Mining, visualizing and comparing multidimensional biomolecular data using the Genomics Data Miner (GMine) web-server

Genomics Data Miner (GMine) is a user-friendly online software that allows non-experts to mine, cluster and compare multidimensional biomolecular datasets. Various powerful visualization techniques are provided, generating high quality figures that can be directly incorporated into scientific publications. Robust and comprehensive analyses are provided via a broad range of data-mining techniques, including univariate and multivariate statistical analysis, supervised learning, correlation networks, clustering and multivariable regression. The software has a focus on multivariate techniques, which can attribute variance in the measurements to multiple explanatory variables and confounders. Various normalization methods are provided. Extensive help pages and a tutorial are available via a wiki server. Using GMine we reanalyzed proteome microarray data of host antibody response against Plasmodium falciparum. Our results support the hypothesis that immunity to malaria is a higher-order phenomenon related to a pattern of responses and not attributable to any single antigen. We also analyzed gene expression across resting and activated T cells, identifying many immune-related genes with differential expression. This highlights both the plasticity of T cells and the operation of a hardwired activation program. These application examples demonstrate that GMine facilitates an accurate and in-depth analysis of complex molecular datasets, including genomics, transcriptomics and proteomics data

What are the causal effects of breastfeeding on IQ, obesity and blood pressure? Evidence from comparing high-income with middle-income cohorts

Background A novel approach is explored for improving causal inference in observational studies by comparing cohorts from high-income with low- or middle-income countries (LMIC), where confounding structures differ. This is applied to assessing causal effects of breastfeeding on child blood pressure (BP), body mass index (BMI) and intelligence quotient (IQ)

What are the causal effects of breastfeeding on IQ, obesity and blood pressure? Evidence from comparing high-income with middle-income cohorts

Background A novel approach is explored for improving causal inference in observational studies by comparing cohorts from high-income with low-or middle-income countries (LMIC), where confounding structures differ. This is applied to assessing causal effects of breastfeeding on child blood pressure (BP), body mass index (BMI) and intelligence quotient (IQ). Methods Standardized approaches for assessing the confounding structure of breastfeeding by socio-economic position were applied to the British Avon Longitudinal Study of Parents and Children (ALSPAC) (N ' 5000) and Brazilian Pelotas 1993 cohorts (N ' 1000). This was used to improve causal inference regarding associations of breastfeeding with child BP, BMI and IQ. Analyses were extended to include results from a meta-analysis of five LMICs (N ' 10 000) and compared with a randomized trial of breastfeeding promotion. Findings Although higher socio-economic position was strongly associated with breastfeeding in ALSPAC, there was little such patterning in Pelotas. In ALSPAC, breastfeeding was associated with lower BP, lower BMI and higher IQ, adjusted for confounders, but in the directions expected if due to socioeconomic patterning. In contrast, in Pelotas, breastfeeding was not strongly associated with BP or BMI but was associated with higher IQ. Differences in associations observed between ALSPAC and the LMIC meta-analysis were in line with those observed between ALSPAC and Pelotas, but with robust evidence of heterogeneity detected between ALSPAC and the LMIC meta-analysis associations. Trial data supported the conclusions inferred by the cross-cohort comparisons, which provided evidence for causal effects on IQ but not for BP or BMI. Conclusion While reported associations of breastfeeding with child BP and BMI are likely to reflect residual confounding, breastfeeding may have causal effects on IQ. Comparing associations between populations This is an Ope

Maternal macronutrient and energy intakes in pregnancy and offspring intake at 10 y: exploring parental comparisons and prenatal effects1234

Background: High maternal dietary intakes in pregnancy may lead to increased fetal growth and program neuroendocrine pathways that result in greater appetite, energy intake, and adiposity in offspring later in life. Few prospective dietary studies have explored this relation

TCTEX1D2 mutations underlie Jeune asphyxiating thoracic dystrophy with impaired retrograde intraflagellar transport

Tiina Paunio on työryhmän UK10K jäsen.The analysis of individuals with ciliary chondrodysplasias can shed light on sensitive mechanisms controlling ciliogenesis and cell signalling that are essential to embryonic development and survival. Here we identify TCTEX1D2 mutations causing Jeune asphyxiating thoracic dystrophy with partially penetrant inheritance. Loss of TCTEX1D2 impairs retrograde intraflagellar transport (IFT) in humans and the protist Chlamydomonas, accompanied by destabilization of the retrograde IFT dynein motor. We thus define TCTEX1D2 as an integral component of the evolutionarily conserved retrograde IFT machinery. In complex with several IFT dynein light chains, it is required for correct vertebrate skeletal formation but may be functionally redundant under certain conditions.Peer reviewe

Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

publisher: Elsevier articletitle: Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes journaltitle: Cell articlelink: https://doi.org/10.1016/j.cell.2018.05.046 content_type: article copyright: © 2018 Elsevier Inc

Early life influences on blood pressure in the Avon longitudinal study of parents and children

Coronary heart disease and its risk factors (e.g. hypertension, diabetes) in adults are associated with infant mortality and low birthweight. These associations may reflect long-term biological changes occurring in fetal and early life that 'program' later risk of disease. Although evidence of progranuning in animals is well established, the role of programming in humans is less clear. In this thesis, the role of early life influences on blood pressure in children is explored in the Avon Longitudinal Study of Parents and Children (ALSPAC), a contemporary British cohort. Prenatal and childhood exposures (maternal smoking and iron status in pregnancy, infant sodium intake, child body composition) were assessed prospectively using questionnaires, diet diaries and in ALSPAC clinic assessments.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

The effect of glucose and mental stress on cutaneous microvascular endothelial function

Glucose and mental stress, independently, have been found to impair arterial endothelial function (an indicator of vascular health). The present study sought to determine whether the combination of glucose and stress would have a greater effect on microvascular endothelial function than each on its own. To assess endothelial function, surges in skin blood flow (reactive hyperemia), following the release of cuff pressure to the upper arm at 200 mmHg for 5 min, were measured with laser Doppler flowmetry in 40 young, healthy females. Endothelial function did not change significantly following a 5-min mathematics stressor or the consumption of 75 g of glucose. However, the combination of glucose and stress impaired endothelium-dependent dilatation 30 min after glucose consumption. These findings suggest that combinations of vascular risk factors may be more threatening to cardiovascular health than singularly occurring factors