QTLminer: identifying genes regulating quantitative traits

Abstract Background Quantitative trait locus (QTL) mapping identifies genomic regions that likely contain genes regulating a quantitative trait. However, QTL regions may encompass tens to hundreds of genes. To find the most promising candidate genes that regulate the trait, the biologist typically collects information from multiple resources about the genes in the QTL interval. This process is very laborious and time consuming. Results QTLminer is a bioinformatics tool that automatically performs QTL region analysis. It is available in GeneNetwork and it integrates information such as gene annotation, gene expression and sequence polymorphisms for all the genes within a given genomic interval. Conclusions QTLminer substantially speeds up discovery of the most promising candidate genes within a QTL region

Weg in den Abgrund. Zur Außerrechtsetzung der deutschen Staatsangehörigen jüdischen Bekenntnisses 1933 bis 1945

In der Reichspogromnacht vom 9. No­vember 1938 wurden 1.400 Synagogen und Beträume, Tausende Wohnun­gen und Geschäfte von Jüdinnen und Juden zerstört und geplündert; mehr mehr als 30.000 Männer in Konzentrationslager verschleppt, un­gefähr hundert wurden ermordet. Dieser vielfach als "Reichskristallnacht" bezeichnete Pogrom, die "Kata­strophe vor der Katastrophe" (Dan Diner), war der Startschuss für die Verdrängung der Juden aus der Wirtschaft und die Arisierung jüdi­schen Eigentums. Er stellte eine Brutalisierung im Umgang mit der jüdischen Bevölkerung dar und war zugleich ein Schritt in Richtung Schoah. Die 75-jährige Wiederkehr der Reichspogromnacht vom 9. auf den 10. No­vember 1938 war für das Landesarchiv Schleswig-Holstein Anlass, dieses Er­eignis im Kontext der jüdischen und der Landes- sowie der nationalsozialis­tischen Gewaltgeschichte erstmals in einer eigenen Ausstellung mit dem Schwerpunkt auf dem Norden Deutschlands zu präsentieren. Die Ausstellung entstand in enger Zusammenarbeit mit der Universität Flensburg und der Landeszentrale für politische Bildung Schleswig-Hol­stein. In Schleswig wurde sie von einer Vortragsreihe begleitet, deren Bei­träge, ergänzt durch weitere Aufsätze, in diesem Band dokumentiert sind. Abbildungen aus der Ausstellung illustrieren die Texte.During the Reichspogromnacht between November 9th and 10th, 1938, in Germany and Austria 1400 synagogues and other Jewish institutions as well as thousands of Jewish homes and shops were destroyed. More than 30.000 men were deported, and at least 100 killed. This pogrom, frequently referred to as „Reichskristallnacht“, marked the beginning of political and economic persecution of Jews in Nazi Germany, and an increasingly brutal treatment of the Jewish minority, thus paving the way for the Holocaust. With regards to the 75th annual recurrence of the Reichspogromnacht, the Landesarchiv Schleswig-Holstein in 2013 presented an exhibition centered around the events of that night in Northern Germany. This exhibition was prepared in close cooperation with the University of Flensburg and the Landeszentrale für politische Bildung Schleswig-Holstein. It was accompanied by a series of lectures that are included in this book as well as some of the illustrations displayed

Fluctuation-Driven Molecular Transport in an Asymmetric Membrane Channel

Channel proteins, that selectively conduct molecules across cell membranes, often exhibit an asymmetric structure. By means of a stochastic model, we argue that channel asymmetry in the presence of non-equilibrium fluctuations, fueled by the cell's metabolism as observed recently, can dramatically influence the transport through such channels by a ratchet-like mechanism. For an aquaglyceroporin that conducts water and glycerol we show that a previously determined asymmetric glycerol potential leads to enhanced inward transport of glycerol, but for unfavorably high glycerol concentrations also to enhanced outward transport that protects a cell against poisoning.Comment: REVTeX4, 4 pages, 3 figures; Accepted for publication in Phys. Rev. Let

Data-driven assessment of eQTL mapping methods

<p>Abstract</p> <p>Background</p> <p>The analysis of expression quantitative trait loci (eQTL) is a potentially powerful way to detect transcriptional regulatory relationships at the genomic scale. However, eQTL data sets often go underexploited because legacy QTL methods are used to map the relationship between the expression trait and genotype. Often these methods are inappropriate for complex traits such as gene expression, particularly in the case of epistasis.</p> <p>Results</p> <p>Here we compare legacy QTL mapping methods with several modern multi-locus methods and evaluate their ability to produce eQTL that agree with independent external data in a systematic way. We found that the modern multi-locus methods (Random Forests, sparse partial least squares, lasso, and elastic net) clearly outperformed the legacy QTL methods (Haley-Knott regression and composite interval mapping) in terms of biological relevance of the mapped eQTL. In particular, we found that our new approach, based on Random Forests, showed superior performance among the multi-locus methods.</p> <p>Conclusions</p> <p>Benchmarks based on the recapitulation of experimental findings provide valuable insight when selecting the appropriate eQTL mapping method. Our battery of tests suggests that Random Forests map eQTL that are more likely to be validated by independent data, when compared to competing multi-locus and legacy eQTL mapping methods.</p

