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  1. Article ; Online: Author Correction: Parkinson's disease and schizophrenia interactomes contain temporally distinct gene clusters underlying comorbid mechanisms and unique disease processes.

    Karunakaran, Kalyani B / Jain, Sanjeev / Brahmachari, Samir K / Balakrishnan, N / Ganapathiraju, Madhavi K

    Schizophrenia (Heidelberg, Germany)

    2024  Volume 10, Issue 1, Page(s) 33

    Language English
    Publishing date 2024-03-13
    Publishing country Germany
    Document type Published Erratum
    ZDB-ID 3133210-9
    ISSN 2754-6993 ; 2754-6993
    ISSN (online) 2754-6993
    ISSN 2754-6993
    DOI 10.1038/s41537-024-00455-3
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  2. Article ; Online: Parkinson's disease and schizophrenia interactomes contain temporally distinct gene clusters underlying comorbid mechanisms and unique disease processes.

    Karunakaran, Kalyani B / Jain, Sanjeev / Brahmachari, Samir K / Balakrishnan, N / Ganapathiraju, Madhavi K

    Schizophrenia (Heidelberg, Germany)

    2024  Volume 10, Issue 1, Page(s) 26

    Abstract: Genome-wide association studies suggest significant overlaps in Parkinson's disease (PD) and schizophrenia (SZ) risks, but the underlying mechanisms remain elusive. The protein-protein interaction network ('interactome') plays a crucial role in PD and SZ ...

    Abstract Genome-wide association studies suggest significant overlaps in Parkinson's disease (PD) and schizophrenia (SZ) risks, but the underlying mechanisms remain elusive. The protein-protein interaction network ('interactome') plays a crucial role in PD and SZ and can incorporate their spatiotemporal specificities. Therefore, to study the linked biology of PD and SZ, we compiled PD- and SZ-associated genes from the DisGeNET database, and constructed their interactomes using BioGRID and HPRD. We examined the interactomes using clustering and enrichment analyses, in conjunction with the transcriptomic data of 26 brain regions spanning foetal stages to adulthood available in the BrainSpan Atlas. PD and SZ interactomes formed four gene clusters with distinct temporal identities (Disease Gene Networks or 'DGNs'1-4). DGN1 had unique SZ interactome genes highly expressed across developmental stages, corresponding to a neurodevelopmental SZ subtype. DGN2, containing unique SZ interactome genes expressed from early infancy to adulthood, correlated with an inflammation-driven SZ subtype and adult SZ risk. DGN3 contained unique PD interactome genes expressed in late infancy, early and late childhood, and adulthood, and involved in mitochondrial pathways. DGN4, containing prenatally-expressed genes common to both the interactomes, involved in stem cell pluripotency and overlapping with the interactome of 22q11 deletion syndrome (comorbid psychosis and Parkinsonism), potentially regulates neurodevelopmental mechanisms in PD-SZ comorbidity. Our findings suggest that disrupted neurodevelopment (regulated by DGN4) could expose risk windows in PD and SZ, later elevating disease risk through inflammation (DGN2). Alternatively, variant clustering in DGNs may produce disease subtypes, e.g., PD-SZ comorbidity with DGN4, and early/late-onset SZ with DGN1/DGN2.
    Language English
    Publishing date 2024-02-27
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 3133210-9
    ISSN 2754-6993 ; 2754-6993
    ISSN (online) 2754-6993
    ISSN 2754-6993
    DOI 10.1038/s41537-024-00439-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Introducing the medical bioinformatics in Journal of Translational Medicine.

    Brahmachari, Samir K

    Journal of translational medicine

    2012  Volume 10, Page(s) 202

    MeSH term(s) Computational Biology ; Translational Medical Research
    Language English
    Publishing date 2012-09-26
    Publishing country England
    Document type Editorial
    ISSN 1479-5876
    ISSN (online) 1479-5876
    DOI 10.1186/1479-5876-10-202
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  4. Article ; Online: Introducing the medical bioinformatics in Journal of Translational Medicine

    Brahmachari Samir K

    Journal of Translational Medicine, Vol 10, Iss 1, p

    2012  Volume 202

    Abstract: Abstract The explosion of genome sequencing data along with genotype to phenotype correlation studies has created data deluge in the area of biomedical sciences. The aim of the Medical bioinformatics section is to aid the development and maturation of ... ...

