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  1. Article ; Online: gene2gauss

    Ghandikota, Sudhir / Jegga, Anil G

    AMIA Joint Summits on Translational Science proceedings. AMIA Joint Summits on Translational Science

    2022  Volume 2022, Page(s) 206–215

    Abstract: Analyzing gene co-expression networks can help in the discovery of biological processes and regulatory mechanisms underlying normal or perturbed states. Unlike standard differential analysis, network-based approaches consider the interactions between the ...

    Abstract Analyzing gene co-expression networks can help in the discovery of biological processes and regulatory mechanisms underlying normal or perturbed states. Unlike standard differential analysis, network-based approaches consider the interactions between the genes involved leading to biologically relevant results. Applying such network-based methods to jointly analyze multiple transcriptomic networks representing independent disease cohorts or studies could lead to the identification of more robust gene modules or gene regulatory networks. We present gene2gauss, a novel feature learning framework that is capable of embedding genes as multivariate gaussian distributions by taking into account their long-range interaction neighborhoods across multiple transcriptomic studies. Using multiple gene co-expression networks from idiopathic pulmonary fibrosis, we demonstrate that these multi-dimensional gaussian features are suitable for identifying regulons of known transcription factors (TF). Using standard TF-target libraries, we demonstrate that the features from our method are highly relevant in comparison with other feature learning approaches on transcriptomic data.
    Language English
    Publishing date 2022-05-23
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2676378-3
    ISSN 2153-4063 ; 2153-4063
    ISSN (online) 2153-4063
    ISSN 2153-4063
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: SEMA3B inhibits TGFβ-induced extracellular matrix protein production and its reduced levels are associated with a decline in lung function in IPF.

    Yombo, Dan Jk / Ghandikota, Sudhir / Vemulapalli, Chanukya P / Singh, Priyanka / Jegga, Anil G / Hardie, William D / Madala, Sathish K

    American journal of physiology. Cell physiology

    2024  

    Abstract: Idiopathic pulmonary fibrosis (IPF) is marked by the activation of fibroblasts, leading to excessive production and deposition of extracellular matrix (ECM) within the lung parenchyma. Despite the pivotal role of ECM overexpression in IPF, potential ... ...

    Abstract Idiopathic pulmonary fibrosis (IPF) is marked by the activation of fibroblasts, leading to excessive production and deposition of extracellular matrix (ECM) within the lung parenchyma. Despite the pivotal role of ECM overexpression in IPF, potential negative regulators of ECM production in fibroblasts have yet to be identified. Semaphorin class 3B (SEMA3B), a secreted protein highly expressed in lung tissues, has established roles in axonal guidance and tumor suppression. However, the role of SEMA3B in ECM production by fibroblasts in the pathogenesis of IPF remains unexplored. Here, we show the downregulation of
    Language English
    Publishing date 2024-04-22
    Publishing country United States
    Document type Journal Article
    ZDB-ID 392098-7
    ISSN 1522-1563 ; 0363-6143
    ISSN (online) 1522-1563
    ISSN 0363-6143
    DOI 10.1152/ajpcell.00681.2023
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Computational workflow for functional characterization of COVID-19 through secondary data analysis.

    Ghandikota, Sudhir / Sharma, Mihika / Jegga, Anil G

    STAR protocols

    2021  Volume 2, Issue 4, Page(s) 100873

    Abstract: ... to many other diseases. For complete details on the use and execution of this protocol, please refer to Ghandikota et al ...

    Abstract Standard transcriptomic analyses cannot fully capture the molecular mechanisms underlying disease pathophysiology and outcomes. We present a computational heterogeneous data integration and mining protocol that combines transcriptional signatures from multiple model systems, protein-protein interactions, single-cell RNA-seq markers, and phenotype-genotype associations to identify functional feature complexes. These feature modules represent a higher order multifeatured machines collectively working toward common pathophysiological goals. We apply this protocol for functional characterization of COVID-19, but it could be applied to many other diseases. For complete details on the use and execution of this protocol, please refer to Ghandikota et al. (2021).
    MeSH term(s) COVID-19/diagnosis ; COVID-19/genetics ; COVID-19/virology ; Computational Biology/methods ; Data Analysis ; Humans ; SARS-CoV-2/genetics ; SARS-CoV-2/isolation & purification ; Software ; Transcriptome ; Workflow
    Language English
    Publishing date 2021-09-24
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2666-1667
    ISSN (online) 2666-1667
    DOI 10.1016/j.xpro.2021.100873
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Secondary analysis of transcriptomes of SARS-CoV-2 infection models to characterize COVID-19.

    Ghandikota, Sudhir / Sharma, Mihika / Jegga, Anil G

    Patterns (New York, N.Y.)

    2021  Volume 2, Issue 5, Page(s) 100247

    Abstract: Standard transcriptomic analyses alone have limited power in capturing the molecular mechanisms driving disease pathophysiology and outcomes. To overcome this, unsupervised network analyses are used to identify clusters of genes that can be associated ... ...

