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Coding recognition of the dose–effect interdependence of small biomolecules encrypted on paired chromatographic-based microassay arrays

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Abstract

The discovery of small biomolecules has suffered from the lack of a comprehensive framework to express the intrinsic correlation between bioactivity and the contribution from small molecules in complex samples with molecular and bioactivity diversity. Here, by mapping a sample’s 2D-HPTLC fingerprint to microplates, paired chromatographic-based microassay arrays are created, which can be used as quasi-chips to characterize multiple attributes of chromatographic components; as the array differential expression of the bioactivity and molecular attributes of irregular chromatographic spots for dose–effect interdependent encoding; and also as the automatic-collimated array mosaics of the multi-attributes of each component itself encrypted by its chromatographic fingerprint. Based on this homologous framework, we propose a correlating recognition strategy for small biomolecules 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 an array matching algorithm, instead of preparing diverse compound monomers of complex test samples for identification item-by-item. Furthermore, 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 bioassays with small biomolecules is established. Therefore, the small molecule contributions and the correlations of bioactivities, as well as their pathways, can be comprehensively revealed, so as to improve the reliability and efficiency of screening. This strategy was successfully applied to galangal, and demonstrated the high-throughput digital preliminary screening of small biomolecules in a natural product.

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Acknowledgements

We thank Yu Zhong (Analysis Centre of Guangdong Medical University, China) for technical assistance during LC-MS analysis, Liubo Lan for help with the initial cell viability assay, and Ning Li (Affiliated Hospital of Guangdong Medical University, China) for providing the A549 and HepG2 cells.

Funding

This study was financially supported by the Bureau of Guangdong Traditional Chinese Medicine, China (No. 20141152 and No. 20181153).

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Authors and Affiliations

  1. Guangdong Key Laboratory for Research & Development of Natural Drugs, Guangdong Medical University, Zhanjiang, 524023, China

    Yifeng Deng, Zhenpeng Lin & Yuan Cheng

Authors
  1. Yifeng Deng
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  2. Zhenpeng Lin
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  3. Yuan Cheng
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Contributions

YD conceived the project, designed all the experiments in this study, and drafted this manuscript for publication. In addition, he performed all the experiments for the G-quadruplex ligand bioassay and consistency analysis of all the experimental data. ZL performed the cell viability assays and the LC–MS analysis, processed the related data, prepared some chromatographic-based microassay arrays, and created some of the CAD drawings. YC carried out the preliminary experiments for this study.

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Correspondence to Yifeng Deng.

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Deng, Y., Lin, Z. & Cheng, Y. Coding recognition of the dose–effect interdependence of small biomolecules encrypted on paired chromatographic-based microassay arrays. Anal Bioanal Chem 414, 5991–6001 (2022). https://doi.org/10.1007/s00216-022-04162-9

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