A supervised Bayesian factor model for the identification of multi-omics signatures DOI Open Access
Jeremy P. Gygi, Anna Konstorum,

Shrikant Pawar

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 26, 2023

Predictive biological signatures provide utility as biomarkers for disease diagnosis and prognosis, well prediction of responses to vaccination or therapy. These are iden-tified from high-throughput profiling assays through a combination dimensionality reduction machine learning techniques. The genes, proteins, metabolites, other analytes that compose also generate hypotheses on the underlying mechanisms driving responses, thus improving understanding. Dimensionality is critical step in signature discovery address large number omics datasets, especially multi-omics studies with tens thousands measurements. Latent factor models, which can account structural heterogeneity across diverse assays, effectively integrate data reduce small factors capture correlations associations among biologically interpretable features predictive model-ing. However, integration modeling generally performed independent-ly sequential steps, leading suboptimal construction. Combining these steps yield better more while still being meaningful.

Language: Английский

The tryptophan catabolite or kynurenine pathway in COVID-19 and critical COVID-19: a systematic review and meta-analysis DOI Creative Commons
Abbas F. Almulla, Thitiporn Supasitthumrong, Chavit Tunvirachaisakul

et al.

BMC Infectious Diseases, Journal Year: 2022, Volume and Issue: 22(1)

Published: July 15, 2022

Coronavirus disease 2019 (COVID-19) is accompanied by activated immune-inflammatory pathways and oxidative stress, which both induce indoleamine-2,3-dioxygenase (IDO), a key enzyme of the tryptophan (TRP) catabolite (TRYCAT) pathway. The aim this study was to systematically review meta-analyze status TRYCAT pathway, including levels TRP kynurenine (KYN) activity IDO, as measured ratio KYN/TRP.

Language: Английский

Citations

60
Peculiarities of the T Cell Immune Response in COVID-19 DOI Creative Commons
D.А. Кudlay, И.А. Кофиади, Musa Khaitov

et al.

Vaccines, Journal Year: 2022, Volume and Issue: 10(2), P. 242 - 242

Published: Feb. 4, 2022

Understanding the T cell response to SARS-CoV-2 is critical vaccine development, epidemiological surveillance, and control strategies for this disease. This review provides data from studies of immune in coronavirus infections. It describes general mechanisms immunity, its components, presents a detailed scheme infection, including standpoint determining most promising targets assessing level. In addition, we reviewed investigating post-vaccination immunity development vaccines against COVID-19. also includes peculiarities different age gender groups, presence number factors, example, comorbidity or disease severity. study summarizes informative methods infection.

Language: Английский

Citations

35
Kynurenine pathway in Coronavirus disease (COVID‐19): Potential role in prognosis DOI Creative Commons
Murat Cihan,

Özlem Doğan,

Ceyhan Ceran Serdar

et al.

Journal of Clinical Laboratory Analysis, Journal Year: 2022, Volume and Issue: 36(3)

Published: Jan. 29, 2022

It is known that inflammatory responses play an important role in the pathophysiology of COVID-19.In this study, we aimed to examine kynurenine (KYN) metabolism on severity COVID-19 disease AQ5.Seventy patients varying and 30 controls were included study. In addition classical laboratory parameters, KYN, tryptophan (TRP), kynurenic acid (KYNA), 3 hydroxykynurenine (3OHKYN), quinolinic (QA), picolinic (PA) measured with mass spectrometry.TRP, KYN:TRP ratio, KYNA, 3OHKYN, PA, QA results found be significantly different (p < 0.001 for all). The ratio PA severe was statistically higher than mild-moderate When examined, significant correlations IL-6, ferritin, procalcitonin only patients. ROC analysis indicated highest AUC values obtained by (0.751 vs 0.742). determining disease, odd ratios (and confidence intervals) levels adjusted according age, gender, comorbidity determined 1.44 (1.1-1.87, p = 0.008) 1.06 (1.02-1.11, 0.006), respectively.According KYN metabolites a COVID-19, especially could markers identification cases.

