bioRxiv | 2021
Coding Recognition of the Dose-Effect Interdependence of Small Biomolecules Encrypted on Paired Chromatographic-Based Microassay Arrays
Abstract
The discovery of small biomolecules in complex samples suffers from the lack of a recognition method that specifically correlates bioactivity and molecular identity, just like the biomacromolecular recognition. Here, by mapping a sample’s 2D-HPTLC fingerprint to microplates, the paired chromatographic-based microassay arrays are created, which can be used to characterize multiple attributes of chromatographic components, and used as the array differential expression of the obtained multi-attributes of the irregular chromatographic spots for mathematical operation, 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 molecules with bioactivity through their chromatographic behavior characteristics. Specifically, on the paired chromatographic-based microassay arrays with a grid size approximated to that of the chromatographic spots and the chromatographic matrix removed, bioassays and bioguided LC-ESI-MS tracing are performed, the expressed array distribution gradients of the bioactivity strength vs. the digital-specific quasimolecular ion intensity derived from the same chromatographic component are self-consistent, and generated a pair of dose-effect interdependent 2D codes encrypted by the chromatographic fingerprint characteristics. Therefore, the small-biomolecule recognition in diverse compounds is transformed into a constraint satisfaction problem, which is addressed through examining the dose-effect interdependence of this 2D code pair by array matching algorithm, instead of preparing diverse compound monomers of complex test sample for identifying item-by-item. This research strategy was successfully applied to galangal, and practiced the high-throughput digital preliminary screening of small biomolecules in a natural product. Highlight Rapid 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