CELLmicrocosmos - Integrative cell modeling at the molecular, mesoscopic and functional level

Sommer B. CELLmicrocosmos - Integrative cell modeling at the  molecular, mesoscopic and functional level. Bielefeld: Bielefeld University; 2012.The modeling of cells is an important application area of Systems Biology. In the context of this work, three cytological levels are defined: the mesoscopic, the molecular and the functional level. A number of related approaches which are quite diverse will be introduced during this work which can be categorized into these disciplines. But none of these approaches covers all areas. In this work, the combination of all three aforementioned cytological levels is presented, realized by the CELLmicrocosmos project, combining and extending different Bioinformatics-related methods. The mesoscopic level is covered by CellEditor which is a simple tool to generate eukaryotic or prokaryotic cell models. These are based on cell components represented by three-dimensional shapes. Different methods to generate these shapes are discussed by using partly external tools such as Amira, 3ds Max and/or Blender; abstract, interpretative, 3D-microscopy-based and molecular-structure-based cell component modeling. To communicate with these tools, CellEditor provides import as well as export capabilities based on the VRML97 format. In addition, different cytological coloring methods are discussed which can be applied to the cell models. MembraneEditor operates at the molecular level. This tool solves heterogeneous Membrane Packing Problems by distributing lipids on rectangular areas using collision detection. It provides fast and intuitive methods supporting a wide range of different application areas based on the PDB format. Moreover, a plugin interface enables the use of custom algorithms. In the context of this work, a high-density-generating lipid packing algorithm is evaluated; The Wanderer. The semi-automatic integration of proteins into the membrane is enabled by using data from the OPM and PDBTM database. Contrasting with the aforementioned structural levels, the third level covers the functional aspects of the cell. Here, protein-related networks or data sets can be imported and mapped into the previously generated cell models using the PathwayIntegration. For this purpose, data integration methods are applied, represented by the data warehouse DAWIS-M.D. which includes a number of established databases. This information is enriched by the text-mining data acquired from the ANDCell database. The localization of proteins is supported by different tools like the interactive Localization Table and the Localization Charts. The correlation of partly multi-layered cell components with protein-related networks is covered by the Network Mapping Problem. A special implementation of the ISOM layout is used for this purpose. Finally, a first approach to combine all these interrelated levels is represented; CellExplorer which integrates CellEditor as well as PathwayIntegration and imports structures generated with MembraneEditor. For this purpose, the shape-based cell components can be correlated with networks as well as molecular membrane structures using Membrane Mapping. It is shown that the tools discussed here can be applied to scientific as well as educational tasks: educational cell visualization, initial membrane modeling for molecular simulations, analysis of interrelated protein sets, cytological disease mapping. These are supported by the user-friendly combination of Java, Java 3D and Web Start technology. In the last part of this thesis the future of Integrative Cell Modeling is discussed. While the approaches discussed here represent basically three-dimensional snapshots of the cell, prospective approaches have to be extended into the fourth dimension; time

The CELLmicrocosmos tools: A small history of Java-based cell and membrane modelling open source software development

For more than one decade, CELLmicrocosmos tools are being developed. Here, we discus some of the technical and administrative hurdles to keep a software suite running so many years. The tools were being developed during a number of student projects and theses, whereas main developers refactored and maintained the code over the years. The focus of this publication is laid on two Java-based Open Source Software frameworks. Firstly, the CellExplorer with the PathwayIntegration combines the mesoscopic and the functional level by mapping biological networks onto cell components using database integration. Secondly, the MembraneEditor enables users to generate membranes of different lipid and protein compositions using the PDB format. Technicalities will be discussed as well as the historical development of these tools with a special focus on group-based development. In this way, university-associated developers of Integrative Bioinformatics applications should be inspired to go similar ways. All tools discussed in this publication can be downloaded and installed from https://www.CELLmicrocosmos.org

Visualization of Metabolic Networks

The metabolism constitutes the universe of biochemical reactions taking place in a cell of an organism. These processes include the synthesis, transformation, and degradation of molecules for an organism to grow, to reproduce and to interact with its environment. A good way to capture the complexity of these processes is the representation as metabolic network, in which sets of molecules are transformed into products by a chemical reaction, and the products are being processed further. The underlying graph model allows a structural analysis of this network using established graphtheoretical algorithms on the one hand, and a visual representation by applying layout algorithms combined with information visualization techniques on the other. In this thesis we will take a look at three different aspects of graph visualization within the context of biochemical systems: the representation and interactive exploration of static networks, the visual analysis of dynamic networks, and the comparison of two network graphs. We will demonstrate, how established infovis techniques can be combined with new algorithms and applied to specific problems in the area of metabolic network visualization. We reconstruct the metabolic network covering the complete set of chemical reactions present in a generalized eucaryotic cell from real world data available from a popular metabolic pathway data base and present a suitable data structure. As the constructed network is very large, it is not feasible for the display as a whole. Instead, we introduce a technique to analyse this static network in a top-down approach starting with an overview and displaying detailed reaction networks on demand. This exploration method is also applied to compare metabolic networks in different species and from different resources. As for the analysis of dynamic networks, we present a framework to capture changes in the connectivity as well as changes in the attributes associated with the network’s elements

