Dataset Information

Prestige centrality-based functional outlier detection in gene expression analysis.

ABSTRACT:

Motivation

Traditional gene expression analysis techniques capture an average gene expression state across sample replicates. However, the average signal across replicates will not capture activated gene networks in different states across replicates. For example, if a particular gene expression network is activated within a subset or all sample replicates, yet the activation state across the sample replicates differs by the specific genes activated in each replicate, the activation of this network will be washed out by averaging across replicates. This situation is likely to occur in single cell gene expression experiments or in noisy experimental settings where a small sub-population of cells contributes to the gene expression signature of interest.

Results and implementation

In this light, we developed a novel network-based approach which considers gene expression within each replicate across its entire gene expression profile, and identifies outliers across replicates. The power of this method is demonstrated by its ability to enrich for distant metastasis related genes derived from noisy expression data of CD44+CD24-/low tumor initiating cells.

SUBMITTER: Torkamani A

PROVIDER: S-EPMC2800353 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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Publications

Prestige centrality-based functional outlier detection in gene expression analysis.

Torkamani Ali A Schork Nicholas J NJ

Bioinformatics (Oxford, England) 20090623 17

<h4>Motivation</h4>Traditional gene expression analysis techniques capture an average gene expression state across sample replicates. However, the average signal across replicates will not capture activated gene networks in different states across replicates. For example, if a particular gene expression network is activated within a subset or all sample replicates, yet the activation state across the sample replicates differs by the specific genes activated in each replicate, the activation of t ...[more]

PMID: 19549629

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Project description:BackgroundOutliers, data points that significantly deviate from the norm, can have a substantial impact on statistical inference and provide valuable insights in data analysis. Multiple methods have been developed for outlier detection, however, almost all available approaches fail to consider the spatial dependence and heterogeneity in spatial data. Spatial data has diverse formats and semantics, requiring specialized outlier detection methodology to handle these unique properties. For now, there is limited research exists on robust spatial outlier detection methods designed specifically under the spatial error model (SEM) structure.MethodWe propose the Spatial-Θ-Iterative Procedure for Outlier Detection (Spatial-Θ-IPOD), which utilizes a mean-shift vector to identify outliers within the SEM. Our method enables an effective detection of spatial outliers while also providing robust coefficient estimates. To assess the performance of our approach, we conducted extensive simulations and applied it to a real-world empirical study using life expectancy data from multiple countries.ResultsSimulation results showed that the masking and JD (Joint Detection) indicators of our Spatial-Θ-IPOD method outperformed several commonly used methods, even in high-dimensional scenarios, demonstrating stable performance. Conversely, the Θ-IPOD method proved to be ineffective in detecting outliers when spatial correlation was present. Moreover, our model successfully provided reliable coefficient estimation alongside outlier detection. The proposed method consistently outperformed other models (both robust and non-robust) in most cases. In the empirical study, our proposed model successfully detected outliers and provided valuable insights in the modeling process.ConclusionsOur proposed Spatial-Θ-IPOD offers an effective solution for detecting spatial outliers for SEM while providing robust coefficient estimates. Notably, our approach showcases its relative superiority even in the presence of high leverage points. By successfully identifying outliers, our method enhances the overall understanding of the data and provides valuable insights for further analysis.

Project description:BACKGROUND:Learning accurate models from 'omics data is bringing many challenges due to their inherent high-dimensionality, e.g. the number of gene expression variables, and comparatively lower sample sizes, which leads to ill-posed inverse problems. Furthermore, the presence of outliers, either experimental errors or interesting abnormal clinical cases, may severely hamper a correct classification of patients and the identification of reliable biomarkers for a particular disease. We propose to address this problem through an ensemble classification setting based on distinct feature selection and modeling strategies, including logistic regression with elastic net regularization, Sparse Partial Least Squares - Discriminant Analysis (SPLS-DA) and Sparse Generalized PLS (SGPLS), coupled with an evaluation of the individuals' outlierness based on the Cook's distance. The consensus is achieved with the Rank Product statistics corrected for multiple testing, which gives a final list of sorted observations by their outlierness level. RESULTS:We applied this strategy for the classification of Triple-Negative Breast Cancer (TNBC) RNA-Seq and clinical data from the Cancer Genome Atlas (TCGA). The detected 24 outliers were identified as putative mislabeled samples, corresponding to individuals with discrepant clinical labels for the HER2 receptor, but also individuals with abnormal expression values of ER, PR and HER2, contradictory with the corresponding clinical labels, which may invalidate the initial TNBC label. Moreover, the model consensus approach leads to the selection of a set of genes that may be linked to the disease. These results are robust to a resampling approach, either by selecting a subset of patients or a subset of genes, with a significant overlap of the outlier patients identified. CONCLUSIONS:The proposed ensemble outlier detection approach constitutes a robust procedure to identify abnormal cases and consensus covariates, which may improve biomarker selection for precision medicine applications. The method can also be easily extended to other regression models and datasets.

Dataset Information

Prestige centrality-based functional outlier detection in gene expression analysis.

Motivation

Results and implementation

Publications

Prestige centrality-based functional outlier detection in gene expression analysis.

Similar Datasets

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