TY  - THES
A1  - Krüger, Beate
T1  - Integration und Kombination bioinformatischer Methoden in Biotechnologie, synthetischer Biologie und Pharmaindustrie
T1  - Intgration and combination of bioinformatical methods in biotechnology, synthetic biology and pharmaceutical industry
N2  - Die Bioinformatik ist eine interdisziplinäre Wissenschaft, welche Probleme aus allen Lebenswissenschaften mit Hilfe computergestützter Methoden bearbeitet. Ihr Ziel ist es, die Verarbeitung und Interpretation großer Datenmengen zu ermöglichen. Zudem unterstützt sie den Designprozess von Experimenten in der Synthetischen Biologie. Die synthetische Biologie beschäftigt sich mit der Generierung neuer Komponenten und deren Eigenschaften, welche durch die Behandlung und Manipulation lebender Organismen oder Teilen daraus entstehen. Ein besonders interessantes Themengebiet hierbei sind Zweikomponenten-Systeme (Two-Component System, TCS). TCS sind wichtige Signalkaskaden in Bakterien, welche in der Lage sind Informationen aus der Umgebung in eine Zelle zu übertragen und darauf zu reagieren. Die vorliegende Dissertation beschäftigt sich mit der Beurteilung, Nutzung und Weiterentwicklung von bioinformatischen Methoden zur Untersuchung von Proteininteraktionen und biologischen Systemen. Der wissenschaftliche Beitrag der vorliegenden Arbeit kann in drei Aspekte unterteilt werden: - Untersuchung und Beurteilung von bioinformatischen Methoden und Weiterführung der Ergebnisse aus der vorhergehenden Diplomarbeit zum Thema Protein-Protein-Interaktionsvorhersagen. - Analyse genereller evolutionärer Modifikationsmöglichkeiten von TCS sowie deren Design und spezifische Unterschiede. - Abstraktion bzw. Transfer der gewonnenen Erkenntnisse auf technische und biologische Zusammenhänge. Mit dem Ziel das Design neuer Experimente in der synthetischen Biologie zu vereinfachen und die Vergleichbarkeit von technischen und biologischen Prozessen sowie zwischen Organismen zu ermöglichen. Das Ergebnis der durchgeführten Studie zeigte, dass Zweikomponenten-Systeme in ihrem Aufbau sehr konserviert sind. Nichtsdestotrotz konnten viele spezifische Eigenschaften und drei generelle Modifikationsmöglichkeiten entdeckt werden. Die Untersuchungen ermöglichten die Identifikation neuer Promotorstellen, erlaubten aber auch die Beschreibung der Beschaffenheit unterschiedlicher Signalbindestellen. Zudem konnten bisher fehlende Komponenten aus TCS entdeckt werden, ebenso wie neue divergierte TCS-Domänen im Organismus Mycoplasma. Eine Kombination aus technischen Ansätzen und synthetischer Biologie vereinfachte die gezielte Manipulation von TCS oder anderen modularen Systemen. Die Etablierung der vorgestellten zweistufigen Modul-Klassifikation ermöglichte eine effizientere Analyse modular aufgebauter Prozesse und erlaubte somit das molekulare Design synthetischer, biologischer Anwendungen. Zur einfachen Nutzung dieses Ansatzes wurde eine frei zugängliche Software GoSynthetic entwickelt. Konkrete Beispiele demonstrierten die praktische Anwendbarkeit dieser Analysesoftware. Die vorgestellte Klassifikation der synthetisch-biologischen und technischen Einheiten soll die Planung zukünftiger Designexperimente vereinfachen und neue Wege für sinnverwandte Bereiche aufzeigen. Es ist nicht die Hauptaufgabe der Bioinformatik, Experimente zu ersetzen, sondern resultierende große Datenmengen sinnvoll und effizient auszuwerten. Daraus sollen neue Ideen für weitere Analysen und alternative Anwendungen gewonnen werden, um fehlerhafte oder falsche Ansätze frühzeitig zu erkennen. Die Bioinformatik bietet moderne, technische Verfahren, um vertraute, aber oft mühsame experimentelle Wege durch neue, vielversprechende Ansätze zur Datenstrukturierung und Auswertung großer Datenmengen zu ergänzen. Neue Sichtweisen werden durch die Erleichterung des Testprozederes gefördert. Die resultierende Zeitersparnis führt zudem zu einer Kostenreduktion.