    Abstract Abstract The explosion of genome sequencing data along with genotype to phenotype correlation studies has created data deluge in the area of biomedical sciences. The aim of the Medical bioinformatics section is to aid the development and maturation of the field by providing a platform for the translation of these datasets into useful clinical applications. The increase in computing capabilities and availability of different data from advanced technologies will allow researchers to build System Biology models of various diseases in order to efficiently develop new therapeutic interventions and reduce the current prohibitively large costs of drug discovery. The section welcomes studies on the development of Biomedical Informatics for translational medicine and clinical applications, including tools, methodologies and data integration.
    Keywords Medicine ; R
    Language English
    Publishing date 2012-09-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Metformin as a potential combination therapy with existing front-line antibiotics for Tuberculosis.

    Vashisht, Rohit / Brahmachari, Samir K

    Journal of translational medicine

    2015  Volume 13, Page(s) 83

    Abstract: Tuberculosis (TB), the disease caused by Mycobacterium tuberculosis (Mtb) remains a global health concern. The evolution of various multi-drug resistant strains through genetic mutations or drug tolerant strains through bacterial persistence renders ... ...

    Abstract Tuberculosis (TB), the disease caused by Mycobacterium tuberculosis (Mtb) remains a global health concern. The evolution of various multi-drug resistant strains through genetic mutations or drug tolerant strains through bacterial persistence renders existing antibiotics ineffective. Hence there is need for the development of either new antibiotics or rationalizing approved drugs that can be utilized in combination with existing antibiotics as a therapeutic strategy. A comprehensive systems level mapping of metabolic complexity in Mtb revels a putative role of NDH-I in the formation of bacterial persistence under the influence of front-line antibiotics. Possibilities of targeting bacterial NDH-I with existing FDA approved drug for type-II diabetes, Metformin, along with existing front-line antibiotics is discussed and proposed as a potential combination therapy for TB.
    MeSH term(s) Anti-Bacterial Agents/therapeutic use ; Antitubercular Agents/therapeutic use ; Drug Therapy, Combination ; Humans ; Metformin/therapeutic use ; Tuberculosis/drug therapy
    Chemical Substances Anti-Bacterial Agents ; Antitubercular Agents ; Metformin (9100L32L2N)
    Language English
    Publishing date 2015-03-07
    Publishing country England
    Document type Editorial
    ISSN 1479-5876
    ISSN (online) 1479-5876
    DOI 10.1186/s12967-015-0443-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Intronic miRNA mediated gene expression regulation controls protein crowding inside the cell.

    Sinha, Prashant / Jaiswal, Pragya / Jainarayanan, Ashwin K / Brahmachari, Samir K

    Gene

    2018  Volume 679, Page(s) 172–178

    Abstract: Gene regulatory effects of microRNAs at a posttranscriptional level have been established over the last decade. In this study, we analyze the interaction networks of mRNA translation regulation through intronic miRNA, under various tissue-specific ... ...

    Abstract Gene regulatory effects of microRNAs at a posttranscriptional level have been established over the last decade. In this study, we analyze the interaction networks of mRNA translation regulation through intronic miRNA, under various tissue-specific cellular contexts, taking into account the thermodynamic affinity, chemical kinetics, co-localization, concentration levels, network parameters and the presence of competitive interactors. This database, and analysis has been made available through an open-access web-server, miRiam, to promote further exploration. Here we report that expression of genes involved in Apoptosis Processes, Immune System Processes, Translation Regulator Activities, and Molecular Transport Activities within the cell are predominately regulated by miRNA mediation. Our findings further indicate that this regulatory effect has a profound effect in controlling protein crowding inside the cell. A miRNA mediated gene expression regulation serves as a temporal regulator, allowing the cellular machinery to temporarily 'pause' the translation of mRNA, indicating that the miRNA-mRNA interactions may be important for governing the optimal usage of cell volume.
    MeSH term(s) Computational Biology ; Gene Expression Profiling/methods ; Gene Expression Regulation ; Gene Regulatory Networks ; Humans ; Introns ; MicroRNAs/genetics ; Organ Specificity ; RNA, Messenger/genetics
    Chemical Substances MicroRNAs ; RNA, Messenger
    Language English
    Publishing date 2018-09-04
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 391792-7
    ISSN 1879-0038 ; 0378-1119
    ISSN (online) 1879-0038
    ISSN 0378-1119
    DOI 10.1016/j.gene.2018.08.082
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Data Intensive Genome Level Analysis for Identifying Novel, Non-Toxic Drug Targets for Multi Drug Resistant Mycobacterium tuberculosis.

