RESUMEN
We generalize the notion of λ-superstrings, presented in a previous paper, to the notion of weighted λ-superstrings. This generalization entails an important improvement in the applications to vaccine designs, as it allows epitopes to be weighted by their immunogenicities. Motivated by these potential applications of constructing short weighted λ-superstrings to vaccine design, we approach this problem in two ways. First, we formalize the problem as a combinatorial optimization problem (in fact, as two polynomially equivalent problems) and develop an integer programming (IP) formulation for solving it optimally. Second, we describe a model that also takes into account good pairwise alignments of the obtained superstring with the input strings, and present a genetic algorithm that solves the problem approximately. We apply both algorithms to a set of 169 strings corresponding to the Nef protein taken from patiens infected with HIV-1. In the IP-based algorithm, we take the epitopes and the estimation of the immunogenicities from databases of experimental epitopes. In the genetic algorithm we take as candidate epitopes all 9-mers present in the 169 strings and estimate their immunogenicities using a public bioinformatics tool. Finally, we used several bioinformatic tools to evaluate the properties of the candidates generated by our method, which indicated that we can score high immunogenic λ-superstrings that at the same time present similar conformations to the Nef virus proteins.
Asunto(s)
Cadenas lambda de Inmunoglobulina/inmunología , Vacunas/síntesis química , Vacunas contra el SIDA/síntesis química , Vacunas contra el SIDA/inmunología , Algoritmos , Epítopos/genética , Epítopos/inmunología , VIH-1/genética , VIH-1/inmunología , Humanos , Cadenas lambda de Inmunoglobulina/genética , Modelos Teóricos , Alineación de Secuencia , Vacunas/inmunología , Productos del Gen nef del Virus de la Inmunodeficiencia Humana/genética , Productos del Gen nef del Virus de la Inmunodeficiencia Humana/inmunologíaRESUMEN
PURPOSE: To introduce LEIOA, a new screening method to forecast which patients admitted to the hospital because of suspected threatened premature delivery will give birth in < 7 days, so that it can be used to assist in the prognosis and treatment jointly with other clinical tools. METHODS: From 2010 to 2013, 286 tocographies from women with gestational ages comprehended between 24 and 37 weeks were collected and studied. Then, we developed a new predictive model based on uterine contractions which combine the Generalized Hurst Exponent and the Approximate Entropy by logistic regression (LEIOA model). We compared it with a model using exclusively obstetric variables, and afterwards, we joined both to evaluate the gain. Finally, a cross validation was performed. RESULTS: The combination of LEIOA with the medical model resulted in an increase (in average) of predictive values of 12% with respect to the medical model alone, giving a sensitivity of 0.937, a specificity of 0.747, a positive predictive value of 0.907 and a negative predictive value of 0.819. Besides, adding LEIOA reduced the percentage of incorrectly classified cases by the medical model by almost 50%. CONCLUSIONS: Due to the significant increase in predictive parameters and the reduction of incorrectly classified cases when LEIOA was combined with the medical variables, we conclude that it could be a very useful tool to improve the estimation of the immediacy of preterm delivery.
Asunto(s)
Trabajo de Parto Prematuro , Nacimiento Prematuro/diagnóstico , Contracción Uterina , Monitoreo Uterino , Adulto , Femenino , Predicción , Edad Gestacional , Humanos , Recién Nacido , Modelos Logísticos , Parto , Valor Predictivo de las Pruebas , Embarazo , Pronóstico , Sensibilidad y EspecificidadRESUMEN
Preterm delivery affects about one tenth of human births and is associated with an increased perinatal morbimortality as well as with remarkable costs. Even if there are a number of predictors and markers of preterm delivery, none of them has a high accuracy. In order to find quantitative indicators of the immediacy of labor, 142 cardiotocographies (CTG) recorded from women consulting because of suspected threatened premature delivery with gestational ages comprehended between 24 and 35 weeks were collected and analyzed. These 142 samples were divided into two groups: the delayed labor group (n = 75), formed by the women who delivered more than seven days after the tocography was performed, and the anticipated labor group (n = 67), which corresponded to the women whose labor took place during the seven days following the recording. As a means of finding significant differences between the two groups, some key informational properties were analyzed by applying nonlinear techniques on the tocography recordings. Both the regularity and the persistence levels of the delayed labor group, which were measured by Approximate Entropy (ApEn) and Generalized Hurst Exponent (GHE) respectively, were found to be significantly different from the anticipated labor group. As delivery approached, the values of ApEn tended to increase while the values of GHE tended to decrease, suggesting that these two methods are sensitive to labor immediacy. On this paper, for the first time, we have been able to estimate childbirth immediacy by applying nonlinear methods on tocographies. We propose the use of the techniques herein described as new quantitative diagnosis tools for premature birth that significantly improve the current protocols for preterm labor prediction worldwide.