ChEMBL contains a broad range of binding, functional and ADMET type assays in formats ranging from in vitro single protein assays to anti proliferative cell-based assays. Some variation is expected, even for very similar assays, since these are often performed by different groups and institutes. ChEMBL includes references for all bioactivity values so that full assay details can be reviewed if needed, however there are a number of other data checks that can be used to identify potentially problematic results.
1) Data validity comments:
The data validity column was first included in ChEMBL v15 and flags activities with potential validity issues such as a non-standard unit for type or activities outside of the expected range. Users can review flagged activities and decide how these should be handled. The data validity column can be viewed on the interface (click 'Show/Hide columns' and select 'data validity comments') and can be found in the activities table in the full database.
* Acceptable ranges/units for standard_types are provided in the ACTIVITY_STDS_LOOKUP table. An exception is made for certain fragment-based activities (MW <= 350) where the data validity comment is not applied.
2) Confidence scores:
The confidence scores reflect both the target type and the confidence that the mapped target is correct (e.g. score 0 = no target assigned, score 9 = direct single protein target assigned). In cases where target protein accessions were unavailable during initial mapping, homologues from different species/strains have sometimes been assigned with lower confidence scores. Curation is ongoing and confidence scores may change between releases as additional assays are mapped (or re-mapped) to targets. The confidence scores can be viewed on the interface and are found in the assays table in the database.
3) Activity comments:
Activity comments capture the author or depositor’s overall activity conclusions and may take into account counter screens, curve fitting etc. It may be worth reviewing the activity comments to identify cases where apparently potent compounds have been deemed inactive by depositors. For further details on activity comments, see our previous Blog post. The activity comments can be viewed on the interface and are available in the activities table of the database.
4) Potential duplicates:
Bioactivity data is extracted from seven core journals and this may include secondary citations. Potential duplicates are flagged when identical compound, target, activity, type and unit values are reported. The potential duplicates field is available on the interface and is found in the activities table of the database.
5) Variants:
Protein variation can change the affinity of drugs for targets. On the interface, variant proteins are recorded in the assay descriptions which can be used to check whether activities correspond to variant or 'wild-type' targets. The variant sequences table was added to the database in version 22 and is linked to the assays table through the variant ID. The variant ID can be used to include or exclude variants from assay results. Curation is underway to annotate additional variants from historical assays (more on this to follow).
Hopefully this provides an idea of some of the available data checks. Questions? Please get in touch on the Helpdesk or have a look through our training materials and FAQs.
Data checks using Imatinib as an example:
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