A Reproducibility-Based Computational Framework Identifies an Inducible, Enhanced Antiviral State in Dendritic Cells from HIV-1 Elite Controllers

Abstract Background Human immunity relies on the coordinated responses of many cellular subsets and functional states. Inter-individual variations in cellular composition and communication could thus potentially alter host protection. Here, we explore this hypothesis by applying single-cell RNA-sequ...
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Autor*in:	Enrique Martin-Gayo [verfasserIn] Michael B. Cole [verfasserIn] Kellie E. Kolb [verfasserIn] Zhengyu Ouyang [verfasserIn] Jacqueline Cronin [verfasserIn] Samuel W. Kazer [verfasserIn] Jose Ordovas-Montanes [verfasserIn] Mathias Lichterfeld [verfasserIn] Bruce D. Walker [verfasserIn] Nir Yosef [verfasserIn] Alex K. Shalek [verfasserIn] Xu G. Yu [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2018

Schlagwörter:	HIV-1 Dendritic cell Single-cell RNA-seq Single-cell genomics Elite controller Adjuvant

Übergeordnetes Werk:	In: Genome Biology - BMC, 2014, 19(2018), 1, Seite 21
Übergeordnetes Werk:	volume:19 ; year:2018 ; number:1 ; pages:21

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/s13059-017-1385-x

Katalog-ID:	DOAJ033793786

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520			\|a Abstract Background Human immunity relies on the coordinated responses of many cellular subsets and functional states. Inter-individual variations in cellular composition and communication could thus potentially alter host protection. Here, we explore this hypothesis by applying single-cell RNA-sequencing to examine viral responses among the dendritic cells (DCs) of three elite controllers (ECs) of HIV-1 infection. Results To overcome the potentially confounding effects of donor-to-donor variability, we present a generally applicable computational framework for identifying reproducible patterns in gene expression across donors who share a unifying classification. Applying it, we discover a highly functional antiviral DC state in ECs whose fractional abundance after in vitro exposure to HIV-1 correlates with higher CD4+ T cell counts and lower HIV-1 viral loads, and that effectively primes polyfunctional T cell responses in vitro. By integrating information from existing genomic databases into our reproducibility-based analysis, we identify and validate select immunomodulators that increase the fractional abundance of this state in primary peripheral blood mononuclear cells from healthy individuals in vitro. Conclusions Overall, our results demonstrate how single-cell approaches can reveal previously unappreciated, yet important, immune behaviors and empower rational frameworks for modulating systems-level immune responses that may prove therapeutically and prophylactically useful.
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spelling	10.1186/s13059-017-1385-x doi (DE-627)DOAJ033793786 (DE-599)DOAJ49d6cbdd74584883a09c5c667e8590f0 DE-627 ger DE-627 rakwb eng QH301-705.5 QH426-470 Enrique Martin-Gayo verfasserin aut A Reproducibility-Based Computational Framework Identifies an Inducible, Enhanced Antiviral State in Dendritic Cells from HIV-1 Elite Controllers 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Human immunity relies on the coordinated responses of many cellular subsets and functional states. Inter-individual variations in cellular composition and communication could thus potentially alter host protection. Here, we explore this hypothesis by applying single-cell RNA-sequencing to examine viral responses among the dendritic cells (DCs) of three elite controllers (ECs) of HIV-1 infection. Results To overcome the potentially confounding effects of donor-to-donor variability, we present a generally applicable computational framework for identifying reproducible patterns in gene expression across donors who share a unifying classification. Applying it, we discover a highly functional antiviral DC state in ECs whose fractional abundance after in vitro exposure to HIV-1 correlates with higher CD4+ T cell counts and lower HIV-1 viral loads, and that effectively primes polyfunctional T cell responses in vitro. By integrating information from existing genomic databases into our reproducibility-based analysis, we identify and validate select immunomodulators that increase the fractional abundance of this state in primary peripheral blood mononuclear cells from healthy individuals in vitro. Conclusions Overall, our results demonstrate