scholarly journals CytoTalk: De novo construction of signal transduction networks using single-cell transcriptomic data

2021 ◽  
Vol 7 (16) ◽  
pp. eabf1356
Author(s):  
Yuxuan Hu ◽  
Tao Peng ◽  
Lin Gao ◽  
Kai Tan
Keyword(s):  
Signal Transduction ◽  
Comparative Analysis ◽  
Single Cell ◽  
Developmental Stages ◽  
De Novo ◽  
Receptor Gene ◽  
Signaling Networks ◽  
Sequencing Data ◽  
Transcriptomic Data ◽  
Steiner Forest

Single-cell technology enables study of signal transduction in a complex tissue at unprecedented resolution. We describe CytoTalk for de novo construction of cell type–specific signaling networks using single-cell transcriptomic data. Using an integrated intracellular and intercellular gene network as the input, CytoTalk identifies candidate pathways using the prize-collecting Steiner forest algorithm. Using high-throughput spatial transcriptomic data and single-cell RNA sequencing data with receptor gene perturbation, we demonstrate that CytoTalk has substantial improvement over existing algorithms. To better understand plasticity of signaling networks across tissues and developmental stages, we perform a comparative analysis of signaling networks between macrophages and endothelial cells across human adult and fetal tissues. Our analysis reveals an overall increased plasticity of signaling networks across adult tissues and specific network nodes that contribute to increased plasticity. CytoTalk enables de novo construction of signal transduction pathways and facilitates comparative analysis of these pathways across tissues and conditions.

scholarly journals CytoTalk: De novo construction of signal transduction networks using single-cell RNA-Seq data

2020 ◽  
Author(s):  
Yuxuan Hu ◽  
Tao Peng ◽  
Lin Gao ◽  
Kai Tan
Keyword(s):  
Signal Transduction ◽  
Single Cell ◽  
De Novo ◽  
Receptor Gene ◽  
Computational Method ◽  
Signal Transduction Pathways ◽  
Rna Seq ◽  
Data Set ◽  
Signal Transduction Networks ◽  
Steiner Forest

AbstractSingle-cell technology has opened the door for studying signal transduction in a complex tissue at unprecedented resolution. However, there is a lack of analytical methods for de novo construction of signal transduction pathways using single-cell omics data. Here we present CytoTalk, a computational method for de novo constructing cell type-specific signal transduction networks using single-cell RNA-Seq data. CytoTalk first constructs intracellular and intercellular gene-gene interaction networks using an information-theoretic measure between two cell types. Candidate signal transduction pathways in the integrated network are identified using the prize-collecting Steiner forest algorithm. We applied CytoTalk to a single-cell RNA-Seq data set on mouse visual cortex and evaluated predictions using high-throughput spatial transcriptomics data generated from the same tissue. Compared to published methods, genes in our inferred signaling pathways have significantly higher spatial expression correlation only in cells that are spatially closer to each other, suggesting improved accuracy of CytoTalk. Furthermore, using single-cell RNA-Seq data with receptor gene perturbation, we found that predicted pathways are enriched for differentially expressed genes between the receptor knockout and wild type cells, further validating the accuracy of CytoTalk. In summary, CytoTalk enables de novo construction of signal transduction pathways and facilitates comparative analysis of these pathways across tissues and conditions.

scholarly journals Comparative analysis of single cell lung atlas of bat, cat, tiger and pangolin

2021 ◽  
Author(s):  
Xiran Wang ◽  
Zhihua Ou ◽  
Peiwen Ding ◽  
Chengcheng Sun ◽  
Daxi Wang ◽  
...  
Keyword(s):  
Immune System ◽  
Comparative Analysis ◽  
Single Cell ◽  
Animal Species ◽  
Respiratory Viruses ◽  
Virus Infections ◽  
Species Comparison ◽  
Transcriptomic Data ◽  
Horseshoe Bat ◽  
Horseshoe Bats

Horseshoe bats (Rhinolophus sinicus) might help maintain coronaviruses severely affecting human health, such as SARS-CoV and SARS-CoV-2. It has long been suggested that bats may be more tolerant of viral infection than other mammals due to their unique immune system, but the exact mechanism remains to be fully explored. During the COVID-19 pandemic, multiple animal species were diseased by SARS-CoV-2 infection, especially in the respiratory system. Herein, single-cell transcriptomic data of the lungs of a horseshoe bat, a cat, a tiger, and a pangolin were generated. The receptor distribution of twenty-eight respiratory viruses belonging to fourteen viral families were characterized for the four species. Comparison on the immune-related transcripts further revealed limited cytokine activations in bats, which might explain the reason why bats experienced only mild diseases or even no symptoms upon virus infection. Our findings might increase our understanding of the immune background of horseshoe bats and their insensitivity to virus infections.

