Furthermore, the hierarchical structure can highlight inconsistent edges likely to be false positives or of lesser importance, and suggest new relationships among distinct biological complexes and processes.

Aside from a few pioneering efforts, the space of hierarchical network modeling remains largely unexplored. Biological networks are increasingly being applied to study the mechanisms by which genetic alterations cause phenotypic changes at the cellular level. Network organization and structure can help explain many disease phenomena such as locus heterogeneity, variable penetrance, pleiotropy, inheritance models and comorbidity. We click here believe these efforts are in their infancy. Limited knowledge of the dynamic and context-specific interplay of molecules within cell and our incomplete understanding of the makeup of the human genome mTOR inhibitor has prevented effective modeling of the heritable contributions to human disease. Advances in experimental measurement technologies will soon enable large-scale screens to fill in much of our missing knowledge. The authors declare no conflict of interest. Papers of particular interest, published within the period of review, have been highlighted as: • of special interest This work was supported by NIH Grants P41 GM103504, R01 GM070743 and P50 GM085764. “
“Current Opinion in Genetics & Development 2013, 23:504–511 This

review comes from a themed issue on Cell reprogramming Edited by Huck Hui Ng and Patrick Tam For a complete overview see the Issue and the Editorial Available online 7th August 2013 0959-437X/$ – see front matter, © 2013 The Authors. Published by Elsevier Ltd. All rights Florfenicol reserved. http://dx.doi.org/10.1016/j.gde.2013.06.003 The formation of epiblast cells within the inner cell mass (ICM) of pre-implantation mammalian embryos marks the establishment of pluripotency [1]. The resulting pluripotent cells are the cells from which all specialised cells that make up the developing embryo and indeed all tissues of the adult organism trace their origins. Despite the transient requirement for such cells, pluripotency is a capacity that lasts for several days spanning implantation and that can be propagated

indefinitely in vitro by the establishment of pluripotent cell lines. Although they share the functional capacity for multilineage differentiation, pluripotent cell lines show differences in their properties. Not only are there differences between the growth factor requirements of pluripotent cell lines with an established pre-implantation (embryonic stem; ES) or post-implantation (so-called epiblast stem; EpiSC) identity but these cells also differ in the TFs that impinge upon the PGRN [ 2 and 3]. In this review we discuss recent insights into the operation of the PGRN with a particular focus on Nanog. We discuss how changes in the network can alter cell state as cells move from a pre-implantation to post-implantation identity and beyond, as well as when cells are reprogrammed to an ES cell state.