ATR-FTIR spectroscopy reveals genomic loci regulating the tissue response in high fat diet fed BXD recombinant inbred mouse strains

Background: Obesity-associated organ-specific pathological states can be ensued from the dysregulation of the functions of the adipose tissues, liver and muscle. However, the influence of genetic differences underlying gross-compositional differences in these tissues is largely unknown. In the present study, the analytical method of ATR-FTIR spectroscopy has been combined with a genetic approach to identify genetic differences responsible for phenotypic alterations in adipose, liver and muscle tissues. Results: Mice from 29 BXD recombinant inbred mouse strains were put on high fat diet and gross-compositional changes in adipose, liver and muscle tissues were measured by ATR-FTIR spectroscopy. The analysis of genotype-phenotype correlations revealed significant quantitative trait loci (QTL) on chromosome 12 for the content of fat and collagen, collagen integrity, and the lipid to protein ratio in adipose tissue and on chromosome 17 for lipid to protein ratio in liver. Using gene expression and sequence information, we suggest Rsad2 (viperin) and Colec11 (collectin-11) on chromosome 12 as potential quantitative trait candidate genes. Rsad2 may act as a modulator of lipid droplet contents and lipid biosynthesis; Colec11 might play a role in apoptopic cell clearance and maintenance of adipose tissue. An increased level of Rsad2 transcripts in adipose tissue of DBA/2J compared to C57BL/6J mice suggests a cis-acting genetic variant leading to differential gene activation. Conclusion: The results demonstrate that the analytical method of ATR-FTIR spectroscopy effectively contributed to decompose the macromolecular composition of tissues that accumulate fat and to link this information with genetic determinants. The candidate genes in the QTL regions may contribute to obesity-related diseases in humans, in particular if the results can be verified in a bigger BXD cohort

Towards the integration of mouse databases - definition and implementation of solutions to two use-cases in mouse functional genomics.

BACKGROUND: The integration of information present in many disparate biological databases represents a major challenge in biomedical research. To define the problems and needs, and to explore strategies for database integration in mouse functional genomics, we consulted the biologist user community and implemented solutions to two user-defined use-cases. RESULTS: We organised workshops, meetings and used a questionnaire to identify the needs of biologist database users in mouse functional genomics. As a result, two use-cases were developed that can be used to drive future designs or extensions of mouse databases. Here, we present the use-cases and describe some initial computational solutions for them. The application for the gene-centric use-case, "MUSIG-Gen" starts from a list of gene names and collects a wide range of data types from several distributed databases in a "shopping cart"-like manner. The iterative user-driven approach is a response to strongly articulated requests from users, especially those without computational biology backgrounds. The application for the phenotype-centric use-case, "MUSIG-Phen", is based on a similar concept and starting from phenotype descriptions retrieves information for associated genes. CONCLUSION: The use-cases created, and their prototype software implementations should help to better define biologists' needs for database integration and may serve as a starting point for future bioinformatics solutions aimed at end-user biologists.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

精神看護実習における構造判別図作成に対する学生の評価

本研究では，精神看護実習で用いた「構造判別図自己評価表」および「実習自己評価表」について，統計的に記述し，実習指導における示唆を得ることを目的とした．記述統計量を検討した結果，学生は構造判別図を用いることにより，対象者の【過去】【現在】の状態理解と対象者の問題・強みの【把握】が進み，根拠を捉えた【思考】能力を実感し，看護現象診断の候補の【立案】へつなげていることが考えられた．また実習の自己評価【自評】と中程度の相関が認められた2 項目（【未来】【投影】）において，学生の自己評価が低かったことから，【未来】の情報の展開を強化すること，対象者に対する自分自身のありようをうまく【投影】できるように，指導者を交えて探求し，自己理解を促すことという精神看護実習指導上の課題が示唆された

XGAP: a uniform and extensible data model and software platform for genotype and phenotype experiments.

We present an extensible software model for the genotype and phenotype community, XGAP. Readers can download a standard XGAP (http://www.xgap.org) or auto-generate a custom version using MOLGENIS with programming interfaces to R-software and web-services or user interfaces for biologists. XGAP has simple load formats for any type of genotype, epigenotype, transcript, protein, metabolite or other phenotype data. Current functionality includes tools ranging from eQTL analysis in mouse to genome-wide association studies in humans.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are