Geometric Sketching Compactly Summarizes the Single-Cell Transcriptomic Landscape.

Abstract:

:Large-scale single-cell RNA sequencing (scRNA-seq) studies that profile hundreds of thousands of cells are becoming increasingly common, overwhelming existing analysis pipelines. Here, we describe how to enhance and accelerate single-cell data analysis by summarizing the transcriptomic heterogeneity within a dataset using a small subset of cells, which we refer to as a geometric sketch. Our sketches provide more comprehensive visualization of transcriptional diversity, capture rare cell types with high sensitivity, and reveal biological cell types via clustering. Our sketch of umbilical cord blood cells uncovers a rare subpopulation of inflammatory macrophages, which we experimentally validated. The construction of our sketches is extremely fast, which enabled us to accelerate other crucial resource-intensive tasks, such as scRNA-seq data integration, while maintaining accuracy. We anticipate our algorithm will become an increasingly essential step when sharing and analyzing the rapidly growing volume of scRNA-seq data and help enable the democratization of single-cell omics.

journal_name

Cell Syst

journal_title

Cell systems

authors

Hie B,Cho H,DeMeo B,Bryson B,Berger B

doi

10.1016/j.cels.2019.05.003

subject

Has Abstract

pub_date

2019-06-26 00:00:00

pages

483-493.e7

issue

6

eissn

2405-4712

issn

2405-4720

pii

S2405-4712(19)30152-8

journal_volume

8

pub_type

杂志文章
  • Systems Analyses Reveal Shared and Diverse Attributes of Oct4 Regulation in Pluripotent Cells.

    abstract::We combine a genome-scale RNAi screen in mouse epiblast stem cells (EpiSCs) with genetic interaction, protein localization, and "protein-level dependency" studies-a systematic technique that uncovers post-transcriptional regulation-to delineate the network of factors that control the expression of Oct4, a key regulato...

    journal_title:Cell systems

    pub_type: 杂志文章

    doi:10.1016/j.cels.2015.08.002

    authors: Ding L,Paszkowski-Rogacz M,Winzi M,Chakraborty D,Theis M,Singh S,Ciotta G,Poser I,Roguev A,Chu WK,Choudhary C,Mann M,Stewart AF,Krogan N,Buchholz F

    更新日期:2015-08-26 00:00:00

  • Defining Human Tyrosine Kinase Phosphorylation Networks Using Yeast as an In Vivo Model Substrate.

    abstract::Systematic assessment of tyrosine kinase-substrate relationships is fundamental to a better understanding of cellular signaling and its profound alterations in human diseases such as cancer. In human cells, such assessments are confounded by complex signaling networks, feedback loops, conditional activity, and intra-k...

    journal_title:Cell systems

    pub_type: 杂志文章

    doi:10.1016/j.cels.2017.08.001

    authors: Corwin T,Woodsmith J,Apelt F,Fontaine JF,Meierhofer D,Helmuth J,Grossmann A,Andrade-Navarro MA,Ballif BA,Stelzl U

    更新日期:2017-08-23 00:00:00

  • Juicebox Provides a Visualization System for Hi-C Contact Maps with Unlimited Zoom.

    abstract::Hi-C experiments study how genomes fold in 3D, generating contact maps containing features as small as 20 bp and as large as 200 Mb. Here we introduce Juicebox, a tool for exploring Hi-C and other contact map data. Juicebox allows users to zoom in and out of Hi-C maps interactively, just as a user of Google Earth migh...

    journal_title:Cell systems

    pub_type: 杂志文章

    doi:10.1016/j.cels.2015.07.012

    authors: Durand NC,Robinson JT,Shamim MS,Machol I,Mesirov JP,Lander ES,Aiden EL

    更新日期:2016-07-01 00:00:00

  • tRNA Methylation Is a Global Determinant of Bacterial Multi-drug Resistance.

    abstract::Gram-negative bacteria are intrinsically resistant to drugs because of their double-membrane envelope structure that acts as a permeability barrier and as an anchor for efflux pumps. Antibiotics are blocked and expelled from cells and cannot reach high-enough intracellular concentrations to exert a therapeutic effect....

