Feature selection revisited in the single-cell era.
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ABSTRACT:
SUBMITTER: Yang P
PROVIDER: S-EPMC8638336 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Cell clustering is one of the most important and commonly performed tasks in single-cell RNA sequencing (scRNA-seq) data analysis. An important step in cell clustering is to select a subset of genes (referred to as 'features'), whose expression patterns will then be used for downstream clustering. A good set of features should include the ones that distinguish different cell types, and the quality of such set could have a significant impact on the clustering accuracy. All existing scRNA-seq clustering tools include a feature selection step relying on some simple unsupervised feature selection methods, mostly based on the statistical moments of gene-wise expression distributions. In this work, we carefully evaluate the impact of feature selection on cell clustering accuracy. In addition, we develop a feature selection algorithm named FEAture SelecTion (FEAST), which provides more representative features. We apply the method on 12 public scRNA-seq datasets and demonstrate that using features selected by FEAST with existing clustering tools significantly improve the clustering accuracy.
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Project description:Unsupervised feature selection is a critical step for efficient and accurate analysis of single-cell RNA-seq data. Previous benchmarks used two different criteria to compare feature selection methods: (i) proportion of ground-truth marker genes included in the selected features and (ii) accuracy of cell clustering using ground-truth cell types. Here, we systematically compare the performance of 11 feature selection methods for both criteria. We first demonstrate the discordance between these criteria and suggest using the latter. We then compare the distribution of selected genes in their means between feature selection methods. We show that lowly expressed genes exhibit seriously high coefficients of variation and are mostly excluded by high-performance methods. In particular, high-deviation- and high-expression-based methods outperform the widely used in Seurat package in clustering cells and data visualization. We further show they also enable a clear separation of the same cell type from different tissues as well as accurate estimation of cell trajectories.
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Project description:A key challenge in studying organisms and diseases is to detect rare molecular programs and rare cell populations (RCPs) that drive development, differentiation, and transformation. Molecular features such as genes and proteins defining RCPs are often unknown and difficult to detect from unenriched single-cell data, using conventional dimensionality reduction and clustering-based approaches. Here, we propose an unsupervised approach, SCMER (Single-Cell Manifold presERving feature selection), which selects a compact set of molecular features with definitive meanings that preserve the manifold of the data. We applied SCMER in the context of hematopoiesis, lymphogenesis, tumorigenesis, and drug resistance and response. We found that SCMER can identify non-redundant features that sensitively delineate both common cell lineages and rare cellular states. SCMER can be used for discovering molecular features in a high dimensional dataset, designing targeted, cost-effective assays for clinical applications, and facilitating multi-modality integration.
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Project description:Single-cell technologies can readily measure the expression of thousands of molecular features from individual cells undergoing dynamic biological processes, such as cellular differentiation, immune response, and disease progression. While examining cells along a computationally ordered pseudotime offers the potential to study how subtle changes in gene or protein expression impact cell fate decision-making, identifying characteristic features that drive continuous biological processes remains difficult to detect from unenriched and noisy single-cell data. Given that all profiled sources of feature variation contribute to the cell-to-cell distances that define an inferred cellular trajectory, including confounding sources of biological variation (e.g. cell cycle or metabolic state) or noisy and irrelevant features (e.g. measurements with low signal-to-noise ratio) can mask the underlying trajectory of study and hinder inference. Here, we present DELVE (dynamic selection of locally covarying features), an unsupervised feature selection method for identifying a representative subset of dynamically-expressed molecular features that recapitulates cellular trajectories. In contrast to previous work, DELVE uses a bottom-up approach to mitigate the effect of unwanted sources of variation confounding inference, and instead models cell states from dynamic feature modules that constitute core regulatory complexes. Using simulations, single-cell RNA sequencing data, and iterative immunofluorescence imaging data in the context of the cell cycle and cellular differentiation, we demonstrate that DELVE selects features that more accurately characterize cell populations and improve the recovery of cell type transitions. This feature selection framework provides an alternative approach for improving trajectory inference and uncovering co-variation amongst features along a biological trajectory. DELVE is implemented as an open-source python package and is publicly available at: https://github.com/jranek/delve.
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Project description:Single-cell technologies can measure the expression of thousands of molecular features in individual cells undergoing dynamic biological processes. While examining cells along a computationally-ordered pseudotime trajectory can reveal how changes in gene or protein expression impact cell fate, identifying such dynamic features is challenging due to the inherent noise in single-cell data. Here, we present DELVE, an unsupervised feature selection method for identifying a representative subset of molecular features which robustly recapitulate cellular trajectories. In contrast to previous work, DELVE uses a bottom-up approach to mitigate the effects of confounding sources of variation, and instead models cell states from dynamic gene or protein modules based on core regulatory complexes. Using simulations, single-cell RNA sequencing, and iterative immunofluorescence imaging data in the context of cell cycle and cellular differentiation, we demonstrate how DELVE selects features that better define cell-types and cell-type transitions. DELVE is available as an open-source python package: https://github.com/jranek/delve .