how single-cell approaches can reveal previously unappreciated, yet important, immune behaviors and empower rational frameworks for modulating systems-level immune responses that may prove therapeutically and prophylactically useful. HIV-1 Dendritic cell Single-cell RNA-seq Single-cell genomics Elite controller Adjuvant Biology (General) Genetics Michael B. Cole verfasserin aut Kellie E. Kolb verfasserin aut Zhengyu Ouyang verfasserin aut Jacqueline Cronin verfasserin aut Samuel W. Kazer verfasserin aut Jose Ordovas-Montanes verfasserin aut Mathias Lichterfeld verfasserin aut Bruce D. Walker verfasserin aut Nir Yosef verfasserin aut Alex K. Shalek verfasserin aut Xu G. Yu verfasserin aut In Genome Biology BMC, 2014 19(2018), 1, Seite 21 (DE-627)326173617 (DE-600)2040529-7 1474760X nnns volume:19 year:2018 number:1 pages:21 https://doi.org/10.1186/s13059-017-1385-x kostenfrei https://doaj.org/article/49d6cbdd74584883a09c5c667e8590f0 kostenfrei http://link.springer.com/article/10.1186/s13059-017-1385-x kostenfrei https://doaj.org/toc/1474-760X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 19 2018 1 21
allfields_unstemmed	10.1186/s13059-017-1385-x doi (DE-627)DOAJ033793786 (DE-599)DOAJ49d6cbdd74584883a09c5c667e8590f0 DE-627 ger DE-627 rakwb eng QH301-705.5 QH426-470 Enrique Martin-Gayo verfasserin aut A Reproducibility-Based Computational Framework Identifies an Inducible, Enhanced Antiviral State in Dendritic Cells from HIV-1 Elite Controllers 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Human immunity relies on the coordinated responses of many cellular subsets and functional states. Inter-individual variations in cellular composition and communication could thus potentially alter host protection. Here, we explore this hypothesis by applying single-cell RNA-sequencing to examine viral responses among the dendritic cells (DCs) of three elite controllers (ECs) of HIV-1 infection. Results To overcome the potentially confounding effects of donor-to-donor variability, we present a generally applicable computational framework for identifying reproducible patterns in gene expression across donors who share a unifying classification. Applying it, we discover a highly functional antiviral DC state in ECs whose fractional abundance after in vitro exposure to HIV-1 correlates with higher CD4+ T cell counts and lower HIV-1 viral loads, and that effectively primes polyfunctional T cell responses in vitro. By integrating information from existing genomic databases into our reproducibility-based analysis, we identify and validate select immunomodulators that increase the fractional abundance of this state in primary peripheral blood mononuclear cells from healthy individuals in vitro. Conclusions Overall, our results demonstrate how single-cell approaches can reveal previously unappreciated, yet important, immune behaviors and empower rational frameworks for modulating systems-level immune responses that may prove therapeutically and prophylactically useful. HIV-1 Dendritic cell Single-cell RNA-seq Single-cell genomics Elite controller Adjuvant Biology (General) Genetics Michael B. Cole verfasserin aut Kellie E. Kolb verfasserin aut Zhengyu Ouyang verfasserin aut Jacqueline Cronin verfasserin aut Samuel W. Kazer verfasserin aut Jose Ordovas-Montanes verfasserin aut Mathias Lichterfeld verfasserin aut Bruce D. Walker verfasserin aut Nir Yosef verfasserin aut Alex K. Shalek verfasserin aut Xu G. Yu verfasserin aut In Genome Biology BMC, 2014 19(2018), 1, Seite 21 (DE-627)326173617 (DE-600)2040529-7 1474760X nnns volume:19 year:2018 number:1 pages:21 https://doi.org/10.1186/s13059-017-1385-x kostenfrei https://doaj.org/article/49d6cbdd74584883a09c5c667e8590f0 kostenfrei http://link.springer.com/article/10.1186/s13059-017-1385-x kostenfrei https://doaj.org/toc/1474-760X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 19 2018 1 21
