Transcriptome profiles discriminate between Gram-positive and Gram-negative sepsis in preterm neonates

Cernada, María; Pinilla-González, Alejandro; Kuligowski, Julia; Morales, José Manuel; Lorente-Pozo, Sheila; Piñeiro-Ramos, José David; Parra-Llorca, Anna; Lara-Cantón, Inmaculada; Vento, Máximo; Serna, Eva

doi:10.1038/s41390-021-01444-3

Cited by 10 publications

(9 citation statements)

References 42 publications

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“…Although recent work suggests that a different gene expression signature might be present in the case of different bacteria (gram-positive vs. gram-negative) 36 , we found no significant difference between neonates with positive culture results of gram-positive and gram-negative. Also, despite some in vitro stimulation experiments (to imitate sepsis-like conditions), revealed that conventional antibiotic therapy might be associated with immunomodulatory properties associated with the change in transcriptomic signature for some TLRs and related cytokines 37 , 38 , none of the studied gene transcript levels in the present study were significantly altered at the second sampling time point (after three days of receiving antibiotics).…”

Section: Discussioncontrasting

confidence: 99%

MYD88, NFKB1, and IL6 transcripts overexpression are associated with poor outcomes and short survival in neonatal sepsis

AbdAllah

Toraih

Ageeli

et al. 2021

Sci Rep

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Toll-like receptor (TLR) family signature has been implicated in sepsis etiopathology. We aimed to evaluate the genetic profile of TLR pathway-related key genes; the myeloid differentiation protein 88 (MYD88), IL1 receptor-associated kinase 1 (IRAK1), the nuclear factor kappa-B1 (NFKB1), and interleukin 6 (IL6) in the blood of neonates with sepsis at the time of admission and post-treatment for the available paired-samples. This case–control study included 124 infants with sepsis admitted to the neonatal intensive care unit and 17 controls. The relative gene expressions were quantified by TaqMan Real-Time qPCR and correlated to the clinic-laboratory data. MYD88, NFKB1, and IL6 relative expressions were significantly higher in sepsis cases than controls. Higher levels of MYD88 and IL6 were found in male neonates and contributed to the sex-based separation of the cases by the principal component analysis. ROC analysis revealed MYD88 and NFKB1 transcripts to be good biomarkers for sepsis. Furthermore, patients with high circulatory MYD88 levels were associated with poor survival, as revealed by Kaplan–Meier curves analysis. MYD88, NFKB1, and IL6 transcripts showed association with different poor-outcome manifestations. Clustering analysis split the patient cohort into three distinct groups according to their transcriptomic signature and CRP levels. In conclusion, the study TLR pathway-related transcripts have a gender-specific signature, diagnostic, and prognostic clinical utility in neonatal sepsis.

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Section: Discussioncontrasting

confidence: 99%

MYD88, NFKB1, and IL6 transcripts overexpression are associated with poor outcomes and short survival in neonatal sepsis

AbdAllah

Toraih

Ageeli

et al. 2021

Sci Rep

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“…We have focused on a very specific type of sepsis to obtain a homogenous signature as different transcriptomic profiles have been described between Gram-positive and Gramnegative neonatal sepsis [43] This could explain why we have not obtained the same significant miRNA profile as previous studies that focused on different types of sepsis or in those that explored the regulatory role of miRNA in the LPS-induced inflammatory response, which is more characteristic of Gram-negative sepsis [23,44].…”

Section: Discussionmentioning

confidence: 87%

miRNomic Signature in Very Low Birth-Weight Neonates Discriminates Late-Onset Gram-Positive Sepsis from Controls

et al. 2021

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Background and Objectives. Neonatal sepsis is a serious condition with a high rate of mortality and morbidity. Currently, the gold standard for sepsis diagnosis is a positive blood culture, which takes 48–72 h to yield results. We hypothesized that identifying differentially expressed miRNA pattern in neonates with late-onset Gram-positive sepsis would help with an earlier diagnosis and therapy. Methods. This is a prospective observational study in newborn infants with late-onset Gram positive bacterial sepsis and non-septic controls. Complementary to blood culture, an aliquot of 0.5 mL of blood was used to determine small non-coding RNA expression profiling using the GeneChip miRNA 4.0 Array. Results. A total of 11 very low birth-weight neonates with late-onset Gram-positive sepsis and 16 controls were analyzed. Further, 217 differentially expressed miRNAs were obtained between both groups. Subsequently, a combined analysis was performed with these miRNAs and 4297 differentially expressed genes. We identified 33 miRNAs that regulate our mRNAs, and the most relevant biological processes are associated with the immune system and the inflammatory response. Conclusions. The miRNA profiling in very low birth-weight neonates distinguishes late-onset Gram-positive sepsis versus control neonates.

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“…Other patient classification methods exist, for example, according to microbial characteristics based on gram staining. Cernada et al (2021) differentiated patients with gram-positive versus gram-negative neonatal sepsis using transcript patterns 43 . Using blood samples from septic infants with very low birth weight (VLBW), 21 genes were shown to be significantly differentially expressed.…”

Section: Resultsmentioning

confidence: 99%

Applying Transcriptomics for an Enhanced Clinical Research Framework, Implications for an Improved Research Strategy based on an Omics Approach: A Scoping Review

Rashid

Wiredu

Hanisch

et al. 2022

Preprint

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Background Sepsis is a syndromic response to infection that carries a significant global health burden, with 11 million deaths reported globally in 2017. Many biomarkers have been developed over the years for early identification and prognosis in patients with sepsis. However, they lack the sensitivity and specificity for routine use in clinical practice. A significant challenge in developing a sepsis biomarker has been the lack of a robust pathobiological framework: a factor with a weak immunological basis to assess therapeutic efficacy. The transcript can aid in extrapolating immunological changes to the clinical arena. Given that transcriptomic processing forms a part of a systems biology analysis, we undertook to address the question: What is known about the relationship of the transcript to clinical sepsis? Objective Consequently, this review article envisages a systems-based approach to better understand sepsis using mRNA gene expression information. This was achieved through an examination of peer-reviewed literature identifying the relationship of the transcript to clinical sepsis. Methods Information sources included peer-reviewed PubMed-indexed journals using the PubMed database. Articles specific to sepsis were selected, being published between the years 2012 to 2022 inclusive. A content analysis of findings was conducted. Results The search strategy elicited 14,048 studies. Keywords and or mesh terms were applied as single terms or Boolean string search combinations, generating 36 studies. Literature was analyzed concerning the specific use of the transcript and its application to sepsis. Five main descriptive Sepsis categories were identified: (1) Definition; (2) Classification; (3) Severity, (4) Molecular Biomarkers, and (5) Benchmarking. Conclusions Evidence of the connection of the transcript to clinical sepsis was identified. This provided a systems perspective, interfacing transcriptomic data to parameters important in the clinical arena. The use of transcriptomic data in advancing patient sepsis care, thereby aiming to improve precision, requires further investigation.

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Transcriptome profiles discriminate between Gram-positive and Gram-negative sepsis in preterm neonates

Cited by 10 publications

References 42 publications

MYD88, NFKB1, and IL6 transcripts overexpression are associated with poor outcomes and short survival in neonatal sepsis

MYD88, NFKB1, and IL6 transcripts overexpression are associated with poor outcomes and short survival in neonatal sepsis

miRNomic Signature in Very Low Birth-Weight Neonates Discriminates Late-Onset Gram-Positive Sepsis from Controls

Applying Transcriptomics for an Enhanced Clinical Research Framework, Implications for an Improved Research Strategy based on an Omics Approach: A Scoping Review

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