    journal_title:Cell systems

    pub_type: 杂志文章

    doi:10.1016/j.cels.2019.03.008

    authors: Masuda I,Matsubara R,Christian T,Rojas ER,Yadavalli SS,Zhang L,Goulian M,Foster LJ,Huang KC,Hou YM

    更新日期:2019-04-24 00:00:00

  • Hunting for Cis-Regulatory Elements in Proteins.

    abstract::A new bioinformatics tool predicts natively disordered protein control elements that function in cis, opening the door to more systematic studies of this biomedically important class of protein modules. ...

    journal_title:Cell systems

    pub_type: 评论,杂志文章

    doi:10.1016/j.cels.2016.02.011

    authors: Gibson TJ,Kumar M

    更新日期:2016-02-24 00:00:00

  • Orchestration of DNA Damage Checkpoint Dynamics across the Human Cell Cycle.

    abstract::Although molecular mechanisms that prompt cell-cycle arrest in response to DNA damage have been elucidated, the systems-level properties of DNA damage checkpoints are not understood. Here, using time-lapse microscopy and simulations that model the cell cycle as a series of Poisson processes, we characterize DNA damage...

    journal_title:Cell systems

    pub_type: 杂志文章

    doi:10.1016/j.cels.2017.09.015

    authors: Chao HX,Poovey CE,Privette AA,Grant GD,Chao HY,Cook JG,Purvis JE

    更新日期:2017-11-22 00:00:00

  • Optogenetic Control of Calcium Oscillation Waveform Defines NFAT as an Integrator of Calcium Load.

    abstract::It is known that the calcium-dependent transcription factor NFAT initiates transcription in response to pulsatile loads of calcium signal. However, the relative contributions of calcium oscillation frequency, amplitude, and duty cycle to transcriptional activity remain unclear. Here, we engineer HeLa cells to permit o...

    journal_title:Cell systems

    pub_type: 杂志文章

    doi:10.1016/j.cels.2016.03.010

    authors: Hannanta-Anan P,Chow BY

    更新日期:2016-04-27 00:00:00

  • PROBer Provides a General Toolkit for Analyzing Sequencing-Based Toeprinting Assays.

    abstract::A number of sequencing-based transcriptase drop-off assays have recently been developed to probe post-transcriptional dynamics of RNA-protein interaction, RNA structure, and RNA modification. Although these assays survey a diverse set of epitranscriptomic marks, we use the term toeprinting assays since they share meth...

    journal_title:Cell systems

    pub_type: 杂志文章

    doi:10.1016/j.cels.2017.04.007

    authors: Li B,Tambe A,Aviran S,Pachter L

    更新日期:2017-05-24 00:00:00

  • exceRpt: A Comprehensive Analytic Platform for Extracellular RNA Profiling.

    abstract::Small RNA sequencing has been widely adopted to study the diversity of extracellular RNAs (exRNAs) in biofluids; however, the analysis of exRNA samples can be challenging: they are vulnerable to contamination and artifacts from different isolation techniques, present in lower concentrations than cellular RNA, and occa...

    journal_title:Cell systems

    pub_type: 杂志文章

    doi:10.1016/j.cels.2019.03.004

    authors: Rozowsky J,Kitchen RR,Park JJ,Galeev TR,Diao J,Warrell J,Thistlethwaite W,Subramanian SL,Milosavljevic A,Gerstein M

    更新日期:2019-04-24 00:00:00

  • Principles of Systems Biology, No. 8.

    abstract::Advances in biological engineering headline this month's Cell Systems call (Cell Systems 1, 307), alongside intriguing applications of modeling from the Elf, Goentoro, and Wolf groups. Check out our recent blogpost: http://crosstalk.cell.com/blog/a-call-for-papers-on-biological-engineering-and-synthetic-biology. ...

