scholarly journals Hubness reduction improves clustering and trajectory inference in single-cell transcriptomic data

2021 ◽  
Author(s):  
Elise Claire Amblard ◽  
Jonathan Bac ◽  
Alexander Chervov ◽  
Vassili Soumelis ◽  
Andrei Zinovyev
Keyword(s):  
Dimensionality Reduction ◽  
Single Cell ◽  
High Dimension ◽  
Sequencing Data ◽  
Reduction Methods ◽  
Data Points ◽  
Cell Trajectory ◽  
Low Dimensional ◽  
Neighbourhood Graph ◽  
Intrinsic Dimensionality

Background. Single-cell RNA-seq datasets are characterized by large ambient dimensionality, and their analyses, such as clustering or cell trajectory inference, can be affected by various manifestations of the dimensionality curse. One of these manifestations is the hubness phenomenon, i.e. existence of data points with surprisingly large incoming connectivity degree in the neighbourhood graph. Conventional approach to dampen the unwanted effects of high dimension consists in applying drastic dimensionality reduction, which is critical especially in scRNA-seq. It remains unexplored if this step can be avoided thus retaining more information than contained in the low-dimensional projections, by correcting directly an effect of the high dimension. Results. We investigate the phenomenon of hubness in scRNA-seq data, and its manifestation in spaces of increasing dimensionality. We also link increasing hubness to increased levels of dropout in sequencing data. We show that hub cells do not represent any visible technical or biological bias. The effect of various hubness reduction methods is investigated with respect to the visualization, clustering and trajectory inference tasks in scRNA-seq datasets. We show that applying hubness reduction generates neighbourhood graphs with properties more suitable for applying machine learning methods; and that hubness reduction outperforms other state-of-the-art methods for improving neighbourhood graphs. As a consequence, clustering, trajectory inference and visualisation perform better, especially for datasets characterized by large intrinsic dimensionality. Conclusion. Hubness is an important phenomenon in sequencing data. Reducing hubness can be beneficial for the analysis of scRNA-seq data characterized by large intrinsic dimensionality in which case it can be used as an alternative to drastic dimensionality reduction.

scholarly journals A quantitative framework for evaluating single-cell data structure preservation by dimensionality reduction techniques

2019 ◽  
Author(s):  
Cody N. Heiser ◽  
Ken S. Lau
Keyword(s):  
Data Structure ◽  
Dimensionality Reduction ◽  
Single Cell ◽  
Structure Preservation ◽  
Reduction Techniques ◽  
Reduction Methods ◽  
Biological Interpretation ◽  
Low Dimensional ◽  
Genome Scale ◽  
Global And Local

SummaryHigh-dimensional data, such as those generated using single-cell RNA sequencing, 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 scRNA-seq datasets, we find that input cell distribution and method parameters are largely determinant of global, local, and organizational data structure preservation by eleven published dimensionality reduction methods. Code available atgithub.com/KenLauLab/DR-structure-preservationallows for rapid evaluation of further datasets and methods.

scholarly journals Interpretable dimensionality reduction of single cell transcriptome data with deep generative models

2017 ◽  
Author(s):  
Jiarui Ding ◽  
Anne Condon ◽  
Sohrab P. Shah
Keyword(s):  
Single Cell ◽  
Rna Sequencing ◽  
Spatial Organization ◽  
Mapping Function ◽  
Cell Types ◽  
Generative Models ◽  
Sequencing Data ◽  
Single Cell Rna Sequencing ◽  
Data Points ◽  
Low Dimensional

Single-cell RNA-sequencing has great potential to discover cell types, identify cell states, trace development lineages, and reconstruct the spatial organization of cells. However, dimension reduction to interpret structure in single-cell sequencing data remains a challenge. Existing algorithms are either not able to uncover the clustering structures in the data, or lose global information such as groups of clusters that are close to each other. We present a robust statistical model, scvis, to capture and visualize the low-dimensional structures in single-cell gene expression data. Simulation results demonstrate that low-dimensional representations learned by scvis preserve both the local and global neighbour structures in the data. In addition, scvis is robust to the number of data points and learns a probabilistic parametric mapping function to add new data points to an existing embedding. We then use scvis to analyze four single-cell RNA-sequencing datasets, exemplifying interpretable two-dimensional representations of the high-dimensional single-cell RNA-sequencing data.

