Analyzing gene expression data with linear mixed models: applications to variable pool sizes and biomarkers

This work is about the design and statistical analysis of gene expression experiments with variable pool sizes. Conditions for unbiased contrasts in such experiments were derived. They were analyzed with linear mixed models, introducing a new type of variance component that accounts for unequal shares of individual samples in common pools. The relevance of this blending error variance was then investigated for four experimental data sets from different species. Finally a biomarker search for hygienic behavior in Apis mellifera workers was conducted, using nerve tissue gene expression data.Diese Arbeit behandelt Fragen der statistischen Planung und Auswertung von Genexpressionsexperimenten mit Mischproben (Pools) und variabler Zahl von individuellen Proben je Pool (Poolgröße). Eine Bedingung für die Verzerrungsfreiheit von Kontrasten im linearen Modell wurde abgeleitet. Die Relevanz der zur Auswertung mit gemischten linearen Modellen eingeführten Mischungsvarianz zeigte sich auch in experimentellen Daten. Eine Biomarkersuche für das individuelle Hygieneverhalten von Arbeiterinnen der Honigbiene leistet einen methodischen Beitrag zur Zucht von Varroa-resistenten Bienenvölkern

Die Agenda der deutschen EU-Ratspräsidentschaft

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Развитие подхода к моделированию процесса получения этилбензола

На примере процесса синтеза этилбензола предложен подход к формализации схемы превращений углеводородов, заключающийся в группировании компонентов по их реакционной способности в отношении определенной реакции. Рассчитаны значения степеней компенсации реакций как показателя реакционной способности компонентов. Разработаны кинетические модели процессов алкилирования бензола этиленом и трансалкилирования полиалкилатов

Uric acid, lung function, physical capacity and exacerbation frequency in patients with COPD: a multi-dimensional approach

Background: Recent investigations showed single associations between uric acid levels, functional parameters, exacerbations and mortality in COPD patients. The aim of this study was to describe the role of uric acid within the network of multiple relationships between function, exacerbation and comorbidities. Methods: We used baseline data from the German COPD cohort COSYCONET which were evaluated by standard multiple regression analyses as well as path analysis to quantify the network of relations between parameters, particularly uric acid. Results: Data from 1966 patients were analyzed. Uric acid was significantly associated with reduced FEV1, reduced 6-MWD, higher burden of exacerbations (GOLD criteria) and cardiovascular comorbidities, in addition to risk factors such as BMI and packyears. These associations remained significant after taking into account their multiple interdependences. Compared to uric acid levels the diagnosis of hyperuricemia and its medication played a minor role. Conclusion: Within the limits of a cross-sectional approach, our results strongly suggest that uric acid is a biomarker of high impact in COPD and plays a genuine role for relevant outcomes such as physical capacity and exacerbations. These findings suggest that more attention should be paid to uric acid in the evaluation of COPD disease status

On the relevance of technical variation due to building pools in microarray experiments

Background Pooled samples are frequently used in experiments measuring gene expression. In this method, RNA from different individuals sharing the same experimental conditions and explanatory variables is blended and their concentrations are jointly measured. As a matter of principle, individuals are represented in equal shares in each pool. However, some degree of disproportionality may arise from the limits of technical precision. As a consequence a special kind of technical error occurs, which can be modelled by a respective variance component. Previously published theory - allowing for variable pool sizes - has been applied to four microarray gene expression data sets from different species in order to assess the practical relevance of this type of technical error in terms of significance and size of this variance component. Results The number of transcripts with a significant variance component due to imperfect blending was found to be 4329 (23 %) in mouse data and 7093 (49 %) in honey bees, but only 6 in rats and none whatsoever in human data. These results correspond to a false discovery rate of 5 % in each data set. The number of transcripts found to be differentially expressed between treatments was always higher when the blending error variance was neglected. Simulations clearly indicated overly-optimistic (anti-conservative) test results in terms of false discovery rates whenever this source of variability was not represented in the model. Conclusions Imperfect equality of shares when blending RNA from different individuals into joint pools of variable size is a source of technical variation with relevance for experimental design, practice at the laboratory bench and data analysis. Its potentially adverse effects, incorrect identification of differentially expressed transcripts and overly-optimistic significance tests, can be fully avoided, however, by the sound application of recently established theory and models for data analysis

