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Integrative Methods and Practical Challenges for Single-Cell Multi-omics.

ABSTRACT: Fast-developing single-cell multimodal omics (scMulti-omics) technologies enable the measurement of multiple modalities, such as DNA methylation, chromatin accessibility, RNA expression, protein abundance, gene perturbation, and spatial information, from the same cell. scMulti-omics can comprehensively explore and identify cell characteristics, while also presenting challenges to the development of computational methods and tools for integrative analyses. Here, we review these integrative methods and summarize the existing tools for studying a variety of scMulti-omics data. The various functionalities and practical challenges in using the available tools in the public domain are explored through several case studies. Finally, we identify remaining challenges and future trends in scMulti-omics modeling and analyses.

SUBMITTER: Ma A

PROVIDER: S-EPMC7442857 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Integrative Methods and Practical Challenges for Single-Cell Multi-omics.

Ma Anjun A McDermaid Adam A Xu Jennifer J Chang Yuzhou Y Ma Qin Q

Trends in biotechnology 20200326 9

Fast-developing single-cell multimodal omics (scMulti-omics) technologies enable the measurement of multiple modalities, such as DNA methylation, chromatin accessibility, RNA expression, protein abundance, gene perturbation, and spatial information, from the same cell. scMulti-omics can comprehensively explore and identify cell characteristics, while also presenting challenges to the development of computational methods and tools for integrative analyses. Here, we review these integrative method ...[more]

PMID: 32818441

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Project description:(1) Background: Single-cell multi-omics is a powerful method for the dissection and detection of complicated immunologic functions and synapses. However, most currently available technologies merge datasets of different omics from separate portions of the same sample to generate combined multi-omics. This process is a source of bias, mainly in the field of immunology on cells originating from pluripotent hematopoietic stem cells with high flexibility during maturation. (2) Methods: Although new multi-omics approaches have been developed to use the advantages of cellular and molecular barcoding and next-generation sequencing to solve this issue, one of the main current challenges is intracellular proteomics, which should be combined with other omics data with high importance for immune system studies. We designed this study to evaluate previously recommended minimal permeabilization and fixation methods on the quality and quantity of transcriptomics and proteomics data generated by the BD Rhapsody™ Single-Cell Analysis System. (3) Results: Our findings showed that high-throughput sequencing with advanced quality and read-out is required for the combination of multi-omics outcomes from a permeabilized single cell. Therefore, the HiseqX platform was selected for further analysis. The effect of immune stimulation was observed clearly as the separated clusters of helper and cytotoxic T cells using unsupervised clustering. Importantly, fixation and permeabilization did not affect the general expression profile of unstimulated cells. However, fixation and permeabilization were proved to negatively impact the detection of the whole transcriptome for single-cell assay. Nevertheless, about 60% of the transcriptomic signature of the stimulation was detected. If the measurement of combined surface and intracellular markers is required to be achieved, the modified fixation and permeabilization method is recommended because of a lower transcriptomic loss and more precise proteomic fingerprint detected. (4) Conclusions: The findings of this study support the potential possibility for integrating intracellular proteomics, which needs to be optimized and tested with newly designed oligonucleotide-tagged antibodies targeting intracellular proteins.

Dataset Information

Integrative Methods and Practical Challenges for Single-Cell Multi-omics.

Publications

Integrative Methods and Practical Challenges for Single-Cell Multi-omics.

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