Growth and remodelling impact the network topology of complex systems, yet a general theory explaining how new links arise between existing nodes has been lacking, and little is known about the topological properties that facilitate link-prediction. Here we investigate the extent to which the connectivity evolution of a network might be predicted by mere topological features. We show how a link/community-based strategy triggers substantial prediction improvements because it accounts for the singular topology of several real networks organised in multiple local communities - a tendency here named local-community-paradigm (LCP). We observe that LCP networks are mainly formed by weak interactions and characterise heterogeneous and dynamic systems that use self-organisation as a major adaptation strategy. These systems seem designed for global delivery of information and processing via multiple local modules. Conversely, non-LCP networks have steady architectures formed by strong interactions, and seem designed for systems in which information/energy storage is crucial.

The increasing number of experimentally detected interactions between proteins makes it difficult for researchers to extract the interactions relevant for specific biological processes or diseases. This makes it necessary to accompany the large-scale detection of protein–protein interactions (PPIs) with strategies and tools to generate meaningful PPI subnetworks. To this end, we generated the Human Integrated Protein–Protein Interaction rEference or HIPPIE (http://cbdm.uni-mainz.de/hippie/). HIPPIE is a one-stop resource for the generation and interpretation of PPI networks relevant to a specific research question. We provide means to generate highly reliable, context-specific PPI networks and to make sense out of them. We just released the second major update of HIPPIE, implementing various new features. HIPPIE grew substantially over the last years and now contains more than 270 000 confidence scored and annotated PPIs. We integrated different types of experimental information for the confidence scoring and the construction of context-specific networks. We implemented basic graph algorithms that highlight important proteins and interactions. HIPPIE's graphical interface implements several ways for wet lab and computational scientists alike to access the PPI data.

Current understanding of cell specification in early mammalian preimplantation development is mainly based on mouse studies. The first lineage differentiation event occurs at the morula stage with outer cells initiating a trophectoderm (TE) program to become the earliest placental progenitors. At subsequent developmental stages, the inner cell mass (ICM) arises from inner cells and is comprised of precursor cells of the embryo proper and yolk sac 1 . Notably, recent gene expression analyses suggest that the mechanisms regulating early lineage specification in the mouse may differ in other mammals, including human 2-5 and cow 6,7 . Here, we examined evolutionary conservation of cell dynamics and a molecular cascade initiating TE segregation in mouse, cow and human embryos using a comparative embryology approach. We discovered that the expression pattern of key TE lineage-associated factors shows a high degree of conservation among all three species. Specifically, at the morula stage outer cells acquire an apico-basal cell polarity, with expression of aPKC and PARD6B at the surface-free domain, nuclear expression of the Hippo signaling pathway effectors, YAP1 and WWTR1, and restricted expression of the transcription factor GATA3, suggesting initiation of a TE program. Furthermore, we demonstrate that inhibition of aPKC, by small-molecule pharmacological modulation and TRIM-Away protein depletion, impairs TE initiation at the morula stage. Altogether, our comparative embryology analysis provides novel insights into early lineage specification in human preimplantation embryos and suggests a similar mechanism initiating a TE program in mouse, cow and human embryos. Main textOur current understanding of cell specification during mammalian preimplantation development mainly relies on mouse studies. At the 8-cell stage, the mouse embryo undergoes a drastic