scholarly journals Supervised dimensionality reduction for big data

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Joshua T. Vogelstein ◽  
Eric W. Bridgeford ◽  
Minh Tang ◽  
Da Zheng ◽  
Christopher Douville ◽  
...  
Keyword(s):  
Dimensionality Reduction ◽  
Data Science ◽  
Real Data ◽  
Low Rank ◽  
Conditional Moment ◽  
Desktop Computer ◽  
Reduction Techniques ◽  
Reduction Methods ◽  
The Individual ◽  
Low Dimensional

AbstractTo solve key biomedical problems, experimentalists now routinely measure millions or billions of features (dimensions) per sample, with the hope that data science techniques will be able to build accurate data-driven inferences. Because sample sizes are typically orders of magnitude smaller than the dimensionality of these data, valid inferences require finding a low-dimensional representation that preserves the discriminating information (e.g., whether the individual suffers from a particular disease). There is a lack of interpretable supervised dimensionality reduction methods that scale to millions of dimensions with strong statistical theoretical guarantees. We introduce an approach to extending principal components analysis by incorporating class-conditional moment estimates into the low-dimensional projection. The simplest version, Linear Optimal Low-rank projection, incorporates the class-conditional means. We prove, and substantiate with both synthetic and real data benchmarks, that Linear Optimal Low-Rank Projection and its generalizations lead to improved data representations for subsequent classification, while maintaining computational efficiency and scalability. Using multiple brain imaging datasets consisting of more than 150 million features, and several genomics datasets with more than 500,000 features, Linear Optimal Low-Rank Projection outperforms other scalable linear dimensionality reduction techniques in terms of accuracy, while only requiring a few minutes on a standard desktop computer.

scholarly journals Unsupervised Text Feature Learning via Deep Variational Auto-encoder

2020 ◽  
Vol 49 (3) ◽  
pp. 421-437
Author(s):  
Genggeng Liu ◽  
Lin Xie ◽  
Chi-Hua Chen
Keyword(s):  
Dimensionality Reduction ◽  
High Dimensional Data ◽  
Image Data ◽  
Original Data ◽  
Feature Representation ◽  
High Dimensional ◽  
Learning To Learn ◽  
Text Feature ◽  
Reduction Methods ◽  
Low Dimensional

Dimensionality reduction plays an important role in the data processing of machine learning and data mining, which makes the processing of high-dimensional data more efficient. Dimensionality reduction can extract the low-dimensional feature representation of high-dimensional data, and an effective dimensionality reduction method can not only extract most of the useful information of the original data, but also realize the function of removing useless noise. The dimensionality reduction methods can be applied to all types of data, especially image data. Although the supervised learning method has achieved good results in the application of dimensionality reduction, its performance depends on the number of labeled training samples. With the growing of information from internet, marking the data requires more resources and is more difficult. Therefore, using unsupervised learning to learn the feature of data has extremely important research value. In this paper, an unsupervised multilayered variational auto-encoder model is studied in the text data, so that the high-dimensional feature to the low-dimensional feature becomes efficient and the low-dimensional feature can retain mainly information as much as possible. Low-dimensional feature obtained by different dimensionality reduction methods are used to compare with the dimensionality reduction results of variational auto-encoder (VAE), and the method can be significantly improved over other comparison methods.

scholarly journals Discovering a sparse set of pairwise discriminating features in high-dimensional data

2020 ◽  
Author(s):  
Samuel Melton ◽  
Sharad Ramanathan
Keyword(s):  
Single Cell ◽  
Dimensional Space ◽  
Cell Types ◽  
Dimensional Subspace ◽  
Supplementary Information ◽  
High Dimensional ◽  
Technological Advances ◽  
Data Points ◽  
Low Dimensional ◽  
Sparse Set

Abstract Motivation Recent technological advances produce a wealth of high-dimensional descriptions of biological processes, yet extracting meaningful insight and mechanistic understanding from these data remains challenging. For example, in developmental biology, the dynamics of differentiation can now be mapped quantitatively using single-cell RNA sequencing, yet it is difficult to infer molecular regulators of developmental transitions. Here, we show that discovering informative features in the data is crucial for statistical analysis as well as making experimental predictions. Results We identify features based on their ability to discriminate between clusters of the data points. We define a class of problems in which linear separability of clusters is hidden in a low-dimensional space. We propose an unsupervised method to identify the subset of features that define a low-dimensional subspace in which clustering can be conducted. This is achieved by averaging over discriminators trained on an ensemble of proposed cluster configurations. We then apply our method to single-cell RNA-seq data from mouse gastrulation, and identify 27 key transcription factors (out of 409 total), 18 of which are known to define cell states through their expression levels. In this inferred subspace, we find clear signatures of known cell types that eluded classification prior to discovery of the correct low-dimensional subspace. Availability and implementation https://github.com/smelton/SMD. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Complex Moment-Based Supervised Eigenmap for Dimensionality Reduction