Language: Английский

Citations

33
Psychological outcomes of COVID-19 survivors at sixth months after diagnose: the role of kynurenine pathway metabolites in depression, anxiety, and stress DOI Open Access
Melike Küçükkarapınar, Ayşegul Yay, Yeşim Yıldız

et al.

Journal of Neural Transmission, Journal Year: 2022, Volume and Issue: 129(8), P. 1077 - 1089

Published: July 7, 2022

Language: Английский

Citations

30
The kynurenine pathway of tryptophan metabolism: a neglected therapeutic target of COVID-19 pathophysiology and immunotherapy DOI Open Access
Abdulla A.‐B. Badawy

Bioscience Reports, Journal Year: 2023, Volume and Issue: 43(8)

Published: July 24, 2023

Abstract SARS-CoV-2 (COVID-19) exerts profound changes in the kynurenine (Kyn) pathway (KP) of tryptophan (Trp) metabolism that may underpin its pathophysiology. The KP is main source vital cellular effector NAD+ and intermediate metabolites modulate immune neuronal functions. Trp top influenced by COVID-19. Sixteen studies established virus-induced activation mediated mainly induction indoleamine 2,3-dioxygenase (IDO1) most affected tissues IDO2 lung increased release proinflammatory cytokines but could additionally involve flux plasma free (TDO) cortisol. major Kyn metabolite targeted COVID-19 kynurenic acid (KA), with greatest affinity for aryl hydrocarbon receptor (AhR), which also activated AhR initiates two important series events: a vicious circle involving IDO1 induction, KA accumulation further activation, poly (ADP-ribose) polymerase (PARP) leading to depletion cell death. virus deprives host inhibiting biosynthetic from quinolinic acid, while simultaneously acquiring promoting synthesis nicotinamide salvage pathway. Additionally, protective effects sirtuin 1 are minimised PARP activation. dysfunction mood neurological disorders acutely during ‘long COVID’. More potential vaccination therapy on required exploration therapeutic strategies modulation proposed.

Language: Английский

Citations

20
The roles of the kynurenine pathway in COVID-19 neuropathogenesis DOI Creative Commons
Mona Dehhaghi,

Mostafa Heydari,

Hamed Kazemi Shariat Panahi

et al.

Infection, Journal Year: 2024, Volume and Issue: 52(5), P. 2043 - 2059

Published: May 27, 2024

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of highly contagious disease Corona Virus Disease 2019 (COVID-19) that may lead to various neurological and psychological disorders can be acute, lasting days weeks or months possibly longer. latter known as long-COVID more recently post-acute sequelae COVID (PASC). During COVID-19 infection, a strong inflammatory response, cytokine storm, occurs in some patients. levels interferon-γ (IFN-γ), interferon-β (IFN-β), interleukin-6 (IL-6) tumour necrosis factor-alpha (TNF-α) are particularly increased. These cytokines activate enzyme indoleamine 2,3-dioxygenase 1 (IDO-1), catalysing first step tryptophan (Trp) catabolism through kynurenine pathway (KP) leading production several neurotoxic immunosuppressive metabolites. There already data showing elevation KP metabolites both acutely PASC, especially regarding cognitive impairment. Thus, it likely involvement significant SARS-CoV-2 pathogenesis neurologically.

Language: Английский

Citations

8
Cross-talk between red blood cells and plasma influences blood flow and omics phenotypes in severe COVID-19 DOI Creative Commons
Steffen M. Recktenwald, Greta Simionato, Marcelle G. M. Lopes

et al.

eLife, Journal Year: 2022, Volume and Issue: 11

Published: Dec. 20, 2022

Coronavirus disease 2019 (COVID-19) is caused by the Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) and can affect multiple organs, among which circulatory system. Inflammation mortality risk markers were previously detected in COVID-19 plasma red blood cells (RBCs) metabolic proteomic profiles. Additionally, biophysical properties, such as deformability, found to be changed during infection. Based on data, we aim better characterize RBC functions COVID-19. We evaluate flow properties of RBCs severe patients admitted intensive care unit using microfluidic techniques automated methods, including artificial neural networks, for an unbiased analysis. find strong shape impairment samples demonstrate that changes are reversible upon suspension healthy plasma. Vice versa, resemble when suspended Proteomics metabolomics analyses allow us detect effect exchanges both a new role maintaining equilibria at expense their properties. Our findings provide framework further investigations clinical relevance therapies against possibly other infectious diseases.

