StatSeq Systems Genetics Benchmark

Description of published synthetic Systems Genetics datasets.The StatSeq benchmark dataset is meant to be used for training and evaluating algorithms and techniques for the inference of networks from systems genetics data. The goal is to comprehend which methodology has the best overall inferring performance, and which eventually performs better under particular conditions (i.e. population size, large or small marker distances, high or low heritability, network size). This short document describes how the data have been generated through SysGenSIM. Detailed information is provided about the construction of the gene networks, the simulation of the genotype and of the gene expression, and the submission and evaluation of the predictions

X=Y–ZH compounds as potential 1,3-dipoles. Part 64: Synthesis of highly substituted conformationally restricted and spiro nitropyrrolidines via Ag(I) catalysed azomethine ylide cycloadditions

1,3-Dipolar reactions of imines of both acyclic and cyclic α-amino esters with a range of nitroolefins using a combination of AgOAc or Ag2O with NEt3 are described. In most cases the reactions were highly regio- and stereospecific and endo-cycloadducts were obtained in good yield. However, in a few cases the initially formed cycloadducts underwent base catalysed epimerisation. The stereochemistry of the cycloadducts was assigned from NOE data and established unequivocally in several cases by X-ray crystallography

Prevalence and Persistence of Breathing Disorders in Chronic Heart Failure Patients: Preliminary Results from Home Telemonitoring in the HHH Study

In this paper we present preliminary results of the European Community multicountry trial HHH (Home or Hospital in Heart Failure), which assessed the prevalence and persistence of nocturnal breathing disorders in mild-to-moderate CHF patients. All subjects (465) carried out a baseline respiratory recording in the hospital, followed by 12 recordings (one per month) at home. The latter were totally self-managed by the patients, and data were transmitted to the referring hospital through telephone lines. We found that 43 % of the patients had a periodic breathing pattern (PB, waxing and waning of ventilation with or without apneas) during the night lasting ≥ 1 hour, and the apnea-hypopnea index (AHI) was ≥ 5 events/hour in 51 % of them. During the 1-year follow-up, a PB ≥ 1 hour and an AHI ≥ 5 events/hour were persistent (i.e., occurred in> 50 % of the recordings) in 43 % and 52 % of the patients. These findings confirm the high prevalence of nocturnal breathing disorders in CHF patients and show that in a large proportion of patients they tend to persist over time. 1

Squatting, a posture test for studying cardiovascular autonomic neuropathy in diabetes.

Cardiovascular autonomic neuropathy (CAN) is a frequent complication of diabetes mellitus, which is associated with increased morbidity and mortality. It involves both the parasympathetic and sympathetic nervous systems, and may be diagnosed by classical dynamic tests with measurements of heart rate (HR) and/or arterial blood pressure (BP). An original squat test (1-min standing, 1-min squatting, 1-min standing) was used with continuous monitoring of HR and BP, using a Finapres((R)) device. This active test imposes greater postural stress than the passive head-up tilt test, and provokes large changes in BP and HR that can be analyzed to derive indices of CAN. In healthy subjects, squatting is associated with BP increases and HR decreases (abolished by atropine: SqTv index), whereas the squat-stand transition is accompanied by a deep but transient drop in BP associated with sympathetic-driven tachycardia (abolished by propranolol: SqTs index). In diabetic patients with CAN, BP increases are accentuated during squatting whereas reflex bradycardia is reduced. When standing from squatting position, the fall in BP tends to be more pronounced and orthostatic hypotension more prolonged, while reflex tachycardia is markedly dampened. The baroreflex gain, similar to that calculated during pharmacological testing with vasodilator/vasopressor agents, can be derived by plotting pulse intervals (R-R) against systolic BP levels during the biphasic response following the squat-stand transition. The slope, which represents baroreflex sensitivity, is significantly reduced in patients with CAN. This discriminatory index allows study of the natural history of CAN in a large cohort of diabetic patients.Peer reviewe

From Knockouts to Networks: Establishing Direct Cause-Effect Relationships through Graph Analysis

Background: Reverse-engineering gene networks from expression profiles is a difficult problem for which a multitude of techniques have been developed over the last decade. The yearly organized DREAM challenges allow for a fair evaluation and unbiased comparison of these methods. Results: We propose an inference algorithm that combines confidence matrices, computed as the standard scores from single-gene knockout data, with the down-ranking of feed-forward edges. Substantial improvements on the predictions can be obtained after the execution of this second step. Conclusions: Our algorithm was awarded the best overall performance at the DREAM4 In Silico 100-gene network subchallenge, proving to be effective in inferring medium-size gene regulatory networks. This success demonstrates once again the decisive importance of gene expression data obtained after systematic gene perturbations and highlights the usefulness of graph analysis to increase the reliability of inference