Previous lectures (2012-)
05.11.2013, 10 a.m., KUBUS, Room 1B
Dr. Sonja Hänzelmann
Computational Biology Group, RTWH Aachen, Germany
Computational methods for the analysis of high-throughput data
The computational biology group focuses on regulatory genomic events such as chromatin remodeling, transcription factor binding site detection, gene expression and influence of non-coding RNA during biological processes as diseases and cell development. In this talk, I will describe two current projects: (1) computational deteciton of long-non coding RNA interactions with the DNA and (2) pathway analyses based on gene expression data. (1) LncRNAs stear key regulatory processes, seem to be involved in regulating gene expression and have been indicated to modify chromatin structure. Further, lncRNAs are able to form triple helices with the DNA. Recent evidence suggests potential regulatory roles of regions where triple helices can be formed. The experimental detection of triple helix forming complexes proves to be difficult, therefore a computational method (Triplexator) was developed. The algorithm efficiently detects triple helix complexes on a genome-wide scale. However, genome-wide search of binding sites leads to a high number of false positive predictions, which are unlikely to be functional in a particular biological context. To address this problem, we developed an extension to the Triplexator method and found that lncRNAs use multiple TFOs to bind to particular sites. Further, DNA-lncRNA interactions might be arising from the combinatorial use of one or more interaction domains of the lncRNA. (2) We developed Gene Set Variation Analysis (GSVA), a method that condenses gene expression profiles into a pathway signature summary over a sample population in an unsupervised manner. GSVA can be applied to microarray and RNA-seq data equally and is available at Bioconductor. We provide examples of its utility in differential pathway activity and survival analysis. We demonstrate the robustness of GSVA in a comparison with current state of the art sample-wise enrichment methods. Further, we provide examples of its utility in differential pathway activity and survival analysis. Lastly, we show how GSVA works analogously with data from both microarray and RNA-seq experiments.
Host: Wibke Busch (Biotox)
23.11.2012, 10 a.m., Building 1, 1st floor, lecture hall (left)
Prof. Takaaki Nishioka
Graduate School of Information Science, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan
Sharing Mass Spectra in Research Community on MassBank
MassBank is a public repository of mass spectrometry (MS) data of endogenous and exogenous small molecules in cells and biological systems. A total of 25 research groups (17 Japan, 4 EU, 2 USA, 1 Switzerland and China groups) deposit 31,153 data (August 2012). Among the data, about eight thousands ESI-MS/MS data are of high mass accuracy analyzed on hybrid-tandem MSs. MassBank project manually annotated the molecular formula to product ions in these data. It provides such highly precise peak data not only by the conventional numerical m/z but also by the molecular formula. The latter data, “chemically exact” data, are useful to analyze the relationships between product ions and chemical substructures.
On the other, some users are afraid of the quality of MS data on the public repository. MassBank project carefully searches and deletes the data poor in the quality. However, users could easily find such poor data, if any. Different laboratories deposit more than five ESI-MS/MS data for each chemical compound on average. By comparing all the data of an identical chemical compound on a viewer, users could find MS data poor in the quality as those of unlike to the others.
Another feature of MassBank is a distributed database. Contributors prepare their data in the common record format and make the formatted data open to the public from their own local data servers distributed on the internet. Thus by a part of their research expenses, the contributors share most of the cost that should be necessary to manage MassBank if this is a centralized database. Currently 10 data servers are distributed on the internet. Researchers of a small data set contribute from either one of 10 data servers. In the distributed database, its users obtain search results in a shorter time because the data are searched in parallel on all the data servers. This is suitable for a large data sets such as MS data of unknowns. However, the time necessary to obtain search results might be longer by the data servers of a poor CPU. Additionally search results would be affected when a data server might be occasionally unavailable.
Other topics including a batch spectral search, a API service connected to KEGG PATHWAY API, consensus reference MS data, and “Bio-MassBank” that is a public repository of MS data of unknown and unidentified chemical compounds will be reported in the lecture.
Host: Tobias Schulze (WANA)
01.11.2012, 3 p.m., Building 1, 1st floor, lecture hall (left)
Prof. Antonia Concetta Elia
University of Perugia, Department of Cellular and Environmental Biology, Italy
Biomarkers for contaminant-mediated oxidative stress in freshwater organisms: an overview of field and laboratory studies
Balance between prooxidants and antioxidants is extremely important for biological functions. Oxidative stress results when the antioxidant defenses are overcome by prooxidant forces, and reactive oxygen species (ROS) are not adequately removed. Antioxidant, enzymatic and non enzymatic systems are biomarkers for contaminant-mediated oxidative stress and can also indicate the magnitude of response in organisms exposed to contaminants. Heavy metals, organochlorine and organophosphate pesticides, polychlorinated biphenyls, antibiotics and additives in diets fed in aquaculture play important roles in the mechanistic aspects of oxidative damage. The role of the antioxidant systems and their sensitivity in freshwater organisms can be of great importance in environmental toxicology studies.
In this presentation we expose our current knowledge and advancement in the understanding of oxidative processes in freshwater organisms caused by the contaminants listed above, and specific applications carried out in field and laboratory studies will be presented. For example, oxidative stress biomarkers in aquatic organisms can also be applied to evaluate the human healthiness of several disinfectants employed to make drinkable superficial water. Moreover, we will introduce some target species and tissues of aquatic pollution and show that their biochemical antioxidant alterations can provide useful information for the implementation of biomarker-based monitoring programs in freshwater biotopes. Furthermore, a multiple biomarker approach is recommended as an integrated tool to evaluate different short and long-term toxic effects of aquatic contaminants.
