PTML Model of ChEMBL Compounds Assays for Vitamin Derivatives

Ricardo Santana, Robin Zuluaga, Piedad Gañán, Sonia Arrasate, Enrique Onieva Caracuel, Humbert González-Díaz

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    6 Scopus citations


    Determining the biological activity of vitamin derivatives is needed given that organic synthesis of analogs of vitamins is an active field of interest for medicinal chemistry, pharmaceuticals, and food additives. Accordingly, scientists from different disciplines perform preclinical assays (nij) with a considerable combination of assay conditions (cj). Indeed, the ChEMBL platform contains a database that includes results from 36â »220 different biological activity bioassays of 21â »240 different vitamins and vitamin derivatives. These assays present are heterogeneous in terms of assay combinations of cj. They are focused on >500 different biological activity parameters (c0), >340 different targets (c1), >6200 types of cell (c2), >120 organisms of assay (c3), and >60 assay strains (c4). It includes a total of >1850 niacin assays, >1580 tretinoin assays, >1580 retinol assays, 857 ascorbic acid assays, etc. Given the complexity of this combinatorial data in terms of being assimilated by researchers, we propose to build a model by combining perturbation theory (PT) and machine learning (ML). Through this study, we propose a PTML (PT + ML) combinatorial model for ChEMBL results on biological activity of vitamins and vitamins derivatives. The linear discriminant analysis (LDA) model presented the following results for training subset a: specificity (%) = 90.38, sensitivity (%) = 87.51, and accuracy (%) = 89.89. The model showed the following results for the external validation subset: specificity (%) = 90.58, sensitivity (%) = 87.72, and accuracy (%) = 90.09. Different types of linear and nonlinear PTML models, such as logistic regression (LR), classification tree (CT), näive Bayes (NB), and random Forest (RF), were applied to contrast the capacity of prediction. The PTML-LDA model predicts with more accuracy by applying combinatorial descriptors. In addition, a PCA experiment with chemical structure descriptors allowed us to characterize the high structural diversity of the chemical space studied. In any case, PTML models using chemical structure descriptors do not improve the performance of the PTML-LDA model based on ALOGP and PSA. We can conclude that the three variable PTML-LDA model is a simplified and adaptable tool for the prediction, for different experiment combinations, the biological activity of derivative vitamins.

    Original languageEnglish
    Pages (from-to)129-141
    Number of pages13
    JournalACS Combinatorial Science
    Issue number3
    StatePublished - 9 Mar 2020

    Bibliographical note

    Publisher Copyright:
    Copyright © 2020 American Chemical Society.


    • big data
    • ChEMBL
    • machine learning
    • multitarget models
    • perturbation theory
    • vitamins


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