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Characterizing efficient feature selection for single-cell expression analysis.

ABSTRACT: 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.

SUBMITTER: Cho J

PROVIDER: S-EPMC11229035 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature

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Characterizing efficient feature selection for single-cell expression analysis.

Cho Juok J Baik Bukyung B Nguyen Hai C T HCT Park Daeui D Nam Dougu D

Briefings in bioinformatics 20240501 4

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 cri ...[more]

PMID: 38975891

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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.

Dataset Information

Characterizing efficient feature selection for single-cell expression analysis.

Publications

Characterizing efficient feature selection for single-cell expression analysis.

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