Language: Английский

Citations

27
Tryptophan regulatesDrosophilazinc stores DOI Creative Commons
Erika Garay, Nils Schuth, Alessandra Barbanente

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(16)

Published: April 11, 2022

Zinc deficiency is commonly attributed to inadequate absorption of the metal. Instead, we show that body zinc stores in Drosophila melanogaster depend on tryptophan consumption. Hence, a dietary amino acid regulates status whole insect—a finding consistent with widespread requirement as protein cofactor. Specifically, metabolite kynurenine released from insect fat bodies and induces formation storage granules Malpighian tubules, where 3-hydroxykynurenine xanthurenic act endogenous chelators. Kynurenine functions peripheral zinc-regulating hormone converted into 3-hydroxykynurenine–zinc–chloride complex, precipitating within granules. Thus, pathway—well-known modulators immunity, blood pressure, aging, neurodegeneration—are physiologically connected.

Language: Английский

Citations

25
Metabolic Profiling at COVID-19 Onset Shows Disease Severity and Sex-Specific Dysregulation DOI Creative Commons
Francisco C. Ceballos, Ana Virseda‐Berdices, Salvador Resino

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: June 30, 2022

Background metabolic changes through SARS-CoV-2 infection has been reported but not fully comprehended. This dysregulation affects multiple organs during COVID-19 and its early detection can be used as a prognosis marker of severity. Therefore, we aimed to characterize cytokine profile at onset relationship with disease severity identify profiles predicting progression. Material Methods performed retrospective cross-sectional study in 123 patients which were stratified asymptomatic/mild, moderate severe according the highest status, group healthy controls. We an untargeted plasma profiling (gas chromatography capillary electrophoresis-mass spectrometry (GC CE-MS)) evaluation. Results After data filtering identification observed 105 metabolites dysregulated (66 GC-MS 40 CE-MS) shown different expression patterns for each status. These belonged pathways including amino acid, energy, nitrogen metabolism among others. Severity-specific was observed, increased transformation L-tryptophan into L-kynurenine. Thus, hospital admission differentiate between later phase worse evolution. Several pro-inflammatory biomarkers showed significant correlation deregulated metabolites, specially L-kynurenine L-tryptophan. Finally, describe strong sex-related cytokines chemokines patients. In conclusion, is powerful tool unravel molecular pathogenesis. Conclusions technique makes it possible phenoconversion that predicts progression explains pronounced pathogenesis differences sexes.

Language: Английский

Citations

24
Tryptophan: Its Metabolism along the Kynurenine, Serotonin, and Indole Pathway in Malignant Melanoma DOI Open Access
Beáta Hubková, Marcela Valko-Rokytovská, Beáta Čižmárová

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(16), P. 9160 - 9160

Published: Aug. 15, 2022

(1) Background: Tryptophan metabolism is known to be one of the important mechanisms used by cancer evade immune surveillance. Altered tryptophan was studied in patients with pigmented malignant melanoma confirmed histologically anatomic stage grouping for cutaneous using clinical staging on basis Breslow thickness melanoma, degree spread regional lymph nodes, and presence distant metastasis. (2) Methods: Urinary metabolites were detected RP-HPLC method. (3) Results: In present work, we provided evidence altered all pathways patients. (4) Conclusions: Knowledge shifted serotonin pathway toward DHICA formation kynurenine NAD+ production could serve early detection disease initiation treatment melanoma.

Language: Английский

Citations

24