Empirical Bayes analysis of single nucleotide polymorphisms

<p>Abstract</p> <p>Background</p> <p>An important goal of whole-genome studies concerned with single nucleotide polymorphisms (SNPs) is the identification of SNPs associated with a covariate of interest such as the case-control status or the type of cancer. Since these studies often comprise the genotypes of hundreds of thousands of SNPs, methods are required that can cope with the corresponding multiple testing problem. For the analysis of gene expression data, approaches such as the empirical Bayes analysis of microarrays have been developed particularly for the detection of genes associated with the response. However, the empirical Bayes analysis of microarrays has only been suggested for binary responses when considering expression values, i.e. continuous predictors.</p> <p>Results</p> <p>In this paper, we propose a modification of this empirical Bayes analysis that can be used to analyze high-dimensional categorical SNP data. This approach along with a generalized version of the original empirical Bayes method are available in the R package siggenes version 1.10.0 and later that can be downloaded from <url>http://www.bioconductor.org</url>.</p> <p>Conclusion</p> <p>As applications to two subsets of the HapMap data show, the empirical Bayes analysis of microarrays cannot only be used to analyze continuous gene expression data, but also be applied to categorical SNP data, where the response is not restricted to be binary. In association studies in which typically several ten to a few hundred SNPs are considered, our approach can furthermore be employed to test interactions of SNPs. Moreover, the posterior probabilities resulting from the empirical Bayes analysis of (prespecified) interactions/genotypes can also be used to quantify the importance of these interactions.</p

Application of Volcano Plots in Analyses of mRNA Differential Expressions with Microarrays

Volcano plot displays unstandardized signal (e.g. log-fold-change) against noise-adjusted/standardized signal (e.g. t-statistic or -log10(p-value) from the t test). We review the basic and an interactive use of the volcano plot, and its crucial role in understanding the regularized t-statistic. The joint filtering gene selection criterion based on regularized statistics has a curved discriminant line in the volcano plot, as compared to the two perpendicular lines for the "double filtering" criterion. This review attempts to provide an unifying framework for discussions on alternative measures of differential expression, improved methods for estimating variance, and visual display of a microarray analysis result. We also discuss the possibility to apply volcano plots to other fields beyond microarray.Comment: 8 figure

The role of alanine and aspartate aminotransferases in C₄ photosynthesis

Schlüter U, Bräutigam A, Droz J‐M, Schwender J, Weber APM. The role of alanine and aspartate aminotransferases in C&lt;sub&gt;4&lt;/sub&gt; photosynthesis. Plant Biology. 2019;21(S1):64-76.• Alanine and aspartate are essential transfer metabolites for C4 species of the NADmalic enzyme and phosphoenolpyruvate carboxykinase subtype. To some degree both amino acids are also part of the metabolite shuttle in NADP-malic enzyme plants. In comparison with C3 species, the majority of C4 species are therefore characterised by enhanced expression and activity of alanine and aspartate aminotransferases (AT) in the photosynthetically active tissue. Both enzymes exist in multiple copies and have been found in different subcellular compartments. We tested whether different C4 species show preferential recruitment of enzymes from specific lineages and subcellular compartments. • Phylogenetic analysis of alanine and aspartate ATs from a variety of monocot and eudicot C4 species and their C3 relatives was combined with subcellular prediction tools and analysis of the subsequent transcript amounts in mature leaves. • Recruitment of aspartate AT from a specific subcellular compartment was strongly connected to the biochemical subtype. Deviation from the main model was however observed in Gynandropsis gynandra. The configuration of alanine AT generally differed in monocot and eudicot species. C4 monocots recruited an alanine AT from a specific cytosolic branch, but eudicots use alanine AT copies from a mitochondrial branch. • Generally, plants display high plasticity in the setup of the C4 pathway. Beside the common models for the different C4 subtypes, individual solutions were found for plant groups or lineages

How Do Persons with Young and Late Onset Dementia Die?

