Track papers across labs, topics, and trends.
Search papers, labs, and topics across Lattice.
This study introduces a framework for predicting the quantifiability of drug compounds from low-cost primary screening assays, distinguishing it from merely confirming biological activity. The authors demonstrate that quantifiability can be effectively modeled using features from the screening data, rather than relying on molecular structure, and that this approach generalizes across different chemical scaffolds and assay mechanisms. By prioritizing compounds based on their likelihood of yielding usable potency estimates, the framework enhances the efficiency of dose-response profiling in drug development.
Predicting quantifiability from primary screens can significantly optimize the allocation of costly dose-response profiling resources in drug discovery.
High-throughput drug screening relies on low-cost primary assays to prioritize compounds for more expensive dose-response profiling, where potency is ultimately quantified. Current screening strategies largely focus on identifying compounds that will confirm biological activity on follow-up, implicitly assuming that confirmed activity will also yield a usable potency estimate. However, confirmed biological activity in screening does not necessarily translate into a quantifiable potency, because active compounds can still fail to produce a reportable dose-response estimate. We therefore present a framework for modeling quantifiability, whether follow-up testing will yield a usable potency estimate, as a distinct triage objective from biological activity. Quantifiability was strongly predictable from the preceding low-cost screen, with most predictive information arising from the observed screening features rather than molecular structure. Response-based predictors remained robust on previously unseen chemical scaffolds and generalized across held-out assay-mechanism families, while the probability of successful quantification varied strongly with response amplitude and assay context. These findings establish experimental measurability, distinct from biological activity, as a predictable property of screening outcomes and show that quantifiability-aware triage can improve the allocation of costly dose-response profiling capacity.