allfieldsGer	10.1186/s13059-017-1385-x doi (DE-627)DOAJ033793786 (DE-599)DOAJ49d6cbdd74584883a09c5c667e8590f0 DE-627 ger DE-627 rakwb eng QH301-705.5 QH426-470 Enrique Martin-Gayo verfasserin aut A Reproducibility-Based Computational Framework Identifies an Inducible, Enhanced Antiviral State in Dendritic Cells from HIV-1 Elite Controllers 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Human immunity relies on the coordinated responses of many cellular subsets and functional states. Inter-individual variations in cellular composition and communication could thus potentially alter host protection. Here, we explore this hypothesis by applying single-cell RNA-sequencing to examine viral responses among the dendritic cells (DCs) of three elite controllers (ECs) of HIV-1 infection. Results To overcome the potentially confounding effects of donor-to-donor variability, we present a generally applicable computational framework for identifying reproducible patterns in gene expression across donors who share a unifying classification. Applying it, we discover a highly functional antiviral DC state in ECs whose fractional abundance after in vitro exposure to HIV-1 correlates with higher CD4+ T cell counts and lower HIV-1 viral loads, and that effectively primes polyfunctional T cell responses in vitro. By integrating information from existing genomic databases into our reproducibility-based analysis, we identify and validate select immunomodulators that increase the fractional abundance of this state in primary peripheral blood mononuclear cells from healthy individuals in vitro. Conclusions Overall, our results demonstrate how single-cell approaches can reveal previously unappreciated, yet important, immune behaviors and empower rational frameworks for modulating systems-level immune responses that may prove therapeutically and prophylactically useful. HIV-1 Dendritic cell Single-cell RNA-seq Single-cell genomics Elite controller Adjuvant Biology (General) Genetics Michael B. Cole verfasserin aut Kellie E. Kolb verfasserin aut Zhengyu Ouyang verfasserin aut Jacqueline Cronin verfasserin aut Samuel W. Kazer verfasserin aut Jose Ordovas-Montanes verfasserin aut Mathias Lichterfeld verfasserin aut Bruce D. Walker verfasserin aut Nir Yosef verfasserin aut Alex K. Shalek verfasserin aut Xu G. Yu verfasserin aut In Genome Biology BMC, 2014 19(2018), 1, Seite 21 (DE-627)326173617 (DE-600)2040529-7 1474760X nnns volume:19 year:2018 number:1 pages:21 https://doi.org/10.1186/s13059-017-1385-x kostenfrei https://doaj.org/article/49d6cbdd74584883a09c5c667e8590f0 kostenfrei http://link.springer.com/article/10.1186/s13059-017-1385-x kostenfrei https://doaj.org/toc/1474-760X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 19 2018 1 21
allfieldsSound	10.1186/s13059-017-1385-x doi (DE-627)DOAJ033793786 (DE-599)DOAJ49d6cbdd74584883a09c5c667e8590f0 DE-627 ger DE-627 rakwb eng QH301-705.5 QH426-470 Enrique Martin-Gayo verfasserin aut A Reproducibility-Based Computational Framework Identifies an Inducible, Enhanced Antiviral State in Dendritic Cells from HIV-1 Elite Controllers 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Human immunity relies on the coordinated responses of many cellular subsets and functional states. Inter-individual variations in cellular composition and communication could thus potentially alter host protection. Here, we explore this hypothesis by applying single-cell RNA-sequencing to examine viral responses among the dendritic cells (DCs) of three elite controllers (ECs) of HIV-1 infection. Results To overcome the potentially confounding effects of donor-to-donor variability, we present a generally applicable computational framework for identifying reproducible patterns in gene expression across donors who share a unifying classification. Applying it, we discover a highly functional antiviral DC state in ECs whose fractional abundance after in vitro exposure to HIV-1 correlates with higher CD4+ T cell counts and lower HIV-1 viral loads, and that effectively primes polyfunctional T cell responses in vitro. By integrating information from existing genomic databases into our reproducibility-based analysis, we identify and validate select immunomodulators that increase the fractional abundance of this state in primary peripheral blood mononuclear cells from healthy individuals in vitro. Conclusions Overall, our results demonstrate how single-cell approaches can reveal previously unappreciated, yet important, immune behaviors and empower rational frameworks for modulating systems-level immune responses that may prove therapeutically and prophylactically useful. HIV-1 Dendritic cell Single-cell RNA-seq Single-cell genomics Elite controller Adjuvant Biology (General) Genetics Michael B. Cole verfasserin aut Kellie E. Kolb verfasserin aut Zhengyu Ouyang verfasserin aut Jacqueline Cronin verfasserin aut Samuel W. Kazer verfasserin aut Jose Ordovas-Montanes verfasserin aut Mathias Lichterfeld verfasserin aut Bruce D. Walker verfasserin aut Nir Yosef verfasserin aut Alex K. Shalek verfasserin aut Xu G. Yu verfasserin aut In Genome Biology BMC, 2014 19(2018), 1, Seite 21 (DE-627)326173617 (DE-600)2040529-7 1474760X nnns volume:19 year:2018 number:1 pages:21 https://doi.org/10.1186/s13059-017-1385-x kostenfrei https://doaj.org/article/49d6cbdd74584883a09c5c667e8590f0 kostenfrei http://link.springer.com/article/10.1186/s13059-017-1385-x kostenfrei https://doaj.org/toc/1474-760X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 19 2018 1 21
