ADD use all parents for gene to drug mapping (#53)

* ADD use all parents for gene to drug mapping

confers_resistance_to() now gets drugs for the whole AMR gene family. This is done by navigating up ARO tree and getting drugs for parent terms of input genes.

For example, OXA-19 previously only returned cephalosporin and penam, but now will also return oxacillin (from AMR gene family).

CHANGELOG.md

@@ -2,6 +2,9 @@
 
 ## Unreleased
 
+### Update drug categorization
+- confers_resistance_to() now gets drugs for the whole AMR gene family. For example, OXA-19 previously only returned cephalosporin and penam, but now will also return oxacillin (from AMR gene family).
+
 ### Manual curation
 - argannot_curation: (Tet)tetH:EF460464:6286-7839:1554 was incorrectly annotated as ARO:3004797 which is a beta-lactamase due to a loose RGI hit. This was manually curated to ARO:3000175.
 

argnorm/drug_categorization.py

@@ -16,18 +16,27 @@ def confers_resistance_to(aro_num: str) -> List[str]:
         target (list[str]):
             A list with ARO number of the drugs/antibiotics to which the input gene confers resistance to.
     '''
-
+    antibiotic_molecule_node = [ARO['ARO:1000003'], ARO['ARO:1000001']]
+    # some gene superclasses can map to drugs which are immediate children of 'antibiotic molecule'
+    # only use these if no other drugs can be found, as this information will be present in
+    # drugs to drug classes
+    backup_drugs = []
     target = set()
-
     for term in ARO[aro_num].superclasses():
         for drug in term.relationships.get(confers_resistance_to_drug_class_rel, []):
-            target.add(drug.id)
+            if list(ARO[drug.id].superclasses())[1:] == antibiotic_molecule_node:
+                backup_drugs.append(drug.id)
+            else:
+                target.add(drug.id)
 
         for drug in term.relationships.get(confers_resistance_to_antibiotic_rel, []):
-            target.add(drug.id)
+            if list(ARO[drug.id].superclasses())[1:] == antibiotic_molecule_node:
+                backup_drugs.append(drug.id)
+            else:
+                target.add(drug.id)
 
-        if target:
-            break
+    if not target:
+        target.update(backup_drugs)
 
     return sorted(target)
 

tests/test_arg_category.py

@@ -2,23 +2,57 @@
     confers_resistance_to,
     drugs_to_drug_classes
 )
+from argnorm.lib import get_aro_ontology
+
+def _assert_aro_name(aro_id, name):
+    ARO = get_aro_ontology()
+    assert ARO[aro_id].name == name
+    return aro_id
 
 def test_confers_resistance_to():
     test_cases = [
         "ARO:3003938",
         "ARO:3000014",
-        "ARO:3003725"
+        "ARO:3003725",
+        "ARO:3000230",
+        "ARO:3005046",
+        "ARO:3001414"
     ]
 
     expected_output = [
         ["ARO:3000008", "ARO:0000032", "ARO:0000044"],
         ["ARO:3000008", "ARO:0000004", "ARO:3003706", "ARO:0000032", "ARO:3000637"],
-        ["ARO:3000081"]
+        ["ARO:3000081"],
+        ["ARO:3007382", "ARO:0000052", "ARO:0000007", "ARO:0000035", "ARO:0000049"],
+        ["ARO:0000015", "ARO:3000008"],
+        ['ARO:0000032', 'ARO:0000056', 'ARO:3000008']
     ]
 
     for t,e in zip(test_cases, expected_output):
         assert sorted(confers_resistance_to(t)) == sorted(e)
 
+def test_oxa19_drugs():
+    oxa_19 = _assert_aro_name('ARO:3001414', 'OXA-19')
+    cephalosporin = _assert_aro_name('ARO:0000032', 'cephalosporin')
+    penam = _assert_aro_name('ARO:3000008', 'penam')
+    oxacillin = _assert_aro_name('ARO:0000056', 'oxacillin')
+    assert sorted(confers_resistance_to(oxa_19)) == sorted([cephalosporin, penam, oxacillin])
+
+def test_aadb_drugs():
+    # aadb is a synonym for ANT(2'')-Ia
+    aadb = _assert_aro_name('ARO:3000230', "ANT(2'')-Ia")
+    gentamicin = _assert_aro_name('ARO:3007382', 'gentamicin')
+    tobramycin = _assert_aro_name('ARO:0000052', 'tobramycin')
+    dibekacin = _assert_aro_name('ARO:0000007', 'dibekacin')
+    sisomicin = _assert_aro_name('ARO:0000035', 'sisomicin')
+    kanamycin_a = _assert_aro_name('ARO:0000049', 'kanamycin A')
+    assert sorted(confers_resistance_to(aadb)) == sorted([
+        gentamicin,
+        tobramycin,
+        dibekacin,
+        sisomicin,
+        kanamycin_a
+    ])
 
 def test_drug_to_drug_classes():
     test_cases = [