Protein interactions play a crucial role among the different functions of a cell and are central to our understanding of cellular processes both in health and disease. Here we present Galaxy InteractoMIX (http://galaxy.interactomix.com), a platform composed of 13 different computational tools each addressing specific aspects of the study of protein-protein interactions, ranging from large-scale cross-species protein-wide interactomes to atomic resolution level of protein complexes. Galaxy InteractoMIX provides an intuitive interface where users can retrieve consolidated interactomics data distributed across several databases or uncover links between diseases and genes by analyzing the interactomes underlying these diseases. The platform makes possible large-scale prediction and curation protein interactions using the conservation of motifs, interology, or presence or absence of key sequence signatures. The range of structure-based tools includes modeling and analysis of protein complexes, delineation of interfaces and the modeling of peptides acting as inhibitors of protein-protein interactions. Galaxy InteractoMIX includes a range of ready-to-use workflows to run complex analyses requiring minimal intervention by users. The potential range of applications of the platform covers different aspects of life science, biomedicine, biotechnology and drug discovery where protein associations are studied.

• Klíčová slova
• Galaxy platform, integration, interactomics, network analyses, workflows,
• MeSH
• aminokyselinové motivy MeSH
• konzervovaná sekvence MeSH
• mapování interakce mezi proteiny * MeSH
• molekulární modely MeSH
• průběh práce MeSH
• software * MeSH
• uživatelské rozhraní počítače MeSH
• výpočetní biologie metody   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

UNLABELLED: Development of progressive muscle spasticity resulting from spinal traumatic injury can be mediated by loss of local segmental inhibition and/or by an increased sensory afferent drive with resulting exacerbated α-motoneuron activity. To identify potential contributions of neuroactive substances in the development of such spasticity state, we employed a well-defined spinal injury-evoked spasticity rat model. Signaling molecules were analyzed in the spinal parenchyma below the level of spinal injury and in the corresponding dorsal root ganglion cells using Kinex™ antibody microarrays. The results uncovered the involvement of angiogenesis and neurodegeneration pathways together with direct cross-talk mediated by several hub proteins with SH-2 domains. At 2 and 5weeks after transection, up-regulation of several proteins including CaMKIV, RONα and PKCδ as well as MAPK3/ERK1 phosphorylation was observed in the spinal ventral horns. Our results indicate that these signaling molecules and their neuronal effector systems cannot only play an important role in the initiation but also in the maintenance of spasticity states after spinal trauma. The exclusivity of specific protein changes observed in lumbar spinal parenchyma but not in dorsal root ganglia indicates that new treatment strategies should primarily target specific spinal segments to prevent or attenuate spasticity states. BIOLOGICAL SIGNIFICANCE: Development of progressive muscle spasticity and rigidity represents a serious complication associated with spinal ischemic or traumatic injury. Signaling proteins, including their phosphorylation status, were analyzed in the spinal parenchyma below the level of spinal injury and in the corresponding dorsal root ganglion cells in a rat model of spinal injury using Kinex™ antibody microarrays. The results uncovered direct protein interaction mediated cross-talk between angiogenesis and neurodegeneration pathways, which may significantly contribute to the healing process in the damaged region. Importantly, we identified several target proteins exclusively observed in the spinal lumbar ventral horns, where such proteins may not only play an important role in the initiation but also in the maintenance of spasticity states after spinal trauma. Hence, potential new treatment strategies such as gene silencing or drug treatment should primarily target spinal parenchymal sites at and around the injury epicenter and most likely employ intrathecal or targeted spinal segment-specific vector or drug delivery. We believe that this work will stimulate future translational research, ultimately leading to the improvement of quality of life of patients with spinal traumatic injury.

• Klíčová slova
• AMPA, CASP, CK, CREB, CaMK, DRG, Dorsal root ganglia, EMG, ERK, FAK, FGFR, GABA, Hyper-reflexia, I2D, IGFR, JNK, LTP, Lck, MAPK, MAPK/ERK kinase kinase 4, MEKK4, MSP, N-methyl d-aspartate, NMDA, PK, Proteomic profiling, RONα, SCI, Spasticity, Spinal cord trauma, Spinal gray matter, TEK/TIE2, VEGFR, angiopoietin-1 receptor-tyrosine kinase, c-Jun N-terminal kinase, cAMP response element binding protein, calcium/calmodulin-dependent protein-serine kinase, casein protein-serine kinase, dorsal root ganglion, eIF4G, eNOS, electromyography, endothelial nitric oxide synthase, eukaryotic translation initiation factor 4 gamma, extracellular signal-regulated kinase, fibroblast growth factor receptor, focal adhesion protein-tyrosine kinase, gamma-aminobutyric acid, iNOS, inducible nitric oxide synthase, insulin-like growth factor receptor, interologous interaction database, long-term potentiation, lymphocyte-specific protein-tyrosine kinase, macrophage-stimulating protein, macrophage-stimulating protein receptor alpha chain, mitogen-activated protein kinase, pro-caspase, protein kinase, spinal cord injury, vascular endothelial growth factor receptor, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid,
• MeSH
• fosforylace MeSH
• krysa rodu Rattus MeSH
• mapování interakce mezi proteiny MeSH
• mícha patologie   MeSH
• mikročipová analýza MeSH
• neurodegenerativní nemoci metabolismus   MeSH
• patologická angiogeneze MeSH
• poranění páteře metabolismus   MeSH
• potkani Sprague-Dawley MeSH
• protilátky MeSH
• regulace genové exprese * MeSH
• signální transdukce * MeSH
• spinální ganglia metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• protilátky MeSH