Project description:The Vaginal Microbiome Consortium team at Virginia Commonwealth University has conducted the Multi-Omic Microbiome Study: Pregnancy Initiative (MOMS-PI) in collaboration with the Global Alliance to Prevent Prematurity and Stillbirth (GAPPS) to better understand how microbiome and host profiles change throughout pregnancy and influence the establishment of the nascent microbiome in neonates. The team particularly focused on elucidation of the role of the microbiome and its components in the etiology of preterm birth, which occurs in slightly over 10% of pregnancies and which is the leading cause of death in neonates. Samples from ~ 1500 women and their neonates were collected throughout pregnancy, at delivery and postpartum. The group has generated a comprehensive dataset of multiple "omics" technologies. This longitudinal, large-scale effort was designed to provide a large-scale resource for the scientific community. The study also permits characterization... (for more see dbGaP study page.)
Project description:Phosphatase activities on PI(3,4,5)P3 and
This model describes the action of various phosphatases on
PI(3,4,5)P3 and PI(3,4)P2, in response to a stimulation by EGF. It
contains boolean switches to simulate knock-down and knock-out of
phosphatases as well as inhibition of PI3 kinase.
This model is described in the article:
PTEN Regulates PI(3,4)P2
Signaling Downstream of Class I PI3K
Mouhannad Malek, Anna Kielkowska,
Tamara Chessa, Karen E. Anderson, David Barneda, P?nar Pir,
Hiroki Nakanishi, Satoshi Eguchi, Atsushi Koizumi, Junko Sasaki,
Véronique Juvin, Vladimir Y. Kiselev, Izabella Niewczas,
Alexander Gray, Alexandre Valayer, Dominik Spensberger, Marine
Imbert, Sergio Felisbino, Tomonori Habuchi, Soren Beinke, Sabina
Cosulich, Nicolas Le Novère, Takehiko Sasaki, Jonathan
Clark, Phillip T. Hawkins and Len R. Stephens
The PI3K signaling pathway regulates cell growth and
movement and is heavily mutated in cancer. Class I PI3Ks
synthesize the lipid messenger PI(3,4,5)P3. PI(3,4,5)P3 can be
dephosphorylated by 3- or 5-phosphatases, the latter producing
PI(3,4)P2. The PTEN tumor suppressor is thought to function
primarily as a PI(3,4,5)P3 3-phosphatase, limiting activation
of this pathway. Here we show that PTEN also functions as a
PI(3,4)P2 3-phosphatase, both in vitro and in vivo. PTEN is a
major PI(3,4)P2 phosphatase in Mcf10a cytosol, and loss of PTEN
and INPP4B, a known PI(3,4)P2 4-phosphatase, leads to
synergistic accumulation of PI(3,4)P2, which correlated with
increased invadopodia in epidermal growth factor
(EGF)-stimulated cells. PTEN deletion increased PI(3,4)P2
levels in a mouse model of prostate cancer, and it inversely
correlated with PI(3,4)P2 levels across several EGF-stimulated
prostate and breast cancer lines. These results point to a role
for PI(3,4)P2 in the phenotype caused by loss-of-function
mutations or deletions in PTEN.
This model is hosted on
and identified by:
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
Public Domain Dedication for more information.
Project description:Background and aims: To gain insight into the pathogenesis of chronic colonic inflammation (colitis), we performed a multi-omic analysis that integrates RNA microarray, total protein mass spectrometry, and phospho-protein measurements from a mouse model. We used this multi-dimensional dataset to track information flow from RNA to protein to phospho-protein and to ascertain which facets of inflammation are described by each data stream. Using trans-omic co-expression network analysis, we find that there are distinct modes of regulation present in the conserved and divergent correlation structures of the three data streams. As a result, each data stream provides a unique viewpoint on the molecular pathogenesis of colitis. Nevertheless, multiple independent computational analyses identified increased signaling through p21-activated kinase (Pak) during colitis, and chemical inhibition of Pak1/2 suppressed inflammation in mice. These studies provide a comprehensive view of the state of signaling in the context of colitis and identify Pak as a therapeutic target. We used microarrays to examine changes in global gene expression patterns associated with chronic inflammation induced by the T cell transfer model of Inflammatory Bowel Disease. Overall design: Rag1 knockout mice were injected with inflammation-inducing Naïve T cells or, as a negative control, regulatory T cells. Animals were sacrificed when they showed signs of severe inflammation (weight loss, diarrhea). Colons were opened longitudinally and a thin strip of tissue was excised and snap frozen from the cecum to the rectum. This experiment includes data from 5 control animals and 3 severely inflamed animals.
Project description:All subjects were enrolled from Grady Memorial and Emory Midtown Hospitals. Subjects provided blood samples at two timepoints during pregnancy. Medical record abstraction was used to determine the presence of fetal intolerance of labor. Overall design: Subjects provided blood samples at two timepoints during pregnancy, which were processed into peripheral blood mononuclear cells (PBMC). DNA was extracted usingthe AllPrep RNA/DNA Mini Kit (Qiagen). DNA methylation was assessed on the Human Methylation450 BeadChip.
Project description:All subjects were enrolled from Grady Memorial and Emory Midtown Hospitals. Subjects provided blood samples at two timepoints during pregnancy. Medical record abstraction was used to determine the presence of fetal intolerance of labor. Overall design: Subjects provided blood samples at two timepoints during pregnancy, which were processed into peripheral blood mononuclear cells (PBMC). RNA was extracted usingthe AllPrep RNA/DNA Mini Kit (Qiagen).RNA expression was assessed on the Human HT-12v4 Expression Array
Project description:We used genome-scale modeling and multi-omics (transcriptomics, proteomics, and metabolomics) analysis to assess metabolic features that are critical for macrophage activation. We constructed a genome-scale metabolic network for the RAW 264.7 cell line to determine metabolic modulators of activation. Metabolites well-known to be associated with immunoactivation (glucose and arginine) and immunosuppression (tryptophan and vitamin D3) were among the most critical effectors. Intracellular metabolic mechanisms were assessed, identifying a suppressive role for de-novo nucleotide synthesis. Finally, underlying metabolic mechanisms of macrophage activation are identified by analyzing multi-omic data obtained from LPS-stimulated RAW cells in the context of our flux-based predictions. Two condition (flagellin and LPS) time course exposure of RAW 264.7 cell line at 1, 2, 4, and 24 hours. Two replicates for each condition and time point. All conditions compared to a pool of untreated cells at a 0 hour time point.
Project description:RNA profiling of Drosophila sensory organs precursor cells (SOP/pI) compared with neighbouring epithelial cells. Two-condition experiment, SOP/pI vs. epithelial cells from animals at similar developmental age.