Influence of acidic characteristics of zeolites on activity and selectivity to diesel fraction of NiMo hydrocracking catalysts

In the present study, we investigated the influence of acid properties of NiMo hydrocracking catalysts on activity and selectivity to the diesel fraction. NiMo catalysts were prepared with using following acid components: ultrastable zeolite Y (UZ-Y), recrystallized zeolite Y (RMZ-Y) and nanocrystalline zeolite BEA (NCZ-BEA). Hydrocracking catalysts were tested in a down-flow, fixed bed reactor. Concentration and strength of Bronsted (BAS) and Lewis (LAS) acid sites of the zeolites were determined by infrared spectroscopy of adsorbed CO. Supports containing γ-Al2O3 and 20, 30 or 40 wt. % of UC-Y zeolite were prepared. It was shown that the higher zeolite content the higher activity and the lower selectivity to diesel fraction of the catalysts are. Testing of the catalysts prepared from different zeolites in hydrocracking showed that selectivity to diesel fraction is greatly influenced by the ratio of BAS concentration on outer surface of zeolite crystals to concentration strongest BAS on internal surface

Relationship of spirometric, body plethysmographic, and diffusing capacity parameters to emphysema scores derived from CT scans

Phenotyping of chronic obstructive pulmonary disease (COPD) with computed tomography (CT) is used to distinguish between emphysema- and airway-dominated type. The phenotype is reflected in correlations with lung function measures. Among these, the relative value of body plethysmography has not been quantified. We addressed this question using CT scans retrospectively collected from clinical routine in a large COPD cohort. Three hundred and thirty five patients with baseline data of the German COPD cohort COPD and Systemic Consequences-Comorbidities Network were included. CT scans were primarily evaluated using a qualitative binary emphysema score. The binary score was positive for emphysema in 52.5% of patients, and there were significant differences between the positive/negative groups regarding forced expiratory volume in 1 second (FEV1), FEV1/forced vital capacity (FVC), intrathoracic gas volume (ITGV), residual volume (RV), specific airway resistance (sRaw), transfer coefficient (KCO), transfer factor for carbon monoxide (TLCO), age, pack-years, and body mass index (BMI). Stepwise discriminant analyses revealed the combination of FEV1/FVC, RV, sRaw, and KCO to be significantly related to the binary emphysema score. The additional positive predictive value of body plethysmography, however, was only slightly higher than that of the conventional combination of spirometry and diffusing capacity, which if taken alone also achieved high predictive values, in contrast to body plethysmography. The additional information on the presence of CT-diagnosed emphysema as conferred by body plethysmography appeared to be minor compared to the well-known combination of spirometry and CO diffusing capacity. </jats:p

Crowdsourcing, open innovation and collective intelligence in the scientific method : a research agenda and operational framework

Open Access PublikationThe lonely researcher trying to crack a problem in her office still plays an important role in fundamental research. However, a vast exchange, often with participants from different fields is taking place in modern research activities and projects. In the “Research Value Chain” (a simplified depiction of the Scientific Method as a process used for the analyses in this paper), interactions between researchers and other individuals (intentional or not) within or outside their respective institutions can be regarded as occurrences of Collective Intelligence. “Crowdsourcing” (Howe 2006) is a special case of such Collective Intelligence. It leverages the wisdom of crowds (Surowiecki 2004) and is already changing the way groups of people produce knowledge, generate ideas and make them actionable. A very famous example of a Crowdsourcing outcome is the distributed encyclopedia „Wikipedia“. Published research agendas are asking how techniques addressing “the crowd” can be applied to non-profit environments, namely universities, and fundamental research in general. This paper discusses how the non-profit “Research Value Chain” can potentially benefit from Crowdsourcing. Further, a research agenda is proposed that investigates a) the applicability of Crowdsourcing to fundamental science and b) the impact of distributed agent principles from Artificial Intelligence research on the robustness of Crowdsourcing. Insights and methods from different research fields will be combined, such as complex networks, spatially embedded interacting agents or swarms and dynamic networks. Although the ideas in this paper essentially outline a research agenda, preliminary data from two pilot studies show that nonscientists can support scientific projects with high quality contributions. Intrinsic motivators (such as “fun”) are present, which suggests individuals are not (only) contributing to such projects with a view to large monetary rewards