GeneBasis: an iterative approach for unsupervised selection of targeted gene panels from scRNA-seq.
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ABSTRACT:
SUBMITTER: Missarova A
PROVIDER: S-EPMC8650258 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Several studies profile similar single cell RNA-Seq (scRNA-Seq) data using different technologies and platforms. A number of alignment methods have been developed to enable the integration and comparison of scRNA-Seq data from such studies. While each performs well on some of the datasets, to date no method was able to both perform the alignment using the original expression space and generalize to new data. To enable such analysis we developed Single Cell Iterative Point set Registration (SCIPR) which extends methods that were successfully applied to align image data to scRNA-Seq. We discuss the required changes needed, the resulting optimization function, and algorithms for learning a transformation function for aligning data. We tested SCIPR on several scRNA-Seq datasets. As we show it successfully aligns data from several different cell types, improving upon prior methods proposed for this task. In addition, we show the parameters learned by SCIPR can be used to align data not used in the training and to identify key cell type-specific genes.
| S-EPMC7647120 | biostudies-literature
Project description:Single-cell RNA sequencing allows high-resolution views of individual cells for libraries of up to millions of samples, thus motivating the use of deep learning for analysis. In this study, we introduce the use of graph neural networks for the unsupervised exploration of scRNA-seq data by developing a variational graph autoencoder architecture with graph attention layers that operates directly on the connectivity between cells, focusing on dimensionality reduction and clustering. With the help of several case studies, we show that our model, named CellVGAE, can be effectively used for exploratory analysis even on challenging datasets, by extracting meaningful features from the data and providing the means to visualise and interpret different aspects of the model. We show that CellVGAE is more interpretable than existing scRNA-seq variational architectures by analysing the graph attention coefficients. By drawing parallels with other scRNA-seq studies on interpretability, we assess the validity of the relationships modelled by attention, and furthermore, we show that CellVGAE can intrinsically capture information such as pseudotime and NF-ĸB activation dynamics, the latter being a property that is not generally shared by existing neural alternatives. We then evaluate the dimensionality reduction and clustering performance on 9 difficult and well-annotated datasets by comparing with three leading neural and non-neural techniques, concluding that CellVGAE outperforms competing methods. Finally, we report a decrease in training times of up to × 20 on a dataset of 1.3 million cells compared to existing deep learning architectures. The CellVGAE code is available at https://github.com/davidbuterez/CellVGAE. Supplementary data are available at Bioinformatics online.
| S-EPMC8825872 | biostudies-literature
Project description:Recent advances of single-cell RNA sequencing (scRNA-seq) technologies have led to extensive study of cellular heterogeneity and cell-to-cell variation. However, the high frequency of dropout events and noise in scRNA-seq data confounds the accuracy of the downstream analysis, i.e. clustering analysis, whose accuracy depends heavily on the selected feature genes. Here, by deriving an entropy decomposition formula, we propose a feature selection method, i.e. an intrinsic entropy (IE) model, to identify the informative genes for accurately clustering analysis. Specifically, by eliminating the 'noisy' fluctuation or extrinsic entropy (EE), we extract the IE of each gene from the total entropy (TE), i.e. TE = IE + EE. We show that the IE of each gene actually reflects the regulatory fluctuation of this gene in a cellular process, and thus high-IE genes provide rich information on cell type or state analysis. To validate the performance of the high-IE genes, we conduct computational analysis on both simulated datasets and real single-cell datasets by comparing with other representative methods. The results show that our IE model is not only broadly applicable and robust for different clustering and classification methods, but also sensitive for novel cell types. Our results also demonstrate that the intrinsic entropy/fluctuation of a gene serves as information rather than noise in contrast to its total entropy/fluctuation.
| S-EPMC9175189 | biostudies-literature
Project description:BackgroundRecently, pioneering expression quantitative trait loci (eQTL) studies on single cell RNA sequencing (scRNA-seq) data have revealed new and cell-specific regulatory single nucleotide variants (SNVs). Here, we present an alternative QTL-related approach applicable to transcribed SNV loci from scRNA-seq data: scReQTL. ScReQTL uses Variant Allele Fraction (VAFRNA) at expressed biallelic loci, and corelates it to gene expression from the corresponding cell.ResultsOur approach employs the advantage that, when estimated from multiple cells, VAFRNA can be used to assess effects of SNVs in a single sample or individual. In this setting scReQTL operates in the context of identical genotypes, where it is likely to capture RNA-mediated genetic interactions with cell-specific and transient effects. Applying scReQTL on scRNA-seq data generated on the 10 × Genomics Chromium platform using 26,640 mesenchymal cells derived from adipose tissue obtained from three healthy female donors, we identified 1272 unique scReQTLs. ScReQTLs common between individuals or cell types were consistent in terms of the directionality of the relationship and the effect size. Comparative assessment with eQTLs from bulk sequencing data showed that scReQTL analysis identifies a distinct set of SNV-gene correlations, that are substantially enriched in known gene-gene interactions and significant genome-wide association studies (GWAS) loci.ConclusionScReQTL is relevant to the rapidly growing source of scRNA-seq data and can be applied to outline SNVs potentially contributing to cell type-specific and/or dynamic genetic interactions from an individual scRNA-seq dataset.Availabilityhttps://github.com/HorvathLab/NGS/tree/master/scReQTL.
