Coding Recognition of the Dose-Effect Interdependence of Small Biomolecules Encrypted on Paired Chromatographic-Based Microassay Arrays

Abstract

ABSTRACTThe discovery of small biomolecules suffers from the lack of a comprehensive framework to specifically correlate bioactivities and the contributing small molecules in complex samples with molecular and bioactivity diversity. Here, by mapping a sample’s 2D-HPTLC fingerprint to microplates, the paired chromatographic-based microassay arrays are created, which can be used as quasi-chip to characterize multiple attributes of chromatographic components, and as the array differential expression of the bioactivity and molecular attributes of irregular chromatographic spots for interdependent encoding, as well as the automatic-collimated array mosaics of the multi-attributes of each component itself encrypted by its chromatographic fingerprint. Based on this framework, we propose a correlating recognition strategy for small biomolecules with the modulating bioactivities through their self-consistent chromatographic behavior characteristics. In the approach, the small-biomolecule recognition in diverse compounds is transformed into a constraint satisfaction problem, which is addressed through examining the dose-effect interdependence of the homologous 2D code pairs by array matching algorithm, instead of preparing diverse compound monomers of complex test sample for identifying item-by-item. Furtherly, considering the dose-effect interdependent 2D code pairs as links and the digital-specific quasimolecular ions as nodes, an extendable self-consistent framework that correlates mammalian cell phenotypic and target-based bioassay with small biomolecules is established. Therefore, the small molecule contributions and the correlations of bioactivities, as well as their pathway can be comprehensively revealed, so as to improve the reliability and efficiency of screening. This strategy was successfully applied to galangal, and practiced the high-throughput digital preliminary screening of small-biomolecules in a natural product.HighlightRapid self-recognition of small biomolecules in diverse samples without pre-isolation Matching of HPTLC-based molecular imprinting and bioautography on microassay arrays Microarray–based differential expression of substance attributes instead of spot scan Array auto-collimation of multi-attributes derived from the same 2D-HPTLC component An array framework for combining phenotype-based and target-based assays with TLC-MS ToC graphic