scholarly journals Multi-regional characterisation of renal cell carcinoma and microenvironment at single cell resolution

2021 ◽  
Author(s):  
Ruoyan Li ◽  
John R. Ferdinand ◽  
Kevin W. Loudon ◽  
Georgina S. Bowyer ◽  
Lira Mamanova ◽  
...  
Keyword(s):  
Single Cell ◽  
Cell Function ◽  
De Novo ◽  
Epithelial Mesenchymal Transition ◽  
Spatial Location ◽  
De Novo Mutation ◽  
Cellular Interactions ◽  
Sequencing Data ◽  
Mesenchymal Transition ◽  
Multiple Regions

Tumour behaviour is dependent on the oncogenic properties of cancer cells and their multi-cellular interactions. These dependencies were examined through 270,000 single cell transcriptomes and 100 micro-dissected whole exomes obtained from 12 patients with kidney tumours. Tissue was sampled from multiple regions of tumour core, tumour-normal interface, normal surrounding tissues, and peripheral blood. We found the principal spatial location of CD8+ T cell clonotypes largely defined exhaustion state, with clonotypic heterogeneity not explained by somatic intra-tumoural heterogeneity. De novo mutation calling from single cell RNA sequencing data allows us to lineage-trace and infer clonality of cells. We discovered six meta-programmes that distinguish tumour cell function. An epithelial-mesenchymal transition meta-programme, enriched at the tumour-normal interface appears modulated through macrophage expressed IL1B, potentially forming a therapeutic target.

scholarly journals Fully phased human genome assembly without parental data using single-cell strand sequencing and long reads

2020 ◽  
Author(s):  
David Porubsky ◽  
◽  
Peter Ebert ◽  
Peter A. Audano ◽  
Mitchell R. Vollger ◽  
...  
Keyword(s):  
Single Cell ◽  
Genome Assembly ◽  
De Novo ◽  
Error Rates ◽  
Sequencing Data ◽  
Single Nucleotide Variants ◽  
De Novo Genome Assembly ◽  
Parental Data ◽  
Human Genome Assembly ◽  
Long Read

AbstractHuman genomes are typically assembled as consensus sequences that lack information on parental haplotypes. Here we describe a reference-free workflow for diploid de novo genome assembly that combines the chromosome-wide phasing and scaffolding capabilities of single-cell strand sequencing1,2 with continuous long-read or high-fidelity3 sequencing data. Employing this strategy, we produced a completely phased de novo genome assembly for each haplotype of an individual of Puerto Rican descent (HG00733) in the absence of parental data. The assemblies are accurate (quality value > 40) and highly contiguous (contig N50 > 23 Mbp) with low switch error rates (0.17%), providing fully phased single-nucleotide variants, indels and structural variants. A comparison of Oxford Nanopore Technologies and Pacific Biosciences phased assemblies identified 154 regions that are preferential sites of contig breaks, irrespective of sequencing technology or phasing algorithms.

scholarly journals A study of the heterochronic sense/antisense RNA representation in florets of sexual and apomictic Paspalum notatum

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Maricel Podio ◽  
Carolina Colono ◽  
Lorena Siena ◽  
Juan Pablo A. Ortiz ◽  
Silvina Claudia Pessino
Keyword(s):  
Comparative Analysis ◽  
Developmental Stages ◽  
De Novo ◽  
Wrky Transcription Factor ◽  
Hormonal Control ◽  
Differentially Expressed ◽  
Paspalum Notatum ◽  
Antisense Transcripts ◽  
Antisense Gene ◽  
Heritable Trait

Abstract Background Apomixis, an asexual mode of plant reproduction, is a genetically heritable trait evolutionarily related to sexuality, which enables the fixation of heterozygous genetic combinations through the development of maternal seeds. Recently, reference floral transcriptomes were generated from sexual and apomictic biotypes of Paspalum notatum, one of the most well-known plant models for the study of apomixis. However, the transcriptome dynamics, the occurrence of apomixis vs. sexual expression heterochronicity across consecutive developmental steps and the orientation of transcription (sense/antisense) remain unexplored. Results We produced 24 Illumina TruSeq®/ Hiseq 1500 sense/antisense floral transcriptome libraries covering four developmental stages (premeiosis, meiosis, postmeiosis, and anthesis) in biological triplicates, from an obligate apomictic and a full sexual genotype. De novo assemblies with Trinity yielded 103,699 and 100,114 transcripts for the apomictic and sexual samples respectively. A global comparative analysis involving reads from all developmental stages revealed 19,352 differentially expressed sense transcripts, of which 13,205 (68%) and 6147 (32%) were up- and down-regulated in apomictic samples with respect to the sexual ones. Interestingly, 100 differentially expressed antisense transcripts were detected, 55 (55%) of them up- and 45 (45%) down-regulated in apomictic libraries. A stage-by-stage comparative analysis showed a higher number of differentially expressed candidates due to heterochronicity discrimination: the highest number of differential sense transcripts was detected at premeiosis (23,651), followed by meiosis (22,830), postmeiosis (19,100), and anthesis (17,962), while the highest number of differential antisense transcripts were detected at anthesis (495), followed by postmeiosis (164), meiosis (120) and premeiosis (115). Members of the AP2, ARF, MYB and WRKY transcription factor families, as well as the auxin, jasmonate and cytokinin plant hormone families appeared broadly deregulated. Moreover, the chronological expression profile of several well-characterized apomixis controllers was examined in detail. Conclusions This work provides a quantitative sense/antisense gene expression catalogue covering several subsequent reproductive developmental stages from premeiosis to anthesis for apomictic and sexual P. notatum, with potential to reveal heterochronic expression between reproductive types and discover sense/antisense mediated regulation. We detected a contrasting transcriptional and hormonal control in apomixis and sexuality as well as specific sense/antisense modulation occurring at the onset of parthenogenesis.

