A modular transcriptional signature identifies phenotypic heterogeneity of human tuberculosis infection

Singhania, Akul; Verma, Raman; Graham, Christine M.; Lee, Jo; Tran, Trang Anh Thi; Richardson, Matthew; Lécine, Patrick; Leissner, Philippe; Berry, Matthew; Wilkinson, Robert J.; Kaiser, Karine; Rodrigue, Marc; Woltmann, Gerrit; Haldar, Pranabashis; O’Garra, Anne

doi:10.1038/s41467-018-04579-w

Nat Commun

2018

DOI: 10.1038/s41467-018-04579-w

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A modular transcriptional signature identifies phenotypic heterogeneity of human tuberculosis infection

Akul Singhania

¹

,

Raman Verma

²

,

Christine M. Graham

³

et al.

Abstract: Whole blood transcriptional signatures distinguishing active tuberculosis patients from asymptomatic latently infected individuals exist. Consensus has not been achieved regarding the optimal reduced gene sets as diagnostic biomarkers that also achieve discrimination from other diseases. Here we show a blood transcriptional signature of active tuberculosis using RNA-Seq, confirming microarray results, that discriminates active tuberculosis from latently infected and healthy individuals, validating this signatu… Show more

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Cited by 235 publications

(241 citation statements)

References 65 publications

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214

Contrasting

1

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“…However, we found that neutrophil genes inducible by IFN-β alone are reduced in actively infected individuals indicating that IFN-γ may be more dominant than type 1 interferons in driving the interferon-inducible signature of neutrophils during active tuberculosis. This is in contrast to a recent report showing that IFNG (which encodes IFN-γ) and TBX21 (which encodes the transcription factor T-bet) are downregulated in patients with active TB (17). Hence, the ratio of type 1 interferon vs IFN-γ inducible genes in neutrophils needs to be better clarified in future studies.…”

Section: Discussioncontrasting

confidence: 99%

Distinct features of human myeloid cell cytokine response profiles identify neutrophil activation by cytokines as a prognostic feature during tuberculosis and cancer1

Devlin

¹

,

Zwack

²

,

Tang

³

et al. 2019

Preprint

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Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

show abstract

“…However, we found that neutrophil genes inducible by IFN-β alone are reduced in actively infected individuals indicating that IFN-γ may be more dominant than type 1 interferons in driving the interferon-inducible signature of neutrophils during active tuberculosis. This is in contrast to a recent report showing that IFNG (which encodes IFN-γ) and TBX21 (which encodes the transcription factor T-bet) are downregulated in patients with active TB (17). Hence, the ratio of type 1 interferon vs IFN-γ inducible genes in neutrophils needs to be better clarified in future studies.…”

Section: Discussioncontrasting

confidence: 99%

Distinct features of human myeloid cell cytokine response profiles identify neutrophil activation by cytokines as a prognostic feature during tuberculosis and cancer1

Devlin

¹

,

Zwack

²

,

Tang

³

et al. 2019

Preprint

Get access via publisher Add to dashboard Cite

Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

show abstract

“…While the 42 ISGs were upregulated in the blood of CL patients ( Fig 2A and 2B ), 133 ISGs were upregulated in the blood of patients with active TB, in which 85% is composed by type I and type II ISG ( Fig 5B ). These results are consistent with the previous analysis of this dataset [ 13 , 14 ]. In contrast, malaria was marked by a much larger number of DEGs that included 1,288 ISGs, as well as many genes not annotated as part of the Interferome ( Fig 5B ) (FDR≤0.01 and FC≥2).…”

Section: Resultssupporting

confidence: 94%

Localized skin inflammation during cutaneous leishmaniasis drives a chronic, systemic IFN-γ signature

Amorim

¹

,

Novais

²

,

Nguyen

³

et al. 2021

Get access via publisher Add to dashboard Cite

Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

show abstract

“…While the 42 ISGs were upregulated in the blood of CL patients (Fig 2A left and Fig 2B left), 133 ISGs were upregulated in the blood of patients with active TB, in which 85% is composed by type I and type II ISG (Fig 5B top and bottom-left). These results are consistent with the previous analysis of this dataset [13,14]. In contrast, malaria was marked by a much larger number of DEGs that included 1,288 ISGs, as well as many genes not annotated as part of the Interferome (Fig 5B top and bottom-right) (FDR≤.01 and FC≥2).…”

Section: Resultssupporting

confidence: 92%

Localized skin inflammation during cutaneous leishmaniasis drives a chronic, systemic IFN-γ signature

Amorim

¹

,

Novais

²

,

Nguyen

³

et al. 2020

Preprint

Get access via publisher Add to dashboard Cite

Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

show abstract

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