    journal_title:Cell systems

    pub_type: 杂志文章

    doi:10.1016/j.cels.2016.08.006

    authors:

    更新日期:2016-08-01 00:00:00

  • Reconstruction of Cell-type-Specific Interactomes at Single-Cell Resolution.

    abstract::The human interactome is instrumental in the systems-level study of the cell and the contextualization of disease-associated gene perturbations. However, reference organismal interactomes do not capture the cell-type-specific context in which proteins and modules preferentially act. Here, we introduce SCINET, a comput...

    journal_title:Cell systems

    pub_type: 杂志文章

    doi:10.1016/j.cels.2019.10.007

    authors: Mohammadi S,Davila-Velderrain J,Kellis M

    更新日期:2019-12-18 00:00:00

  • Measuring Signaling and RNA-Seq in the Same Cell Links Gene Expression to Dynamic Patterns of NF-κB Activation.

    abstract::Signaling proteins display remarkable cell-to-cell heterogeneity in their dynamic responses to stimuli, but the consequences of this heterogeneity remain largely unknown. For instance, the contribution of the dynamics of the innate immune transcription factor nuclear factor κB (NF-κB) to gene expression output is disp...

    journal_title:Cell systems

    pub_type: 杂志文章

    doi:10.1016/j.cels.2017.03.010

    authors: Lane K,Van Valen D,DeFelice MM,Macklin DN,Kudo T,Jaimovich A,Carr A,Meyer T,Pe'er D,Boutet SC,Covert MW

    更新日期:2017-04-26 00:00:00

  • How Do Chaperones Protect a Cell's Proteins from Oxidative Damage?

    abstract::The accumulation of protein damage in aging organisms is thought to contribute to many aging-related diseases. Yet the properties determining which proteins are most susceptible remain poorly understood. Are certain conformations more vulnerable? Which chaperones are the main guardians? We address these questions with...

    journal_title:Cell systems

    pub_type: 杂志文章

    doi:10.1016/j.cels.2018.05.001

    authors: Santra M,Dill KA,de Graff AMR

    更新日期:2018-06-27 00:00:00

  • Escaping Circadian Regulation: An Emerging Hallmark of Cancer?

    abstract::Alterations of circadian clock genes are associated with patient survival, tumor stage, and clinical subtype across various cancer types, highlighting the importance of timing in cancer treatment. ...

    journal_title:Cell systems

    pub_type: 评论

    doi:10.1016/j.cels.2018.03.006

    authors: El-Athman R,Relógio A

    更新日期:2018-03-28 00:00:00

  • Principles of Systems Biology, No. 31.

    abstract::This month: selected work from the 2018 RECOMB meeting, organized by Ecole Polytechnique and held last April in Paris. ...

    journal_title:Cell systems

    pub_type: 杂志文章

    doi:10.1016/j.cels.2018.08.005

    authors: Cho H,Berger B,Peng J,Galitzine C,Vitek O,Beltran PMJ,Cristea IM,Görtler F,Solbrig S,Wettig T,Oefner PJ,Spang R,Altenbuchinger M,Basso RS,Hochbaum D,Vandin F,Silverbush D,Cristea S,Yanovich G,Geiger T,Beerenwinkel

    更新日期:2018-08-22 00:00:00

  • Studying Autism in Context.

    abstract::Studying autism genes in the context of the protein complexes to which they belong illustrates the potential of network-centric approaches for understanding complex genetic disease. ...

    journal_title:Cell systems

    pub_type: 杂志文章

    doi:10.1016/j.cels.2015.11.004

    authors: Das J,Meyer MJ,Yu H

    更新日期:2015-11-25 00:00:00

  • Mapping Complex Traits in a Diversity Outbred F1 Mouse Population Identifies Germline Modifiers of Metastasis in Human Prostate Cancer.

    abstract::It is unclear how standing genetic variation affects the prognosis of prostate cancer patients. To provide one controlled answer to this problem, we crossed a dominant, penetrant mouse model of prostate cancer to Diversity Outbred mice, a collection of animals that carries over 40 million SNPs. Integration of disease ...

