Cell composition analysis of bulk genomics using single-cell data.

Abstract:

:Single-cell RNA sequencing (scRNA-seq) is a rich resource of cellular heterogeneity, opening new avenues in the study of complex tissues. We introduce Cell Population Mapping (CPM), a deconvolution algorithm in which reference scRNA-seq profiles are leveraged to infer the composition of cell types and states from bulk transcriptome data ('scBio' CRAN R-package). Analysis of individual variations in lungs of influenza-virus-infected mice reveals that the relationship between cell abundance and clinical symptoms is a cell-state-specific property that varies gradually along the continuum of cell-activation states. The gradual change is confirmed in subsequent experiments and is further explained by a mathematical model in which clinical outcomes relate to cell-state dynamics along the activation process. Our results demonstrate the power of CPM in reconstructing the continuous spectrum of cell states within heterogeneous tissues.

journal_name

Nat Methods

journal_title

Nature methods

authors

Frishberg A,Peshes-Yaloz N,Cohn O,Rosentul D,Steuerman Y,Valadarsky L,Yankovitz G,Mandelboim M,Iraqi FA,Amit I,Mayo L,Bacharach E,Gat-Viks I

doi

10.1038/s41592-019-0355-5

subject

Has Abstract

pub_date

2019-04-01 00:00:00

pages

327-332

issue

4

eissn

1548-7091

issn

1548-7105

pii

10.1038/s41592-019-0355-5

journal_volume

16

pub_type

杂志文章
  • Author Correction: Resolution upgrades for light-sheet microscopy.

    abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title:Nature methods

    pub_type: 已发布勘误

    doi:10.1038/s41592-019-0588-3

    authors: Fiolka R

    更新日期:2019-10-01 00:00:00

  • Metabolic biotinylation of cell surface receptors for in vivo imaging.

    abstract::We have developed a versatile, potent technique for imaging cells in culture and in vivo by expressing a metabolically biotinylated cell-surface receptor and visualizing it with labeled streptavidin moieties. The recombinant reporter protein, which incorporates a biotin acceptor peptide (BAP) between an N-terminal sig...

    journal_title:Nature methods

    pub_type: 杂志文章

    doi:10.1038/nmeth875

    authors: Tannous BA,Grimm J,Perry KF,Chen JW,Weissleder R,Breakefield XO

    更新日期:2006-05-01 00:00:00

  • The GEM mapper: fast, accurate and versatile alignment by filtration.

    abstract::Because of ever-increasing throughput requirements of sequencing data, most existing short-read aligners have been designed to focus on speed at the expense of accuracy. The Genome Multitool (GEM) mapper can leverage string matching by filtration to search the alignment space more efficiently, simultaneously deliverin...

    journal_title:Nature methods

    pub_type: 杂志文章

    doi:10.1038/nmeth.2221

    authors: Marco-Sola S,Sammeth M,Guigó R,Ribeca P

    更新日期:2012-12-01 00:00:00

  • Quantitative analysis of gene expression in a single cell by qPCR.

    abstract::We developed a quantitative PCR method featuring a reusable single-cell cDNA library immobilized on beads for measuring the expression of multiple genes in a single cell. We used this method to analyze multiple cDNA targets (from several copies to several hundred thousand copies) with an experimental error of 15.9% or...

    journal_title:Nature methods

    pub_type: 杂志文章

    doi:10.1038/nmeth.1338

    authors: Taniguchi K,Kajiyama T,Kambara H

    更新日期:2009-07-01 00:00:00

  • Induction of linear tracks of DNA double-strand breaks by alpha-particle irradiation of cells.

    abstract::Understanding how cells maintain genome integrity when challenged with DNA double-strand breaks (DSBs) is of major importance, particularly since the discovery of multiple links of DSBs with genome instability and cancer-predisposition disorders. Ionizing radiation is the agent of choice to produce DSBs in cells; howe...

    journal_title:Nature methods

    pub_type: 杂志文章

    doi:10.1038/nmeth.f.206

    authors: Stap J,Krawczyk PM,Van Oven CH,Barendsen GW,Essers J,Kanaar R,Aten JA

    更新日期:2008-03-01 00:00:00

  • Cas9 as a versatile tool for engineering biology.

    abstract::RNA-guided Cas9 nucleases derived from clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems have dramatically transformed our ability to edit the genomes of diverse organisms. We believe tools and techniques based on Cas9, a single unifying factor capable of colocalizing RNA, DNA and protein,...

    journal_title:Nature methods

    pub_type: 杂志文章,评审

    doi:10.1038/nmeth.2649

    authors: Mali P,Esvelt KM,Church GM

    更新日期:2013-10-01 00:00:00

  • Rapid selection of transgenic C. elegans using antibiotic resistance.

