diff --git a/panpipes/python_scripts/run_preprocess_prot.py b/panpipes/python_scripts/run_preprocess_prot.py
index e221138d..12fbc67f 100644
--- a/panpipes/python_scripts/run_preprocess_prot.py
+++ b/panpipes/python_scripts/run_preprocess_prot.py
@@ -103,6 +103,22 @@
     else:
         L.error("You must specify a background MuData to run dsb, containing both rna and prot")
         sys.exit("You must specify a background MuData to run dsb, containing both rna and prot")
+
+    # RNA and PROT layer must be present in the object to run dsb
+    mods = list(all_mdata_bg.mod.keys())
+    if 'prot' not in mods:
+      L.error("The MuData you specified does not contain prot modality. Cannot run dsb")
+      sys.exit("The MuData you specified does not contain prot modality. Cannot run dsb")
+    if 'rna' not in mods:
+      L.error("The MuData you specified does not contain rna modality. Cannot run dsb")
+      sys.exit("The MuData you specified does not contain rna modality. Cannot run dsb")
+    del mods
+
+    # the RNA and PROT must intersect - they won't if experimental design included some cells without PROT data
+    L.info("Checking that only cells with PROT signal present are in the bacground object")
+    if all_mdata_bg['rna'].shape[0] != all_mdata_bg['prot'].shape[0]:
+        mu.pp.intersect_obs(mdata_bg)
+        all_mdata_bg.update()
     
     # checking that the same proteins are in foreground and background (since foreground might have been filtered)
     L.info("Checking that the same proteins are in foreground and background")