    journal_title:Cell systems

    pub_type: 杂志文章

    doi:10.1016/j.cels.2016.10.018

    authors: Winter JM,Gildea DE,Andreas JP,Gatti DM,Williams KA,Lee M,Hu Y,Zhang S,NISC Comparative Sequencing Program.,Mullikin JC,Wolfsberg TG,McDonnell SK,Fogarty ZC,Larson MC,French AJ,Schaid DJ,Thibodeau SN,Churchill GA,Craw

    更新日期:2017-01-25 00:00:00

  • Proteomics Moves into the Fast Lane.

    abstract::Three studies demonstrate the potential of state-of-the-art mass spectrometry-based proteomics for rapid, deep characterization of proteomes. ...

    journal_title:Cell systems

    pub_type: 评论,杂志文章

    doi:10.1016/j.cels.2016.03.002

    authors: Riley NM,Hebert AS,Coon JJ

    更新日期:2016-03-23 00:00:00

  • Synthetic Biology and Engineered Live Biotherapeutics: Toward Increasing System Complexity.

    abstract::Recent advances in synthetic biology and biological system engineering have allowed the design and construction of engineered live biotherapeutics targeting a range of human clinical applications. In this review, we outline how systems approaches have been used to move from simple constitutive systems, where a single ...

    journal_title:Cell systems

    pub_type: 杂志文章,评审

    doi:10.1016/j.cels.2018.06.008

    authors: Ozdemir T,Fedorec AJH,Danino T,Barnes CP

    更新日期:2018-07-25 00:00:00

  • Unsupervised Extraction of Stable Expression Signatures from Public Compendia with an Ensemble of Neural Networks.

    abstract::Cross-experiment comparisons in public data compendia are challenged by unmatched conditions and technical noise. The ADAGE method, which performs unsupervised integration with denoising autoencoder neural networks, can identify biological patterns, but because ADAGE models, like many neural networks, are over-paramet...

    journal_title:Cell systems

    pub_type: 杂志文章

    doi:10.1016/j.cels.2017.06.003

    authors: Tan J,Doing G,Lewis KA,Price CE,Chen KM,Cady KC,Perchuk B,Laub MT,Hogan DA,Greene CS

    更新日期:2017-07-26 00:00:00

  • Orientation of Turing-like Patterns by Morphogen Gradients and Tissue Anisotropies.

    abstract::Patterning of periodic stripes during development requires mechanisms to control both stripe spacing and orientation. A number of models can explain how stripe spacing is controlled, including molecular mechanisms, such as Turing's reaction-diffusion model, as well as cell-based and mechanical mechanisms. However, how...

    journal_title:Cell systems

    pub_type: 杂志文章

    doi:10.1016/j.cels.2015.12.001

    authors: Hiscock TW,Megason SG

    更新日期:2015-12-23 00:00:00

  • Evaluation of Hansen et al.: Nuance Is Crucial in Comparisons of Noise.

    abstract::One snapshot of the peer review process for "Cytoplasmic Amplification of Transcriptional Noise Generates Substantial Cell-to-Cell Variability" (Hansen et al., 2018). ...

    journal_title:Cell systems

    pub_type: 评论,杂志文章

    doi:10.1016/j.cels.2018.10.003

    authors: Olsman N,Xiao F,Doyle J

    更新日期:2018-10-24 00:00:00

  • Computational Recipes in Enzymology.

    abstract::How do rich biological behaviors arise from bi-molecular collisions? ...

    journal_title:Cell systems

    pub_type: 杂志文章

    doi:10.1016/j.cels.2015.09.006

    authors: Rust MJ

    更新日期:2015-09-23 00:00:00

  • Genotype-Fitness Maps of EGFR-Mutant Lung Adenocarcinoma Chart the Evolutionary Landscape of Resistance for Combination Therapy Optimization.

    abstract::Cancer evolution poses a central obstacle to cure, as resistant clones expand under therapeutic selection pressures. Genome sequencing of relapsed disease can nominate genomic alterations conferring resistance but sample collection lags behind, limiting therapeutic innovation. Genome-wide screens offer a complementary...

