Progress in single-cell multimodal sequencing and multi-omics data integrationWang, Xuefei; Wu, Xinchao; Hong, Ni; Jin, Wenfei
doi: 10.1007/s12551-023-01092-3pmid: 38495443
With the rapid advance of single-cell sequencing technology, cell heterogeneity in various biological processes was dissected at different omics levels. However, single-cell mono-omics results in fragmentation of information and could not provide complete cell states. In the past several years, a variety of single-cell multimodal omics technologies have been developed to jointly profile multiple molecular modalities, including genome, transcriptome, epigenome, and proteome, from the same single cell. With the availability of single-cell multimodal omics data, we can simultaneously investigate the effects of genomic mutation or epigenetic modification on transcription and translation, and reveal the potential mechanisms underlying disease pathogenesis. Driven by the massive single-cell omics data, the integration method of single-cell multi-omics data has rapidly developed. Integration of the massive multi-omics single-cell data in public databases in the future will make it possible to construct a cell atlas of multi-omics, enabling us to comprehensively understand cell state and gene regulation at single-cell resolution. In this review, we summarized the experimental methods for single-cell multimodal omics data and computational methods for multi-omics data integration. We also discussed the future development of this field.
Representing and extracting knowledge from single-cell dataMihai, Ionut Sebastian; Chafle, Sarang; Henriksson, Johan
doi: 10.1007/s12551-023-01091-4pmid: 38495441
Single-cell analysis is currently one of the most high-resolution techniques to study biology. The large complex datasets that have been generated have spurred numerous developments in computational biology, in particular the use of advanced statistics and machine learning. This review attempts to explain the deeper theoretical concepts that underpin current state-of-the-art analysis methods. Single-cell analysis is covered from cell, through instruments, to current and upcoming models. The aim of this review is to spread concepts which are not yet in common use, especially from topology and generative processes, and how new statistical models can be developed to capture more of biology. This opens epistemological questions regarding our ontology and models, and some pointers will be given to how natural language processing (NLP) may help overcome our cognitive limitations for understanding single-cell data.
Studying temporal dynamics of single cells: expression, lineage and regulatory networksPan, Xinhai; Zhang, Xiuwei
doi: 10.1007/s12551-023-01090-5pmid: 38495440
Learning how multicellular organs are developed from single cells to different cell types is a fundamental problem in biology. With the high-throughput scRNA-seq technology, computational methods have been developed to reveal the temporal dynamics of single cells from transcriptomic data, from phenomena on cell trajectories to the underlying mechanism that formed the trajectory. There are several distinct families of computational methods including Trajectory Inference (TI), Lineage Tracing (LT), and Gene Regulatory Network (GRN) Inference which are involved in such studies. This review summarizes these computational approaches which use scRNA-seq data to study cell differentiation and cell fate specification as well as the advantages and limitations of different methods. We further discuss how GRNs can potentially affect cell fate decisions and trajectory structures.
Tools for microbial single-cell genomics for obtaining uncultured microbial genomesHosokawa, Masahito; Nishikawa, Yohei
doi: 10.1007/s12551-023-01124-ypmid: 38495448
The advent of next-generation sequencing technologies has facilitated the acquisition of large amounts of DNA sequence data at a relatively low cost, leading to numerous breakthroughs in decoding microbial genomes. Among the various genome sequencing activities, metagenomic analysis, which entails the direct analysis of uncultured microbial DNA, has had a profound impact on microbiome research and has emerged as an indispensable technology in this field. Despite its valuable contributions, metagenomic analysis is a “bulk analysis” technique that analyzes samples containing a wide diversity of microbes, such as bacteria, yielding information that is averaged across the entire microbial population. In order to gain a deeper understanding of the heterogeneous nature of the microbial world, there is a growing need for single-cell analysis, similar to its use in human cell biology. With this paradigm shift in mind, comprehensive single-cell genomics technology has become a much-anticipated innovation that is now poised to revolutionize microbiome research. It has the potential to enable the discovery of differences at the strain level and to facilitate a more comprehensive examination of microbial ecosystems. In this review, we summarize the current state-of-the-art in microbial single-cell genomics, highlighting the potential impact of this technology on our understanding of the microbial world. The successful implementation of this technology is expected to have a profound impact in the field, leading to new discoveries and insights into the diversity and evolution of microbes.
Heterogeneity of chemical modifications on RNAGoh, W. S. Sho; Kuang, Yi
doi: 10.1007/s12551-023-01128-8pmid: 38495447
The chemical modifications of RNAs broadly impact almost all cellular events and influence various diseases. The rapid advance of sequencing and other technologies opened the door to global methods for profiling all RNA modifications, namely the “epitranscriptome.” The mapping of epitranscriptomes in different cells and tissues unveiled that RNA modifications exhibit extensive heterogeneity, in type, amount, and in location. In this mini review, we first introduce the current understanding of modifications on major types of RNAs and the methods that enabled their discovery. We next discuss the tissue and cell heterogeneity of RNA modifications and briefly address the limitations of current technologies. With much still remaining unknown, the development of the epitranscriptomic field lies in the further developments of novel technologies.
Integrating single-cell transcriptomics with cellular phenotypes: cell morphology, Ca2+ imaging and electrophysiologyCamunas-Soler, Joan
doi: 10.1007/s12551-023-01174-2pmid: 38495444
I review recent technological advancements in coupling single-cell transcriptomics with cellular phenotypes including morphology, calcium signaling, and electrophysiology. Single-cell RNA sequencing (scRNAseq) has revolutionized cell type classifications by capturing the transcriptional diversity of cells. A new wave of methods to integrate scRNAseq and biophysical measurements is facilitating the linkage of transcriptomic data to cellular function, which provides physiological insight into cellular states. I briefly discuss critical factors of these phenotypical characterizations such as timescales, information content, and analytical tools. Dedicated sections focus on the integration with cell morphology, calcium imaging, and electrophysiology (patch-seq), emphasizing their complementary roles. I discuss their application in elucidating cellular states, refining cell type classifications, and uncovering functional differences in cell subtypes. To illustrate the practical applications and benefits of these methods, I highlight their use in tissues with excitable cell-types such as the brain, pancreatic islets, and the retina. The potential of combining functional phenotyping with spatial transcriptomics for a detailed mapping of cell phenotypes in situ is explored. Finally, I discuss open questions and future perspectives, emphasizing the need for a shift towards broader accessibility through increased throughput.
Emerging tools for uncovering genetic and transcriptomic heterogeneities in bacteriaLiao, Yi
doi: 10.1007/s12551-023-01178-ypmid: 38495445
Bacterial communities display an astonishing degree of heterogeneities among their constituent cells across both the genomic and transcriptomic levels, giving rise to diverse social interactions and stress-adaptation strategies indispensable for proliferating in the natural environment (Ackermann in Nat Rev Microbiol 13:497–508, 2015). Our knowledge about bacterial heterogeneities and their physiological ramifications critically depends on our ability to unambiguously resolve the genetic and phenotypic states of the individual cells that make up the population. In this short review, I highlight several recently developed methods for studying bacterial heterogeneities, primarily focusing on single-cell techniques based on advanced sequencing and microscopy technologies. I will discuss the working principle of each technique as well as the types of problems each technique is best positioned to address. With significant improvements in resolution and throughput, these emerging tools together offer unprecedented and complementary views of various types of heterogeneities found within bacterial populations, paving the way for mechanistic dissections and systematic interventions in laboratory and clinical settings.