add_dti_annotations module

Add DTI (Drug-Target Interaction) Annotations to the dataset.

add_dti_annotations.add_dti_annotations(dataset: Dataset)

Every compound-target pair is assigned a DTI (drug target interaction) annotation.

The assignment is based on three questions:

• Is the compound-target pair in the drug_mechanisms table? = Is it a known relevant compound-target interaction?

• What is the max_phase of the compound? = Is it a drug / clinical compound?

• Is the target in the drug_mechanisms table = Is it a therapeutic target?

The assigments are based on the following table:

in DM table?	max_phase?	th. target?	DTI	explanation
yes	4	–	D_DT [1]	drug - drug target
yes	3	–	C3_DT	clinical candidate in phase 3 - drug target
yes	2	–	C2_DT	clinical candidate in phase 2 - drug target
yes	1	–	C1_DT	clinical candidate in phase 1 - drug target
yes	<1	–	C0_DT	compound in unknown phase [2] - drug target
no	–	yes	DT	drug target
no	–	no	NDT	not drug target

[1]

The annotation D_DT instead of C4_DT was chosen to be consistent with the annotations in a previous version of the dataset. For the same reason the column is named DTI (drug-target interaction) instead of CTI (compound-target interaction) despite having specific annotations for clinical canidates.

[2]

C0_DT groups together all compounds with a max_phase not between 1 and 4.

Since ChEMBL32 there are three possible annotations in ChEMBL with a max_phase value not between 1 and 4:

• 0.5 = early phase 1 clinical trials

• -1 = clinical phase unknown for drug or clinical candidate drug, i.e., where ChEMBL cannot assign a clinical phase

• NULL = preclinical compounds with bioactivity data

All three are grouped together into the annotation C0_DT.

Compound-target pairs that were annotated with NDT, i.e., compound-target pairs that are not in the drug_mechanisms table and for which the target was also not in the drug_mechanisms table (not a comparator compound), are discarded.

Parameters:

dataset (Dataset) – Dataset with all relevant information: - Pandas DataFrame with compound-target pairs based on activities AND drug_mechanism table - set of compound-target pairs in the drug_mechanism table - set of targets in the drug_mechanism table