    Kaur, Divneet / Kutum, Rintu / Dash, Debasis / Brahmachari, Samir K

    Scientific reports

    2017  Volume 7, Page(s) 46595

    Abstract: We report the construction of a novel Systems Biology based virtual drug discovery model for the prediction of non-toxic metabolic targets in Mycobacterium tuberculosis (Mtb). This is based on a data-intensive genome level analysis and the principle of ... ...

    Abstract We report the construction of a novel Systems Biology based virtual drug discovery model for the prediction of non-toxic metabolic targets in Mycobacterium tuberculosis (Mtb). This is based on a data-intensive genome level analysis and the principle of conservation of the evolutionarily important genes. In the 1623 sequenced Mtb strains, 890 metabolic genes identified through a systems approach in Mtb were evaluated for non-synonymous mutations. The 33 genes showed none or one variation in the entire 1623 strains, including 1084 Russian MDR strains. These invariant targets were further evaluated for their experimental and in silico essentiality as well as availability of their crystal structure in Protein Data Bank (PDB). Along with this, targets for the common existing antibiotics and the new Tb drug candidates were also screened for their variation across 1623 strains of Mtb for understanding the drug resistance. We propose that the reduced set of these reported targets could be a more effective starting point for medicinal chemists in generating new chemical leads. This approach has the potential of fueling the dried up Tuberculosis (Tb) drug discovery pipeline.
    MeSH term(s) Antitubercular Agents/pharmacology ; Drug Discovery/methods ; Drug Resistance, Multiple, Bacterial/drug effects ; Extensively Drug-Resistant Tuberculosis/drug therapy ; Extensively Drug-Resistant Tuberculosis/microbiology ; Host-Pathogen Interactions/drug effects ; Humans ; Mycobacterium tuberculosis/drug effects ; Mycobacterium tuberculosis/genetics ; Mycobacterium tuberculosis/physiology ; Reproducibility of Results ; Russia ; Systems Biology/methods ; Tuberculosis, Multidrug-Resistant/drug therapy ; Tuberculosis, Multidrug-Resistant/microbiology
    Chemical Substances Antitubercular Agents
    Language English
    Publishing date 2017-04-20
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/srep46595
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Erratum: Data Intensive Genome Level Analysis for Identifying Novel, Non-Toxic Drug Targets for Multi Drug Resistant Mycobacterium tuberculosis.

    Kaur, Divneet / Kutum, Rintu / Dash, Debasis / Brahmachari, Samir K

    Scientific reports

    2017  Volume 7, Page(s) 46825

    Abstract: This corrects the article DOI: 10.1038/srep46595. ...

    Abstract This corrects the article DOI: 10.1038/srep46595.
    Language English
    Publishing date 2017--07
    Publishing country England
    Document type Journal Article ; Published Erratum
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/srep46825
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Meta-analysis of genomic variants and gene expression data in schizophrenia suggests the potential need for adjunctive therapeutic interventions for neuropsychiatric disorders

    Chellappa, S. Anirudh / Pathak, Ankit Kumar / Sinha, Prashant / Jainarayanan, ASHWIN K / Jain, Sanjeev / Brahmachari, Samir K

    Journal of genetics. 2019 June, v. 98, no. 2

    2019  

    Abstract: Schizophrenia (SZ) is a debilitating mental illness with a multigenic aetiology and significant heritability. Despite extensive genetic studies, the molecular aetiology has remained enigmatic. A recent systems biology study suggested a protein–protein ... ...

