As the basis for managing the risks of chemical exposure, the Chemical Risk Assessment (CRA) process can impact a substantial part of the economy, the health of hundreds of millions of people, and the condition of the environment. However, the number of properly assessed chemicals falls short of societal needs due to a lack of experts for evaluation, interference of third party interests, and the sheer volume of potentially relevant information on the chemicals from disparate sources. In order to explore ways in which computational methods may help overcome this discrepancy between the number of chemical risk assessments required on the one hand and the number and adequateness of assessments actually being conducted on the other, the European Commission's Joint Research Centre organised a workshop on Artificial Intelligence for Chemical Risk Assessment (AI4CRA).
View Article and Find Full Text PDFObjectives: To investigate how depression is recognised in the year after child birth and treatment given in clinical practice.
Design: Cohort study based on UK primary care electronic health records.
Setting: Primary care.
Motivation: Precision medicine requires the ability to predict the efficacies of different treatments for a given individual using high-dimensional genomic measurements. However, identifying predictive features remains a challenge when the sample size is small. Incorporating expert knowledge offers a promising approach to improve predictions, but collecting such knowledge is laborious if the number of candidate features is very large.
View Article and Find Full Text PDFIn metazoans, epithelial architecture provides a context that dynamically modulates most if not all epithelial cell responses to intrinsic and extrinsic signals, including growth or survival signalling and transforming oncogene action. Three-dimensional (3D) epithelial culture systems provide tractable models to interrogate the function of human genetic determinants in establishment of context-dependency. We performed an arrayed genetic shRNA screen in mammary epithelial 3D cultures to identify new determinants of epithelial architecture, finding that the key phenotype impacting shRNAs altered not only the data population average but even more noticeably the population distribution.
View Article and Find Full Text PDFSeeing an action may activate the corresponding action motor code in the observer. It remains unresolved whether seeing and performing an action activates similar action-specific motor codes in the observer and the actor. We used novel hyperclassification approach to reveal shared brain activation signatures of action execution and observation in interacting human subjects.
View Article and Find Full Text PDFHigh-dimensional datasets with large amounts of redundant information are nowadays available for hypothesis-free exploration of scientific questions. A particular case is genome-wide association analysis, where variations in the genome are searched for effects on disease or other traits. Bayesian variable selection has been demonstrated as a possible analysis approach, which can account for the multifactorial nature of the genetic effects in a linear regression model.
View Article and Find Full Text PDFDiabetic kidney disease, diagnosed by urinary albumin excretion rate (AER), is a critical symptom of chronic vascular injury in diabetes, and is associated with dyslipidemia and increased mortality. We investigated serum lipids in 326 subjects with type 1 diabetes: 56% of patients had normal AER, 17% had microalbuminuria (20 ≤ AER < 200 μg/min or 30 ≤ AER < 300 mg/24 h) and 26% had overt kidney disease (macroalbuminuria AER ≥ 200 μg/min or AER ≥ 300 mg/24 h). Lipoprotein subclass lipids and low-molecular-weight metabolites were quantified from native serum, and individual lipid species from the lipid extract of the native sample, using a proton NMR metabonomics platform.
View Article and Find Full Text PDFAlthough complex diseases and traits are thought to have multifactorial genetic basis, the common methods in genome-wide association analyses test each variant for association independent of the others. This computational simplification may lead to reduced power to identify variants with small effect sizes and requires correcting for multiple hypothesis tests with complex relationships. However, advances in computational methods and increase in computational resources are enabling the computation of models that adhere more closely to the theory of multifactorial inheritance.
View Article and Find Full Text PDFType 1 diabetic patients with varying severity of kidney disease were investigated to create multimetabolite models of the disease process. Urinary albumin excretion rate was measured for 3358 patients with type 1 diabetes. Prospective records were available for 1051 patients, of whom 163 showed progression of albuminuria (8.
View Article and Find Full Text PDFContext And Objective: Lipoproteins are involved in the pathophysiology of several metabolic diseases. Here we focus on the interplay between lipoprotein metabolism and adiponectin with the extension of alcohol intake.
Design And Subjects: Eighty-three low-to-moderate and 80 heavy alcohol drinkers were studied.
Introduction/aims: While patients with type 1 diabetes (T1D) are known to suffer from early cardiovascular disease (CVD), we examined associations between arterial stiffness and diabetic complications in a large patient group with T1D.
Methods: This study included 807 subjects (622 T1D and 185 healthy volunteers (age 40.6 ± 0.