Motivation: Spatially resolved transcriptomics (SRT) shows its impressive power in yielding biological insights into neuroscience, disease study, and even plant biology. However, current methods do not sufficiently explore the expressiveness of the multi-modal SRT data, leaving a large room for improvement of performance. Moreover, the current deep learning based methods lack interpretability due to the "black box" nature, impeding its further applications in the areas that require explanation. Results: We propose conST, a powerful and flexible SRT data analysis framework utilizing contrastive learning techniques. conST can learn low-dimensional embeddings by effectively integrating multi-modal SRT data, i.e. gene expression, spatial information, and morphology (if applicable). The learned embeddings can be then used for various downstream tasks, including clustering, trajectory and pseudotime inference, cell-to-cell interaction, etc. Extensive experiments in various datasets have been conducted to demonstrate the effectiveness and robustness of the proposed conST, achieving up to 10% improvement in clustering ARI in the commonly used benchmark dataset. We also show that the learned embedding can be used in complicated scenarios, such as predicting cancer progression by analyzing the tumour microenvironment and cell-to-cell interaction (CCI) of breast cancer. Our framework is interpretable in that it is able to find the correlated spots that support the clustering, which matches the CCI interaction pairs as well, providing more confidence to clinicians when making clinical decisions.
Muilti-modality data are ubiquitous in biology, especially that we have entered the multi-omics era, when we can measure the same biological object (cell) from different aspects (omics) to provide a more comprehensive insight into the cellular system. When dealing with such multi-omics data, the first step is to determine the correspondence among different modalities. In other words, we should match data from different spaces corresponding to the same object. This problem is particularly challenging in the single-cell multi-omics scenario because such data are very sparse with extremely high dimensions. Secondly, matched single-cell multi-omics data are rare and hard to collect. Furthermore, due to the limitations of the experimental environment, the data are usually highly noisy. To promote the single-cell multi-omics research, we overcome the above challenges, proposing a novel framework to align and integrate single-cell RNA-seq data and single-cell ATAC-seq data. Our approach can efficiently map the above data with high sparsity and noise from different spaces to a low-dimensional manifold in a unified space, making the downstream alignment and integration straightforward. Compared with the other state-of-the-art methods, our method performs better in both simulated and real single-cell data. The proposed method is helpful for the single-cell multi-omics research. The improvement for integration on the simulated data is significant.
Motivation We have entered the multi-omics era and can measure cells from different aspects. Hence, we can get a more comprehensive view by integrating or matching data from different spaces corresponding to the same object. However, it is particularly challenging in the single-cell multi-omics scenario because such data are very sparse with extremely high dimensions. Though some techniques can be used to measure scATAC-seq and scRNA-seq simultaneously, the data are usually highly noisy due to the limitations of the experimental environment. Results To promote single-cell multi-omics research, we overcome the above challenges, proposing a novel framework, contrastive cycle adversarial autoencoders, which can align and integrate single-cell RNA-seq data and single-cell ATAC-seq data. Con-AAE can efficiently map the above data with high sparsity and noise from different spaces to a coordinated subspace, where alignment and integration tasks can be easier. We demonstrate its advantages on several datasets. Availability Zenodo link: https://zenodo.org/badge/latestdoi/368779433 github: https://github.com/kakarotcq/Con-AAE. Supplementary information Supplementary data are available at Bioinformatics online.
The development of single-cell multi-omics technologies profiles DNA, mRNA, and proteins at a single-cell resolution. To meet the demand, we present scMinerva for single-cell multi-omics integration utilizing graph convolutional networks and a new random walk strategy, which outperforms existing methods on various datasets. Our method is especially robust on high-noise more-omics data and is lightweight concerning speed and memory. scMinerva can effectively perform downstream tasks, such as biomarker detection and cell differentiation analysis. We extensively interpret the robustness of scMinerva by analyzing components’ occurrence frequency in walks during training at omics level, cell-type level, and single-cell level.
Muilti-modality data are ubiquitous in biology, especially that we have entered the multi-omics era, when we can measure the same biological object (cell) from different aspects (omics) to provide a more comprehensive insight into the cellular system. When dealing with such multi-omics data, the first step is to determine the correspondence among different modalities. In other words, we should match data from different spaces corresponding to the same object. This problem is particularly challenging in the single-cell multi-omics scenario because such data are very sparse with extremely high dimensions. Secondly, matched single-cell multi-omics data are rare and hard to collect. Furthermore, due to the limitations of the experimental environment, the data are usually highly noisy. To promote the single-cell multi-omics research, we overcome the above challenges, proposing a novel framework to align and integrate single-cell RNA-seq data and single-cell ATAC-seq data. Our approach can efficiently map the above data with high sparsity and noise from different spaces to a low-dimensional manifold in a unified space, making the downstream alignment and integration straightforward. Compared with the other state-of-the-art methods, our method performs better in both simulated and real single-cell data. The proposed method is helpful for the single-cell multi-omics research. The improvement for integration on the simulated data is significant.
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