Multi-omics personalized network analyses highlight progressive disruption of central metabolism associated with COVID-19 severity

Ambikan, Anoop T.; Yang, Hong; Krishnan, Shuba; Akusjärvi, Sara Svensson; Gupta, Soham; Lourda, Magda; Sperk, Maike; Arif, Muhammad; Zhang, Cheng Cheng; Nordqvist, Hampus; Ponnan, Sivasankaran Munusamy; Sönnerborg, Anders; Treutiger, Carl Johan; O’Mahony, Liam; Mardinoğlu, Adil; Benfeitas, Rui; Neogi, Ujjwal

doi:10.1016/j.cels.2022.06.006

Cited by 24 publications

(23 citation statements)

References 89 publications

(120 reference statements)

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“…20 Independent investigations confirmed similar changes in central carbon metabolism in cohorts of patients and in in vivo/in vitro models of infection. [59][60][61][62][63][64][65][66] Our data indicate that a KD increases hepatic metabolic associations with other tissues, a metabolic adaptation also observed in the infected CD group. This suggests that a KD anticipates the systemic metabolic rewiring induced by the virus.…”

Section: Discussionmentioning

confidence: 62%

A ketogenic diet can mitigate SARS-CoV-2 induced systemic reprogramming and inflammation

Palermo¹,

Shen²,

Hoeve

et al. 2022

Preprint

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The ketogenic diet (KD) has demonstrated benefits in numerous clinical studies and animal models of disease in modulating the immune response and promoting a systemic anti-inflammatory state. Here we investigate the effects of a KD on systemic toxicity in mice following SARS-CoV-2 infection. Our data indicate that under KD, SARS-CoV-2 reduces weight loss with overall improved animal survival. Muted multi-organ transcriptional reprogramming and metabolism rewiring suggest that a KD initiates and mitigates systemic changes induced by the virus. We observed reduced metalloproteases and increased inflammatory homeostatic protein transcription in the heart, with decreased serum pro-inflammatory cytokines (i.e., TNF-α, IL-15, IL-22, G-CSF, M-CSF, MCP-1), metabolic markers of inflammation (i.e., kynurenine/tryptophane ratio), and inflammatory prostaglandins, indicative of reduced systemic inflammation in animals infected under a KD. Taken together, these data suggest that a KD can alter the transcriptional and metabolic response in animals following SARS-CoV-2 infection with improved mice health, reduced inflammation, and restored amino acid, nucleotide, lipid, and energy currency metabolism.

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Section: Discussionmentioning

confidence: 62%

A ketogenic diet can mitigate SARS-CoV-2 induced systemic reprogramming and inflammation

Palermo¹,

Shen²,

Hoeve

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Finally, both microbiome and metabolomics are highly dependent upon the genetics, environment, and diet of an individual. The interaction noted may characterize the epiphenomena of a personalized immune system that can be an avenue for future studies to develop a more personalized model for integrative omics to phenotype the disease states that we recently reported (Ambikan et al, 2022).…”

Section: Discussionmentioning

confidence: 98%

“…The similarity network fusion-based patient stratification has been used primarily in non-communicable diseases like cancer [to identify cancer subtypes (Chierici et al , 2020; Wang et al ., 2014) and prognosis(Wang et al , 2021)], respiratory diseases (Narayana et al , 2021) and to study the influence of diet on human health (Burton-Pimentel et al , 2021). Recently we developed SNF-based patient stratification by integrating transcriptomics and metabolomics to define disease severity in COVID-19 that are predictive of the most robust biological features (Ambikan et al , 2022). We also reported the influence of gut microbiota on the systemic metabolic profile associated with disease severity (Albrich et al , 2022).…”

Section: Discussionmentioning

confidence: 99%

Network-based multi-omics integration reveals metabolic at-risk profile within treated HIV-infection

Mikaeloff

Gelpi

Benfeitas

et al. 2022

Preprint

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Applying omics technologies improve biological understanding of pathology and systemic health status in people living with HIV on antiretroviral therapy (PLWHART). Still, a systematic and in-depth characterization of metabolic risk profile during successful long-term treatment is lacking. In this study, we used multi-omics (plasma lipidomic and metabolomic, and fecal 16s microbiome) data-driven stratification and characterization to identify the metabolic at-risk profile within PLWHART. Through network analysis and similarity network fusion (SNF), we identified three groups of PLWHART (SNF-1 to 3). The SNF-2 (n=44; 45%) had obesity-related clinical features (increased visceral adipose tissue, BMI), higher incidence of metabolic syndrome (MetS), and increased di- and triglycerides despite having higher CD4+ T-cell counts than the other two clusters. The influence of sexual orientation in the microbiome was observed in the SNF-2 and SNF-3, with increased α-diversity compared to SNF-1. Our multi-omics integrative analysis reveals a complex microbial interplay by microbiome-derived metabolites in PLWHART. It identifies a risk cluster of PLWH who may benefit from personalized medicine and lifestyle intervention to improve their metabolic profile and enhance healthy aging.

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“…Ambikan et al presented multi-omics (blood RNA-seq and plasma metabolomics) analyses of personalised networks in which patients were stratified according to the severity of the disease, and which also included reconstruction and analysis of personalised and group-specific GEMs [ 108 ]. Human-GEM [ 23 ] was used as a reference model in the reconstruction.…”

Section: Covid-19 Applications Of Context-specific Genome-scale Metab...mentioning

confidence: 99%

Context-Specific Genome-Scale Metabolic Modelling and Its Application to the Analysis of COVID-19 Metabolic Signatures

Moškon

Režen

2023

Metabolites

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Genome-scale metabolic models (GEMs) have found numerous applications in different domains, ranging from biotechnology to systems medicine. Herein, we overview the most popular algorithms for the automated reconstruction of context-specific GEMs using high-throughput experimental data. Moreover, we describe different datasets applied in the process, and protocols that can be used to further automate the model reconstruction and validation. Finally, we describe recent COVID-19 applications of context-specific GEMs, focusing on the analysis of metabolic implications, identification of biomarkers and potential drug targets.

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Multi-omics personalized network analyses highlight progressive disruption of central metabolism associated with COVID-19 severity

Cited by 24 publications

References 89 publications

A ketogenic diet can mitigate SARS-CoV-2 induced systemic reprogramming and inflammation

A ketogenic diet can mitigate SARS-CoV-2 induced systemic reprogramming and inflammation

Network-based multi-omics integration reveals metabolic at-risk profile within treated HIV-infection

Context-Specific Genome-Scale Metabolic Modelling and Its Application to the Analysis of COVID-19 Metabolic Signatures

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