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By integrating information from existing genomic databases into our reproducibility-based analysis, we identify and validate select immunomodulators that increase the fractional abundance of this state in primary peripheral blood mononuclear cells from healthy individuals in vitro. 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callnumber-first	Q - Science
author	Enrique Martin-Gayo
spellingShingle	Enrique Martin-Gayo misc QH301-705.5 misc QH426-470 misc HIV-1 misc Dendritic cell misc Single-cell RNA-seq misc Single-cell genomics misc Elite controller misc Adjuvant misc Biology (General) misc Genetics A Reproducibility-Based Computational Framework Identifies an Inducible, Enhanced Antiviral State in Dendritic Cells from HIV-1 Elite Controllers
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topic_title	QH301-705.5 QH426-470 A Reproducibility-Based Computational Framework Identifies an Inducible, Enhanced Antiviral State in Dendritic Cells from HIV-1 Elite Controllers HIV-1 Dendritic cell Single-cell RNA-seq Single-cell genomics Elite controller Adjuvant
topic	misc QH301-705.5 misc QH426-470 misc HIV-1 misc Dendritic cell misc Single-cell RNA-seq misc Single-cell genomics misc Elite controller misc Adjuvant misc Biology (General) misc Genetics
topic_unstemmed	misc QH301-705.5 misc QH426-470 misc HIV-1 misc Dendritic cell misc Single-cell RNA-seq misc Single-cell genomics misc Elite controller misc Adjuvant misc Biology (General) misc Genetics
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title	A Reproducibility-Based Computational Framework Identifies an Inducible, Enhanced Antiviral State in Dendritic Cells from HIV-1 Elite Controllers
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title_full	A Reproducibility-Based Computational Framework Identifies an Inducible, Enhanced Antiviral State in Dendritic Cells from HIV-1 Elite Controllers
author_sort	Enrique Martin-Gayo
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author_browse	Enrique Martin-Gayo Michael B. Cole Kellie E. Kolb Zhengyu Ouyang Jacqueline Cronin Samuel W. Kazer Jose Ordovas-Montanes Mathias Lichterfeld Bruce D. Walker Nir Yosef Alex K. Shalek Xu G. Yu
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title_sort	reproducibility-based computational framework identifies an inducible, enhanced antiviral state in dendritic cells from hiv-1 elite controllers
callnumber	QH301-705.5
title_auth	A Reproducibility-Based Computational Framework Identifies an Inducible, Enhanced Antiviral State in Dendritic Cells from HIV-1 Elite Controllers
abstract	Abstract Background Human immunity relies on the coordinated responses of many cellular subsets and functional states. Inter-individual variations in cellular composition and communication could thus potentially alter host protection. Here, we explore this hypothesis by applying single-cell RNA-sequencing to examine viral responses among the dendritic cells (DCs) of three elite controllers (ECs) of HIV-1 infection. Results To overcome the potentially confounding effects of donor-to-donor variability, we present a generally applicable computational framework for identifying reproducible patterns in gene expression across donors who share a unifying classification. Applying it, we discover a highly functional antiviral DC state in ECs whose fractional abundance after in vitro exposure to HIV-1 correlates with higher CD4+ T cell counts and lower HIV-1 viral loads, and that effectively primes polyfunctional T cell responses in vitro. By integrating information from existing genomic databases into our reproducibility-based analysis, we identify and validate select immunomodulators that increase the fractional abundance of this state in primary peripheral blood mononuclear cells from healthy individuals in vitro. Conclusions Overall, our results demonstrate how single-cell approaches can reveal previously unappreciated, yet important, immune behaviors and empower rational frameworks for modulating systems-level immune responses that may prove therapeutically and prophylactically useful.