scholarly journals STREAM: Single-cell Trajectories Reconstruction, Exploration And Mapping of omics data

2018 ◽  
Author(s):  
Huidong Chen ◽  
Luca Albergante ◽  
Jonathan Y Hsu ◽  
Caleb A Lareau ◽  
Giosue` Lo Bosco ◽  
...  
Keyword(s):  
Single Cell ◽  
De Novo ◽  
Developmental Trajectories ◽  
Cellular Heterogeneity ◽  
State Transitions ◽  
Omics Data ◽  
Transcriptomic Data ◽  
Lineage Differentiation ◽  
Cell Trajectories

AbstractSingle-cell transcriptomic assays have enabled the de novo reconstruction of lineage differentiation trajectories, along with the characterization of cellular heterogeneity and state transitions. Several methods have been developed for reconstructing developmental trajectories from single-cell transcriptomic data, but efforts on analyzing single-cell epigenomic data and on trajectory visualization remain limited. Here we present STREAM, an interactive pipeline capable of disentangling and visualizing complex branching trajectories from both single-cell transcriptomic and epigenomic data.

scholarly journals The chromosomal-level genome assembly and comprehensive transcriptomes of Chinese razor clam (Sinonovacula constricta) with deep-burrowing life style and broad-range salinity adaptation

2019 ◽  
Author(s):  
Yinghui Dong ◽  
Qifan Zeng ◽  
Jianfeng Ren ◽  
Hanhan Yao ◽  
Wenbin Ruan ◽  
...  
Keyword(s):  
Genome Assembly ◽  
Developmental Stages ◽  
De Novo ◽  
Gene Families ◽  
Sequencing Data ◽  
High Quality ◽  
Protein Coding ◽  
Sinonovacula Constricta ◽  
Razor Clam ◽  
Genomic Resources

AbstractBackgroundThe Chinese razor clam, Sinonovacula constricta, is one of the commercially important marine bivalves with deep-burrowing lifestyle and remarkable adaptability of broad-range salinity. Despite its economic impact and representative of the less-understood deep-burrowing bivalve lifestyle, there are few genomic resources for exploring its unique biology and adaptive evolution. Herein, we reported a high-quality chromosomal-level reference genome of S. constricta, the first genome of the family Solenidae, along with a large amount of short-read/full-length transcriptomic data of whole-ontogeny developmental stages, all major adult tissues, and gill tissues under salinity challenge.FindingsA total of 101.79 Gb and 129.73 Gb sequencing data were obtained with the PacBio and Illumina platforms, which represented approximately 186.63X genome coverage. In addition, a total of 160.90 Gb and 24.55 Gb clean data were also obtained with the Illumina and PacBio platforms for transcriptomic investigation. A de novo genome assembly of 1,340.13 Mb was generated, with a contig N50 of 689.18 kb. Hi-C scaffolding resulted in 19 chromosomes with a scaffold N50 of 57.99 Mb. The repeat sequences account for 50.71% of the assembled genome. A total of 26,273 protein-coding genes were predicted and 99.5% of them were annotated. Phylogenetic analysis revealed that S. constricta diverged from the lineage of Pteriomorphia at approximately 494 million years ago. Notably, cytoskeletal protein tubulin and motor protein dynein gene families are rapidly expanded in the S. constricta genome and are highly expressed in the mantle and gill, implicating potential genomic bases for the well-developed ciliary system in the S. constricta.ConclusionsThe high-quality genome assembly and comprehensive transcriptomes generated in this work not only provides highly valuable genomic resources for future studies of S. constricta, but also lays a solid foundation for further investigation into the adaptive mechanisms of benthic burrowing mollusks.

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