| S-EPMC7791999 | biostudies-literature
Project description:Single-cell technologies are emerging fast due to their ability to unravel the heterogeneity of biological systems. While scRNA-seq is a powerful tool that measures whole-transcriptome expression of single cells, it lacks their spatial localization. Novel spatial transcriptomics methods do retain cells spatial information but some methods can only measure tens to hundreds of transcripts. To resolve this discrepancy, we developed SpaGE, a method that integrates spatial and scRNA-seq datasets to predict whole-transcriptome expressions in their spatial configuration. Using five dataset-pairs, SpaGE outperformed previously published methods and showed scalability to large datasets. Moreover, SpaGE predicted new spatial gene patterns that are confirmed independently using in situ hybridization data from the Allen Mouse Brain Atlas.
| S-EPMC7544237 | biostudies-literature
Project description: Not available
| S-BSST858 | biostudies-other
Project description:BackgroundHigh throughput microfluidic protocols in single cell RNA sequencing (scRNA-seq) collect mRNA counts from up to one million individual cells in a single experiment; this enables high resolution studies of rare cell types and cell development pathways. Determining small sets of genetic markers that can identify specific cell populations is thus one of the major objectives of computational analysis of mRNA counts data. Many tools have been developed for marker selection on single cell data; most of them, however, are based on complex statistical models and handle the multi-class case in an ad-hoc manner.ResultsWe introduce RANKCORR, a fast method with strong mathematical underpinnings that performs multi-class marker selection in an informed manner. RANKCORR proceeds by ranking the mRNA counts data before linearly separating the ranked data using a small number of genes. The step of ranking is intuitively natural for scRNA-seq data and provides a non-parametric method for analyzing count data. In addition, we present several performance measures for evaluating the quality of a set of markers when there is no known ground truth. Using these metrics, we compare the performance of RANKCORR to a variety of other marker selection methods on an assortment of experimental and synthetic data sets that range in size from several thousand to one million cells.ConclusionsAccording to the metrics introduced in this work, RANKCORR is consistently one of most optimal marker selection methods on scRNA-seq data. Most methods show similar overall performance, however; thus, the speed of the algorithm is the most important consideration for large data sets (and comparing the markers selected by several methods can be fruitful). RANKCORR is fast enough to easily handle the largest data sets and, as such, it is a useful tool to add into computational pipelines when dealing with high throughput scRNA-seq data. RANKCORR software is available for download at https://github.com/ahsv/RankCorr with extensive documentation.
| S-EPMC7585212 | biostudies-literature
Project description:Single-cell RNA sequencing (scRNA-seq) has become a revolutionary technology to characterize cells under different biological conditions. Unlike bulk RNA-seq, gene expression from scRNA-seq is highly sparse due to limited sequencing depth per cell. This is worsened by tossing away a significant portion of reads that attribute to gene quantification. To overcome data sparsity and fully utilize original reads, we propose scSimClassify, a reference-free and alignment-free approach to classify cell types with k-mer level features. The compressed k-mer groups (CKGs), identified by the simhash method, contain k-mers with similar abundance profiles and serve as the cells' features. Our experiments demonstrate that CKG features lend themselves to better performance than gene expression features in scRNA-seq classification accuracy in the majority of experimental cases. Because CKGs are derived from raw reads without alignment to reference genome, scSimClassify offers an effective alternative to existing methods especially when reference genome is incomplete or insufficient to represent subject genomes.
| S-EPMC8335627 | biostudies-literature
Project description:MotivationThe emergence of single-cell RNA-sequencing has enabled analyses that leverage transitioning cell states to reconstruct pseudotemporal trajectories. Multidimensional data sparsity, zero inflation and technical variation necessitate the selection of high-quality features that feed downstream analyses. Despite the development of numerous algorithms for the unsupervised selection of biologically relevant features, their differential performance remains largely unaddressed.ResultsWe implemented the neighborhood variance ratio (NVR) feature selection approach as a Python package with substantial improvements in performance. In comparing NVR with multiple unsupervised algorithms such as dpFeature, we observed striking differences in features selected. We present evidence that quantifiable dataset properties have observable and predictable effects on the performance of these algorithms.Availability and implementationpyNVR is freely available at https://github.com/KenLauLab/NVR.Supplementary informationSupplementary data are available at Bioinformatics online.
| S-EPMC6596893 | biostudies-literature
Project description:Understanding the dynamics of gene regulatory networks (GRNs) across diverse cell types poses a challenge yet holds immense value in unraveling the molecular mechanisms governing cellular processes. Current computational methods, which rely solely on expression changes from bulk RNA-seq and/or scRNA-seq data, often result in high rates of false positives and low precision. Here, we introduce an advanced computational tool, DeepIMAGER, for inferring cell-specific GRNs through deep learning and data integration. DeepIMAGER employs a supervised approach that transforms the co-expression patterns of gene pairs into image-like representations and leverages transcription factor (TF) binding information for model training. It is trained using comprehensive datasets that encompass scRNA-seq profiles and ChIP-seq data, capturing TF-gene pair information across various cell types. Comprehensive validations on six cell lines show DeepIMAGER exhibits superior performance in ten popular GRN inference tools and has remarkable robustness against dropout-zero events. DeepIMAGER was applied to scRNA-seq datasets of multiple myeloma (MM) and detected potential GRNs for TFs of RORC, MITF, and FOXD2 in MM dendritic cells. This technical innovation, combined with its capability to accurately decode GRNs from scRNA-seq, establishes DeepIMAGER as a valuable tool for unraveling complex regulatory networks in various cell types.
| S-EPMC11274664 | biostudies-literature