An interactive reference framework for modeling a dynamic immune system

Matthew H. Spitzer; Pier Federico Gherardini; Gabriela K. Fragiadakis; Nupur Bhattacharya; Robert T. Yuan; Andrew N. Hotson; Rachel Finck; Yaron Carmi; Eli R. Zunder; Wendy J. Fantl; Sean C. Bendall; Edgar G. Engleman; Garry P. Nolan

doi:10.1126/science.1259425

An interactive reference framework for modeling a dynamic immune system

Matthew H. Spitzer^*, Pier Federico Gherardini, Gabriela K. Fragiadakis, Nupur Bhattacharya, Robert T. Yuan, Andrew N. Hotson, Rachel Finck, Yaron Carmi, Eli R. Zunder, Wendy J. Fantl, Sean C. Bendall, Edgar G. Engleman, Garry P. Nolan

^*Corresponding author for this work

Stanford University

Research output: Contribution to journal › Article › peer-review

197 Scopus citations

Abstract

Immune cells function in an interacting hierarchy that coordinates the activities of various cell types according to genetic and environmental contexts. We developed graphical approaches to construct an extensible immune reference map from mass cytometry data of cells from different organs, incorporating landmark cell populations as flags on the map to compare cells from distinct samples. The maps recapitulated canonical cellular phenotypes and revealed reproducible, tissue-specific deviations. The approach revealed influences of genetic variation and circadian rhythms on immune system structure, enabled direct comparisons of murine and human blood cell phenotypes, and even enabled archival fluorescence-based flow cytometry data to be mapped onto the reference framework. This foundational reference map provides a working definition of systemic immune organization to which new data can be integrated to reveal deviations driven by genetics, environment, or pathology.

Original language	English
Article number	1259425
Journal	Science
Volume	349
Issue number	6244
DOIs	https://doi.org/10.1126/science.1259425
State	Published - 10 Jul 2015
Externally published	Yes

Funding

Funders	Funder number
California Institute for Regenerative Medicine	RB2-01592, DR1-01477
Damon Runyon Cancer Research Foundation	DRG-2017-09
European Commission	HEALTH.2010.1.2-1
Howard Hughes Medical Institute
National Institute of Allergy and Infectious Diseases	R33 CA183654, N01-HV-00242, P01 CA034233-22A1, 1R01CA130826, 5-24927, HHSN272201200028C, PN2EY018228 0158 G KB065, RFA CA 09-009, U54CA149145, R01CA184968, 1R01NS089533, 5R01AI073724, RFA CA 09-011, HHSN272200700038C, 41000411217, U19 AI057229, 201303028, R33 CA183692, 5U54CA143907NIH
National Institutes of Health	T32GM007276, NRSA F32 GM093508-01, 7500108142, F31CA189331, 1R01GM109836, 1U19AI100627, K99GM104148-01
U.S. Department of Defense	OC110674, 11491122
U.S. Food and Drug Administration	HHSF223201210194C BAA-12-00118
National Institute of Diabetes and Digestive and Kidney Diseases	R01DK082537

Access to Document

10.1126/science.1259425

Cite this

@article{00c6e773eb1649e4a53b957d012ca01e,

title = "An interactive reference framework for modeling a dynamic immune system",

abstract = "Immune cells function in an interacting hierarchy that coordinates the activities of various cell types according to genetic and environmental contexts. We developed graphical approaches to construct an extensible immune reference map from mass cytometry data of cells from different organs, incorporating landmark cell populations as flags on the map to compare cells from distinct samples. The maps recapitulated canonical cellular phenotypes and revealed reproducible, tissue-specific deviations. The approach revealed influences of genetic variation and circadian rhythms on immune system structure, enabled direct comparisons of murine and human blood cell phenotypes, and even enabled archival fluorescence-based flow cytometry data to be mapped onto the reference framework. This foundational reference map provides a working definition of systemic immune organization to which new data can be integrated to reveal deviations driven by genetics, environment, or pathology.",

author = "Spitzer, {Matthew H.} and Gherardini, {Pier Federico} and Fragiadakis, {Gabriela K.} and Nupur Bhattacharya and Yuan, {Robert T.} and Hotson, {Andrew N.} and Rachel Finck and Yaron Carmi and Zunder, {Eli R.} and Fantl, {Wendy J.} and Bendall, {Sean C.} and Engleman, {Edgar G.} and Nolan, {Garry P.}",

year = "2015",

month = jul,

day = "10",

doi = "10.1126/science.1259425",

language = "אנגלית",

volume = "349",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6244",

}

TY - JOUR

T1 - An interactive reference framework for modeling a dynamic immune system

AU - Spitzer, Matthew H.

AU - Gherardini, Pier Federico

AU - Fragiadakis, Gabriela K.

AU - Bhattacharya, Nupur

AU - Yuan, Robert T.

AU - Hotson, Andrew N.

AU - Finck, Rachel

AU - Carmi, Yaron

AU - Zunder, Eli R.

AU - Fantl, Wendy J.

AU - Bendall, Sean C.

AU - Engleman, Edgar G.

AU - Nolan, Garry P.

PY - 2015/7/10

Y1 - 2015/7/10

N2 - Immune cells function in an interacting hierarchy that coordinates the activities of various cell types according to genetic and environmental contexts. We developed graphical approaches to construct an extensible immune reference map from mass cytometry data of cells from different organs, incorporating landmark cell populations as flags on the map to compare cells from distinct samples. The maps recapitulated canonical cellular phenotypes and revealed reproducible, tissue-specific deviations. The approach revealed influences of genetic variation and circadian rhythms on immune system structure, enabled direct comparisons of murine and human blood cell phenotypes, and even enabled archival fluorescence-based flow cytometry data to be mapped onto the reference framework. This foundational reference map provides a working definition of systemic immune organization to which new data can be integrated to reveal deviations driven by genetics, environment, or pathology.

AB - Immune cells function in an interacting hierarchy that coordinates the activities of various cell types according to genetic and environmental contexts. We developed graphical approaches to construct an extensible immune reference map from mass cytometry data of cells from different organs, incorporating landmark cell populations as flags on the map to compare cells from distinct samples. The maps recapitulated canonical cellular phenotypes and revealed reproducible, tissue-specific deviations. The approach revealed influences of genetic variation and circadian rhythms on immune system structure, enabled direct comparisons of murine and human blood cell phenotypes, and even enabled archival fluorescence-based flow cytometry data to be mapped onto the reference framework. This foundational reference map provides a working definition of systemic immune organization to which new data can be integrated to reveal deviations driven by genetics, environment, or pathology.

UR - http://www.scopus.com/inward/record.url?scp=84937604921&partnerID=8YFLogxK

U2 - 10.1126/science.1259425

DO - 10.1126/science.1259425

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 26160952

AN - SCOPUS:84937604921

SN - 0036-8075

VL - 349

JO - Science

JF - Science

IS - 6244

M1 - 1259425

ER -

An interactive reference framework for modeling a dynamic immune system

Abstract

Funding

Access to Document

Other files and links

Fingerprint

Cite this