ps = pt.tl.PseudobulkSpace()\n",
+ "ps_adata = ps.compute(\n",
+ " cell_adata,\n",
+ " target_col=\"perturbation\",\n",
+ " mode=\"mean\",\n",
+ ")\n",
+ "ps_adata = ps.compute_control_diff(\n",
+ " ps_adata,\n",
+ " target_col=\"perturbation\",\n",
+ " reference_key=\"control\",\n",
+ ")\n",
+ "ps_adata = ps_adata[ps_adata.obs[\"perturbation\"] != \"control\"].copy()"
+ ]
+ },
+ {
+ "cell_type": "markdown",
+ "metadata": {},
+ "source": [
+ "To keep this example self-contained, the query is defined as the opposite of one observed CRISPR perturbation signature.\n",
+ "In a real analysis, use an independently derived disease or state signature."
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": null,
+ "metadata": {},
+ "outputs": [],
+ "source": [
+ "query_profile = -ps_adata[ps_adata.obs[\"perturbation\"] == \"p-sgCREB1-2\"].to_df().iloc[0]\n",
+ "up_genes = query_profile[query_profile > 0].nlargest(20).index.tolist()\n",
+ "down_genes = query_profile[query_profile < 0].nsmallest(20).index.tolist()\n",
+ "\n",
+ "enr = pt.tl.Enrichment()\n",
+ "enr.signature_reversal(\n",
+ " ps_adata,\n",
+ " up_genes=up_genes,\n",
+ " down_genes=down_genes,\n",
+ ")\n",
+ "ps_adata.obs.sort_values(\"signature_reversal_rank\")[\n",
+ " [\"perturbation\", \"signature_reversal_score\", \"signature_reversal_rank\"]\n",
+ "].head(10)"
+ ]
+ },
+ {
+ "cell_type": "code",
+ "execution_count": null,
+ "metadata": {},
+ "outputs": [],
+ "source": [
+ "top = ps_adata.obs.nsmallest(10, \"signature_reversal_rank\").index\n",
+ "plot_genes = up_genes[:5] + down_genes[:5]\n",
+ "sc.pl.matrixplot(\n",
+ " ps_adata[top],\n",
+ " var_names=plot_genes,\n",
+ " groupby=\"perturbation\",\n",
+ ")"
+ ]
+ },
+ {
+ "cell_type": "markdown",
+ "metadata": {},
+ "source": [
+ "A high reversal score is a hypothesis for follow-up rather than evidence of efficacy or safety."
+ ]
+ },
{
"cell_type": "markdown",
"metadata": {},
From 49b16d5ec4f4025038251d50edbc9b3ce85e23dd Mon Sep 17 00:00:00 2001
From: daveringelberg <141670222+daveringelberg@users.noreply.github.com>
Date: Wed, 26 Aug 2026 16:16:04 +0200
Subject: [PATCH 2/3] Execute signature reversal tutorial cells
---
enrichment.ipynb | 131 +++++++++++++++++++++++++++++++++++++++++++++--
1 file changed, 126 insertions(+), 5 deletions(-)
diff --git a/enrichment.ipynb b/enrichment.ipynb
index ec69731..5c69150 100644
--- a/enrichment.ipynb
+++ b/enrichment.ipynb
@@ -714,7 +714,7 @@
},
{
"cell_type": "code",
- "execution_count": null,
+ "execution_count": 19,
"metadata": {},
"outputs": [],
"source": [
@@ -743,9 +743,119 @@
},
{
"cell_type": "code",
- "execution_count": null,
+ "execution_count": 20,
"metadata": {},
- "outputs": [],
+ "outputs": [
+ {
+ "data": {
+ "text/html": [
+ "\n",
+ "\n",
+ "
\n",
+ " \n",
+ " \n",
+ " | \n",
+ " perturbation | \n",
+ " signature_reversal_score | \n",
+ " signature_reversal_rank | \n",
+ "
\n",
+ " \n",
+ " \n",
+ " \n",
+ " | p-sgCREB1-2 | \n",
+ " p-sgCREB1-2 | \n",
+ " 1.000000 | \n",
+ " 1 | \n",
+ "
\n",
+ " \n",
+ " | p-sgEGR1-4 | \n",
+ " p-sgEGR1-4 | \n",
+ " 0.936307 | \n",
+ " 2 | \n",
+ "
\n",
+ " \n",
+ " | p-sgGABPA-9 | \n",
+ " p-sgGABPA-9 | \n",
+ " 0.931187 | \n",
+ " 3 | \n",
+ "
\n",
+ " \n",
+ " | p-sgNR2C2-2 | \n",
+ " p-sgNR2C2-2 | \n",
+ " 0.930610 | \n",
+ " 4 | \n",
+ "
\n",
+ " \n",
+ " | p-sgYY1-3 | \n",
+ " p-sgYY1-3 | \n",
+ " 0.930470 | \n",
+ " 5 | \n",
+ "
\n",
+ " \n",
+ " | p-sgNR2C2-3 | \n",
+ " p-sgNR2C2-3 | \n",
+ " 0.929137 | \n",
+ " 6 | \n",
+ "
\n",
+ " \n",
+ " | p-sgELK1-1 | \n",
+ " p-sgELK1-1 | \n",
+ " 0.925710 | \n",
+ " 7 | \n",
+ "
\n",
+ " \n",
+ " | p-sgEGR1-2 | \n",
+ " p-sgEGR1-2 | \n",
+ " 0.924965 | \n",
+ " 8 | \n",
+ "
\n",
+ " \n",
+ " | p-sgELF1-5 | \n",
+ " p-sgELF1-5 | \n",
+ " 0.924789 | \n",
+ " 9 | \n",
+ "
\n",
+ " \n",
+ " | p-sgIRF1-2 | \n",
+ " p-sgIRF1-2 | \n",
+ " 0.918981 | \n",
+ " 10 | \n",
+ "
\n",
+ " \n",
+ "
\n",
+ "