abstractGer	Abstract Background Human immunity relies on the coordinated responses of many cellular subsets and functional states. Inter-individual variations in cellular composition and communication could thus potentially alter host protection. Here, we explore this hypothesis by applying single-cell RNA-sequencing to examine viral responses among the dendritic cells (DCs) of three elite controllers (ECs) of HIV-1 infection. Results To overcome the potentially confounding effects of donor-to-donor variability, we present a generally applicable computational framework for identifying reproducible patterns in gene expression across donors who share a unifying classification. Applying it, we discover a highly functional antiviral DC state in ECs whose fractional abundance after in vitro exposure to HIV-1 correlates with higher CD4+ T cell counts and lower HIV-1 viral loads, and that effectively primes polyfunctional T cell responses in vitro. By integrating information from existing genomic databases into our reproducibility-based analysis, we identify and validate select immunomodulators that increase the fractional abundance of this state in primary peripheral blood mononuclear cells from healthy individuals in vitro. Conclusions Overall, our results demonstrate how single-cell approaches can reveal previously unappreciated, yet important, immune behaviors and empower rational frameworks for modulating systems-level immune responses that may prove therapeutically and prophylactically useful.
abstract_unstemmed	Abstract Background Human immunity relies on the coordinated responses of many cellular subsets and functional states. Inter-individual variations in cellular composition and communication could thus potentially alter host protection. Here, we explore this hypothesis by applying single-cell RNA-sequencing to examine viral responses among the dendritic cells (DCs) of three elite controllers (ECs) of HIV-1 infection. Results To overcome the potentially confounding effects of donor-to-donor variability, we present a generally applicable computational framework for identifying reproducible patterns in gene expression across donors who share a unifying classification. Applying it, we discover a highly functional antiviral DC state in ECs whose fractional abundance after in vitro exposure to HIV-1 correlates with higher CD4+ T cell counts and lower HIV-1 viral loads, and that effectively primes polyfunctional T cell responses in vitro. By integrating information from existing genomic databases into our reproducibility-based analysis, we identify and validate select immunomodulators that increase the fractional abundance of this state in primary peripheral blood mononuclear cells from healthy individuals in vitro. Conclusions Overall, our results demonstrate how single-cell approaches can reveal previously unappreciated, yet important, immune behaviors and empower rational frameworks for modulating systems-level immune responses that may prove therapeutically and prophylactically useful.
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title_short	A Reproducibility-Based Computational Framework Identifies an Inducible, Enhanced Antiviral State in Dendritic Cells from HIV-1 Elite Controllers
url	https://doi.org/10.1186/s13059-017-1385-x https://doaj.org/article/49d6cbdd74584883a09c5c667e8590f0 http://link.springer.com/article/10.1186/s13059-017-1385-x https://doaj.org/toc/1474-760X
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author2	Michael B. Cole Kellie E. Kolb Zhengyu Ouyang Jacqueline Cronin Samuel W. Kazer Jose Ordovas-Montanes Mathias Lichterfeld Bruce D. Walker Nir Yosef Alex K. Shalek Xu G. Yu
author2Str	Michael B. Cole Kellie E. Kolb Zhengyu Ouyang Jacqueline Cronin Samuel W. Kazer Jose Ordovas-Montanes Mathias Lichterfeld Bruce D. Walker Nir Yosef Alex K. Shalek Xu G. Yu
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up_date	2024-07-03T19:41:27.476Z
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Inter-individual variations in cellular composition and communication could thus potentially alter host protection. Here, we explore this hypothesis by applying single-cell RNA-sequencing to examine viral responses among the dendritic cells (DCs) of three elite controllers (ECs) of HIV-1 infection. Results To overcome the potentially confounding effects of donor-to-donor variability, we present a generally applicable computational framework for identifying reproducible patterns in gene expression across donors who share a unifying classification. Applying it, we discover a highly functional antiviral DC state in ECs whose fractional abundance after in vitro exposure to HIV-1 correlates with higher CD4+ T cell counts and lower HIV-1 viral loads, and that effectively primes polyfunctional T cell responses in vitro. By integrating information from existing genomic databases into our reproducibility-based analysis, we identify and validate select immunomodulators that increase the fractional abundance of this state in primary peripheral blood mononuclear cells from healthy individuals in vitro. Conclusions Overall, our results demonstrate how single-cell approaches can reveal previously unappreciated, yet important, immune behaviors and empower rational frameworks for modulating systems-level immune responses that may prove therapeutically and prophylactically useful.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">HIV-1</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Dendritic cell</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Single-cell RNA-seq</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Single-cell genomics</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Elite controller</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Adjuvant</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Biology (General)</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Genetics</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Michael B. 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A Reproducibility-Based Computational Framework Identifies an Inducible, Enhanced Antiviral State in Dendritic Cells from HIV-1 Elite Controllers

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