A unified model-based framework for doublet or multiplet detection in single-cell multiomics data.

Droplet-based single-cell sequencing techniques rely on the fundamental assumption that each droplet encapsulates a single cell, enabling individual cell omics profiling. However, the inevitable issue of multiplets, where two or more cells are encapsulated within a single droplet, can lead to spurious cell type annotations and obscure true biological findings. The issue of multiplets is exacerbated in single-cell multiomics settings, where integrating cross-modality information for clustering can inadvertently promote the aggregation of multiplet clusters and increase the risk of erroneous cell type annotations. Here, we propose a compound Poisson model-based framework for multiplet detection in single-cell multiomics data. Leveraging experimental cell hashing results as the ground truth for multiplet status, we conducted trimodal DOGMA-seq experiments and generated 17 benchmarking datasets from two tissues, involving a total of 280,123 droplets. We demonstrated that the proposed method is an essential tool for integrating cross-modality multiplet signals, effectively eliminating multiplet clusters in single-cell multiomics data-a task at which the benchmarked single-omics methods proved inadequate.

Deep autoencoder for interpretable tissue-adaptive deconvolution and cell-type-specific gene analysis.

Single-cell RNA-sequencing has become a powerful tool to study biologically significant characteristics at explicitly high resolution. However, its application on emerging data is currently limited by its intrinsic techniques. Here, we introduce Tissue-AdaPtive autoEncoder (TAPE), a deep learning method connecting bulk RNA-seq and single-cell RNA-seq to achieve precise deconvolution in a short time. By constructing an interpretable decoder and training under a unique scheme, TAPE can predict cell-type fractions and cell-type-specific gene expression tissue-adaptively. Compared with popular methods on several datasets, TAPE has a better overall performance and comparable accuracy at cell type level. Additionally, it is more robust among different cell types, faster, and sensitive to provide biologically meaningful predictions. Moreover, through the analysis of clinical data, TAPE shows its ability to predict cell-type-specific gene expression profiles with biological significance. We believe that TAPE will enable and accelerate the precise analysis of high-throughput clinical data in a wide range.