Different responses of the oral, nasal and lung microbiomes to cigarette smoke.

To examine the role of smoking on the bacterial community composition of the upper and the lower respiratory tract, a monocentric, controlled prospective study was performed, including healthy smokers, ex-smokers and never-smokers. Smokers were further grouped according to their smoking history. Bacterial diversity was analysed using a molecular barcoding approach based on directly extracted DNA. Our study shows for the first time distinct bacterial response patterns in the upper and lower respiratory tract to cigarette smoking leading to a higher abundance of opportunistic pathogens. The clinical significance of these dysbioses for health needs to be further explored

A novel sarcoidosis risk locus for Europeans on chromosome 11q13.1.

Rationale: Sarcoidosis is a complex inflammatory disease with a heterogeneous clinical picture. Among others, an acute and chronic clinical course can be distinguished, for which specific genetic risk factors are known. Objectives: To identify additional risk loci for sarcoidosis and its acute and chronic subforms, we analyzed imputed data from a genomewide association scan for these phenotypes. Methods: After quality control, the genome-wide association scan comprised nearly 1.3 million imputed single-nucleotide polymorphisms based on an Affymetrix 6.0 Gene Chip dataset of 564 German sarcoidosis cases, including 176 acute and 354 chronic cases and 1,575 control subjects. Measurements and Main Results: We identified chromosome 11q13.1 (rs479777) as a novel locus influencing susceptibility to sarcoidosis with genome-wide significance. The marker was significantly associated in three distinct German case-control populations and in an additional German family sample with odds ratios ranging from 0.67 to 0.77. This finding was further replicated in two independent European case-control populations from the Czech Republic (odds ratio, 0.75) and from Sweden (odds ratio, 0.79). In a meta-analysis of the included European case-control samples the marker yielded a P value of 2.68 x 10(-18). The locus was previously reported to be associated with Crohn disease, psoriasis, alopecia areata, and leprosy. For sarcoidosis, fine-mapping and expression analysis suggest KCNK4, PRDX5, PCLB3, and most promising CCDC88B as candidates for the underlying risk gene in the associated region. Conclusions: This study provides striking evidence for association of chromosome 11q13.1 with sarcoidosis in Europeans, and thus identified a further genetic risk locus shared by sarcoidosis, Crohn disease and psoriasis

Analogy–based reasoning in classifier construction

Analogy-based reasoning methods in machine learning make it possible to reason about properties of objects on the basis of similarities between objects. A specific similarity based method is the k nearest neighbors (k-nn) classification algorithm. In the k-nn algorithm, a decision about a new object x is inferred on the basis of a fixed number k of the objects most similar to x in a given set of examples. The primary contribution of the dissertation is the introduction of two new classification models based on the k-nn algorithm. The first model is a hybrid combination of the k-nn algorithm with rule induction. The proposed combination uses minimal consistent rules defined by local reducts of a set of examples. To make this combination possible the model of minimal consistent rules is generalized to a metric-dependent form. An effective polynomial algorithm implementing the classification model based on minimal consistent rules has been proposed by Bazan. We modify this algorithm in such a way that afte

Detailed stratified GWAS analysis for severe COVID-19 in four European populations

Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended GWAS meta-analysis of a well-characterized cohort of 3255 COVID-19 patients with respiratory failure and 12 488 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen (HLA) region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.31 to a ~ 0.9-Mb inversion polymorphism that creates two highly differentiated haplotypes and characterized the potential effects of the inversion in detail. Our data, together with the 5th release of summary statistics from the COVID-19 Host Genetics Initiative including non-Caucasian individuals, also identified a new locus at 19q13.33, including NAPSA, a gene which is expressed primarily in alveolar cells responsible for gas exchange in the lung