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A Quantitative Framework for Evaluating Single-Cell Data Structure Preservation by Dimensionality Reduction Techniques.

ABSTRACT: High-dimensional data, such as those generated by single-cell RNA sequencing (scRNA-seq), present challenges in interpretation and visualization. Numerical and computational methods for dimensionality reduction allow for low-dimensional representation of genome-scale expression data for downstream clustering, trajectory reconstruction, and biological interpretation. However, a comprehensive and quantitative evaluation of the performance of these techniques has not been established. We present an unbiased framework that defines metrics of global and local structure preservation in dimensionality reduction transformations. Using discrete and continuous real-world and synthetic scRNA-seq datasets, we show how input cell distribution and method parameters are largely determinant of global, local, and organizational data structure preservation by 11 common dimensionality reduction methods.

SUBMITTER: Heiser CN

PROVIDER: S-EPMC7305633 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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A Quantitative Framework for Evaluating Single-Cell Data Structure Preservation by Dimensionality Reduction Techniques.

Heiser Cody N CN Lau Ken S KS

Cell reports 20200501 5

High-dimensional data, such as those generated by single-cell RNA sequencing (scRNA-seq), present challenges in interpretation and visualization. Numerical and computational methods for dimensionality reduction allow for low-dimensional representation of genome-scale expression data for downstream clustering, trajectory reconstruction, and biological interpretation. However, a comprehensive and quantitative evaluation of the performance of these techniques has not been established. We present an ...[more]

PMID: 32375029

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Project description:BackgroundIt is hypothesized that common, complex diseases may be due to complex interactions between genetic and environmental factors, which are difficult to detect in high-dimensional data using traditional statistical approaches. Multifactor Dimensionality Reduction (MDR) is the most commonly used data-mining method to detect epistatic interactions. In all data-mining methods, it is important to consider internal validation procedures to obtain prediction estimates to prevent model over-fitting and reduce potential false positive findings. Currently, MDR utilizes cross-validation for internal validation. In this study, we incorporate the use of a three-way split (3WS) of the data in combination with a post-hoc pruning procedure as an alternative to cross-validation for internal model validation to reduce computation time without impairing performance. We compare the power to detect true disease causing loci using MDR with both 5- and 10-fold cross-validation to MDR with 3WS for a range of single-locus and epistatic disease models. Additionally, we analyze a dataset in HIV immunogenetics to demonstrate the results of the two strategies on real data.ResultsMDR with 3WS is computationally approximately five times faster than 5-fold cross-validation. The power to find the exact true disease loci without detecting false positive loci is higher with 5-fold cross-validation than with 3WS before pruning. However, the power to find the true disease causing loci in addition to false positive loci is equivalent to the 3WS. With the incorporation of a pruning procedure after the 3WS, the power of the 3WS approach to detect only the exact disease loci is equivalent to that of MDR with cross-validation. In the real data application, the cross-validation and 3WS analyses indicate the same two-locus model.ConclusionsOur results reveal that the performance of the two internal validation methods is equivalent with the use of pruning procedures. The specific pruning procedure should be chosen understanding the trade-off between identifying all relevant genetic effects but including false positives and missing important genetic factors. This implies 3WS may be a powerful and computationally efficient approach to screen for epistatic effects, and could be used to identify candidate interactions in large-scale genetic studies.

Dataset Information

A Quantitative Framework for Evaluating Single-Cell Data Structure Preservation by Dimensionality Reduction Techniques.

Publications

A Quantitative Framework for Evaluating Single-Cell Data Structure Preservation by Dimensionality Reduction Techniques.

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