A Scalable Approach for Discovering Conserved Active Subnetworks across Species

Overlaying differential changes in gene expression on protein interaction networks has proven to be a useful approach to interpreting the cell's dynamic response to a changing environment. Despite successes in finding active subnetworks in the context of a single species, the idea of overlaying lists of differentially expressed genes on networks has not yet been extended to support the analysis of multiple species' interaction networks. To address this problem, we designed a scalable, cross-species network search algorithm, neXus (Network - cross(X)-species - Search), that discovers conserved, active subnetworks based on parallel differential expression studies in multiple species. Our approach leverages functional linkage networks, which provide more comprehensive coverage of functional relationships than physical interaction networks by combining heterogeneous types of genomic data. We applied our cross-species approach to identify conserved modules that are differentially active in stem cells relative to differentiated cells based on parallel gene expression studies and functional linkage networks from mouse and human. We find hundreds of conserved active subnetworks enriched for stem cell-associated functions such as cell cycle, DNA repair, and chromatin modification processes. Using a variation of this approach, we also find a number of species-specific networks, which likely reflect mechanisms of stem cell function that have diverged between mouse and human. We assess the statistical significance of the subnetworks by comparing them with subnetworks discovered on random permutations of the differential expression data. We also describe several case examples that illustrate the utility of comparative analysis of active subnetworks

ENDOGLIN is dispensable for vasculogenesis, but required for vascular endothelial growth factor-induced angiogenesis

ENDOGLIN (ENG) is a co-receptor for transforming growth factor-β (TGF-β) family members that is highly expressed in endothelial cells and has a critical function in the development of the vascular system. Mutations in Eng are associated with the vascular disease known as hereditary hemorrhagic telangiectasia type l. Using mouse embryonic stem cells we observed that angiogenic factors, including vascular endothelial growth factor (VEGF), induce vasculogenesis in embryoid bodies even when Eng deficient cells or cells depleted of Eng using shRNA are used. However, ENG is required for the stem cell-derived endothelial cells to organize effectively into tubular structures. Consistent with this finding, fetal metatarsals isolated from E17.5 Eng heterozygous mouse embryos showed reduced VEGF-induced vascular network formation. Moreover, shRNA-mediated depletion and pharmacological inhibition of ENG in human umbilical vein cells mitigated VEGF-induced angiogenesis. In summary, we demonstrate that ENG is required for efficient VEGF-induced angiogenesis

Fatores preditivos de lesões abdominais em vítimas de trauma fechado

OBJETIVO: Identificar fatores preditivos de lesões abdominais em vítimas de trauma fechado. MÉTODOS: Análise retrospectiva dos dados das vítimas de trauma fechado com idade superior a 13 anos, em um período de 15 meses. Comparamos as variáveis entre os doentes com lesões abdominais diagnosticadas por tomografia computadorizada e/ou laparotomia - grupo I (Abbreviated Injury Scale abdome>0, grupo I) e os demais - grupo II (Abbreviated Injury Scale abdome=0,). RESULTADOS: Foram incluídos 3783 casos, com média etária de 39,1 +17,7 anos (14 a 99 anos), sendo 76,1% do sexo masculino. Foram identificadas lesões abdominais em 130 doentes (3,4%). Os traumatizados com lesões abdominais apresentaram, significativamente, menor média etária (35,4 + 15,4 anos vs. 39,2 + 17,7 anos), menor média da pressão arterial sistólica à admissão (114,7 + 32,4mmHg vs. 129,1 + 21,7mmHg), menor média na escala de coma de Glasgow à admissão (12,9 + 3,9 vs. 14,3 + 2,0), maior média de AIS em segmento cefálico (0,95 + 1,5 vs. 0,67 + 1,1), maior média de AIS em segmento torácico (1,10 + 1,5 vs. 0,11 + 0,6) e maior média de AIS em extremidades (1,70 ± 1,8 vs. 1,03 ± 1,2). Os maiores Odds ratio foram presença de tórax flácido (21,8) e fraturas de pelve (21,0). CONCLUSÃO: As lesões abdominais foram mais frequentemente observadas nos doentes com instabilidade hemodinâmica, alteração na escala de coma de Glasgow, lesões graves em crânio, tórax ou extremidades