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@ARTICLE{Arasappan:889988,
      author       = {Arasappan, Dhivya and Eickhoff, Simon B. and Nemeroff,
                      Charles B and Hofmann, Hans A. and Jabbi, Mbemba},
      title        = {{T}ranscription factor motifs associated with anterior
                      insula gene-expression underlying mood disorder phenotypes},
      journal      = {Molecular neurobiology},
      issn         = {0893-7648},
      address      = {Totowa, NJ},
      publisher    = {Humana Press},
      reportid     = {FZJ-2021-00583},
      year         = {2019},
      abstract     = {Background: Mood disorders represent a major cause of
                      morbidity and mortality worldwide but the brain-related
                      molecular pathophysiology in mood disorders remains largely
                      undefined. Methods: Because the anterior insula is reduced
                      in volume in patients with mood disorders, RNA was extracted
                      from postmortem mood disorder samples and compared with
                      unaffected control samples for RNA-sequencing identification
                      of differentially expressed genes (DEGs) in a) bipolar
                      disorder (BD; n=37) versus (vs.) controls (n=33), and b)
                      major depressive disorder (MDD n=30) vs controls, and c) low
                      vs. high Axis-I comorbidity (a measure of cumulative
                      psychiatric disease burden). Given the regulatory role of
                      transcription factors (TFs) in gene expression via
                      specific-DNA-binding domains (motifs), we used JASPAR TF
                      binding database to identify TF-motifs. Results: We found
                      that DEGs in BD vs. controls, MDD vs. controls, and high vs.
                      low Axis-I comorbidity were associated with TF-motifs that
                      are known to regulate expression of toll-like receptor
                      genes, cellular homeostatic-control genes, and genes
                      involved in embryonic, cellular/organ and brain development.
                      Discussion: Robust imaging-guided transcriptomics (i.e.,
                      using meta-analytic imaging results to guide independent
                      post-mortem dissection for RNA-sequencing) was applied by
                      targeting the gray matter volume reduction in the anterior
                      insula in mood disorders, to guide independent postmortem
                      identification of TF motifs regulating DEG. TF motifs were
                      identified for immune, cellular, embryonic and
                      neurodevelopmental processes. Conclusion: Our findings of
                      TF-motifs that regulate the expression of immune, cellular
                      homeostatic-control, and developmental genes provides novel
                      information about the hierarchical .CC-BY-NC-ND 4.0
                      International licenseunder anot certified by peer review) is
                      the author/funder, who has granted bioRxiv a license to
                      display the preprint in perpetuity. It is made available The
                      copyright holder for this preprint (which wasthis version
                      posted September 28, 2020. ;
                      https://doi.org/10.1101/864900doi: bioRxiv preprint 3
                      relationship between gene regulatory networks, the TFs that
                      control them, and proximate underlying neuroanatomical
                      phenotypes in mood disorders.},
      cin          = {INM-7},
      ddc          = {570},
      cid          = {I:(DE-Juel1)INM-7-20090406},
      pnm          = {572 - (Dys-)function and Plasticity (POF3-572)},
      pid          = {G:(DE-HGF)POF3-572},
      typ          = {PUB:(DE-HGF)25},
      doi          = {10.1101/864900},
      url          = {https://juser.fz-juelich.de/record/889988},
}