Evidence map›Paper›PMID 25342659›Full record

ArticleScience (New York, N.Y.)2014

Systems biology. Conditional density-based analysis of T cell signaling in single-cell data.

Smita Krishnaswamy, Matthew H Spitzer, Michael Mingueneau, Sean C Bendall, Oren Litvin, Erica Stone, Dana Pe'er, Garry P Nolan

Open access · greenAbstract readValidation Study
In one paragraph

Article in Science (New York, N.Y.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers.

0numbers the graph read from it
0cells of the map it votes in
124citing papers in PubMed
11.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

124 citing papers in PubMed, 242 citations in OpenAlex.

  1. Article
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  7. Existence of Causation without Correlation in Transcriptional Networks.bioRxiv : the preprint server for biology · 2026
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  12. Review
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64 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 1 country.

Smita KrishnaswamyDepartment of Biological Sciences, Department of Systems Biology, Columbia University, New York, NY, USA.
Matthew H SpitzerBaxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA.
Michael MingueneauDivision of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA.
Sean C BendallBaxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA.
Oren LitvinDepartment of Biological Sciences, Department of Systems Biology, Columbia University, New York, NY, USA.
Erica StoneMolecular Biology Section, Division of Biological Sciences, Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
Dana Pe'erDepartment of Biological Sciences, Department of Systems Biology, Columbia University, New York, NY, USA. dpeer@biology.columbia.edu.
Garry P NolanBaxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA.
Columbia University · USStanford University · USBaxter (United States) · USHarvard University · US

Funding

Using a tonsil organoid system to probe conditions for the induction of protective antibody and T cell responses to influenza.U19AI057229 · NIAID · STANFORD UNIVERSITY · PI Mark Morris Davis · 2003 to 2026
$88.5M
Systems Biology CoreU19AI100627 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI ULEVITCH, RICHARD J · 2012 to 2021
$49.1M
Nation Center: Multi-Scale Study- Cellular Networks(RMI)U54CA121852 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CALIFANO, ANDREA · 2005 to 2015
$37.4M
TRIGGERING CELL DEATH IN B CELL LYMPHOMAP01CA034233 · NCI · STANFORD UNIVERSITY · PI TIBSHIRANI, ROB · 1985 to 2010
$19.5M
MODELING THE ROLE OF PROGRESSION IN FOLLICULAR LYMPHOMAU54CA149145 · NCI · STANFORD UNIVERSITY · PI PLEVRITIS, SYLVIA KATINA · 2010 to 2014
$12.1M
Software & Hardware Inference Engines for Automated Determination of Primary CellR01CA130826 · NCI · STANFORD UNIVERSITY · PI NOLAN, GARRY P · 2008 to 2011
$6.7M
A single-cell platform to discover and study regulators of human developmentR00GM104148 · NIGMS · STANFORD UNIVERSITY · PI BENDALL, SEAN CURTIS · 2014 to 2016
$747k
Regulation of Adipose Tissue Inflammation and Insulin Resistance by T Cell SubsetK01DK095008 · NIDDK · WISTAR INSTITUTE · PI STONE, ERICA LYN · 2012 to 2015
$662k
CyTOF Mass CytometerS10RR027582 · NCRR · STANFORD UNIVERSITY · PI NOLAN, GARRY P · 2010 to 2010
$500k
MECHANISTIC STUDIES IN THE BIOSYNTHESIS OF ACETYLENESF32CA009011 · NCI · BROWN UNIVERSITY · PI CASEBIER, DAVID S · 1990 to 1992
–
NCI NIH HHS 1R01CA130826NCI NIH HHS 1U54CA121852-01A1NCI NIH HHS CA 09-011NCI NIH HHS P01 CA034233NCI NIH HHS R01 CA130826NCI NIH HHS U54 CA121852NCI NIH HHS U54 CA149145NCRR NIH HHS S10 RR027582NCRR NIH HHS S10RR027582-01NHLBI NIH HHS HHSN268201000034CNHLBI NIH HHS HV-10-05NIAID NIH HHS HHSN272200700038CNIAID NIH HHS U19 AI057229NIAID NIH HHS U19 AI100627NIDDK NIH HHS 1K01DK095008NIDDK NIH HHS K01 DK095008NIGMS NIH HHS R00 GM104148
6 · The paper itself

Abstract

Cellular circuits sense the environment, process signals, and compute decisions using networks of interacting proteins. To model such a system, the abundance of each activated protein species can be described as a stochastic function of the abundance of other proteins. High-dimensional single-cell technologies, such as mass cytometry, offer an opportunity to characterize signaling circuit-wide. However, the challenge of developing and applying computational approaches to interpret such complex data remains. Here, we developed computational methods, based on established statistical concepts, to characterize signaling network relationships by quantifying the strengths of network edges and deriving signaling response functions. In comparing signaling between naïve and antigen-exposed CD4(+) T lymphocytes, we find that although these two cell subtypes had similarly wired networks, naïve cells transmitted more information along a key signaling cascade than did antigen-exposed cells. We validated our characterization on mice lacking the extracellular-regulated mitogen-activated protein kinase (MAPK) ERK2, which showed stronger influence of pERK on pS6 (phosphorylated-ribosomal protein S6), in naïve cells as compared with antigen-exposed cells, as predicted. We demonstrate that by using cell-to-cell variation inherent in single-cell data, we can derive response functions underlying molecular circuits and drive the understanding of how cells process signals.

Indexed as

AnimalsCD4-Positive T-LymphocytesComputer SimulationeIF-2 KinaseImage CytometryMaleMiceMice, Mutant StrainsMitogen-Activated Protein Kinase 1Receptors, Antigen, T-CellRibosomal Protein S6Signal TransductionSingle-Cell AnalysisSystems BiologyeIF-2 KinaseMapk1 protein, mouseMitogen-Activated Protein Kinase 1Receptors, Antigen, T-CellRibosomal Protein S6ribosomal protein S6, mouse

Identifiers

PMID25342659
PMCPMC4334155
OpenAlexW2079296583

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.