title: Systems-level perspective of sudden infant death syndrome.
abstract: Sudden infant death syndrome (SIDS) remains one of the primary causes of infant mortality in developed countries. Although the causes of SIDS remain largely inconclusive, some of the most informative associations implicate molecular, genetic, anatomical, physiological, and environmental (i.e., infant sleep) factors. Thus, a comprehensive and evolving systems-level model is required to understand SIDS susceptibility. Such models, by being powerful enough to uncover indirect associations, could be used to expand our list of candidate targets for in-depth analysis. We present an integrated WikiPathways model for SIDS susceptibility that includes associated cell systems, signaling pathways, genetics, and animal phenotypes. Experimental and literature-based gene-regulatory data have been integrated into this model to identify intersecting upstream control elements and associated interactions. To expand this pathway model, we performed a comprehensive analysis of existing proteomics data from brainstem samples of infants with SIDS. From this analysis, we discovered changes in the expression of several proteins linked to known SIDS pathologies, including factors involved in glial cell production, hypoxia regulation, and synaptic vesicle release, in addition to interactions with annotated SIDS markers. Our results highlight new targets for further consideration that further enrich this pathway model, which, over time, can improve as a wiki-based, community curation project.
authors: Department of Pediatrics, Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center Research Foundation, Cincinnati, Ohio.
authors: Nathan
authors: N
authors: Salomonis
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000378:metabolism; D002423:Cause of Death; D003198:Computer Simulation; D030541:Databases, Genetic; D030562:Databases, Protein; D053263:Gene Regulatory Networks; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D023281:Genomics; D006801:Humans; D007223:Infant; D007226:Infant Mortality; D007231:Infant, Newborn; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010641:Phenotype; D060066:Protein Interaction Maps; D040901:Proteomics; D018570:Risk Assessment; D012307:Risk Factors; D013398:Sudden Infant Death / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics; D049490:Systems Biology
chemical_list: D005819:Genetic Markers; D009419:Nerve Tissue Proteins