    journal_title:Cell systems

    pub_type: 杂志文章

    doi:10.1016/j.cels.2019.10.002

    authors: Bolan PO,Zviran A,Brenan L,Schiffman JS,Dusaj N,Goodale A,Piccioni F,Johannessen CM,Landau DA

    更新日期:2020-01-22 00:00:00

  • Metabolism-Centric Trans-Omics.

    abstract::Two recent studies in Cell and Science demonstrate the reconstruction of global mechanistic networks and identification of regulatory principles from multi-omics data. ...

    journal_title:Cell systems

    pub_type: 评论,杂志文章

    doi:10.1016/j.cels.2017.01.007

    authors: Yugi K,Kuroda S

    更新日期:2017-01-25 00:00:00

  • Quantitative Translation of Dog-to-Human Aging by Conserved Remodeling of the DNA Methylome.

    abstract::All mammals progress through similar physiological stages throughout life, from early development to puberty, aging, and death. Yet, the extent to which this conserved physiology reflects underlying genomic events is unclear. Here, we map the common methylation changes experienced by mammalian genomes as they age, foc...

    journal_title:Cell systems

    pub_type: 杂志文章

    doi:10.1016/j.cels.2020.06.006

    authors: Wang T,Ma J,Hogan AN,Fong S,Licon K,Tsui B,Kreisberg JF,Adams PD,Carvunis AR,Bannasch DL,Ostrander EA,Ideker T

    更新日期:2020-08-26 00:00:00

  • Divergent Aging of Isogenic Yeast Cells Revealed through Single-Cell Phenotypic Dynamics.

    abstract::Although genetic mutations that alter organisms' average lifespans have been identified in aging research, our understanding of the dynamic changes during aging remains limited. Here, we integrate single-cell imaging, microfluidics, and computational modeling to investigate phenotypic divergence and cellular heterogen...

    journal_title:Cell systems

    pub_type: 杂志文章

    doi:10.1016/j.cels.2019.02.002

    authors: Jin M,Li Y,O'Laughlin R,Bittihn P,Pillus L,Tsimring LS,Hasty J,Hao N

    更新日期:2019-03-27 00:00:00

  • How Can Systems Biology Test Principles and Tools Using Immune Cells as a Model?

    abstract::The field of systems immunology has grown extensively over the last few years, spurred by the generation of large datasets, new analytical tools, and modeling approaches. In this piece and its counterpart in Trends in Immunology [http://www.cell.com/trends/immunology/fulltext/S1471-4906(18)30013-9], eight authors disc...

    journal_title:Cell systems

    pub_type: 社论,面试

    doi:10.1016/j.cels.2018.02.005

    authors:

    更新日期:2018-02-28 00:00:00

  • Breaking New Ground in the Landscape of Single-Cell Analysis.

    abstract::Here, we outline p-Creode, a new algorithm to construct multi-branching cell lineage trajectories from single-cell data. Application of this platform to diverse sources of single-cell data demonstrates its robustness and scalability, while the discovery of a new origin for rare gut tuft cells showcases the utility of ...

    journal_title:Cell systems

    pub_type: 评论,杂志文章

    doi:10.1016/j.cels.2017.12.015

    authors: Kamimoto K,Morris SA

    更新日期:2018-01-24 00:00:00

  • Systems-wide Studies Uncover Commander, a Multiprotein Complex Essential to Human Development.

    abstract::Recent mass spectrometry maps of the human interactome independently support the existence of a large multiprotein complex, dubbed "Commander." Broadly conserved across animals and ubiquitously expressed in nearly every human cell type examined thus far, Commander likely plays a fundamental cellular function, akin to ...

    journal_title:Cell systems

    pub_type: 杂志文章,评审

    doi:10.1016/j.cels.2017.04.006

    authors: Mallam AL,Marcotte EM

    更新日期:2017-05-24 00:00:00