Dataset Information

RNA profiling 2.0: Enhanced cluster analysis of structural ensembles.

ABSTRACT: Understanding the base pairing of an RNA sequence provides insight into its molecular structure. By mining suboptimal sampling data, RNAprofiling 1.0 identifies the dominant helices in low-energy secondary structures as features, organizes them into profiles which partition the Boltzmann sample, and highlights key similarities/differences among the most informative, i.e. selected, profiles in a graphical format. Version 2.0 enhances every step of this approach. First, the featured substructures are expanded from helices to stems. Second, profile selection includes low-frequency pairings similar to featured ones. In conjunction, these updates extend the utility of the method to sequences up to length 600, as evaluated over a sizable dataset. Third, relationships are visualized in a decision tree which highlights the most important structural differences. Finally, this cluster analysis is made accessible to experimental researchers in a portable format as an interactive webpage, permitting a much greater understanding of trade-offs among different possible base pairing combinations.

SUBMITTER: Hurley F

PROVIDER: S-EPMC10081340 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Publications

RNA profiling 2.0: Enhanced cluster analysis of structural ensembles.

Hurley Forrest F Heitsch Christine C

ArXiv 20230327

Understanding the base pairing of an RNA sequence provides insight into its molecular structure. By mining suboptimal sampling data, RNAprofiling 1.0 identifies the dominant helices in low-energy secondary structures as features, organizes them into profiles which partition the Boltzmann sample, and highlights key similarities/differences among the most informative, i.e. selected, profiles in a graphical format. Version 2.0 enhances every step of this approach. First, the featured substructures ...[more]

PMID: 37033453

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Project description:BACKGROUND:Single-cell RNA-sequencing (scRNA-seq) is a transformative technology, allowing global transcriptomes of individual cells to be profiled with high accuracy. An essential task in scRNA-seq data analysis is the identification of cell types from complex samples or tissues profiled in an experiment. To this end, clustering has become a key computational technique for grouping cells based on their transcriptome profiles, enabling subsequent cell type identification from each cluster of cells. Due to the high feature-dimensionality of the transcriptome (i.e. the large number of measured genes in each cell) and because only a small fraction of genes are cell type-specific and therefore informative for generating cell type-specific clusters, clustering directly on the original feature/gene dimension may lead to uninformative clusters and hinder correct cell type identification. RESULTS:Here, we propose an autoencoder-based cluster ensemble framework in which we first take random subspace projections from the data, then compress each random projection to a low-dimensional space using an autoencoder artificial neural network, and finally apply ensemble clustering across all encoded datasets to generate clusters of cells. We employ four evaluation metrics to benchmark clustering performance and our experiments demonstrate that the proposed autoencoder-based cluster ensemble can lead to substantially improved cell type-specific clusters when applied with both the standard k-means clustering algorithm and a state-of-the-art kernel-based clustering algorithm (SIMLR) designed specifically for scRNA-seq data. Compared to directly using these clustering algorithms on the original datasets, the performance improvement in some cases is up to 100%, depending on the evaluation metric used. CONCLUSIONS:Our results suggest that the proposed framework can facilitate more accurate cell type identification as well as other downstream analyses. The code for creating the proposed autoencoder-based cluster ensemble framework is freely available from https://github.com/gedcom/scCCESS.

Dataset Information

RNA profiling 2.0: Enhanced cluster analysis of structural ensembles.

Publications

RNA profiling 2.0: Enhanced cluster analysis of structural ensembles.

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