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Integrative analysis of metabolomics and proteomics reveals amino acid metabolism disorder in sepsis.

Background Sepsis is defined as a systemic inflammatory response to microbial infections with multiple organ dysfunction. This study analysed untargeted metabolomics combined with proteomics of serum from patients with sepsis to reveal the underlying pathological mechanisms involved in sepsis. Methods A total of 63 patients with sepsis and 43 normal controls were enrolled from a prospective multicentre cohort. The biological functions of the metabolome were assessed by coexpression network analysis. A molecular network based on metabolomics and proteomics data was constructed to investigate the key molecules. Results Untargeted metabolomics analysis revealed widespread dysregulation of amino acid metabolism, which regulates inflammation and immunity, in patients with sepsis. Seventy-three differentially expressed metabolites (|log 2 fold change| > 1.5, adjusted P value 1.5) that could predict sepsis were identified. External validation of the hub metabolites was consistent with the der

Integrative analysis of metabolomics and proteomics reveals amino acid metabolism disorder in sepsis.

> 商业许可源文 · EUROPE_PMC · [CC-BY](https://creativecommons.org/licenses/by/)

书目信息

  • 引用:Chen Q, Liang X, Wu T, Jiang J, Jiang Y, Zhang S, Ruan Y, Zhang H, Zhang C, Chen P, Lv Y, Xin J, Shi D, Chen X, Li J, Xu Y. (2022). Integrative analysis of metabolomics and proteomics reveals amino acid metabolism disorder in sepsis. Journal of translational medicine. PMID 35287674 · PMC8919526 · DOI 10.1186/s12967-022-03320-y
  • 证据类型:PRIMARY_RESEARCH
  • 主题:proteomics、metabolomics、multi-omics
  • 被引次数(采集时):111
  • 原始记录:[Europe PMC](https://europepmc.org/article/MED/35287674)
  • 来源许可:[CC-BY](https://creativecommons.org/licenses/by/)
  • 作者摘要(按来源许可复用)

    Background Sepsis is defined as a systemic inflammatory response to microbial infections with multiple organ dysfunction. This study analysed untargeted metabolomics combined with proteomics of serum from patients with sepsis to reveal the underlying pathological mechanisms involved in sepsis. Methods A total of 63 patients with sepsis and 43 normal controls were enrolled from a prospective multicentre cohort. The biological functions of the metabolome were assessed by coexpression network analysis. A molecular network based on metabolomics and proteomics data was constructed to investigate the key molecules. Results Untargeted metabolomics analysis revealed widespread dysregulation of amino acid metabolism, which regulates inflammation and immunity, in patients with sepsis. Seventy-three differentially expressed metabolites (|log 2 fold change| > 1.5, adjusted P value 1.5) that could predict sepsis were identified. External validation of the hub metabolites was consistent with the derivation results (area under the receiver operating characteristic curve (AUROC): 0.81-0.96/0.62-1.00). The pentose phosphate pathway was found to be related to sepsis-associated encephalopathy. Phenylalanine metabolism was associated with sepsis-associated acute kidney injury. The key molecular alterations of the multiomics network in sepsis compared to normal controls implicate acute inflammatory response, platelet degranulation, myeloid cell activation involved in immune response and phenylalanine, tyrosine and tryptophan biosynthesis, and arginine biosynthesis. Conclusions Integrated analysis of untargeted metabolomics and proteomics revealed characteristic metabolite and protein alterations in sepsis, which were mainly involved in inflammation-related pathways and amino acid metabolism. This study depicted the pathological characteristics and pathways involved in sepsis and potential therapeutic targets.

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    Integrative analysis of metabolomics and proteomics reveals amino acid metabolism disorder in sepsis. · GeniOmics