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  1. Article ; Online: Genome-scale metabolic modelling predicts biomarkers and therapeutic targets for neuropsychiatric disorders.

    Moolamalla, S T R / Vinod, P K

    Computers in biology and medicine

    2020  Volume 125, Page(s) 103994

    Abstract: Distinguishing neuropsychiatric disorders is challenging due to the overlap in symptoms and genetic risk factors. People suffering from these disorders face personal and professional challenges. Understanding the dysregulation of brain metabolism under ... ...

    Abstract Distinguishing neuropsychiatric disorders is challenging due to the overlap in symptoms and genetic risk factors. People suffering from these disorders face personal and professional challenges. Understanding the dysregulation of brain metabolism under disease condition can aid in effective diagnosis and in developing treatment strategies based on the metabolism. In this study, we reconstructed the metabolic network of three major neuropsychiatric disorders, schizophrenia (SCZ), bipolar disorder (BD) and major depressive disorder (MDD) using transcriptomic data and constrained based modelling approach. We integrated brain transcriptomic data from six independent studies with a recent comprehensive genome-scale metabolic model Recon3D. The analysis of the reconstructed network revealed the flux-level alterations in the peroxisome-mitochondria-golgi axis in neuropsychiatric disorders. We also extracted reporter metabolites and pathways that distinguish these three neuropsychiatric disorders. We found differences with respect to fatty acid oxidation, aromatic and branched chain amino acid metabolism, bile acid synthesis, glycosaminoglycans synthesis and modifications, and phospholipid metabolism. Further, we predicted network perturbations that transform the disease metabolic state to a healthy metabolic state for each disorder. These analyses provide local and global views of the metabolic changes in SCZ, BD and MDD, which may have clinical implications.
    MeSH term(s) Biomarkers ; Bipolar Disorder/genetics ; Brain ; Depressive Disorder, Major/genetics ; Humans ; Schizophrenia
    Chemical Substances Biomarkers
    Language English
    Publishing date 2020-09-17
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 127557-4
    ISSN 1879-0534 ; 0010-4825
    ISSN (online) 1879-0534
    ISSN 0010-4825
    DOI 10.1016/j.compbiomed.2020.103994
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  2. Article: Host metabolic reprogramming in response to SARS-CoV-2 infection: A systems biology approach

    Moolamalla, S.T.R. / Balasubramanian, Rami / Chauhan, Ruchi / Priyakumar, U. Deva / Vinod, P.K.

    Microbial pathogenesis. 2021 Sept., v. 158

    2021  

    Abstract: Understanding the pathogenesis of SARS-CoV-2 is essential for developing effective treatment strategies. Viruses hijack the host metabolism to redirect the resources for their replication and survival. The influence of SARS-CoV-2 on host metabolism is ... ...

    Abstract Understanding the pathogenesis of SARS-CoV-2 is essential for developing effective treatment strategies. Viruses hijack the host metabolism to redirect the resources for their replication and survival. The influence of SARS-CoV-2 on host metabolism is yet to be fully understood. In this study, we analyzed the transcriptomic data obtained from different human respiratory cell lines and patient samples (nasopharyngeal swab, peripheral blood mononuclear cells, lung biopsy, bronchoalveolar lavage fluid) to understand metabolic alterations in response to SARS-CoV-2 infection. We explored the expression pattern of metabolic genes in the comprehensive genome-scale network model of human metabolism, Recon3D, to extract key metabolic genes, pathways, and reporter metabolites under each SARS-CoV-2-infected condition. A SARS-CoV-2 core metabolic interactome was constructed for network-based drug repurposing. Our analysis revealed the host-dependent dysregulation of glycolysis, mitochondrial metabolism, amino acid metabolism, nucleotide metabolism, glutathione metabolism, polyamine synthesis, and lipid metabolism. We observed different pro- and antiviral metabolic changes and generated hypotheses on how the host metabolism can be targeted for reducing viral titers and immunomodulation. These findings warrant further exploration with more samples and in vitro studies to test predictions.
    Keywords Severe acute respiratory syndrome coronavirus 2 ; amino acid metabolism ; biopsy ; drugs ; glutathione ; glycolysis ; humans ; immunomodulation ; lipid metabolism ; lungs ; metabolites ; mitochondria ; models ; pathogenesis ; patients ; polyamines ; transcriptomics
    Language English
    Dates of publication 2021-09
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 632772-2
    ISSN 1096-1208 ; 0882-4010
    ISSN (online) 1096-1208
    ISSN 0882-4010
    DOI 10.1016/j.micpath.2021.105114
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Cologne/Königswinter

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  3. Article ; Online: Host metabolic reprogramming in response to SARS-CoV-2 infection: A systems biology approach.