2019 ◽  
Vol 33 ◽  
pp. 3910-3918 ◽  
Author(s):  
Akira Imakura ◽  
Momo Matsuda ◽  
Xiucai Ye ◽  
Tetsuya Sakurai
Keyword(s):  
Dimensionality Reduction ◽  
Parallel Implementation ◽  
Dimensional Space ◽  
Recognition Performance ◽  
Optimization Methods ◽  
Original Data ◽  
Dimensional Subspace ◽  
Reduction Methods ◽  
Low Dimensional ◽  
Matrix Trace

Dimensionality reduction methods that project highdimensional data to a low-dimensional space by matrix trace optimization are widely used for clustering and classification. The matrix trace optimization problem leads to an eigenvalue problem for a low-dimensional subspace construction, preserving certain properties of the original data. However, most of the existing methods use only a few eigenvectors to construct the low-dimensional space, which may lead to a loss of useful information for achieving successful classification. Herein, to overcome the deficiency of the information loss, we propose a novel complex moment-based supervised eigenmap including multiple eigenvectors for dimensionality reduction. Furthermore, the proposed method provides a general formulation for matrix trace optimization methods to incorporate with ridge regression, which models the linear dependency between covariate variables and univariate labels. To reduce the computational complexity, we also propose an efficient and parallel implementation of the proposed method. Numerical experiments indicate that the proposed method is competitive compared with the existing dimensionality reduction methods for the recognition performance. Additionally, the proposed method exhibits high parallel efficiency.

scholarly journals Electromyography Classification during Reach-to-Grasp Motion using Manifold Learning

2020 ◽  
Author(s):  
Elnaz Lashgari ◽  
Uri Maoz
Keyword(s):  
Dimensionality Reduction ◽  
Cost Effective ◽  
Human Hand ◽  
Reach To Grasp ◽  
K Nearest Neighbors ◽  
Laplacian Eigenmaps ◽  
Non Invasive ◽  
Reduction Methods ◽  
Machine Interface ◽  
Low Dimensional

AbstractElectromyography (EMG) is a simple, non-invasive, and cost-effective technology for sensing muscle activity. However, EMG is also noisy, complex, and high-dimensional. It has nevertheless been widely used in a host of human-machine-interface applications (electrical wheelchairs, virtual computer mice, prosthesis, robotic fingers, etc.) and in particular to measure reaching and grasping motions of the human hand. Here, we developd a more automated pipeline to predict object weight in a reach-and-grasp task from an open dataset relying only on EMG data. In that we shifted the focus from manual feature-engineering to automated feature-extraction by using raw (filtered) EMG signals and thus letting the algorithms select the features. We further compared intrinsic EMG features, derived from several dimensionality-reduction methods, and then ran some classification algorithms on these low-dimensional representations. We found that the Laplacian Eigenmap algorithm generally outperformed other dimensionality-reduction methods. What is more, optimal classification accuracy was achieved using a combination of Laplacian Eigenmaps (simple-minded) and k-Nearest Neighbors (88% for 3-way classification). Our results, using EMG alone, are comparable to others in the literature that used EMG and EEG together. They also demonstrate the usefulness of dimensionality reduction when classifying movement based on EMG signals and more generally the usefulness of EMG for movement classification.

scholarly journals Accuracy, Robustness and Scalability of Dimensionality Reduction Methods for Single Cell RNAseq Analysis

2019 ◽  
Author(s):  
Shiquan Sun ◽  
Jiaqiang Zhu ◽  
Ying Ma ◽  
Xiang Zhou
Keyword(s):  
Data Analysis ◽  
Dimensionality Reduction ◽  
Single Cell ◽  
Comprehensive Evaluation ◽  
Computational Cost ◽  
Noise Removal ◽  
Data Sets ◽  
Vast Number ◽  
Cell Clustering ◽  
Reduction Methods

