Project description:MotivationSingle-cell multi-omics assays simultaneously measure different molecular features from the same cell. A key question is how to benefit from the complementary data available and perform cross-modal clustering of cells.ResultsWe propose Single-Cell Multi-omics Clustering (scMoC), an approach to identify cell clusters from data with comeasurements of scRNA-seq and scATAC-seq from the same cell. We overcome the high sparsity of the scATAC-seq data by using an imputation strategy that exploits the less-sparse scRNA-seq data available from the same cell. Subsequently, scMoC identifies clusters of cells by merging clusterings derived from both data domains individually. We tested scMoC on datasets generated using different protocols with variable data sparsity levels. We show that scMoC (i) is able to generate informative scATAC-seq data due to its RNA-guided imputation strategy and (ii) results in integrated clusters based on both RNA and ATAC information that are biologically meaningful either from the RNA or from the ATAC perspective.Availability and implementationThe data used in this manuscript is publicly available, and we refer to the original manuscript for their description and availability. For convience sci-CAR data is available at NCBI GEO under the accession number of GSE117089. SNARE-seq data is available at NCBI GEO under the accession number of GSE126074. The 10X multiome data is available at the following link https://www.10xgenomics.com/resources/datasets/pbmc-from-a-healthy-donor-no-cell-sorting-3-k-1-standard-2-0-0.Supplementary informationSupplementary data are available at Bioinformatics Advances online.
Project description:Joint profiling of chromatin accessibility and gene expression from the same single cell provides critical information about cell types in a tissue and cell states during a dynamic process. These emerging multi-omics techniques help the investigation of cell-type resolved gene regulatory mechanisms. Here, we developed in situ SHERRY after ATAC-seq (ISSAAC-seq), a highly sensitive and flexible single cell multi-omics method to interrogate chromatin accessibility and gene expression from the same single cell. We demonstrated that ISSAAC-seq is sensitive and provides high quality data with orders of magnitude more features than existing methods. Using the joint profiles from thousands of nuclei from the mouse cerebral cortex, we uncovered major and rare cell types together with their cell-type specific regulatory elements and expression profiles. Finally, we revealed distinct dynamics and relationships of transcription and chromatin accessibility during an oligodendrocyte maturation trajectory.
Project description:MotivationSingle-cell multi-omics sequencing techniques have rapidly developed in the past few years. Clustering analysis with single-cell multi-omics data may give us novel perspectives to dissect cellular heterogeneity. However, multi-omics data have the properties of inherited large dimension, high sparsity and existence of doublets. Moreover, representations of different omics from even the same cell follow diverse distributions. Without proper distribution alignment techniques, clustering methods will encounter less separable clusters easily affected by less informative omics data.ResultsWe developed MoClust, a novel joint clustering framework that can be applied to several types of single-cell multi-omics data. A selective automatic doublet detection module that can identify and filter out doublets is introduced in the pretraining stage to improve data quality. Omics-specific autoencoders are introduced to characterize the multi-omics data. A contrastive learning way of distribution alignment is adopted to adaptively fuse omics representations into an omics-invariant representation. This novel way of alignment boosts the compactness and separableness of clusters, while accurately weighting the contribution of each omics to the clustering object. Extensive experiments, over both simulated and real multi-omics datasets, demonstrated the powerful alignment, doublet detection and clustering ability features of MoClust.Availability and implementationAn implementation of MoClust is available from https://doi.org/10.5281/zenodo.7306504.Supplementary informationSupplementary data are available at Bioinformatics online.
Project description:Organoids were generated from H9 cells. Single cells were sorted from 4-month-old brain organoids differentiated using the telencephalon organoids protocol.