    Moolamalla, S T R / Balasubramanian, Rami / Chauhan, Ruchi / Priyakumar, U Deva / Vinod, P K

    Microbial pathogenesis

    2021  Volume 158, Page(s) 105114

    Abstract: Understanding the pathogenesis of SARS-CoV-2 is essential for developing effective treatment strategies. Viruses hijack the host metabolism to redirect the resources for their replication and survival. The influence of SARS-CoV-2 on host metabolism is ... ...

    Abstract Understanding the pathogenesis of SARS-CoV-2 is essential for developing effective treatment strategies. Viruses hijack the host metabolism to redirect the resources for their replication and survival. The influence of SARS-CoV-2 on host metabolism is yet to be fully understood. In this study, we analyzed the transcriptomic data obtained from different human respiratory cell lines and patient samples (nasopharyngeal swab, peripheral blood mononuclear cells, lung biopsy, bronchoalveolar lavage fluid) to understand metabolic alterations in response to SARS-CoV-2 infection. We explored the expression pattern of metabolic genes in the comprehensive genome-scale network model of human metabolism, Recon3D, to extract key metabolic genes, pathways, and reporter metabolites under each SARS-CoV-2-infected condition. A SARS-CoV-2 core metabolic interactome was constructed for network-based drug repurposing. Our analysis revealed the host-dependent dysregulation of glycolysis, mitochondrial metabolism, amino acid metabolism, nucleotide metabolism, glutathione metabolism, polyamine synthesis, and lipid metabolism. We observed different pro- and antiviral metabolic changes and generated hypotheses on how the host metabolism can be targeted for reducing viral titers and immunomodulation. These findings warrant further exploration with more samples and in vitro studies to test predictions.
    MeSH term(s) COVID-19 ; Humans ; Leukocytes, Mononuclear ; SARS-CoV-2 ; Systems Biology ; Transcriptome
    Language English
    Publishing date 2021-07-30
    Publishing country England
    Document type Journal Article
    ZDB-ID 632772-2
    ISSN 1096-1208 ; 0882-4010
    ISSN (online) 1096-1208
    ISSN 0882-4010
    DOI 10.1016/j.micpath.2021.105114
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2136: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  4. Article: Integrative Analysis of Hippocampus Gene Expression Profiles Identifies Network Alterations in Aging and Alzheimer's Disease.

    Lanke, Vinay / Moolamalla, S T R / Roy, Dipanjan / Vinod, P K

    Frontiers in aging neuroscience

    2018  Volume 10, Page(s) 153

    Abstract: Alzheimer's disease (AD) is a neurodegenerative disorder contributing to rapid decline in cognitive function and ultimately dementia. Most cases of AD occur in elderly and later years. There is a growing need for understanding the relationship between ... ...

    Abstract Alzheimer's disease (AD) is a neurodegenerative disorder contributing to rapid decline in cognitive function and ultimately dementia. Most cases of AD occur in elderly and later years. There is a growing need for understanding the relationship between aging and AD to identify shared and unique hallmarks associated with the disease in a region and cell-type specific manner. Although genomic studies on AD have been performed extensively, the molecular mechanism of disease progression is still not clear. The major objective of our study is to obtain a higher-order network-level understanding of aging and AD, and their relationship using the hippocampal gene expression profiles of young (20-50 years), aging (70-99 years), and AD (70-99 years). The hippocampus is vulnerable to damage at early stages of AD and altered neurogenesis in the hippocampus is linked to the onset of AD. We combined the weighted gene co-expression network and weighted protein-protein interaction network-level approaches to study the transition from young to aging to AD. The network analysis revealed the organization of co-expression network into functional modules that are cell-type specific in aging and AD. We found that modules associated with astrocytes, endothelial cells and microglial cells are upregulated and significantly correlate with both aging and AD. The modules associated with neurons, mitochondria and endoplasmic reticulum are downregulated and significantly correlate with AD than aging. The oligodendrocytes module does not show significant correlation with neither aging nor disease. Further, we identified aging- and AD-specific interactions/subnetworks by integrating the gene expression with a human protein-protein interaction network. We found dysregulation of genes encoding protein kinases (FYN, SYK, SRC, PKC, MAPK1, ephrin receptors) and transcription factors (FOS, STAT3, CEBPB, MYC, NFKβ, and EGR1) in AD. Further, we found genes that encode proteins with neuroprotective function (14-3-3 proteins, PIN1, ATXN1, BDNF, VEGFA) to be part of the downregulated AD subnetwork. Our study highlights that simultaneously analyzing aging and AD will help to understand the pre-clinical and clinical phase of AD and aid in developing the treatment strategies.
    Language English
    Publishing date 2018-05-23
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2558898-9
    ISSN 1663-4365
    ISSN 1663-4365
    DOI 10.3389/fnagi.2018.00153
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Host metabolic reprogramming in response to SARS-Cov-2 infection

