Leveraging multiple data types for improved compound-kinase bioactivity prediction

Ryan Theisen (), Tianduanyi Wang, Balaguru Ravikumar, Rayees Rahman and Anna Cichońska ()
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Ryan Theisen: Harmonic Discovery Inc.
Tianduanyi Wang: Harmonic Discovery Inc.
Balaguru Ravikumar: Harmonic Discovery Inc.
Rayees Rahman: Harmonic Discovery Inc.
Anna Cichońska: Harmonic Discovery Inc.

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: Abstract Machine learning provides efficient ways to map compound-kinase interactions. However, diverse bioactivity data types, including single-dose and multi-dose-response assay results, present challenges. Traditional models utilize only multi-dose data, overlooking information contained in single-dose measurements. Here, we propose a machine learning methodology for compound-kinase activity prediction that leverages both single-dose and dose-response data. We demonstrate that our two-stage approach yields accurate activity predictions and significantly improves model performance compared to training solely on dose-response labels. This superior performance is consistent across five diverse machine learning methods. Using the best performing model, we carried out extensive experimental profiling on a total of 347 selected compound-kinase pairs, achieving a high hit rate of 40% and a negative predictive value of 78%. We show that these rates can be improved further by incorporating model uncertainty estimates into the compound selection process. By integrating multiple activity data types, we demonstrate that our approach holds promise for facilitating the development of training activity datasets in a more efficient and cost-effective way.

Date: 2024
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DOI: 10.1038/s41467-024-52055-5

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