Dataset Information

Identification of Subtype-Specific Prognostic Genes for Early-Stage Lung Adenocarcinoma and Squamous Cell Carcinoma Patients Using an Embedded Feature Selection Algorithm.

ABSTRACT: The existence of fundamental differences between lung adenocarcinoma (AC) and squamous cell carcinoma (SCC) in their underlying mechanisms motivated us to postulate that specific genes might exist relevant to prognosis of each histology subtype. To test on this research hypothesis, we previously proposed a simple Cox-regression model based feature selection algorithm and identified successfully some subtype-specific prognostic genes when applying this method to real-world data. In this article, we continue our effort on identification of subtype-specific prognostic genes for AC and SCC, and propose a novel embedded feature selection method by extending Threshold Gradient Descent Regularization (TGDR) algorithm and minimizing on a corresponding negative partial likelihood function. Using real-world datasets and simulated ones, we show these two proposed methods have comparable performance whereas the new proposal is superior in terms of model parsimony. Our analysis provides some evidence on the existence of such subtype-specific prognostic genes, more investigation is warranted.

SUBMITTER: Tian S

PROVIDER: S-EPMC4520527 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

Identification of Subtype-Specific Prognostic Genes for Early-Stage Lung Adenocarcinoma and Squamous Cell Carcinoma Patients Using an Embedded Feature Selection Algorithm.

Tian Suyan S

PloS one 20150730 7

The existence of fundamental differences between lung adenocarcinoma (AC) and squamous cell carcinoma (SCC) in their underlying mechanisms motivated us to postulate that specific genes might exist relevant to prognosis of each histology subtype. To test on this research hypothesis, we previously proposed a simple Cox-regression model based feature selection algorithm and identified successfully some subtype-specific prognostic genes when applying this method to real-world data. In this article, ...[more]

PMID: 26226392

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Project description:The discovery of subtypes is pivotal for disease diagnosis and targeted therapy, considering the diverse responses of different cells or patients to specific treatments. Exploring the heterogeneity within disease or cell states provides insights into disease progression mechanisms and cell differentiation. The advent of high-throughput technologies has enabled the generation and analysis of various molecular data types, such as single-cell RNA-seq, proteomic, and imaging datasets, at large scales. While presenting opportunities for subtype discovery, these datasets pose challenges in finding relevant signatures due to their high dimensionality. Feature selection, a crucial step in the analysis pipeline, involves choosing signatures that reduce the feature size for more efficient downstream computational analysis. Numerous existing methods focus on selecting signatures that differentiate known diseases or cell states, yet they often fall short in identifying features that preserve heterogeneity and reveal subtypes. To identify features that can capture the diversity within each class while also maintaining the discrimination of known disease states, we employed deep metric learning-based feature embedding to conduct a detailed exploration of the statistical properties of features essential in preserving heterogeneity. Our analysis revealed that features with a significant difference in interquartile range (IQR) between classes possess crucial subtype information. Guided by this insight, we developed a robust statistical method, termed PHet (Preserving Heterogeneity) that performs iterative subsampling differential analysis of IQR and Fisher's method between classes, identifying a minimal set of heterogeneity-preserving discriminative features to optimize subtype clustering quality. Validation using public single-cell RNA-seq and microarray datasets showcased PHet's effectiveness in preserving sample heterogeneity while maintaining discrimination of known disease/cell states, surpassing the performance of previous outlier-based methods. Furthermore, analysis of a single-cell RNA-seq dataset from mouse tracheal epithelial cells revealed, through PHet-based features, the presence of two distinct basal cell subtypes undergoing differentiation toward a luminal secretory phenotype. Notably, one of these subtypes exhibited high expression of BPIFA1. Interestingly, previous studies have linked BPIFA1 secretion to the emergence of secretory cells during mucociliary differentiation of airway epithelial cells. PHet successfully pinpointed the basal cell subtype associated with this phenomenon, a distinction that pre-annotated markers and dispersion-based features failed to make due to their admixed feature expression profiles. These findings underscore the potential of our method to deepen our understanding of the mechanisms underlying diseases and cell differentiation and contribute significantly to personalized medicine.

Project description:Feature selection plays a crucial role in classification tasks as part of the data preprocessing process. Effective feature selection can improve the robustness and interpretability of learning algorithms, and accelerate model learning. However, traditional statistical methods for feature selection are no longer practical in the context of high-dimensional data due to the computationally complex. Ensemble learning, a prominent learning method in machine learning, has demonstrated exceptional performance, particularly in classification problems. To address the issue, we propose a three-stage feature selection algorithm framework for high-dimensional data based on ensemble learning (EFS-GINI). Firstly, highly linearly correlated features are eliminated using the Spearman coefficient. Then, a feature selector based on the F-test is employed for the first stage selection. For the second stage, four feature subsets are formed using mutual information (MI), ReliefF, SURF, and SURF* filters in parallel. The third stage involves feature selection using a combinator based on GINI coefficient. Finally, a soft voting approach is proposed to employ for classification, including decision tree, naive Bayes, support vector machine (SVM), k-nearest neighbors (KNN) and random forest classifiers. To demonstrate the effectiveness and efficiency of the proposed algorithm, eight high-dimensional datasets are used and five feature selection methods are employed to compare with our proposed algorithm. Experimental results show that our method effectively enhances the accuracy and speed of feature selection. Moreover, to explore the biological significance of the proposed algorithm, we apply it on the renal cell carcinoma dataset GSE40435 from the Gene Expression Omnibus database. Two feature genes, NOP2 and NSUN5, are selected by our proposed algorithm. They are directly involved in regulating m5c RNA modification, which reveals the biological importance of EFS-GINI. Through bioinformatics analysis, we shows that m5C-related genes play an important role in the occurrence and progression of renal cell carcinoma, and are expected to become an important marker to predict the prognosis of patients.

Dataset Information

Identification of Subtype-Specific Prognostic Genes for Early-Stage Lung Adenocarcinoma and Squamous Cell Carcinoma Patients Using an Embedded Feature Selection Algorithm.

Publications

Identification of Subtype-Specific Prognostic Genes for Early-Stage Lung Adenocarcinoma and Squamous Cell Carcinoma Patients Using an Embedded Feature Selection Algorithm.

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