    Moolamalla, S T R / Chauhan, Ruchi / Priyakumar, U Deva / Vinod, P K

    bioRxiv

    Abstract: Understanding the pathogenesis of SARS-CoV-2 is important for developing effective treatment strategies. Viruses hijack the host metabolism to redirect the resources for their replication and survival. How SARS-CoV-2 influences the host metabolism is ... ...

    Abstract Understanding the pathogenesis of SARS-CoV-2 is important for developing effective treatment strategies. Viruses hijack the host metabolism to redirect the resources for their replication and survival. How SARS-CoV-2 influences the host metabolism is still unclear. In this study, we analyzed transcriptomic data obtained from different human respiratory cell lines and patient samples (Swab, PBMC, lung biopsy, BALF) to understand the metabolic alterations in response to SARS-CoV-2 infection. For this purpose, the expression pattern of metabolic genes in the human genome-scale metabolic network model Recon3D was explored. We identified metabolic genes and pathways and reporter metabolites under each SARS-CoV-2-infected condition and compared them to identify common and unique changes in the metabolism. Our analysis revealed host-dependent dysregulation of glycolysis, mitochondrial metabolism, amino acid metabolism, glutathione metabolism, polyamine synthesis, and lipid metabolism. We observed different metabolic changes that are pro- and antiviral in nature. We generated hypotheses on how antiviral metabolism can be targeted/enhanced for reducing viral titers. These warrant further exploration with more samples and in vitro studies to test predictions.
    Keywords covid19
    Language English
    Publishing date 2020-08-05
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2020.08.02.232645
    Database COVID19

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  6. Article ; Online: Host metabolic reprogramming in response to SARS-Cov-2 infection

    Moolamalla, S T R / Chauhan, Ruchi / Deva Priyakumar, U / Vinod, P K

    bioRxiv

    Abstract: Understanding the pathogenesis of SARS-CoV-2 is important for developing effective treatment strategies. Viruses hijack the host metabolism to redirect the resources for their replication and survival. How SARS-CoV-2 influences the host metabolism is ... ...

    Abstract Understanding the pathogenesis of SARS-CoV-2 is important for developing effective treatment strategies. Viruses hijack the host metabolism to redirect the resources for their replication and survival. How SARS-CoV-2 influences the host metabolism is still unclear. In this study, we analyzed transcriptomic data obtained from different human respiratory cell lines and patient samples (Swab, PBMC, lung biopsy, BALF) to understand the metabolic alterations in response to SARS-CoV-2 infection. For this purpose, the expression pattern of metabolic genes in the human genome-scale metabolic network model Recon3D was explored. We identified metabolic genes and pathways and reporter metabolites under each SARS-CoV-2-infected condition and compared them to identify common and unique changes in the metabolism. Our analysis revealed host-dependent dysregulation of glycolysis, mitochondrial metabolism, amino acid metabolism, glutathione metabolism, polyamine synthesis, and lipid metabolism. We observed different metabolic changes that are pro- and antiviral in nature. We generated hypotheses on how antiviral metabolism can be targeted/enhanced for reducing viral titers. These warrant further exploration with more samples and in vitro studies to test predictions.
    Keywords covid19
    Publisher BioRxiv
    Document type Article ; Online
    DOI 10.1101/2020.08.02.232645
    Database COVID19

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