ENH Update drug categorization logic (#54)

- Always return immediate child of 'antibiotic molecule' for drug categorization
- Antibiotic mixture ARO mapping is excluded for all cases. Return constituent drug classes instead
- Use 'has_part' relationship to handle antibiotic mixtures and give drug class rather than 'antibiotic mixture'

CHANGELOG.md

@@ -4,6 +4,9 @@
 
 ### 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).
+- Implementation of drugs_to_drug_classes() has also been fixed. Previously, the drug class was obtained from the superclasses of the drugs list passed without a thorough check if the drug class was the immediate child of 'antibiotic molecule'. These checks have now been put in place.
+- drugs_to_drug_classes() also uses the 'has_part' ARO relationship now to get drug classes for antibiotic mixtures. In case of antibiotic mixtures, the drug classes of the drugs associated with 'has_part' are returned rather than 'antibiotic mixture' (ARO:3000707).
+- 'antibiotic mixture' will not be reported as a drug class, rather the individual antibiotic classes making up the antibiotic mixture will be reported.
 
 ### 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

@@ -4,6 +4,26 @@
 ARO = lib.get_aro_ontology()
 confers_resistance_to_drug_class_rel = ARO.get_relationship('confers_resistance_to_drug_class')
 confers_resistance_to_antibiotic_rel = ARO.get_relationship('confers_resistance_to_antibiotic')
+has_part_rel = ARO.get_relationship('has_part')
+
+def _get_drug_classes(super_classes_list: List[str]) -> List[str]:
+    """
+    - Helper function to traverse up and record immediate child of 'antibiotic molecule' in ARO
+    - Traverses up ARO until immediate child of 'antibiotic molecule' class reached and 'antibiotic mixture' class not reached
+    - antibiotic molecule -> ARO:1000003
+    - antibiotic mixture -> ARO:3000707
+    """
+    output = []
+
+    for super_class in super_classes_list:
+        super_class_classes = list(super_class.superclasses(1))
+        antibiotic_molecule_node = [ARO['ARO:1000003']]
+
+        # checking if immediate child of 'antibiotic molecule' is reached & it is not 'antibiotic mixture'
+        if super_class_classes[1:] == antibiotic_molecule_node and super_class.id != 'ARO:3000707':
+            output.append(super_class.id)
+
+    return output
 
 def confers_resistance_to(aro_num: str) -> List[str]:
     '''
@@ -55,15 +75,25 @@ def drugs_to_drug_classes(drugs_list: List[str]) -> List[str]:
             to the function in the drugs_list.
     '''
     drug_classes = []
+    temp_drug_classes = []
 
     for drug in drugs_list:
         drug_instance = ARO[drug]
         drug_instance_superclasses = list(drug_instance.superclasses())
-        superclasses_len = len(drug_instance_superclasses)
+        temp_drug_classes += _get_drug_classes(drug_instance_superclasses)
+
+        has_part_nodes = drug_instance.relationships.get(has_part_rel, [])
+        for has_part_node in has_part_nodes:
+            has_part_node_superclasses = list(has_part_node.superclasses())[1:]
+
+            for super_class in has_part_node_superclasses:
+                super_class_categories = list(super_class.superclasses())
+                temp_drug_classes += _get_drug_classes(super_class_categories)
+
+        if temp_drug_classes == []:
+            temp_drug_classes.append(drug_instance.id)
 
-        if superclasses_len >= 3:
-            drug_classes.append(drug_instance_superclasses[superclasses_len - 3].id)
-        else:
-            drug_classes.append(drug_instance_superclasses[0].id)
+        drug_classes += list(set(temp_drug_classes))
+        temp_drug_classes = []
 
     return sorted(drug_classes)