    abstract::Caenorhabditis elegans is an important model organism in biology, but until now no antibiotic selection markers have been successfully demonstrated for this species. We have developed a selection system using puromycin that allows the rapid and easy isolation of large populations of transgenic worms. This approach is ...

    journal_title:Nature methods

    pub_type: 杂志文章

    doi:10.1038/nmeth.1495

    authors: Semple JI,Garcia-Verdugo R,Lehner B

    更新日期:2010-09-01 00:00:00

  • Proteomics data reuse with MassIVE-KB.

    abstract:: ...

    journal_title:Nature methods

    pub_type: 评论,杂志文章

    doi:10.1038/s41592-018-0283-9

    authors: Doerr A

    更新日期:2019-01-01 00:00:00

  • Terminal exon characterization with TECtool reveals an abundance of cell-specific isoforms.

    abstract::Sequencing of RNA 3' ends has uncovered numerous sites that do not correspond to the termination sites of known transcripts. Through their 3' untranslated regions, protein-coding RNAs interact with RNA-binding proteins and microRNAs, which regulate many properties, including RNA stability and subcellular localization....

    journal_title:Nature methods

    pub_type: 杂志文章

    doi:10.1038/s41592-018-0114-z

    authors: Gruber AJ,Gypas F,Riba A,Schmidt R,Zavolan M

    更新日期:2018-10-01 00:00:00

  • Fluorogenic DNA sequencing in PDMS microreactors.

    abstract::We developed a multiplex sequencing-by-synthesis method combining terminal phosphate-labeled fluorogenic nucleotides (TPLFNs) and resealable polydimethylsiloxane (PDMS) microreactors. In the presence of phosphatase, primer extension by DNA polymerase using nonfluorescent TPLFNs generates fluorophores, which are confin...

    journal_title:Nature methods

    pub_type: 杂志文章

    doi:10.1038/nmeth.1629

    authors: Sims PA,Greenleaf WJ,Duan H,Xie XS

    更新日期:2011-06-12 00:00:00

  • DIA-Umpire: comprehensive computational framework for data-independent acquisition proteomics.

    abstract::As a result of recent improvements in mass spectrometry (MS), there is increased interest in data-independent acquisition (DIA) strategies in which all peptides are systematically fragmented using wide mass-isolation windows ('multiplex fragmentation'). DIA-Umpire (http://diaumpire.sourceforge.net/), a comprehensive c...

    journal_title:Nature methods

    pub_type: 杂志文章

    doi:10.1038/nmeth.3255

    authors: Tsou CC,Avtonomov D,Larsen B,Tucholska M,Choi H,Gingras AC,Nesvizhskii AI

    更新日期:2015-03-01 00:00:00

  • In vivo three-photon imaging of activity of GCaMP6-labeled neurons deep in intact mouse brain.

    abstract::High-resolution optical imaging is critical to understanding brain function. We demonstrate that three-photon microscopy at 1,300-nm excitation enables functional imaging of GCaMP6s-labeled neurons beyond the depth limit of two-photon microscopy. We record spontaneous activity from up to 150 neurons in the hippocampal...

    journal_title:Nature methods

    pub_type: 杂志文章

    doi:10.1038/nmeth.4183

    authors: Ouzounov DG,Wang T,Wang M,Feng DD,Horton NG,Cruz-Hernández JC,Cheng YT,Reimer J,Tolias AS,Nishimura N,Xu C

    更新日期:2017-04-01 00:00:00

  • LambdaN-GFP: an RNA reporter system for live-cell imaging.

    abstract::We describe a GFP-based RNA reporter system (lambdaN-GFP) to visualize RNA molecules in live mammalian cells. It consists of GFP fused to an arginine-rich peptide derived from the phage lambda N protein, lambdaN22, which binds a unique minimal RNA motif and can be used to tag any RNA molecule. LambdaN-GFP uses a small...

    journal_title:Nature methods

    pub_type: 杂志文章

    doi:10.1038/nmeth1065

    authors: Daigle N,Ellenberg J

    更新日期:2007-08-01 00:00:00

  • Lost in presumption: stochastic reactions in spatial models.

    abstract::Physical modeling is increasingly important for generating insights into intracellular processes. We describe situations in which combined spatial and stochastic aspects of chemical reactions are needed to capture the relevant dynamics of biochemical systems. ...

    journal_title:Nature methods

    pub_type: 杂志文章

    doi:10.1038/nmeth.2253

    authors: Mahmutovic A,Fange D,Berg OG,Elf J

    更新日期:2012-12-01 00:00:00

  • Single-cell systems biology by super-resolution imaging and combinatorial labeling.

