title: Examining the predictive accuracy of the novel 3D N-linear algebraic molecular codifications on benchmark datasets.
abstract: BACKGROUND
  Recently, novel 3D alignment-free molecular descriptors (also known as QuBiLS-MIDAS) based on two-linear, three-linear and four-linear algebraic forms have been introduced. These descriptors codify chemical information for relations between two, three and four atoms by using several (dis-)similarity metrics and multi-metrics. Several studies aimed at assessing the quality of these novel descriptors have been performed. However, a deeper analysis of their performance is necessary. Therefore, in the present manuscript an assessment and statistical validation of the performance of these novel descriptors in QSAR studies is performed.
  
  
  RESULTS
  To this end, eight molecular datasets (angiotensin converting enzyme, acetylcholinesterase inhibitors, benzodiazepine receptor, cyclooxygenase-2 inhibitors, dihydrofolate reductase inhibitors, glycogen phosphorylase b, thermolysin inhibitors, thrombin inhibitors) widely used as benchmarks in the evaluation of several procedures are utilized. Three to nine variable QSAR models based on Multiple Linear Regression are built for each chemical dataset according to the original division into training/test sets. Comparisons with respect to leave-one-out cross-validation correlation coefficients[Formula: see text] reveal that the models based on QuBiLS-MIDAS indices possess superior predictive ability in 7 of the 8 datasets analyzed, outperforming methodologies based on similar or more complex techniques such as: Partial Least Square, Neural Networks, Support Vector Machine and others. On the other hand, superior external correlation coefficients[Formula: see text] are attained in 6 of the 8 test sets considered, confirming the good predictive power of the obtained models. For the [Formula: see text] values non-parametric statistic tests were performed, which demonstrated that the models based on QuBiLS-MIDAS indices have the best global performance and yield significantly better predictions in 11 of the 12 QSAR procedures used in the comparison. Lastly, a study concerning to the performance of the indices according to several conformer generation methods was performed. This demonstrated that the quality of predictions of the QSAR models based on QuBiLS-MIDAS indices depend on 3D structure generation method considered, although in this preliminary study the results achieved do not present significant statistical differences among them.
  
  
  CONCLUSIONS
  As conclusions it can be stated that the QuBiLS-MIDAS indices are suitable for extracting structural information of the molecules and thus, constitute a promissory alternative to build models that contribute to the prediction of pharmacokinetic, pharmacodynamics and toxicological properties on novel compounds.Graphical abstractComparative graphical representation of the performance of the novel QuBiLS-MIDAS 3D-MDs with respect to other methodologies in QSAR modeling of eight chemical datasets.
authors.affiliation: Escuela de Sistemas y Computación, Pontificia Universidad Católica del Ecuador Sede Esmeraldas (PUCESE), Esmeraldas, Ecuador ; Grupo de Investigación de Bioinformática, Centro de Estudio de Matemática Computacional (CEMC), Universidad de las Ciencias Informáticas, La Habana, Cuba ; Computer-Aided Molecular "Biosilico" Discovery and Bioinformatics Research International Network (CAMD-BIR IN), Cumbayá, Quito, Ecuador ; Instituto de Simulación Computacional (ISC-USFQ), Universidad San Francisco de Quito (USFQ), Diego de Robles y vía Interoceánica, 17-1200-841 Quito, Ecuador.
authors.forename: César R
authors.initials: CR
authors.lastname: García-Jacas
authors.affiliation: Departamento de Técnicas de Programación, Facultad 6, Universidad de las Ciencias Informáticas, La Habana, Cuba.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Contreras-Torres
authors.affiliation: Computer-Aided Molecular "Biosilico" Discovery and Bioinformatics Research International Network (CAMD-BIR IN), Cumbayá, Quito, Ecuador ; Instituto de Simulación Computacional (ISC-USFQ), Universidad San Francisco de Quito (USFQ), Diego de Robles y vía Interoceánica, 17-1200-841 Quito, Ecuador ; Escuela de Medicina, Colegio de Ciencias de la Salud, Edificio de Especialidades Médicas, Hospital de los Valles, Universidad San Francisco de Quito (USFQ), Av. Interoceánica Km 12 ½ - Cumbayá, Quito, Ecuador.
authors.forename: Yovani
authors.initials: Y
authors.lastname: Marrero-Ponce
authors.affiliation: Grupo de Investigación de Bioinformática, Centro de Estudio de Matemática Computacional (CEMC), Universidad de las Ciencias Informáticas, La Habana, Cuba.
authors.forename: Mario
authors.initials: M
authors.lastname: Pupo-Meriño
authors.affiliation: Computer-Aided Molecular "Biosilico" Discovery and Bioinformatics Research International Network (CAMD-BIR IN), Cumbayá, Quito, Ecuador ; Departamento de Química, Universidade Federal de Lavras, UFLA, Caixa Postal 3037, Lavras, MG 37200-000 Brazil.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Barigye
authors.affiliation: Escuela de Sistemas y Computación, Pontificia Universidad Católica del Ecuador Sede Esmeraldas (PUCESE), Esmeraldas, Ecuador ; Grupo de Investigación de Inteligencia Artificial (AIRES), Facultad de Informática, Universidad de Camagüey, Camagüey, Cuba.
authors.forename: Lisset
authors.initials: L
authors.lastname: Cabrera-Leyva
keywords: 3D-QSAR; Multiple Linear Regression; QuBiLS-MIDAS; TOMOCOMD-CARDD