outputs/hamronized/amrfinderplus.ncbi.orfs.tsv

@@ -5,7 +5,7 @@ amrfinderplus.ncbi.orfs.tsv	tet(Q)	tetracycline resistance ribosomal protection
 amrfinderplus.ncbi.orfs.tsv	bexA	multidrug efflux MATE transporter BexA	NCBI Reference Gene Database	2023-Nov-01	BAB64566.1	amrfinderplus	3.10.30	gene_presence_detected	EFFLUX	80.36			EFFLUX		18	1085	356			k119_41685										443				-	92.98	ARO:3003953	ARO:0000045,ARO:3000662	ARO:0000001,ARO:3005386
 amrfinderplus.ncbi.orfs.tsv	lnu(C)	lincosamide nucleotidyltransferase Lnu(C)	NCBI Reference Gene Database	2023-Nov-01	WP_063851341.1	amrfinderplus	3.10.30	gene_presence_detected	LINCOSAMIDE	100.0			LINCOSAMIDE		234	725	164			k119_46979										164				-	97.56	ARO:3002837	ARO:0000046	ARO:0000017
 amrfinderplus.ncbi.orfs.tsv	sat4	streptothricin N-acetyltransferase Sat4	NCBI Reference Gene Database	2023-Nov-01	WP_000627290.1	amrfinderplus	3.10.30	gene_presence_detected	STREPTOTHRICIN	86.11			STREPTOTHRICIN		8	472	155			k119_47732										180				-	100.0	ARO:3002897	ARO:0000012	ARO:3000034
-amrfinderplus.ncbi.orfs.tsv	aph(3')-IIIa	aminoglycoside O-phosphotransferase APH(3')-IIIa	NCBI Reference Gene Database	2023-Nov-01	WP_001096887.1	amrfinderplus	3.10.30	gene_presence_detected	AMIKACIN/KANAMYCIN	100.0			AMINOGLYCOSIDE		207	998	264			k119_48139										264				-	100.0	ARO:3002647	ARO:0000005,ARO:0000013,ARO:0000021,ARO:0000024,ARO:0000049,ARO:3000652,ARO:3000655,ARO:3000657,ARO:3000658	ARO:0000016,ARO:0000016,ARO:0000016,ARO:0000016,ARO:0000016,ARO:0000016,ARO:0000016,ARO:0000016,ARO:3000707
+amrfinderplus.ncbi.orfs.tsv	aph(3')-IIIa	aminoglycoside O-phosphotransferase APH(3')-IIIa	NCBI Reference Gene Database	2023-Nov-01	WP_001096887.1	amrfinderplus	3.10.30	gene_presence_detected	AMIKACIN/KANAMYCIN	100.0			AMINOGLYCOSIDE		207	998	264			k119_48139										264				-	100.0	ARO:3002647	ARO:0000005,ARO:0000013,ARO:0000021,ARO:0000024,ARO:0000049,ARO:3000652,ARO:3000655,ARO:3000657,ARO:3000658	ARO:0000016,ARO:0000016,ARO:0000016,ARO:0000016,ARO:0000016,ARO:0000016,ARO:0000016,ARO:0000016,ARO:0000016
 amrfinderplus.ncbi.orfs.tsv	aadS	aminoglycoside 6-adenylyltransferase AadS	NCBI Reference Gene Database	2023-Nov-01	WP_003013318.1	amrfinderplus	3.10.30	gene_presence_detected	STREPTOMYCIN	100.0			AMINOGLYCOSIDE		34628	35488	287			k119_48233										287				+	100.0	ARO:3004683	ARO:0000040	ARO:0000016
 amrfinderplus.ncbi.orfs.tsv	tet(X2)	tetracycline-inactivating monooxygenase Tet(X2)	NCBI Reference Gene Database	2023-Nov-01	WP_008651082.1	amrfinderplus	3.10.30	gene_presence_detected	TETRACYCLINE	100.0			TETRACYCLINE		12370	13533	388			k119_48273										388				+	99.74	ARO:3000205	ARO:0000030,ARO:0000051,ARO:0000069,ARO:3000152,ARO:3000528,ARO:3000667,ARO:3000668	ARO:3000050,ARO:3000050,ARO:3000050,ARO:3000050,ARO:3000050,ARO:3000050,ARO:3000050
 amrfinderplus.ncbi.orfs.tsv	tet(O)	tetracycline resistance ribosomal protection protein Tet(O)	NCBI Reference Gene Database	2023-Nov-01	WP_014636291.1	amrfinderplus	3.10.30	gene_presence_detected	TETRACYCLINE	100.0			TETRACYCLINE		978	2894	639			k119_60190										639				+	99.22	ARO:3000190	ARO:0000051,ARO:0000069,ARO:3000152,ARO:3000528,ARO:3000667,ARO:3000668	ARO:3000050,ARO:3000050,ARO:3000050,ARO:3000050,ARO:3000050,ARO:3000050