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Multithreshold change plane model: Estimation theory and applications in subgroup identification.

ABSTRACT: We propose a multithreshold change plane regression model which naturally partitions the observed subjects into subgroups with different covariate effects. The underlying grouping variable is a linear function of observed covariates and thus multiple thresholds produce change planes in the covariate space. We contribute a novel two-stage estimation approach to determine the number of subgroups, the location of thresholds, and all other regression parameters. In the first stage we adopt a group selection principle to consistently identify the number of subgroups, while in the second stage change point locations and model parameter estimates are refined by a penalized induced smoothing technique. Our procedure allows sparse solutions for relatively moderate- or high-dimensional covariates. We further establish the asymptotic properties of our proposed estimators under appropriate technical conditions. We evaluate the performance of the proposed methods by simulation studies and provide illustrations using two medical data examples. Our proposal for subgroup identification may lead to an immediate application in personalized medicine.

SUBMITTER: Li J

PROVIDER: S-EPMC8180507 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Multithreshold change plane model: Estimation theory and applications in subgroup identification.

Li Jialiang J Li Yaguang Y Jin Baisuo B Kosorok Michael R MR

Statistics in medicine 20210411 15

We propose a multithreshold change plane regression model which naturally partitions the observed subjects into subgroups with different covariate effects. The underlying grouping variable is a linear function of observed covariates and thus multiple thresholds produce change planes in the covariate space. We contribute a novel two-stage estimation approach to determine the number of subgroups, the location of thresholds, and all other regression parameters. In the first stage we adopt a group s ...[more]

PMID: 33843100

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Project description:BackgroundA major challenges in the analysis of large and complex biomedical data is to develop an approach for 1) identifying distinct subgroups in the sampled populations, 2) characterizing their relationships among subgroups, and 3) developing a prediction model to classify subgroup memberships of new samples by finding a set of predictors. Each subgroup can represent different pathogen serotypes of microorganisms, different tumor subtypes in cancer patients, or different genetic makeups of patients related to treatment response.MethodsThis paper proposes a composite model for subgroup identification and prediction using biclusters. A biclustering technique is first used to identify a set of biclusters from the sampled data. For each bicluster, a subgroup-specific binary classifier is built to determine if a particular sample is either inside or outside the bicluster. A composite model, which consists of all binary classifiers, is constructed to classify samples into several disjoint subgroups. The proposed composite model neither depends on any specific biclustering algorithm or patterns of biclusters, nor on any classification algorithms.ResultsThe composite model was shown to have an overall accuracy of 97.4% for a synthetic dataset consisting of four subgroups. The model was applied to two datasets where the sample's subgroup memberships were known. The procedure showed 83.7% accuracy in discriminating lung cancer adenocarcinoma and squamous carcinoma subtypes, and was able to identify 5 serotypes and several subtypes with about 94% accuracy in a pathogen dataset.ConclusionThe composite model presents a novel approach to developing a biclustering-based classification model from unlabeled sampled data. The proposed approach combines unsupervised biclustering and supervised classification techniques to classify samples into disjoint subgroups based on their associated attributes, such as genotypic factors, phenotypic outcomes, efficacy/safety measures, or responses to treatments. The procedure is useful for identification of unknown species or new biomarkers for targeted therapy.

Dataset Information

Multithreshold change plane model: Estimation theory and applications in subgroup identification.

Publications

Multithreshold change plane model: Estimation theory and applications in subgroup identification.

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