    abstract::Fluorescence microscopy is a powerful quantitative tool for exploring regulatory networks in single cells. However, the number of molecular species that can be measured simultaneously is limited by the spectral overlap between fluorophores. Here we demonstrate a simple but general strategy to drastically increase the ...

    journal_title:Nature methods

    pub_type: 杂志文章

    doi:10.1038/nmeth.2069

    authors: Lubeck E,Cai L

    更新日期:2012-06-03 00:00:00

  • Overcoming protein diversity on arrays.

    abstract::Researchers show that to reliably establish protein interaction networks from microarray data it is necessary to measure saturation binding curves for each arrayed protein and its potential binding partners. ...

    journal_title:Nature methods

    pub_type: 杂志文章

    doi:10.1038/nmeth1206-966

    authors: Rusk N

    更新日期:2006-12-01 00:00:00

  • The inside tag.

    abstract::An uncharged CoA precursor that can enter the cell is used for covalent, site-specific labeling of proteins inside living cells. ...

    journal_title:Nature methods

    pub_type: 杂志文章

    doi:10.1038/nmeth1106-872b

    authors: Kaganman I

    更新日期:2006-11-01 00:00:00

  • Ethical reproducibility: towards transparent reporting in biomedical research.

    abstract::Optimism about biomedicine is challenged by the increasingly complex ethical, legal and social issues it raises. Reporting of scientific methods is no longer sufficient to address the complex relationship between science and society. To promote 'ethical reproducibility', we call for transparent reporting of research e...

    journal_title:Nature methods

    pub_type: 杂志文章

    doi:10.1038/nmeth.2564

    authors: Anderson JA,Eijkholt M,Illes J

    更新日期:2013-09-01 00:00:00

  • Imaging without lenses: achievements and remaining challenges of wide-field on-chip microscopy.

    abstract::We discuss unique features of lens-free computational imaging tools and report some of their emerging results for wide-field on-chip microscopy, such as the achievement of a numerical aperture (NA) of ∼0.8-0.9 across a field of view (FOV) of more than 20 mm(2) or an NA of ∼0.1 across a FOV of ∼18 cm(2), which correspo...

    journal_title:Nature methods

    pub_type: 杂志文章

    doi:10.1038/nmeth.2114

    authors: Greenbaum A,Luo W,Su TW,Göröcs Z,Xue L,Isikman SO,Coskun AF,Mudanyali O,Ozcan A

    更新日期:2012-09-01 00:00:00

  • Probabilistic cell-type assignment of single-cell RNA-seq for tumor microenvironment profiling.

    abstract::Single-cell RNA sequencing has enabled the decomposition of complex tissues into functionally distinct cell types. Often, investigators wish to assign cells to cell types through unsupervised clustering followed by manual annotation or via 'mapping' to existing data. However, manual interpretation scales poorly to lar...

    journal_title:Nature methods

    pub_type: 杂志文章

    doi:10.1038/s41592-019-0529-1

    authors: Zhang AW,O'Flanagan C,Chavez EA,Lim JLP,Ceglia N,McPherson A,Wiens M,Walters P,Chan T,Hewitson B,Lai D,Mottok A,Sarkozy C,Chong L,Aoki T,Wang X,Weng AP,McAlpine JN,Aparicio S,Steidl C,Campbell KR,Shah SP

    更新日期:2019-10-01 00:00:00

  • Pulse proteolysis: a simple method for quantitative determination of protein stability and ligand binding.

    abstract::Thermodynamic stability is fundamental to the biology of proteins. Information on protein stability is essential for studying protein structure and folding and can also be used indirectly to monitor protein-ligand or protein-protein interactions. While clearly valuable, the experimental determination of a protein's st...

    journal_title:Nature methods

    pub_type: 杂志文章

    doi:10.1038/nmeth740

    authors: Park C,Marqusee S

    更新日期:2005-03-01 00:00:00

  • Bending the genome.

    abstract:: ...

    journal_title:Nature methods

    pub_type: 杂志文章

    doi:10.1038/s41592-018-0270-1

    authors: Rusk N

    更新日期:2019-01-01 00:00:00

  • CRISPR off-target analysis in genetically engineered rats and mice.

    abstract::Despite widespread use of CRISPR, comprehensive data on the frequency and impact of Cas9-mediated off-targets in modified rodents are limited. Here we present deep-sequencing data from 81 genome-editing projects on mouse and rat genomes at 1,423 predicted off-target sites, 32 of which were confirmed, and show that hig...

