Evidence for anti-angiogenic and pro-survival functions of the cerebral cavernous malformation protein 3

Mutations in CCM1, CCM2, or CCM3 lead to cerebral cavernous malformations, one of the most common hereditary vascular diseases of the brain. Endothelial cells within these lesions are the main disease compartments. Here, we show that adenoviral CCM3 expression inhibits endothelial cell migration, proliferation, and tube formation while downregulation of endogenous CCM3 results in increased formation of tube-like structures. Adenoviral CCM3 expression does not induce apoptosis under normal endothelial cell culture conditions but protects endothelial cells from staurosporine-induced cell death. Tyrosine kinase activity profiling suggests that CCM3 supports PDPK-1/Akt-mediated endothelial cell quiescence and survival

Integrative multi-omics module network inference with Lemon-Tree

Module network inference is an established statistical method to reconstruct co-expression modules and their upstream regulatory programs from integrated multi-omics datasets measuring the activity levels of various cellular components across different individuals, experimental conditions or time points of a dynamic process. We have developed Lemon-Tree, an open-source, platform-independent, modular, extensible software package implementing state-of-the-art ensemble methods for module network inference. We benchmarked Lemon-Tree using large-scale tumor datasets and showed that Lemon-Tree algorithms compare favorably with state-of-the-art module network inference software. We also analyzed a large dataset of somatic copy-number alterations and gene expression levels measured in glioblastoma samples from The Cancer Genome Atlas and found that Lemon-Tree correctly identifies known glioblastoma oncogenes and tumor suppressors as master regulators in the inferred module network. Novel candidate driver genes predicted by Lemon-Tree were validated using tumor pathway and survival analyses. Lemon-Tree is available from http://lemon-tree.googlecode.com under the GNU General Public License version 2.0.Comment: minor revision; 13 pages text + 4 figures + 4 tables + 4 pages supplementary methods; supplementary tables available from the author