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Prediction of survival with alternative modeling techniques using pseudo values.

ABSTRACT: BACKGROUND:The use of alternative modeling techniques for predicting patient survival is complicated by the fact that some alternative techniques cannot readily deal with censoring, which is essential for analyzing survival data. In the current study, we aimed to demonstrate that pseudo values enable statistically appropriate analyses of survival outcomes when used in seven alternative modeling techniques. METHODS:In this case study, we analyzed survival of 1282 Dutch patients with newly diagnosed Head and Neck Squamous Cell Carcinoma (HNSCC) with conventional Kaplan-Meier and Cox regression analysis. We subsequently calculated pseudo values to reflect the individual survival patterns. We used these pseudo values to compare recursive partitioning (RPART), neural nets (NNET), logistic regression (LR) general linear models (GLM) and three variants of support vector machines (SVM) with respect to dichotomous 60-month survival, and continuous pseudo values at 60 months or estimated survival time. We used the area under the ROC curve (AUC) and the root of the mean squared error (RMSE) to compare the performance of these models using bootstrap validation. RESULTS:Of a total of 1282 patients, 986 patients died during a median follow-up of 66 months (60-month survival: 52% [95% CI: 50%-55%]). The LR model had the highest optimism corrected AUC (0.791) to predict 60-month survival, followed by the SVM model with a linear kernel (AUC 0.787). The GLM model had the smallest optimism corrected RMSE when continuous pseudo values were considered for 60-month survival or the estimated survival time followed by SVM models with a linear kernel. The estimated importance of predictors varied substantially by the specific aspect of survival studied and modeling technique used. CONCLUSIONS:The use of pseudo values makes it readily possible to apply alternative modeling techniques to survival problems, to compare their performance and to search further for promising alternative modeling techniques to analyze survival time.

SUBMITTER: van der Ploeg T

PROVIDER: S-EPMC4065009 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Prediction of survival with alternative modeling techniques using pseudo values.

van der Ploeg Tjeerd T Datema Frank F Baatenburg de Jong Robert R Steyerberg Ewout W EW

PloS one 20140620 6

<h4>Background</h4>The use of alternative modeling techniques for predicting patient survival is complicated by the fact that some alternative techniques cannot readily deal with censoring, which is essential for analyzing survival data. In the current study, we aimed to demonstrate that pseudo values enable statistically appropriate analyses of survival outcomes when used in seven alternative modeling techniques.<h4>Methods</h4>In this case study, we analyzed survival of 1282 Dutch patients wit ...[more]

PMID: 24950066

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Project description:BACKGROUND:Cyclic peptide-based drug discovery is attracting increasing interest owing to its potential to avoid target protein depletion. In drug discovery, it is important to maintain the biostability of a drug within the proper range. Plasma protein binding (PPB) is the most important index of biostability, and developing a computational method to predict PPB of drug candidate compounds contributes to the acceleration of drug discovery research. PPB prediction of small molecule drug compounds using machine learning has been conducted thus far; however, no study has investigated cyclic peptides because experimental information of cyclic peptides is scarce. RESULTS:First, we adopted sparse modeling and small molecule information to construct a PPB prediction model for cyclic peptides. As cyclic peptide data are limited, applying multidimensional nonlinear models involves concerns regarding overfitting. However, models constructed by sparse modeling can avoid overfitting, offering high generalization performance and interpretability. More than 1000 PPB data of small molecules are available, and we used them to construct a prediction models with two enumeration methods: enumerating lasso solutions (ELS) and forward beam search (FBS). The accuracies of the prediction models constructed by ELS and FBS were equal to or better than those of conventional non-linear models (MAE?=?0.167-0.174) on cross-validation of a small molecule compound dataset. Moreover, we showed that the prediction accuracies for cyclic peptides were close to those for small molecule compounds (MAE?=?0.194-0.288). Such high accuracy could not be obtained by a simple method of learning from cyclic peptide data directly by lasso regression (MAE?=?0.286-0.671) or ridge regression (MAE?=?0.244-0.354). CONCLUSION:In this study, we proposed a machine learning techniques that uses low-dimensional sparse modeling to predict the PPB value of cyclic peptides computationally. The low-dimensional sparse model not only exhibits excellent generalization performance but also improves interpretation of the prediction model. This can provide common an noteworthy knowledge for future cyclic peptide drug discovery studies.

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Prediction of survival with alternative modeling techniques using pseudo values.

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Prediction of survival with alternative modeling techniques using pseudo values.

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