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The host transcriptional response to Candidemia is dominated by neutrophil activation and heme biosynthesis and supports novel diagnostic approaches.

Publication ,  Journal Article
Steinbrink, JM; Myers, RA; Hua, K; Johnson, MD; Seidelman, JL; Tsalik, EL; Henao, R; Ginsburg, GS; Woods, CW; Alexander, BD; McClain, MT
Published in: Genome Med
July 5, 2021

BACKGROUND: Candidemia is one of the most common nosocomial bloodstream infections in the United States, causing significant morbidity and mortality in hospitalized patients, but the breadth of the host response to Candida infections in human patients remains poorly defined. METHODS: In order to better define the host response to Candida infection at the transcriptional level, we performed RNA sequencing on serial peripheral blood samples from 48 hospitalized patients with blood cultures positive for Candida species and compared them to patients with other acute viral, bacterial, and non-infectious illnesses. Regularized multinomial regression was utilized to develop pathogen class-specific gene expression classifiers. RESULTS: Candidemia triggers a unique, robust, and conserved transcriptomic response in human hosts with 1641 genes differentially upregulated compared to healthy controls. Many of these genes corresponded to components of the immune response to fungal infection, heavily weighted toward neutrophil activation, heme biosynthesis, and T cell signaling. We developed pathogen class-specific classifiers from these unique signals capable of identifying and differentiating candidemia, viral, or bacterial infection across a variety of hosts with a high degree of accuracy (auROC 0.98 for candidemia, 0.99 for viral and bacterial infection). This classifier was validated on two separate human cohorts (auROC 0.88 for viral infection and 0.87 for bacterial infection in one cohort; auROC 0.97 in another cohort) and an in vitro model (auROC 0.94 for fungal infection, 0.96 for bacterial, and 0.90 for viral infection). CONCLUSIONS: Transcriptional analysis of circulating leukocytes in patients with acute Candida infections defines novel aspects of the breadth of the human immune response during candidemia and suggests promising diagnostic approaches for simultaneously differentiating multiple types of clinical illnesses in at-risk, acutely ill patients.

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Published In

Genome Med

DOI

EISSN

1756-994X

Publication Date

July 5, 2021

Volume

13

Issue

1

Start / End Page

108

Location

England

Related Subject Headings

  • Transcriptome
  • Severity of Illness Index
  • Risk Factors
  • Reproducibility of Results
  • ROC Curve
  • Prognosis
  • Neutrophil Activation
  • Middle Aged
  • Male
  • Humans
 

Citation

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Steinbrink, J. M., Myers, R. A., Hua, K., Johnson, M. D., Seidelman, J. L., Tsalik, E. L., … McClain, M. T. (2021). The host transcriptional response to Candidemia is dominated by neutrophil activation and heme biosynthesis and supports novel diagnostic approaches. Genome Med, 13(1), 108. https://doi.org/10.1186/s13073-021-00924-9
Steinbrink, Julie M., Rachel A. Myers, Kaiyuan Hua, Melissa D. Johnson, Jessica L. Seidelman, Ephraim L. Tsalik, Ricardo Henao, et al. “The host transcriptional response to Candidemia is dominated by neutrophil activation and heme biosynthesis and supports novel diagnostic approaches.Genome Med 13, no. 1 (July 5, 2021): 108. https://doi.org/10.1186/s13073-021-00924-9.
Steinbrink JM, Myers RA, Hua K, Johnson MD, Seidelman JL, Tsalik EL, et al. The host transcriptional response to Candidemia is dominated by neutrophil activation and heme biosynthesis and supports novel diagnostic approaches. Genome Med. 2021 Jul 5;13(1):108.
Steinbrink, Julie M., et al. “The host transcriptional response to Candidemia is dominated by neutrophil activation and heme biosynthesis and supports novel diagnostic approaches.Genome Med, vol. 13, no. 1, July 2021, p. 108. Pubmed, doi:10.1186/s13073-021-00924-9.
Steinbrink JM, Myers RA, Hua K, Johnson MD, Seidelman JL, Tsalik EL, Henao R, Ginsburg GS, Woods CW, Alexander BD, McClain MT. The host transcriptional response to Candidemia is dominated by neutrophil activation and heme biosynthesis and supports novel diagnostic approaches. Genome Med. 2021 Jul 5;13(1):108.
Journal cover image

Published In

Genome Med

DOI

EISSN

1756-994X

Publication Date

July 5, 2021

Volume

13

Issue

1

Start / End Page

108

Location

England

Related Subject Headings

  • Transcriptome
  • Severity of Illness Index
  • Risk Factors
  • Reproducibility of Results
  • ROC Curve
  • Prognosis
  • Neutrophil Activation
  • Middle Aged
  • Male
  • Humans