N2  - The field of Bioinformatics is an interdisciplinary science focusing on the application of computer science to solve problems in different areas of life sciences. Its scope is to handle and interpret an immense quantity of data and to support computer-aided design approaches of synthetic biological experiments. Synthetic biology deals with the generation of new components and biological characteristics created by manipulation of living organisms or parts of them. Of particular interest are two-component systems (TCS). TCS describe simple and important signalling cascades in bacteria which transfer information from the environment into the cell as a reaction to changes in the environment. The present thesis is focused on the assessment, applicability and enhancement of bioinformatical methods in order to facilitate analysis of protein interactions and biological systems. The scientific efforts within the thesis can be divided into three aspects: - Analysis and assessment of bioinformatical methods and enhancement of results from the preceding diploma thesis dealing with protein-protein interaction predictions. - Analysis of general evolutionary modification possibilities within TCS as well as specific differences and design for the identification of a common approach. - Abstraction and transfer of the results to technical and biological contexts in order to simplify synthetic biological design experiments. Establishment of comparable vocabulary for both, technical and biological processes as well as different organisms. The outcome of this thesis revealed that TCS structure is very conserved but that it nevertheless contained some very specific characteristics. New promotor sites were discovered whilst additionally allowing the analysis of the signal binding sites. Missing elements from known TCS could be discovered and a completely new diverged TCS domain in the organism Mycoplasma could be identified as well as three general modification possibilities for TCS. The combination between technological approaches and synthetic biology simplifies the systematic manipulation of TCS or other modular systems. The established two-staged module classification simplifies the analysis of modular processes and thereby the molecular design of synthetical-biological questions. Concrete examples showed the functionality and usefulness of the classification. A freely accessible software GoSynthetic provided easy access and application of the developed toolbox. Not only new concrete scientific findings were provided by the given thesis but also a general approach to identify and analyse TCS and even to create similar analytic procedures. The established classification of biological and technical modules will ease the design of future experiments and reveals new pportunities applicable to similar scientific areas. It is not the task of Bioinformatics to replace experiments but to analyse the resulting huge amounts of data meaningfully and efficiently. Hence, new ideas for further analysis and alternative cases need to be generated which may finally help to identify erroneous approaches earlier. Bioinformatics offers modern technical methods to amend familiar and sometimes exhausting experimental procedures with promising new approaches for data structuring and analysis of immense quantities of data. New perceptions are encouraged and speedier progress is possible without increasing the experimental coasts.
KW  - Biotechnologie
KW  - Synthetische Biologie
KW  - Bioinformatik
KW  - Vaccinia-Virus
KW  - Zweikomponentensystem <Molekularbiologie>
KW  - Zweikomponenten-System
KW  - Pharmazeutische Industrie
KW  - biotechnology
KW  - synthetic biology
KW  - bioinformatic
KW  - two-component system
KW  - vaccinia virus
KW  - gene ontology
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-70702
ER  - 
TY  - JOUR
A1  - Dandekar, Thomas
A1  - Liang, Chunguang
A1  - Krüger, Beate
T1  - GoSynthetic database tool to analyse natural and engineered molecular processes
JF  - Database
N2  - An essential topic for synthetic biologists is to understand the structure and function of biological processes and involved proteins and plan experiments accordingly. Remarkable progress has been made in recent years towards this goal. However, efforts to collect and present all information on processes and functions are still cumbersome. The database tool GoSynthetic provides a new, simple and fast way to analyse biological processes applying a hierarchical database. Four different search modes are implemented. Furthermore, protein interaction data, cross-links to organism-specific databases (17 organisms including six model organisms and their interactions), COG/KOG, GO and IntAct are warehoused. The built in connection to technical and engineering terms enables a simple switching between biological concepts and concepts from engineering, electronics and synthetic biology. The current version of GoSynthetic covers more than one million processes, proteins, COGs and GOs. It is illustrated by various application examples probing process differences and designing modifications.
KW  - Bioinformatik
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-97023
ER  - 
TY  - JOUR
A1  - El-Helou, Sabine M.