Genome visualisation and user studies in biologist-computer interaction

We surveyed a number of genome visualisation tools used in biomedical research. We recognised that none of the tools shows all the relevant data geneticists who look for candidate disease genes would like to see. The biological researchers we collaborate with would like to view integrated data from a variety of sources and be able to see both data overviews and details. In response to this need, we developed a new visualisation tool, VisGenome, which allows the users to add their own data or data downloaded from other sources, such as Ensembl. VisGenome visualises single and comparative representations of the rat, the mouse, and the human chromosomes, and can easily be used for other genomes. In the context of VisGenome development we made the following research contributions. We developed a new algorithm (CartoonPlus) which allows the users to see different kinds of data in cartoon scaling depending on a selected basis. Also, two user studies were conducted: an initial quantitative user study and a mixed paradigm user study. The first study showed that neither Ensembl nor VisGenome fulfil all user requirements and can be regarded as user-friendly, as the users make a significant number of mistakes during data navigation. To help users navigate their data easily, we improved existing visualisation techniques in VisGenome and added a new technique CartoonPlus. To verify if this solution was useful, we conducted a second user study. We saw that the users became more familiar with the tool, and found new ways to use the application on its own and in connection with other tools. They frequently used CartoonPlus, which allowed them to see small regions of their data in a way that was not possible before

Enhancing comprehension of complex data visualizations: Framework and techniques based on signature exploration

This thesis presents a framework and set of readily applicable techniques for enhancing comprehension of complex data visualizations. Central to the work has been the definition and exploration of a new concept, signature exploration. Visualization is being used increasingly to help make sense of large sets of data and information. Abstractions of complex data can be performed to reduce the dimensions to 2 or 3 for display. Novel or established representations can be used that allow direct mapping of greater numbers of attributes, and of a variety of data structures. There is an ever expanding set of visualization tools available. Two questions face the user: how to choose appropriate displays and how to understand the resultant graphic. This thesis examines how to support the user’s comprehension in this context. The work makes the following three main contributions to enhancing comprehension of complex data visualizations: the definition and application of signature exploration, a concept describing the exploration of visualization behaviour using specially constructed data; the proposal of a framework for the design of visualization systems for increased comprehension; the introduction of two new forms of interaction - which are here described as visual data tracking and feature fingerprinting. The central theme for the exploration presented in this work is the notion that a user wants to take data that is known in some way, put this into the visualization process and assess the resultant visual depiction. This intuitive desire has been captured in the definition of the concept, signature exploration. Signature exploration describes the exploration of the behaviour of visual representations using specially constructed datasets that contain features of interest. The datasets are used to explore the signatures of different visual representations and mathematical transformations. The thesis defines and illustrates signature exploration, with five proposed approaches: generic dataset provision; user-construction of data; querying; insertion of landmarks; elicitation and application of feedback data. These applications of signature exploration, together with analysis of the comprehension challenges presented by different aspects of visualization, and established work to support user comprehension, form the basis of the framework for increased user comprehension. Example software has been developed within the context of a visualization application that employs a number of visualization algorithms to generate graphics for multivariate or proximity data. Principal Components Analysis, Principal Coordinates Analysis and distance metrics of various kinds are the algorithms used. An additional interface is given to the user, to perform signature exploration. The work has resulted in the specification of a set of techniques that developers can readily apply. Two new interaction forms are described: visual data tracking - bi-directional brushing and linking between representations also allowing change of position or value; feature fingerprinting - synthetic additions to real-world datasets to provide the user with calibration of the visual depiction

Pameran Reka Cipta, Penyelidikan dan Inovasi (PRPI) 2009

PRPI 2009 kini telah memasuki tahun penganjurannya yang ke-7. Pameran penyelidikan di UPM telah bermula sejak tahun 1997 semasa Exhibition & Seminar Harnessing for Industry Advantage. Pada tahun 2002, Pameran Reka Cipta dan Penyelidikan (PRP) buat pertama kali telah diadakan dengan menggunakan konsep pertandingan hasil projek penyelidikan yang telah dijalankan oleh para penyelidik UPM. Kejayaan penganjuran PRP 2002 telah merintis usaha untuk menjadikannya sebagai aktiviti tahunan UPM dan ianya terus berkembang sejajar dengan nama baharunya yang ditukar kepada Pameran Reka Cipta, Penyelidikan dan Inovasi yang bermula penganjurannya pada tahun 2005. Sebagai kesinambungan daripada kejayaan penganjuran PRPI 2006, 2007 dan 2008 yang lalu dan status UPM sebagai salah sebuah Universiti Penyelidikan, PRPI 2009 kali ini yang merupakan pameran penyelidikan yang terbesar di UPM terus dilaksanakan dengan aspirasi dan semangat yang lebih jitu. Pameran ini juga menjadi pelantar kepada para penyelidik untuk mengenengahkan hasil penyelidikan yang dijalankan dan penemuan baharu kepada umum. Di samping itu ianya juga menjadi penanda aras terhadap kualiti sesuatu projek penyelidikan bagi melayakkan para penyelidik UPM untuk menyertai pameran di peringkat kebangsaan dan seterusnya antarabangsa. Adalah diharapkan pelaksanaan PRPI 2009 ini akan dapat menyemarakkan budaya penyelidikan di kalangan staf dan juga pelajar UPM sekaligus menjadikan UPM sebagai Universiti Penyelidikan yang cemerlang di negara ini