Combining IC50 or Ki Values from Different Sources Is a Source of Significant Noise

• Published in: Journal of chemical information and modeling 2024-03, Vol.64 (5), p.1560-1567
• Main Authors: Landrum, Gregory A, Riniker, Sereina
• Format: Article
• Language: English
• Subjects: Assaying; Biological activity; Datasets; Machine learning; Open source software
• ISSN: 1549-9596; 1549-960X; 1549-960X
• DOI: 10.1021/acs.jcim.4c00049

As part of the ongoing quest to find or construct large data sets for use in validating new machine learning (ML) approaches for bioactivity prediction, it has become distressingly common for researchers to combine literature IC50 data generated using different assays into a single data set. It is well-known that there are many situations where this is a scientifically risky thing to do, even when the assays are against exactly the same target, but the risks of assays being incompatible are even higher when pulling data from large collections of literature data like ChEMBL. Here, we estimate the amount of noise present in combined data sets using cases where measurements for the same compound are reported in multiple assays against the same target. This approach shows that IC50 assays selected using minimal curation settings have poor agreement with each other: almost 65% of the points differ by more than 0.3 log units, 27% differ by more than one log unit, and the correlation between the assays, as measured by Kendall's τ, is only 0.51. Requiring that most of the assay metadata in ChEMBL matches ("maximal curation") in order to combine two assays improves the situation (48% of the points differ by more than 0.3 log units, 13% by more than one log unit, and Kendall's τ is 0.71) at the expense of having smaller data sets. Surprisingly, our analysis shows similar amounts of noise when combining data from different literature Ki assays. We suggest that good scientific practice requires careful curation when combining data sets from different assays and hope that our maximal curation strategy will help to improve the quality of the data that are being used to build and validate ML models for bioactivity prediction. To help achieve this, the code and ChEMBL queries that we used for the maximal curation approach are available as open-source software in our GitHub repository, https://github.com/rinikerlab/overlapping_assays.