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DrugLogit: Logistic Discrimination between Drugs and Nondrugs Including Disease-Specificity by Assigning Probabilities Based on Molecular Properties
journal contribution
posted on 2012-08-27, 00:00 authored by Alfonso T. García-Sosa, Mare Oja, Csaba Hetényi, Uko MaranThe increasing knowledge of both structure and activity
of compounds
provides a good basis for enhancing the pharmacological characterization
of chemical libraries. In addition, pharmacology can be seen as incorporating
both advances from molecular biology as well as chemical sciences,
with innovative insight provided from studying target-ligand data
from a ligand molecular point of view. Predictions and profiling of
libraries of drug candidates have previously focused mainly on certain
cases of oral bioavailability. Inclusion of other administration routes
and disease-specificity would improve the precision of drug profiling.
In this work, recent data are extended, and a probability-based approach
is introduced for quantitative and gradual classification of compounds
into categories of drugs/nondrugs, as well as for disease- or organ-specificity.
Using experimental data of over 1067 compounds and multivariate logistic
regressions, the classification shows good performance in training
and independent test cases. The regressions have high statistical
significance in terms of the robustness of coefficients and 95% confidence
intervals provided by a 1000-fold bootstrapping resampling. Besides
their good predictive power, the classification functions remain chemically
interpretable, containing only one to five variables in total, and
the physicochemical terms involved can be easily calculated. The present
approach is useful for an improved description and filtering of compound
libraries. It can also be applied sequentially or in combinations
of filters, as well as adapted to particular use cases. The scores
and equations may be able to suggest possible routes for compound
or library modification. The data is made available for reuse by others,
and the equations are freely accessible at http://hermes.chem.ut.ee/~alfx/druglogit.html .
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Keywords
drug candidatesMolecular PropertiesTheuse casesclassification functionsAssigning Probabilitieschemical librariestest casesapproachcompound librariesLogistic Discriminationbootstrapping resampling1067 compoundschemical sciencesadministration routesequationlibrary modificationregressiondataphysicochemical terms
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