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Simple stochastic fingerprints towards mathematical modeling in biology and medicine. 3. ocular irritability classification model

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Abstract

MARCH-INSIDE methodology and a statistical classification method—linear discriminant analysis (LDA)—is proposed as an alternative method to the Draize eye irritation test. This methodology has been successfully applied to a set of 46 neutral organic chemicals, which have been defined as ocular irritant or nonirritant. The model allow to categorize correctly 37 out of 46 compounds, showing an accuracy of 80.46%. Specifically, this model demonstrates the existence of a good categorization average of 91.67 and 76.47% for irritant and nonirritant compounds, respectively. Validation of the model was carried out using two cross-validation tools: Leave-one-out (LOO) and leave-group-out (LGO), showing a global predictability of the model of 71.7 and 70%, respectively. The average of coincidence of the predictions between leave-one-out/leave-group-out studies and train set were 91.3% (42 out of 46 cases)/89.1% (41 out of 46 cases) proving the robustness of the model obtained. Ocular irritancy distribution diagram is carried out in order to determine the intervals of the property where the probability of finding an irritant compound is maximal relating to the choice of find a false nonirritant one. It seems that, until today, the present model may be the first predictive linear discriminant equation able to discriminate between eye irritant and nonirritant chemicals.

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Abbreviations

LDA:

linear discriminant analysis

MAS:

maximum average score

MMAS:

modified maximum average score

QSAR:

quantitative structure–activity relationships

MLR:

multivariate linear regression

PC:

principal components

QSTR:

quantitative structure–toxicity relationships

MC:

Markov chains

MARCH-INSIDE:

Markovian chemicals in sílico design

Log P:

natural logarithm of 1-octanol/water partition coefficient

ROC curve:

receiver operating characteristic curve

TDD:

toxicological distribution diagram

LOO:

leave-one-out

LGO:

leave-group-out

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Authors and Affiliations

  1. Applied Chemistry Research Center, Central University of “Las Villas,”, Santa Clara, 54830, Cuba

    Maykel Cruz-Monteagudo

  2. Chemical Bioactives Center, Central University of “Las Villas”, Santa Clara, 54830, Cuba

    Maykel Cruz-Monteagudo & Humberto González-Díaz

  3. Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, Santiago de Compostela, 15782, Spain

    Humberto González-Díaz

  4. Physico-Chemical Molecular Research Unit, Department of Organic Chemistry, Faculty of Pharmacy, University of Porto, 4050-047, Porto, Portugal

    Fernanda Borges

  5. Provincial Center for Human Genetics, Las Tunas, 77400, Cuba

    Yenny González-Díaz

  6. ICBP “Victoria de Girón,”, National Center for Human Genetics, La Habana, 11600, Cuba

    Yenny González-Díaz

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  1. Maykel Cruz-Monteagudo
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  2. Humberto González-Díaz
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Correspondence to Humberto González-Díaz.

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Cruz-Monteagudo, M., González-Díaz, H., Borges, F. et al. Simple stochastic fingerprints towards mathematical modeling in biology and medicine. 3. ocular irritability classification model. Bull. Math. Biol. 68, 1555–1572 (2006). https://doi.org/10.1007/s11538-006-9083-y

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