Host: Stefan Scholz (BIOTOX)
22. October 2012, 3 p.m. , KUBUS, hall 2
eawag, Environmental Chemistry, Dübendorf, Switzerland
Characterisation of treated wastewater using high resolution mass spectrometry – extending the boundaries of non-target screening
LC-MS technologies have opened the analytical window to thermolabile, polar compounds within the last 15 years. As a result, polar organic micropollutants such as pharmaceuticals have moved increasingly into the focus of environmental scientists, regulatory agencies, and politicians. To meet the analytical challenges of a mixture of many known and unknown compounds at low concentrations in complex matrices such as wastewater, the coupling of LC to high resolution mass spectrometry (HRMS) with high mass accuracy following electrospray ionization (ESI) is becoming increasingly popular.
In this presentation, the features, advantages, and limitations of LC coupled to HRMS for three conceptually different approaches are illustrated by selected studies in the field of wastewater treatment. These approaches include: (i) quantitative target analysis with reference standards; (ii) suspects screening without reference standards; and (iii) non target screening for unknowns.
In contrast to target and suspects screening, non-target (unknown) screening in a strict sense starts without any a priori information on the compounds to be detected. A tentative identification of non-target analytes in environmental samples with unconstrained boundary conditions is challenging and a structure proposition for a detected peak by high resolution MS and MS/MS spectra involves several work-intensive data and expert processing steps. The workflow involves peak detection by exact mass filtering from the chromatographic run, assignment of an elemental formula to the exact mass of interest, and data base searches for plausible structures for the determined elemental formula.
Especially municipal waste water contains a vast array of organic pollutants even after advanced treatment which may cause adverse effects in the aquatic environment. Characterising the presence of organic micropollutants in wastewater effluents is fraught with challenges and the full assessment of the effectiveness of treatment options is often difficult as many organic micropollutants transform during the treatment process. As a result, a pure target screening approach may indicate that a compounds is no longer present following treatment, while the compound is still present but in a transformed state. This and similar situations can be addressed using a combination of target and non-target screening approach on wastewater effluents.
Host: Tobias Schulze (WANA)
19. September 2012, 1 p.m. , KUBUS, hall 1A
AG Chemische Systembiologie, Leibniz-Institut für Molekulare Pharmakologie (FMP), Berlin
EU-OPENSCREEN, a European Infrastructure of Open-Access Screening Platforms for Chemical Biology
EU-OPENSCREEN is a research infrastructure initiative on the ESFRI roadmap (European Strategy Forum on Research Infrastructures) which aims to offer researchers from academia and SMEs access to shared instrumentation, expertise and resources for the identification of compounds affecting biological targets in all fields of the life sciences. EU-OPENSCREEN integrates high-throughput screening platforms in Europe, chemical libraries, chemical expertise and resources for discovery and optimisation, bio- and chemoinformatics support, and a database containing screening results, assay protocols, and chemical information. EU-OPENSCREEN will deliver bioactive compounds for research and for the development of new and safer products, and will increase our knowledge about how chemicals influence our lives and environment.
(Host: Rolf Altenburger)
10. May, 2012, 2 p.m. , lecture room 1st floor, building 1 (main building)
Beate I. Escher
The University of Queensland, National Research Centre for Environmental Toxicology (Entox), Brisbane QLD 4108, Australia
What’s in our water? Bioanalytical tools for assessment of micropollutants, mixtures and transformation products
Chemical pollution is an increasing threat to our waterways, oceans, and drinking water sources. The impact of chemical pollution will be amplified by population growth and, possibly, by some of the effects of climate change. However, conventional chemical monitoring programs have been criticised on the basis that they cannot include the full range of chemical pollutants that could occur in water sources, and they do not account for the combined effects of mixtures of chemicals. Bioanalytical tools may therefore complement chemical analysis for cost-efficient water quality monitoring.
Bioanalytical tools are cell-based bioassays that target specific mechanisms of toxicity and give a measure of the toxicity of mixtures of known and unknown chemicals, such as pesticides, industrial chemicals, pharmaceuticals and their transformation products. Bioanalytical tools provide measures of the cumulative effects of chemicals that exhibit the same mode of toxic action, for which the selected bioassays are indicative plus they can give a measure of the cytotoxicity of all chemicals acting together in a water sample. Improved detection of the presence of chemicals in water enhances risk assessment and informs water management options, among them water recycling from impaired sources such as sewage, coal seam gas water, or stormwater harvesting and reuse.
In this presentation the design of a modular battery of bioassays will be presented and some illustrative examples from recent applications in South East Queensland, Australia. The bioassays were selected from the three main categories of modes of action, namely non-specific, receptor-mediated specific and reactive toxicity. This bioanalytical test battery was used for monitoring organic micropollutants and disinfection by-products across an indirect potable reuse scheme testing sites across the complete water cycle from sewage to drinking water to assess the efficacy of different treatment barriers, including source control, wastewater treatment plant, microfiltration, reverse osmosis, advance oxidation, natural environment in a reservoir and drinking water treatment plant.
Professor Beate Escher is Deputy Director of the National Research Centre for Environmental Toxicology (Entox) in Brisbane, Australia, which is a joint venture between the University of Queensland and Queensland Health. Beate Escher received her PhD in Environmental Chemistry from the Swiss Federal Institute of Technology in Zürich, ETHZ, Switzerland. In 2002 she completed her habilitation in Environmental Toxicology and Chemistry ETHZ. She held a previous appointment as group leader at the Swiss Federal Institute of Aquatic Science, Eawag, in Dübendorf, Switzerland and was lecturer at ETHZ. Her research interests focus mode-of-action based environmental risk assessment, including methods for initial hazard screening and risk assessment of pharmaceuticals and pesticides, environmental transformation products, and mixtures. More practically oriented aspects of her work include passive sampling and effect-based methods for water quality assessment.