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    A workflow for the integrative transcriptomic description of molecular pathology and the suggestion of normalizing compounds, exemplified by Parkinson's disease.

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    Author
    Hamed, M; Gladbach, Y; Möller, S; Fischer, S; Ernst, M; Struckmann, S; Storch, A; Fuellen, G
    Date
    2018-05-21
    Source Title
    Scientific Reports
    Publisher
    Springer Science and Business Media LLC
    University of Melbourne Author/s
    Ernst, Matthias
    Affiliation
    Surgery (RMH)
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Hamed, M., Gladbach, Y., Möller, S., Fischer, S., Ernst, M., Struckmann, S., Storch, A. & Fuellen, G. (2018). A workflow for the integrative transcriptomic description of molecular pathology and the suggestion of normalizing compounds, exemplified by Parkinson's disease.. Sci Rep, 8 (1), pp.7937-. https://doi.org/10.1038/s41598-018-25754-5.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/253520
    DOI
    10.1038/s41598-018-25754-5
    Open Access at PMC
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5962550
    Abstract
    The volume of molecular observations on human diseases in public databases is continuously increasing at accelerating rates. A bottleneck is their computational integration into a coherent description, from which researchers may derive new well-founded hypotheses. Also, the need to integrate data from different technologies (genetics, coding and regulatory RNA, proteomics) emerged in order to identify biomarkers for early diagnosis and prognosis of complex diseases and therefore facilitating the development of novel treatment approaches. We propose here a workflow for the integrative transcriptomic description of the molecular pathology in Parkinsons's Disease (PD), including suggestions of compounds normalizing disease-induced transcriptional changes as a paradigmatic example. We integrated gene expression profiles, miRNA signatures, and publicly available regulatory databases to specify a partial model of the molecular pathophysiology of PD. Six genetic driver elements (2 genes and 4 miRNAs) and several functional network modules that are associated with PD were identified. Functional modules were assessed for their statistical significance, cellular functional homogeneity, literature evidence, and normalizing small molecules. In summary, our workflow for the joint regulatory analysis of coding and non-coding RNA, has the potential to yield clinically as well as biologically relevant information, as demonstrated here on PD data.

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