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Project description:Single-cell chromatin accessibility sequencing (scCAS) technologies have enabled characterizing the epigenomic heterogeneity of individual cells. However, the identification of features of scCAS data that are relevant to underlying biological processes remains a significant gap. Here, we introduce a novel method Cofea, to fill this gap. Through comprehensive experiments on 5 simulated and 54 real datasets, Cofea demonstrates its superiority in capturing cellular heterogeneity and facilitating downstream analysis. Applying this method to identification of cell type-specific peaks and candidate enhancers, as well as pathway enrichment analysis and partitioned heritability analysis, we illustrate the potential of Cofea to uncover functional biological process.
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Project description:Single-cell RNA sequencing (scRNA-seq) enables researchers to reveal previously unknown cell heterogeneity and functional diversity, which is impossible with bulk RNA sequencing. Clustering approaches are widely used for analyzing scRNA-seq data and identifying cell types and states. In the past few years, various advanced computational strategies emerged. However, the low generalization and high computational cost are the main bottlenecks of existing methods. In this study, we established a novel computational framework, scFseCluster, for scRNA-seq clustering analysis. scFseCluster incorporates a metaheuristic algorithm (Feature Selection based on Quantum Squirrel Search Algorithm) to extract the optimal gene set, which largely guarantees the performance of cell clustering. We conducted simulation experiments in several aspects to verify the performance of the proposed approach. scFseCluster performed very well on eight benchmark scRNA-seq datasets because of the optimal gene sets obtained using the Feature Selection based on Quantum Squirrel Search Algorithm. The comparative study demonstrated the significant advantages of scFseCluster over seven State-of-the-Art algorithms. In addition, our analysis shows that feature selection on high-variable genes can significantly improve clustering performance. In conclusion, our study demonstrates that scFseCluster is a highly versatile tool for enhancing scRNA-seq data clustering analysis.
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Project description:With the advances in high-throughput sequencing technology, an increasing amount of research in revealing heterogeneity among cells has been widely performed. Differences between individual cells' functionality are determined based on the differences in the gene expression profiles. Although the observations indicate a great performance of clustering methods, manual annotation of the clusters of cells is a challenge yet to be addressed more scalable and faster. On the other hand, due to the lack of enough labelled datasets, just a few supervised techniques have been used in cell type identification, and they obtained more robust results compared to clustering methods. A recent study showed that a complementary step of feature selection helped support vector machine (SVM) to outperform other classifiers in different scenarios. In this article, we compare and evaluate the performance of two state-of-the-art supervised methods, XGBoost and SVM, with information gain as a feature selection method. The results of the experiments on three standard scRNA-seq datasets indicate that XGBoost automatically annotates cell types in a simpler and more scalable framework. Additionally, it sheds light on the potential use of boosting tree approaches combined with deep neural networks to capture underlying information of single-cell RNA-Seq data more effectively. It can be used to identify marker genes and other applications in biological studies.
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Project description:Feature selection is a relevant step in the analysis of single-cell RNA sequencing datasets. Most of the current feature selection methods are based on general univariate descriptors of the data such as the dispersion or the percentage of zeros. Despite the use of correction methods, the generality of these feature selection methods biases the genes selected towards highly expressed genes, instead of the genes defining the cell populations of the dataset. Triku is a feature selection method that favors genes defining the main cell populations. It does so by selecting genes expressed by groups of cells that are close in the k-nearest neighbor graph. The expression of these genes is higher than the expected expression if the k-cells were chosen at random. Triku efficiently recovers cell populations present in artificial and biological benchmarking datasets, based on adjusted Rand index, normalized mutual information, supervised classification, and silhouette coefficient measurements. Additionally, gene sets selected by triku are more likely to be related to relevant Gene Ontology terms and contain fewer ribosomal and mitochondrial genes. Triku is developed in Python 3 and is available at https://github.com/alexmascension/triku.
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Project description:MotivationSingle-cell RNA sequencing (scRNA-seq) offers a powerful tool to dissect the complexity of biological tissues through cell sub-population identification in combination with clustering approaches. Feature selection is a critical step for improving the accuracy and interpretability of single-cell clustering. Existing feature selection methods underutilize the discriminatory potential of genes across distinct cell types. We hypothesize that incorporating such information could further boost the performance of single cell clustering.ResultsWe develop CellBRF, a feature selection method that considers genes' relevance to cell types for single-cell clustering. The key idea is to identify genes that are most important for discriminating cell types through random forests guided by predicted cell labels. Moreover, it proposes a class balancing strategy to mitigate the impact of unbalanced cell type distributions on feature importance evaluation. We benchmark CellBRF on 33 scRNA-seq datasets representing diverse biological scenarios and demonstrate that it substantially outperforms state-of-the-art feature selection methods in terms of clustering accuracy and cell neighborhood consistency. Furthermore, we demonstrate the outstanding performance of our selected features through three case studies on cell differentiation stage identification, non-malignant cell subtype identification, and rare cell identification. CellBRF provides a new and effective tool to boost single-cell clustering accuracy.Availability and implementationAll source codes of CellBRF are freely available at https://github.com/xuyp-csu/CellBRF.
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