Dataset Information

Regression trees and ensembles for cumulative incidence functions.

ABSTRACT: The use of cumulative incidence functions for characterizing the risk of one type of event in the presence of others has become increasingly popular over the past two decades. The problems of modeling, estimation and inference have been treated using parametric, nonparametric and semi-parametric methods. Efforts to develop suitable extensions of machine learning methods, such as regression trees and ensemble methods, have begun comparatively recently. In this paper, we propose a novel approach to estimating cumulative incidence curves in a competing risks setting using regression trees and associated ensemble estimators. The proposed methods use augmented estimators of the Brier score risk as the primary basis for building and pruning trees, and lead to methods that are easily implemented using existing R packages. Data from the Radiation Therapy Oncology Group (trial 9410) is used to illustrate these new methods.

SUBMITTER: Cho Y

PROVIDER: S-EPMC9509494 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Regression trees and ensembles for cumulative incidence functions.

Cho Youngjoo Y Molinaro Annette M AM Hu Chen C Strawderman Robert L RL

The international journal of biostatistics 20220325 2

The use of cumulative incidence functions for characterizing the risk of one type of event in the presence of others has become increasingly popular over the past two decades. The problems of modeling, estimation and inference have been treated using parametric, nonparametric and semi-parametric methods. Efforts to develop suitable extensions of machine learning methods, such as regression trees and ensemble methods, have begun comparatively recently. In this paper, we propose a novel approach t ...[more]

PMID: 35334192

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Project description:BackgroundNetwork inference is crucial for biomedicine and systems biology. Biological entities and their associations are often modeled as interaction networks. Examples include drug protein interaction or gene regulatory networks. Studying and elucidating such networks can lead to the comprehension of complex biological processes. However, usually we have only partial knowledge of those networks and the experimental identification of all the existing associations between biological entities is very time consuming and particularly expensive. Many computational approaches have been proposed over the years for network inference, nonetheless, efficiency and accuracy are still persisting open problems. Here, we propose bi-clustering tree ensembles as a new machine learning method for network inference, extending the traditional tree-ensemble models to the global network setting. The proposed approach addresses the network inference problem as a multi-label classification task. More specifically, the nodes of a network (e.g., drugs or proteins in a drug-protein interaction network) are modelled as samples described by features (e.g., chemical structure similarities or protein sequence similarities). The labels in our setting represent the presence or absence of links connecting the nodes of the interaction network (e.g., drug-protein interactions in a drug-protein interaction network).ResultsWe extended traditional tree-ensemble methods, such as extremely randomized trees (ERT) and random forests (RF) to ensembles of bi-clustering trees, integrating background information from both node sets of a heterogeneous network into the same learning framework. We performed an empirical evaluation, comparing the proposed approach to currently used tree-ensemble based approaches as well as other approaches from the literature. We demonstrated the effectiveness of our approach in different interaction prediction (network inference) settings. For evaluation purposes, we used several benchmark datasets that represent drug-protein and gene regulatory networks. We also applied our proposed method to two versions of a chemical-protein association network extracted from the STITCH database, demonstrating the potential of our model in predicting non-reported interactions.ConclusionsBi-clustering trees outperform existing tree-based strategies as well as machine learning methods based on other algorithms. Since our approach is based on tree-ensembles it inherits the advantages of tree-ensemble learning, such as handling of missing values, scalability and interpretability.

Project description:BackgroundNovel strategies are required in order to handle the huge amount of data produced by microarray technologies. To infer gene regulatory networks, the first step is to find direct regulatory relationships between genes building the so-called gene co-expression networks. They are typically generated using correlation statistics as pairwise similarity measures. Correlation-based methods are very useful in order to determine whether two genes have a strong global similarity but do not detect local similarities.ResultsWe propose model trees as a method to identify gene interaction networks. While correlation-based methods analyze each pair of genes, in our approach we generate a single regression tree for each gene from the remaining genes. Finally, a graph from all the relationships among output and input genes is built taking into account whether the pair of genes is statistically significant. For this reason we apply a statistical procedure to control the false discovery rate. The performance of our approach, named REGNET, is experimentally tested on two well-known data sets: Saccharomyces Cerevisiae and E.coli data set. First, the biological coherence of the results are tested. Second the E.coli transcriptional network (in the Regulon database) is used as control to compare the results to that of a correlation-based method. This experiment shows that REGNET performs more accurately at detecting true gene associations than the Pearson and Spearman zeroth and first-order correlation-based methods.ConclusionsREGNET generates gene association networks from gene expression data, and differs from correlation-based methods in that the relationship between one gene and others is calculated simultaneously. Model trees are very useful techniques to estimate the numerical values for the target genes by linear regression functions. They are very often more precise than linear regression models because they can add just different linear regressions to separate areas of the search space favoring to infer localized similarities over a more global similarity. Furthermore, experimental results show the good performance of REGNET.

Dataset Information

Regression trees and ensembles for cumulative incidence functions.

Publications

Regression trees and ensembles for cumulative incidence functions.

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