    Abstract Standard transcriptomic analyses alone have limited power in capturing the molecular mechanisms driving disease pathophysiology and outcomes. To overcome this, unsupervised network analyses are used to identify clusters of genes that can be associated with distinct molecular mechanisms and outcomes for a disease. In this study, we developed an integrated network analysis framework that integrates transcriptional signatures from multiple model systems with protein-protein interaction data to find gene modules. Through a meta-analysis of different enriched features from these gene modules, we extract communities of highly interconnected features. These clusters of higher-order features, working as a multifeatured machine, enable collective assessment of their contribution for disease or phenotype characterization. We show the utility of this workflow using transcriptomics data from three different models of SARS-CoV-2 infection and identify several pathways and biological processes that could enable understanding or hypothesizing molecular signatures inducing pathophysiological changes, risks, or sequelae of COVID-19.
    Language English
    Publishing date 2021-04-05
    Publishing country United States
    Document type Journal Article
    ISSN 2666-3899
    ISSN (online) 2666-3899
    DOI 10.1016/j.patter.2021.100247
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Computational workflow for functional characterization of COVID-19 through secondary data analysis

    Sudhir Ghandikota / Mihika Sharma / Anil G. Jegga

    STAR Protocols, Vol 2, Iss 4, Pp 100873- (2021)

    2021  

    Abstract: ... to many other diseases.For complete details on the use and execution of this protocol, please refer to Ghandikota et al ...

    Abstract Summary: Standard transcriptomic analyses cannot fully capture the molecular mechanisms underlying disease pathophysiology and outcomes. We present a computational heterogeneous data integration and mining protocol that combines transcriptional signatures from multiple model systems, protein-protein interactions, single-cell RNA-seq markers, and phenotype-genotype associations to identify functional feature complexes. These feature modules represent a higher order multifeatured machines collectively working toward common pathophysiological goals. We apply this protocol for functional characterization of COVID-19, but it could be applied to many other diseases.For complete details on the use and execution of this protocol, please refer to Ghandikota et al. (2021).
    Keywords Bioinformatics ; Single Cell ; Health Sciences ; Genomics ; RNAseq ; Immunology ; Science (General) ; Q1-390
    Language English
    Publishing date 2021-12-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Consensus Gene Co-Expression Network Analysis Identifies Novel Genes Associated with Severity of Fibrotic Lung Disease.

    Ghandikota, Sudhir / Sharma, Mihika / Ediga, Harshavardhana H / Madala, Satish K / Jegga, Anil G

    International journal of molecular sciences

    2022  Volume 23, Issue 10

    Abstract: Idiopathic pulmonary fibrosis (IPF) is a severe fibrotic lung disease characterized by irreversible scarring of the lung parenchyma leading to dyspnea, progressive decline in lung function, and respiratory failure. We analyzed lung transcriptomic data ... ...

    Abstract Idiopathic pulmonary fibrosis (IPF) is a severe fibrotic lung disease characterized by irreversible scarring of the lung parenchyma leading to dyspnea, progressive decline in lung function, and respiratory failure. We analyzed lung transcriptomic data from independent IPF cohorts using weighted gene co-expression network analysis (WGCNA) to identify gene modules based on their preservation status in these cohorts. The consensus gene modules were characterized by leveraging existing clinical and molecular data such as lung function, biological processes, pathways, and lung cell types. From a total of 32 consensus gene modules identified, two modules were found to be significantly correlated with the disease, lung function, and preserved in other IPF datasets. The upregulated gene module was enriched for extracellular matrix, collagen metabolic process, and BMP signaling while the downregulated module consisted of genes associated with tube morphogenesis, blood vessel development, and cell migration. Using a combination of connectivity-based and trait-based significance measures, we identified and prioritized 103 "hub" genes (including 25 secretory candidate biomarkers) by their similarity to known IPF genetic markers. Our validation studies demonstrate the dysregulated expression of
    MeSH term(s) Consensus ; Gene Regulatory Networks ; Humans ; Idiopathic Pulmonary Fibrosis/genetics ; Idiopathic Pulmonary Fibrosis/metabolism ; Lung/metabolism ; Transcriptome
    Language English
    Publishing date 2022-05-13
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms23105447
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: AllergyGenDB: A literature and functional annotation-based omics database for allergic diseases.

    Chen, Siqi / Ghandikota, Sudhir / Gautam, Yadu / Mersha, Tesfaye B

    Allergy

    2020  Volume 75, Issue 7, Page(s) 1789–1793

    MeSH term(s) Dermatitis, Atopic ; Food Hypersensitivity ; Humans ; Hypersensitivity/epidemiology ; Hypersensitivity/genetics ; Rhinitis, Allergic
    Language English
    Publishing date 2020-02-27
    Publishing country Denmark
    Document type Letter ; Research Support, N.I.H., Extramural
    ZDB-ID 391933-x
    ISSN 1398-9995 ; 0105-4538
    ISSN (online) 1398-9995
    ISSN 0105-4538
    DOI 10.1111/all.14219
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Correction to: Comprehensive functional annotation of susceptibility variants associated with asthma.