ABSTRACTBackgroundDimensionality reduction (DR) is an indispensable analytic component for many areas of single cell RNA sequencing (scRNAseq) data analysis. Proper DR can allow for effective noise removal and facilitate many downstream analyses that include cell clustering and lineage reconstruction. Unfortunately, despite the critical importance of DR in scRNAseq analysis and the vast number of DR methods developed for scRNAseq studies, however, few comprehensive comparison studies have been performed to evaluate the effectiveness of different DR methods in scRNAseq.ResultsHere, we aim to fill this critical knowledge gap by providing a comparative evaluation of a variety of commonly used DR methods for scRNAseq studies. Specifically, we compared 18 different DR methods on 30 publicly available scRNAseq data sets that cover a range of sequencing techniques and sample sizes. We evaluated the performance of different DR methods for neighborhood preserving in terms of their ability to recover features of the original expression matrix, and for cell clustering and lineage reconstruction in terms of their accuracy and robustness. We also evaluated the computational scalability of different DR methods by recording their computational cost.ConclusionsBased on the comprehensive evaluation results, we provide important guidelines for choosing DR methods for scRNAseq data analysis. We also provide all analysis scripts used in the present study atwww.xzlab.org/reproduce.html. Together, we hope that our results will serve as an important practical reference for practitioners to choose DR methods in the field of scRNAseq analysis.

scholarly journals An Evaluation of Supervised Dimensionality Reduction For Large Scale Data

2022 ◽  
pp. 17-25
Author(s):  
Nancy Jan Sliper
Keyword(s):  
Dimensionality Reduction ◽  
Large Scale ◽  
Simulated Data ◽  
Principal Component ◽  
Low Rank ◽  
Learning Tools ◽  
Large Scale Data ◽  
Reduction Methods ◽  
Low Dimensional ◽  
Scale Data

Experimenters today frequently quantify millions or even billions of characteristics (measurements) each sample to address critical biological issues, in the hopes that machine learning tools would be able to make correct data-driven judgments. An efficient analysis requires a low-dimensional representation that preserves the differentiating features in data whose size and complexity are orders of magnitude apart (e.g., if a certain ailment is present in the person's body). While there are several systems that can handle millions of variables and yet have strong empirical and conceptual guarantees, there are few that can be clearly understood. This research presents an evaluation of supervised dimensionality reduction for large scale data. We provide a methodology for expanding Principal Component Analysis (PCA) by including category moment estimations in low-dimensional projections. Linear Optimum Low-Rank (LOLR) projection, the cheapest variant, includes the class-conditional means. We show that LOLR projections and its extensions enhance representations of data for future classifications while retaining computing flexibility and reliability using both experimental and simulated data benchmark. When it comes to accuracy, LOLR prediction outperforms other modular linear dimension reduction methods that require much longer computation times on conventional computers. LOLR uses more than 150 million attributes in brain image processing datasets, and many genome sequencing datasets have more than half a million attributes.

scholarly journals Unsupervised cell functional annotation for single-cell RNA-Seq

2021 ◽  
Author(s):  
Dongshunyi Li ◽  
Jun Ding ◽  
Ziv Bar-Joseph
Keyword(s):  
Single Cell ◽  
Dimensional Space ◽  
Cell Types ◽  
Specific Gene ◽  
Rna Seq ◽  
Cell Type ◽  
Sequencing Data ◽  
Gene Sets ◽  
Supervised Methods ◽  
Low Dimensional

One of the first steps in the analysis of single cell RNA-Sequencing data (scRNA-Seq) is the assignment of cell types. While a number of supervised methods have been developed for this, in most cases such assignment is performed by first clustering cells in low-dimensional space and then assigning cell types to different clusters. To overcome noise and to improve cell type assignments we developed UNIFAN, a neural network method that simultaneously clusters and annotates cells using known gene sets. UNIFAN combines both, low dimension representation for all genes and cell specific gene set activity scores to determine the clustering. We applied UNIFAN to human and mouse scRNA-Seq datasets from several different organs. As we show, by using knowledge on gene sets, UNIFAN greatly outperforms prior methods developed for clustering scRNA-Seq data. The gene sets assigned by UNIFAN to different clusters provide strong evidence for the cell type that is represented by this cluster making annotations easier.

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