    Abstract Schizophrenia (SZ) is a debilitating mental illness with a multigenic aetiology and significant heritability. Despite extensive genetic studies, the molecular aetiology has remained enigmatic. A recent systems biology study suggested a protein–protein interaction network for SZ with 504 novel interactions. The onset of psychiatric disorders is predominant during adolescence, often accompanied by subtle structural abnormalities in multiple regions of the brain. The availability of BrainSpan Atlas data allowed us to re-examine the genes present in the SZ interactome as a function of space and time. The availability of genomes of healthy centenarians and nonpsychiatric Exome Aggregation Consortium database allowed us to identify the variants of criticality. The expression of the SZ candidate genes responsible for cognition and disease onset was studied in different brain regions during particular developmental stages. A subset of novel interactors detected in the network was further validated using gene expression data of post-mortem brains of patients with psychiatric illness. We have narrowed down the list of drug targets proposed by the previous interactome study to 10 proteins. These proteins belonging to 81 biological pathways are targeted by 34 known Food and Drug Administration-approved drugs that have distinct potential for the treatment of neuropsychiatric disorders. We also report the possibility of targeting key genes belonging to celecoxib pharmacodynamics, [Formula: see text] signalling and cGMP-PKG signalling pathways that are not known to be specific to SZ aetiology.
    Keywords adolescence ; brain ; cognition ; databases ; drugs ; etiology ; gene expression ; genomics ; heritability ; meta-analysis ; pharmacodynamics ; protein-protein interactions ; schizophrenia ; space and time ; therapeutics
    Language English
    Dates of publication 2019-06
    Size p. 60.
    Publishing place Springer India
    Document type Article
    Note NAL-AP-2-clean
    ZDB-ID 3039-9
    ISSN 0973-7731 ; 0958-8361 ; 0022-1333
    ISSN (online) 0973-7731
    ISSN 0958-8361 ; 0022-1333
    DOI 10.1007/s12041-019-1101-6
    Database NAL-Catalogue (AGRICOLA)

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  10. Article ; Online: Paradigm for disease deconvolution in rare neurodegenerative disorders in Indian population: insights from studies in cerebellar ataxias.

    Kumari, Renu / Kumar, Deepak / Brahmachari, Samir K / Srivastava, Achal K / Faruq, Mohammed / Mukerji, Mitali

    Journal of genetics

    2018  Volume 97, Issue 3, Page(s) 589–609

    Abstract: Cerebellar ataxias are a group of rare progressive neurodegenerative disorders with an average prevalence ranges from 4.8 to 13.8 in 100,000 individuals. The inherited disorders affect multiple members of the families, or a community that is endogamous ... ...

    Abstract Cerebellar ataxias are a group of rare progressive neurodegenerative disorders with an average prevalence ranges from 4.8 to 13.8 in 100,000 individuals. The inherited disorders affect multiple members of the families, or a community that is endogamous or consanguineous. Presence of more than 3000 mutations in different genes with overlapping clinical symptoms, genetic anticipation and pleiotropy, as well as incomplete penetrance and variable expressivity due to modifiers pose challenges in genotype-phenotype correlation. Development of a diagnostic algorithm could reduce the time as well as cost in clinicogenetic diagnostics and also help in reducing the economic and social burden of the disease. In a unique research collaboration spanning over 20 years, we have been able to develop a paradigm for studying cerebellar ataxias in the Indian population which would also be relevant in other rare diseases. This has involved clinical and genetic analysis of thousands of families from diverse Indian populations. The extensive resource on ataxia has led to the development of a clinicogenetic algorithm for cost-effective screening of ataxia and a unique ataxia clinic in the tertiary referral centre in All India Institute of Medical Sciences. Utilizing a population polymorphism scanning approach, we have been able to dissect the mechanisms of repeat instability and expansion in many ataxias, and also identify founders, and trace the mutational histories in the Indian population. This provides information for genetic testing of at-risk as well as protected individuals and populations. To dissect uncharacterized cases which comprises more than 50% of the cases, we have explored the potential of next-generation sequencing technologies coupled with the extensive resource of baseline data generated in-house and other public domains. We have also developed a repository of patient-derived peripheral blood mononuclear cells, lymphoblastoid cell lines and neuronal lineages (derived from iPSCs) for ascribing functionality to novel genes/mutations. Through integrating these technologies, novel genes have been identified that has broadened the diagnostic panel, increased the diagnostic yield to over 75%, helped in ascribing pathogenicity to novel mutations and enabled understanding of disease mechanisms. It has also provided a platform for testing novel molecules for amelioration of pathophysiological phenotypes. This review through a perspective on CAs suggests a generic paradigm fromdiagnostics to therapeutic interventions for rare disorders in the context of heterogeneous Indian populations.
    MeSH term(s) Cerebellar Ataxia/diagnosis ; Cerebellar Ataxia/genetics ; Genetic Association Studies ; Genetic Heterogeneity ; Humans ; India ; Neurodegenerative Diseases/genetics ; Systems Biology ; Translational Medical Research
    Language English
    Publishing date 2018-10-12
    Publishing country India
    Document type Journal Article
    ZDB-ID 3039-9
    ISSN 0973-7731 ; 0958-8361 ; 0022-1333
    ISSN (online) 0973-7731
    ISSN 0958-8361 ; 0022-1333
    Database MEDical Literature Analysis and Retrieval System OnLINE

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