    Gautam, Yadu / Afanador, Yashira / Ghandikota, Sudhir / Mersha, Tesfaye B

    Human genetics

    2020  Volume 139, Issue 8, Page(s) 1055

    Abstract: In the original article published, the "p" value in the Fig. 5 legend is incorrectly presented as *p < 0.50. The correct p value is *p < 0.050. ...

    Abstract In the original article published, the "p" value in the Fig. 5 legend is incorrectly presented as *p < 0.50. The correct p value is *p < 0.050.
    Language English
    Publishing date 2020-05-04
    Publishing country Germany
    Document type Published Erratum
    ZDB-ID 223009-4
    ISSN 1432-1203 ; 0340-6717
    ISSN (online) 1432-1203
    ISSN 0340-6717
    DOI 10.1007/s00439-020-02173-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Comprehensive functional annotation of susceptibility variants associated with asthma.

    Gautam, Yadu / Afanador, Yashira / Ghandikota, Sudhir / Mersha, Tesfaye B

    Human genetics

    2020  Volume 139, Issue 8, Page(s) 1037–1053

    Abstract: Genome-wide association studies (GWAS) have identified hundreds of primarily non-coding disease-susceptibility variants that further need functional interpretation to prioritize and discriminate the disease-relevant variants. We present a comprehensive ... ...

    Abstract Genome-wide association studies (GWAS) have identified hundreds of primarily non-coding disease-susceptibility variants that further need functional interpretation to prioritize and discriminate the disease-relevant variants. We present a comprehensive genome-wide non-coding variant prioritization scheme followed by validation using Pyrosequencing and TaqMan assays in asthma. We implemented a composite Functional Annotation Score (cFAS) to investigate over 32,000 variants consisting of 1525 GWAS-lead asthma-susceptibility variants and their LD proxies (r
    MeSH term(s) Acetylation ; Algorithms ; Asthma/genetics ; Computational Biology ; DNA Methylation ; Epigenomics ; Female ; Genetic Predisposition to Disease ; Genetic Variation/genetics ; Genome-Wide Association Study ; Genotype ; Humans ; Male ; Molecular Sequence Annotation ; Organ Specificity ; Phenotype ; Polymorphism, Single Nucleotide/genetics ; Promoter Regions, Genetic/genetics ; Quantitative Trait Loci/genetics ; Risk Factors
    Language English
    Publishing date 2020-04-02
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 223009-4
    ISSN 1432-1203 ; 0340-6717
    ISSN (online) 1432-1203
    ISSN 0340-6717
    DOI 10.1007/s00439-020-02151-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Consensus Gene Co-Expression Network Analysis Identifies Novel Genes Associated with Severity of Fibrotic Lung Disease

    Sudhir Ghandikota / Mihika Sharma / Harshavardhana H. Ediga / Satish K. Madala / Anil G. Jegga

    International Journal of Molecular Sciences, Vol 23, Iss 5447, p

    2022  Volume 5447

    Abstract: Idiopathic pulmonary fibrosis (IPF) is a severe fibrotic lung disease characterized by irreversible scarring of the lung parenchyma leading to dyspnea, progressive decline in lung function, and respiratory failure. We analyzed lung transcriptomic data ... ...

    Abstract Idiopathic pulmonary fibrosis (IPF) is a severe fibrotic lung disease characterized by irreversible scarring of the lung parenchyma leading to dyspnea, progressive decline in lung function, and respiratory failure. We analyzed lung transcriptomic data from independent IPF cohorts using weighted gene co-expression network analysis (WGCNA) to identify gene modules based on their preservation status in these cohorts. The consensus gene modules were characterized by leveraging existing clinical and molecular data such as lung function, biological processes, pathways, and lung cell types. From a total of 32 consensus gene modules identified, two modules were found to be significantly correlated with the disease, lung function, and preserved in other IPF datasets. The upregulated gene module was enriched for extracellular matrix, collagen metabolic process, and BMP signaling while the downregulated module consisted of genes associated with tube morphogenesis, blood vessel development, and cell migration. Using a combination of connectivity-based and trait-based significance measures, we identified and prioritized 103 “hub” genes (including 25 secretory candidate biomarkers) by their similarity to known IPF genetic markers. Our validation studies demonstrate the dysregulated expression of CRABP2 , a retinol-binding protein, in multiple lung cells of IPF, and its correlation with the decline in lung function.
    Keywords Idiopathic pulmonary fibrosis ; weighted gene co-expression network analysis ; lung fibrosis ; gene modules ; consensus network analysis ; CRABP2 ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2022-05-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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