    journal_title:Nature methods

    pub_type: 杂志文章

    doi:10.1038/s41592-018-0011-5

    authors: Anderson KR,Haeussler M,Watanabe C,Janakiraman V,Lund J,Modrusan Z,Stinson J,Bei Q,Buechler A,Yu C,Thamminana SR,Tam L,Sowick MA,Alcantar T,O'Neil N,Li J,Ta L,Lima L,Roose-Girma M,Rairdan X,Durinck S,Warming S

    更新日期:2018-07-01 00:00:00

  • Marker-independent identification of glioma-initiating cells.

    abstract::Tumor-initiating cells with stem cell properties are believed to sustain the growth of gliomas, but proposed markers such as CD133 cannot be used to identify these cells with sufficient specificity. We report an alternative isolation method purely based on phenotypic qualities of glioma-initiating cells (GICs), avoidi...

    journal_title:Nature methods

    pub_type: 杂志文章,收录出版

    doi:10.1038/nmeth.1430

    authors: Clément V,Marino D,Cudalbu C,Hamou MF,Mlynarik V,de Tribolet N,Dietrich PY,Gruetter R,Hegi ME,Radovanovic I

    更新日期:2010-03-01 00:00:00

  • Designer receptors for every body.

    abstract::Using a directed evolution approach, researchers demonstrate a way of creating 'designer' receptors that are specifically activated by a ligand with no other biological activity in the cell. ...

    journal_title:Nature methods

    pub_type: 杂志文章

    doi:10.1038/nmeth0507-382b

    authors: Kaganman I

    更新日期:2007-05-01 00:00:00

  • Correlated light and electron microscopic imaging of multiple endogenous proteins using Quantum dots.

    abstract::The importance of locating proteins in their context within cells has been heightened recently by the accomplishments in molecular structure and systems biology. Although light microscopy (LM) has been extensively used for mapping protein localization, many studies require the additional resolution of the electron mic...

    journal_title:Nature methods

    pub_type: 杂志文章

    doi:10.1038/nmeth791

    authors: Giepmans BN,Deerinck TJ,Smarr BL,Jones YZ,Ellisman MH

    更新日期:2005-10-01 00:00:00

  • Highly parallel assays of tissue-specific enhancers in whole Drosophila embryos.

    abstract::Transcriptional enhancers are a primary mechanism by which tissue-specific gene expression is achieved. Despite the importance of these regulatory elements in development, responses to environmental stresses and disease, testing enhancer activity in animals remains tedious, with a minority of enhancers having been cha...

    journal_title:Nature methods

    pub_type: 杂志文章

    doi:10.1038/nmeth.2558

    authors: Gisselbrecht SS,Barrera LA,Porsch M,Aboukhalil A,Estep PW 3rd,Vedenko A,Palagi A,Kim Y,Zhu X,Busser BW,Gamble CE,Iagovitina A,Singhania A,Michelson AM,Bulyk ML

    更新日期:2013-08-01 00:00:00

  • Efficient incorporation of unnatural amino acids into proteins in Escherichia coli.

    abstract::We have developed a single-plasmid system for the efficient bacterial expression of mutant proteins containing unnatural amino acids at specific sites designated by amber nonsense codons. In this system, multiple copies of a gene encoding an amber suppressor tRNA derived from a Methanocaldococcus jannaschii tyrosyl-tR...

    journal_title:Nature methods

    pub_type: 杂志文章

    doi:10.1038/nmeth864

    authors: Ryu Y,Schultz PG

    更新日期:2006-04-01 00:00:00

  • Ultrastructurally smooth thick partitioning and volume stitching for large-scale connectomics.

    abstract::Focused-ion-beam scanning electron microscopy (FIB-SEM) has become an essential tool for studying neural tissue at resolutions below 10 nm × 10 nm × 10 nm, producing data sets optimized for automatic connectome tracing. We present a technical advance, ultrathick sectioning, which reliably subdivides embedded tissue sa...

    journal_title:Nature methods

    pub_type: 杂志文章

    doi:10.1038/nmeth.3292

    authors: Hayworth KJ,Xu CS,Lu Z,Knott GW,Fetter RD,Tapia JC,Lichtman JW,Hess HF

    更新日期:2015-04-01 00:00:00

  • Gas cluster ion beam SEM for imaging of large tissue samples with 10 nm isotropic resolution.

    abstract::We demonstrate gas cluster ion beam scanning electron microscopy (SEM), in which wide-area ion milling is performed on a series of thick tissue sections. This three-dimensional electron microscopy technique acquires datasets with <10 nm isotropic resolution of each section, and these can then be stitched together to s...

    journal_title:Nature methods

    pub_type: 杂志文章

    doi:10.1038/s41592-019-0641-2

    authors: Hayworth KJ,Peale D,Januszewski M,Knott GW,Lu Z,Xu CS,Hess HF

    更新日期:2020-01-01 00:00:00