Background: End of life symptoms and symptom management as well as the quality of dying (QoD) of persons with advanced dementia (PWAD) have not yet been systematically studied in Germany. Objective: 1) To investigate symptoms, treatment and care at the end of life, advance care planning, and circumstances of death of recently deceased PWAD;2) To determine whether there are differences between young and late onset dementia (YOD and LOD). Methods: The study was performed in the context of the project EPYLOGE (IssuEs in Palliative care for persons in advanced and terminal stages of Young-onset and Late-Onset dementia in Germany). Closest relatives of recently deceased patients with advanced YOD (N = 46) and LOD (N = 54) living at home or in long term care were interviewed. Results: Circumstances of death, symptoms, and treatment appeared to be similar between YOD and LOD, except that persons with LOD had significantly more somatic comorbidities and were admitted to hospital in the last three months of life more often than persons with LOD. At end of life, 60% of PWAD appeared to be at peace. Difficulty swallowing, gurgling, shortness of breath, and discomfort were observed most frequently. Large interindividual differences in suffering and QoD were present. Determinants of QoD were not identified. Conclusion: Our findings suggest that low QoD was caused by inadequate recognition and/or insufficient treatment of burdensome physical and emotional symptoms. PWADs' needs should be assessed regularly, and strategies focusing on treatment and implementing support for both the patient and caregiver must be established

Anti-Allergic Cromones Inhibit Histamine and Eicosanoid Release from Activated Human and Murine Mast Cells by Releasing Annexin A1

PMCID: PMC3601088This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

IssuEs in Palliative care for people in advanced and terminal stages of Young-onset and Late-Onset dementia in GErmany (EPYLOGE): the study protocol.

Scientific research on palliative care in dementia is still underdeveloped. In particular, there are no research studies at all on palliative care issues in young onset dementia (YOD), although significant differences compared to late onset dementia (LOD) are expected. Most studies have focused on persons with dementia in long term care (LTC) facilities but have neglected persons that are cared for at home. We hypothesize that unmet care needs exist in advanced and terminal stages of YOD and LOD and that they differ between YOD and LOD. The EPYLOGE-study (IssuEs in Palliative care for people in advanced and terminal stages of Young-onset and Late-Onset dementia in GErmany) aims to prospectively assess and survey 200 persons with YOD and LOD in advanced stages who are cared for in LTC facilities and at home. Furthermore, EPYLOGE aims to investigate the circumstances of death of 100 persons with YOD and LOD. This includes 1) describing symptoms and management, health care utilization, palliative care provision, quality of life and death, elements of advance care planning, family caregivers' needs and satisfaction; 2) comparing YOD and LOD regarding these factors; 3) developing expert-consensus recommendations derived from the study results for the improvement and implementation of strategies and interventions for palliative care provision; 4) and communicating the recommendations nationally and internationally in order to improve and adapt guidelines, to change current practice and to give a basis and perspectives for future research projects. The results will also be communicated to patients and their families in order to counsel and support them in their decision making processes and their dialogue with professional caregivers and physicians. EPYLOGE is the first study in Germany that assesses palliative care and end-of-life issues in dementia. Furthermore, it is the first study internationally that focuses on the specific palliative care situation of persons with YOD and their families. EPYLOGE serves as a basis for the improvement of palliative care in dementia. The study is registered in ClinicalTrials.gov ( NCT03364179 ; Registered: 6. December 2017

Pharmacotherapeutic management of paediatric heart failure and ACE-I use patterns: A European survey

Objective To characterise heart failure (HF) maintenance pharmacotherapy for children across Europe and investigate how angiotensin-converting enzyme inhibitors (ACE-I) are used in this setting. Methods A Europe-wide web-based survey was conducted between January and May 2015 among European paediatricians dedicated to cardiology. Results Out of 200-eligible, 100 physicians representing 100 hospitals in 27 European countries participated. All participants reported prescribing ACE-I to treat dilated cardiomyopathy-related HF and 97% in the context of congenital heart defects; 87% for single ventricle physiology. Twenty-six per cent avoid ACE-I i