Diabetes is the leading cause of ESRD. Despite evidence for a substantial heritability of diabetic kidney disease, efforts to identify genetic susceptibility variants have had limited success. We extended previous efforts in three dimensions, examining a more comprehensive set of genetic variants in larger numbers of subjects with type 1 diabetes characterized for a wider range of cross-sectional diabetic kidney disease phenotypes. In 2843 subjects, we estimated that the heritability of diabetic kidney disease was 35% (P=6.4×10). Genome-wide association analysis and replication in 12,540 individuals identified no single variants reaching stringent levels of significance and, despite excellent power, provided little independent confirmation of previously published associated variants. Whole-exome sequencing in 997 subjects failed to identify any large-effect coding alleles of lower frequency influencing the risk of diabetic kidney disease. However, sets of alleles increasing body mass index (P=2.2×10) and the risk of type 2 diabetes (P=6.1×10) associated with the risk of diabetic kidney disease. We also found genome-wide genetic correlation between diabetic kidney disease and failure at smoking cessation (P=1.1×10). Pathway analysis implicated ascorbate and aldarate metabolism (P=9.0×10), and pentose and glucuronate interconversions (P=3.0×10) in pathogenesis of diabetic kidney disease. These data provide further evidence for the role of genetic factors influencing diabetic kidney disease in those with type 1 diabetes and highlight some key pathways that may be responsible. Altogether these results reveal important biology behind the major cause of kidney disease.

Supplementary data are available at Bioinformatics online.

BackgroundTargeted amplicon sequencing of the 16S ribosomal RNA gene is one of the key tools for studying microbial diversity. The accuracy of this approach strongly depends on the choice of primer pairs and, in particular, on the balance between efficiency, specificity and sensitivity in the amplification of the different bacterial 16S sequences contained in a sample. There is thus the need for computational methods to design optimal bacterial 16S primers able to take into account the knowledge provided by the new sequencing technologies.ResultsWe propose here a computational method for optimizing the choice of primer sets, based on multi-objective optimization, which simultaneously: 1) maximizes efficiency and specificity of target amplification; 2) maximizes the number of different bacterial 16S sequences matched by at least one primer; 3) minimizes the differences in the number of primers matching each bacterial 16S sequence. Our algorithm can be applied to any desired amplicon length without affecting computational performance. The source code of the developed algorithm is released as the mopo16S software tool (Multi-Objective Primer Optimization for 16S experiments) under the GNU General Public License and is available at http://sysbiobig.dei.unipd.it/?q=Software#mopo16S.ConclusionsResults show that our strategy is able to find better primer pairs than the ones available in the literature according to all three optimization criteria. We also experimentally validated three of the primer pairs identified by our method on multiple bacterial species, belonging to different genera and phyla. Results confirm the predicted efficiency and the ability to maximize the number of different bacterial 16S sequences matched by primers.Electronic supplementary materialThe online version of this article (10.1186/s12859-018-2360-6) contains supplementary material, which is available to authorized users.

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The clinical assessment of mental disorders can be a time-consuming and error-prone procedure, consisting of a sequence of diagnostic hypothesis formulation and testing aimed at restricting the set of plausible diagnoses for the patient. In this article, we propose a novel computerized system for the adaptive testing of psychological disorders. The proposed system combines a mathematical representation of psychological disorders, known as the "formal psychological assessment," with an algorithm designed for the adaptive assessment of an individual's knowledge. The assessment algorithm is extended and adapted to the new application domain. Testing the system on a real sample of 4,324 healthy individuals, screened for obsessive-compulsive disorder, we demonstrate the system's ability to support clinical testing, both by identifying the correct critical areas for each individual and by reducing the number of posed questions with respect to a standard written questionnaire.

The increasing prevalence of diabetes and its related complications is raising the need for effective methods to predict patient evolution and for stratifying cohorts in terms of risk of developing diabetes-related complications. In this paper, we present a novel approach to the simulation of a type 1 diabetes population, based on Dynamic Bayesian Networks, which combines literature knowledge with data mining of a rich longitudinal cohort of type 1 diabetes patients, the DCCT/EDIC study. In particular, in our approach we simulate the patient health state and complications through discretized variables. Two types of models are presented, one entirely learned from the data and the other partially driven by literature derived knowledge. The whole cohort is simulated for fifteen years, and the simulation error (i.e. for each variable, the percentage of patients predicted in the wrong state) is calculated every year on independent test data. For each variable, the population predicted in the wrong state is below 10% on both models over time. Furthermore, the distributions of real vs. simulated patients greatly overlap. Thus, the proposed models are viable tools to support decision making in type 1 diabetes.

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