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MSD-MAP: A Network-Based Systems Biology Platform for Predicting Disease-Metabolite Links
Abstract:
Background: Cancer-associated metabolites result from cell-wide mechanisms of dysregulation. The field of metabolomics has sought to identify these aberrant metabolites as disease biomarkers, clues to understanding disease mechanisms, or even as therapeutic agents. Objective: This study
was undertaken to reliably predict metabolites associated with colorectal, esophageal, and prostate cancers. Metabolite and disease biological action networks were compared in a computational platform called MSD-MAP (Multi Scale Disease-Metabolite Association Platform). Methods: Using
differential gene expression analysis with patient-based RNAseq data from The Cancer Genome Atlas, genes up- or down-regulated in cancer compared to normal tissue were identified. Relational databases were used to map biological entities including pathways, functions, and interacting proteins,
to those differential disease genes. Similar relational maps were built for metabolites, stemming from known and in silico predicted metabolite-protein associations. The hypergeometric test was used to find statistically significant relationships between disease and metabolite biological signatures
at each tier, and metabolites were assessed for multi-scale association with each cancer. Metabolite networks were also directly associated with various other diseases using a disease functional perturbation database. Results: Our platform recapitulated metabolite-disease links that have
been empirically verified in the scientific literature, with network-based mapping of jointly-associated biological activity also matching known disease mechanisms. This was true for colorectal, esophageal, and prostate cancers, using metabolite action networks stemming from both predicted
and known functional protein associations. Conclusion: By employing systems biology concepts, MSD-MAP reliably predicted known cancermetabolite links, and may serve as a predictive tool to streamline conventional metabolomic profiling methodologies.
Autoren:
Wathieu, Henri; T. Issa, Naiem; Mohandoss, Manisha; W. Byers, Stephen; Dakshanamurthy, Sivanesan
Abstract:
Background: Azocalix[4] arene derivative based on 2,6-diamino pyridine has been synthesized from diazo-coupling reaction between tetradiazonium salt of calix[4]arene and 2,6-diaminopyridine, and characterized by various spectroscopic methods such as IR, 1HNMR, 13CNMR and Mass spe ... mehr
Abstract:
Background: Despite a reduction in the global burden of malaria, the disease remains responsible for 214 million cases and 438,000 deaths annually with 88% of the mortality occurring in sub-Saharan Africa. Malaria control largely depends on effective chemotherapy. However, the hi ... mehr
Abstract:
Background: Phosphoinositides (PIs) and their derivatives are essential cellular components that form the building blocks for cell membranes and regulate numerous cell functions. Specifically, the ability to generate myo-inositol 1,4,5-trisphosphate (InsP3) via phospholipase C (P ... mehr