Institute for Systems Biology

About: Institute for Systems Biology is a nonprofit organization based out in Seattle, Washington, United States. It is known for research contribution in the topics: Population & Proteomics. The organization has 1277 authors who have published 2777 publications receiving 353165 citations.

Report of the National Heart, Lung, and Blood Institute Working Group on Epigenetics and Hypertension

Abstract: Hypertension, defined as a condition associated with ≥140-mm Hg systolic blood pressure or ≥90-mm Hg diastolic blood pressure, affects >1 billion people worldwide,1 and in 2009 it cost the US healthcare system more than $73 billion.2 Despite the availability of many antihypertensive therapies, individual responses vary, and efficacy remains a concern. Current treatments have yielded only modest reductions in the overall disease risk even in countries where therapeutics are available and affordable. The initiating causes and the pathogenic mechanisms for disease and its comorbidities remain largely unknown, and prognostic markers for adult hypertension that could improve its diagnosis, prevention, and, ultimately, its management are not yet available. As a result, ≈28% of the US population and a similar proportion of the adult Western European and Canadian populations experience what is known as “essential hypertension,”3 which is a primary component of several complex, multifactorial, multigenic conditions that are commonly associated with high levels of morbidity and mortality from diabetes mellitus, cardiovascular disease, and renal disease. If the current rise in the number of hypertension cases is not abated, total annual global healthcare costs resulting from suboptimal blood pressure for those >30 years of age could amount to $3.6 trillion more over the next 10 years.4 The causes of essential hypertension remain poorly understood, although the complex mechanisms for blood pressure (BP) regulation have been extensively characterized in both humans and animal models.5–7 Comprehensive study of >12 inbred rat strains that recapitulate many aspects of hereditary human hypertension has added substantially throughout the years to our understanding of the underlying physiological and molecular pathways, the genetic complexity of risk and treatment responses, and the pathological consequences of hypertension.8 In fact, many interventions that lead to a …

Prenatal Particulate Air Pollution and DNA Methylation in Newborns: An Epigenome-Wide Meta-Analysis

Abstract: Background: Prenatal exposure to air pollution has been associated with childhood respiratory disease and other adverse outcomes. Epigenetics is a suggested link between exposures and health outcom...

Critical Networks Exhibit Maximal Information Diversity in Structure-Dynamics Relationships

Abstract: Network structure strongly constrains the range of dynamic behaviors available to a complex system. These system dynamics can be classified based on their response to perturbations over time into two distinct regimes, ordered or chaotic, separated by a critical phase transition. Numerous studies have shown that the most complex dynamics arise near the critical regime. Here we use an information theoretic approach to study structure-dynamics relationships within a unified framework and show that these relationships are most diverse in the critical regime.

Genomically amplified Akt3 activates DNA repair pathway and promotes glioma progression.

Abstract: Akt is a robust oncogene that plays key roles in the development and progression of many cancers, including glioma. We evaluated the differential propensities of the Akt isoforms toward progression in the well-characterized RCAS/Ntv-a mouse model of PDGFB-driven low grade glioma. A constitutively active myristoylated form of Akt1 did not induce high-grade glioma (HGG). In stark contrast, Akt2 and Akt3 showed strong progression potential with 78% and 97% of tumors diagnosed as HGG, respectively. We further revealed that significant variations in polarity and hydropathy values among the Akt isoforms in both the pleckstrin homology domain (P domain) and regulatory domain (R domain) were critical in mediating glioma progression. Gene expression profiles from representative Akt-derived tumors indicated dominant and distinct roles for Akt3, consisting primarily of DNA repair pathways. TCGA data from human GBM closely reflected the DNA repair function, as Akt3 was significantly correlated with a 76-gene signature DNA repair panel. Consistently, compared with Akt1 and Akt2 overexpression models, Akt3-expressing human GBM cells had enhanced activation of DNA repair proteins, leading to increased DNA repair and subsequent resistance to radiation and temozolomide. Given the wide range of Akt3-amplified cancers, Akt3 may represent a key resistance factor.

A Review of Computational Tools in microRNA Discovery

Abstract: Since microRNAs (miRNAs) were discovered, their impact on regulating various biological activities has been a surprising and exciting field. Knowing the entire repertoire of these small molecules is the first step to gain a better understanding of their function. High throughput discovery tools such as next-generation sequencing significantly increased the number of known miRNAs in different organisms in recent years. However, the process of being able to accurately identify miRNAs is still a complex and difficult task, requiring the integration of experimental approaches with computational methods. A number of prediction algorithms based on characteristics of miRNA molecules have been developed to identify new miRNA species. Different approaches have certain strengths and weaknesses and in this review, we aim to summarize several commonly used tools in metazoan miRNA discovery.