The Human Cell Atlas: from vision to reality

Rozenblatt-Rosen, Orit; Stubbington, Michael J T; Regev, Aviv; Teichmann, Sarah A.

doi:10.1038/550451a

Cited by 539 publications

(421 citation statements)

References 11 publications

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“…Single-cell RNA sequencing (scRNAseq) is a rapidly growing and widely applying technology [1][2][3]. By measuring gene expression at single cell level, scRNAseq provides an unprecedented opportunity to investigate the cellular heterogeneity of complex tissues [4][5][6][7][8]. However, despite the popularity of scRNAseq, analyzing scRNAseq data remains a challenging task.…”

Section: Introductionmentioning

confidence: 99%

Accuracy, Robustness and Scalability of Dimensionality Reduction Methods for Single Cell RNAseq Analysis

Sun

Zhu

et al. 2019

Preprint

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Background: Dimensionality reduction (DR) is an indispensable analytic component for many areas of single cell RNA sequencing (scRNAseq) data analysis. Proper DR can allow for effective noise removal and facilitate many downstream analyses that include cell clustering and lineage reconstruction. Unfortunately, despite the critical importance of DR in scRNAseq analysis and the vast number of DR methods developed for scRNAseq studies, however, few comprehensive comparison studies have been performed to evaluate the effectiveness of different DR methods in scRNAseq.Results: Here, we aim to fill this critical knowledge gap by providing a comparative evaluation of a variety of commonly used DR methods for scRNAseq studies. Specifically, we compared 18 different DR methods on 30 publicly available scRNAseq data sets that cover a range of sequencing techniques and sample sizes. We evaluated the performance of different DR methods for neighborhood preserving in terms of their ability to recover features of the original expression matrix, and for cell clustering and lineage reconstruction in terms of their accuracy and robustness. We also evaluated the computational scalability of different DR methods by recording their computational cost. Conclusions:Based on the comprehensive evaluation results, we provide important guidelines for choosing DR methods for scRNAseq data analysis. We also provide all analysis scripts used in the present study at www.xzlab.org/reproduce.html. Together, we hope that our results will serve as an important practical reference for practitioners to choose DR methods in the field of scRNAseq analysis. our results can serve as an important guideline for practitioners to choose DR methods in the field of scRNAseq analysis.

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Section: Introductionmentioning

confidence: 99%

Accuracy, Robustness and Scalability of Dimensionality Reduction Methods for Single Cell RNAseq Analysis

Sun

Zhu

et al. 2019

Preprint

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“…Tissues have transcriptomes of different complexities in terms of uniquely-expressed genes, as well as those genes expressed at differential levels [3][4][5][6] . One overarching goal in the life sciences is to characterize the specific transcriptomic signatures of all human tissues, and 5 ultimately each different cell type at the single-cell level 7 .…”

Section: Main Textmentioning

confidence: 99%

Widespread transcriptional scanning in the testis modulates gene evolution rates

Xia

Yan

et al. 2018

Preprint

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Abstract:A long-standing question in molecular biology relates to why the testes express the largest number of genes relative to all other organs. Here, we report a detailed gene expression map of human spermatogenesis using single-cell RNA-Seq. Surprisingly, we found that 20 spermatogenesis-expressed genes contain significantly fewer germline mutations than unexpressed genes, with the lowest mutation rates on the transcribed DNA strands. These results suggest a model of 'transcriptional scanning' to reduce germline mutations by correcting DNA damage. This model also explains the rapid evolution in sensory-and immune-defense related genes, as well as in male reproduction genes. Collectively, our results indicate that widespread 25 expression in the testes achieves a dual mechanism for maintaining the DNA integrity of most genes, while selectively promoting variation of other genes.. CC-BY-NC-ND 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/282129 doi: bioRxiv preprint first posted online Mar. 14, 2018; 2 Main Text:Human tissues and organs are distinguished by the genes that they express and those that they do not 1,2 . Tissues have transcriptomes of different complexities in terms of uniquely-expressed genes, as well as those genes expressed at differential levels [3][4][5][6] . One overarching goal in the life sciences is to characterize the specific transcriptomic signatures of all human tissues, and 5 ultimately each different cell type at the single-cell level 7 .In males, the testis is unique in comparison with somatic tissues in that it contains germ cells which pass the genetic information on to the next generation 8 . Interestingly, it has been known for many years that the testis stands out as having the most complex transcriptome with the highest number of expressed genes [9][10][11][12] . Widespread transcription in the testes has been 10 reported to account for an amazing expression of over 80% of all our protein-coding genes 10,11,13 , as well as across many other mammals 3,10 .Several hypotheses have been proposed to explain this observation. Widespread expression may represent a functional requirement for the gene-products in question 12 .However, other more complex organs such as the brain do not exhibit a corresponding number of 15 expressed genes despite the fact that they consist of a substantially greater number of distinct cell types 3,10,14-16 . Moreover, recent animal studies have shown that many testis-enriched and evolutionarily-conserved genes are not required for male fertility in mice 17 . A second hypothesis implicates leaky transcription during the massive chromatin remodeling that occurs throughout spermatogenesis 12,18,19 . However, this model predicts more expression during later stages of 20 spermatogenesis -when the genome is undergoing the most chromatin changes -contradicting ...

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“…Projects aiming to create reference maps of the cells of an organism such as the Human Cell Atlas can take advantage of this innovative way to label cell types (7). Thesaurus such as the Medical Subject Headings (MESH, https://www.…”

Section: Discussionmentioning

confidence: 99%

“…nlm.nih.gov/pubs/factsheets/mesh.html) can take advantage from the PPS by associating to the terms describing the cell types a unique identifier self-containing the associated markers. Projects aiming to create reference maps of the cells of an organism such as the Human Cell Atlas can take advantage of this innovative way to label cell types (7). Generally, PPS numbers can be used as primary keys in database supporting the above systems since they are unique and always not null by definition.…”

Section: Discussionmentioning

confidence: 99%

Universal cell type identifier based on number theory

Cosma

2018

Cytometry Pt A

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Cell type classification and handling is a key issue for understanding biological systems. The advent of high multiplexing technologies increased the complexity of the classification process and new tools are needed to support the organization of this knowledge. I propose a classification based on both prime numbers and the fundamental theorem of arithmetic. As a not limiting example, I show the application of this method to unambiguously define any existing cell type using the CD nomenclature established by the Human Leukocyte Differentiation Antigens Workshops. This system allows for the unique identification of any possible combination of markers hence any cell population without previous knowledge and without the need to increment the system. This method can be the future basis of any database and ontology system dealing with cell types and beyond the biological field applies to the description of any entity characterized by a list of discrete qualities. © 2018 International Society for Advancement of Cytometry.

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The Human Cell Atlas: from vision to reality

Abstract: A new type of human dendritic cell recently discovered using single-cell RNA sequencing.COMMENT © 2 0 1 7 M a c m i l l a n P u b l i s h e r s L i m i t e d , p a r t o f S p r i n g e r N a t u r e . A l l r i g h t s r e s e r v e d .

Cited by 539 publications

References 11 publications

Accuracy, Robustness and Scalability of Dimensionality Reduction Methods for Single Cell RNAseq Analysis

Accuracy, Robustness and Scalability of Dimensionality Reduction Methods for Single Cell RNAseq Analysis

Widespread transcriptional scanning in the testis modulates gene evolution rates

Universal cell type identifier based on number theory

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