Matched pairs demonstrate robustness against inter-assay variability

• Published in: Journal of cheminformatics Vol. 17; no. 1; p. 8
• Main Authors: Nelen, Jochem, Pérez-Sánchez, Horacio, De Winter, Hans, Van Rompaey, Dries
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 20.01.2025; BioMed Central Ltd; Springer Nature B.V; BMC
• Subjects: Assay noise; Assaying; Brief Report; ChEMBL; Chemistry; Chemistry and Materials Science; Computational Biology/Bioinformatics; Computer Applications in Chemistry; Data curation; Datasets; Documentation and Information in Chemistry; Error reduction; Impact analysis; Information management; Machine learning; Matched structural pairs; Metadata; Noise reduction; Quality assessment; Quality control; Theoretical and Computational Chemistry; Data curation; ChEMBL; Matched structural pairs; Assay noise; Machine learning
• ISSN: 1758-2946; 1758-2946
• DOI: 10.1186/s13321-025-00956-y

Machine learning models for chemistry require large datasets, often compiled by combining data from multiple assays. However, combining data without careful curation can introduce significant noise. While absolute values from different assays are rarely comparable, trends or differences between compounds are often assumed to be consistent. This study evaluates that assumption by analyzing potency differences between matched compound pairs across assays and assessing the impact of assay metadata curation on error reduction. We find that potency differences between matched pairs exhibit less variability than individual compound measurements, suggesting systematic assay differences may partially cancel out in paired data. Metadata curation further improves inter-assay agreement, albeit at the cost of dataset size. For minimally curated compound pairs, agreement within 0.3 pChEMBL units was found to be 44–46% for K i and IC 50 values respectively, which improved to 66–79% after curation. Similarly, the percentage of pairs with differences exceeding 1 pChEMBL unit dropped from 12 to 15% to 6–8% with extensive curation. These results establish a benchmark for expected noise in matched molecular pair data from the ChEMBL database, offering practical metrics for data quality assessment.