Variation In Regulatory Networks Research Articles

Reconstructing the Molecular Function of Genetic Variation in Regulatory Networks.

Over the past decade, genetic studies have recognized hundreds of polymorphic DNA loci called response QTLs (reQTLs) as potential contributors to interindividual variation in transcriptional responses to stimulations. Such reQTLs commonly affect the transduction of signals along the regulatory network that controls gene transcription. Identifying the pathways through which reQTLs perturb the underlying network has been a major challenge. Here, we present GEVIN ("Genome-wide Embedding of Variation In Networks"), a methodology that simultaneously identifies a reQTL and the particular pathway in which the reQTL affects downstream signal transduction along the network. Using synthetic data, we show that this algorithm outperforms existing pathway identification and reQTL identification methods. We applied GEVIN to the analysis of murine and human dendritic cells in response to pathogenic components. These analyses revealed significant reQTLs together with their perturbed Toll-like receptor signaling pathways. GEVIN thus offers a powerful framework that renders a comprehensive picture of disease-related DNA loci and their molecular functions within regulatory networks.

The domestic sources and power dynamics of regulatory networks: evidence from the financial stability forum

ABSTRACTRegulatory networks are key elements of the global economy, but little is known about their variation. Why do some states prefer the creation of state-centered networks, while others advocate technocratic networks? This article addresses this question by examining the creation of the Financial Stability Forum (FSF) in 1999. It advances an argument about how domestic regulatory structures and state power explain the variation in regulatory networks that empower certain actors over others in shaping global financial regulation. This article finds that while the USA favored a state-centered FSF, driven by finance ministries, European states preferred a technocratic forum, driven by international bodies. This is because the USA can secure control of state-centered networks given its bargaining weight, while European states tried to constrain US power through technocratic structures, especially under conditions of domestic regulatory fragmentation. The final outcome was a state-centered FSF dictated by the USA. By analyzing primary archival material and interviews with key policymakers, this study sheds light on the state preferences and bargaining capabilities of G7 states. This article also generates portable and testable implications for the creation of other regulatory networks.