A1  - Biegner, Anika-Kerstin
A1  - Bode, Sebastian
A1  - Ehl, Stephan R.
A1  - Heeg, Maximilian
A1  - Maccari, Maria E.
A1  - Ritterbusch, Henrike
A1  - Speckmann, Carsten
A1  - Rusch, Stephan
A1  - Scheible, Raphael
A1  - Warnatz, Klaus
A1  - Atschekzei, Faranaz
A1  - Beider, Renata
A1  - Ernst, Diana
A1  - Gerschmann, Stev
A1  - Jablonka, Alexandra
A1  - Mielke, Gudrun
A1  - Schmidt, Reinhold E.
A1  - Schürmann, Gesine
A1  - Sogkas, Georgios
A1  - Baumann, Ulrich H.
A1  - Klemann, Christian
A1  - Viemann, Dorothee
A1  - Bernuth, Horst von
A1  - Krüger, Renate
A1  - Hanitsch, Leif G.
A1  - Scheibenbogen, Carmen M.
A1  - Wittke, Kirsten
A1  - Albert, Michael H.
A1  - Eichinger, Anna
A1  - Hauck, Fabian
A1  - Klein, Christoph
A1  - Rack-Hoch, Anita
A1  - Sollinger, Franz M.
A1  - Avila, Anne
A1  - Borte, Michael
A1  - Borte, Stephan
A1  - Fasshauer, Maria
A1  - Hauenherm, Anja
A1  - Kellner, Nils
A1  - Müller, Anna H.
A1  - Ülzen, Anett
A1  - Bader, Peter
A1  - Bakhtiar, Shahrzad
A1  - Lee, Jae-Yun
A1  - Heß, Ursula
A1  - Schubert, Ralf
A1  - Wölke, Sandra
A1  - Zielen, Stefan
A1  - Ghosh, Sujal
A1  - Laws, Hans-Juergen
A1  - Neubert, Jennifer
A1  - Oommen, Prasad T.
A1  - Hönig, Manfred
A1  - Schulz, Ansgar
A1  - Steinmann, Sandra
A1  - Klaus, Schwarz
A1  - Dückers, Gregor
A1  - Lamers, Beate
A1  - Langemeyer, Vanessa
A1  - Niehues, Tim
A1  - Shai, Sonu
A1  - Graf, Dagmar
A1  - Müglich, Carmen
A1  - Schmalzing, Marc T.
A1  - Schwaneck, Eva C.
A1  - Tony, Hans-Peter
A1  - Dirks, Johannes
A1  - Haase, Gabriele
A1  - Liese, Johannes G.
A1  - Morbach, Henner
A1  - Foell, Dirk
A1  - Hellige, Antje
A1  - Wittkowski, Helmut
A1  - Masjosthusmann, Katja
A1  - Mohr, Michael
A1  - Geberzahn, Linda
A1  - Hedrich, Christian M.
A1  - Müller, Christiane
A1  - Rösen-Wolff, Angela
A1  - Roesler, Joachim
A1  - Zimmermann, Antje
A1  - Behrends, Uta
A1  - Rieber, Nikolaus
A1  - Schauer, Uwe
A1  - Handgretinger, Rupert
A1  - Holzer, Ursula
A1  - Henes, Jörg
A1  - Kanz, Lothar
A1  - Boesecke, Christoph
A1  - Rockstroh, Jürgen K.
A1  - Schwarze-Zander, Carolynne
A1  - Wasmuth, Jan-Christian
A1  - Dilloo, Dagmar
A1  - Hülsmann, Brigitte
A1  - Schönberger, Stefan
A1  - Schreiber, Stefan
A1  - Zeuner, Rainald
A1  - Ankermann, Tobias
A1  - Bismarck, Philipp von
A1  - Huppertz, Hans-Iko
A1  - Kaiser-Labusch, Petra
A1  - Greil, Johann
A1  - Jakoby, Donate
A1  - Kulozik, Andreas E.
A1  - Metzler, Markus
A1  - Naumann-Bartsch, Nora
A1  - Sobik, Bettina
A1  - Graf, Norbert
A1  - Heine, Sabine
A1  - Kobbe, Robin
A1  - Lehmberg, Kai
A1  - Müller, Ingo
A1  - Herrmann, Friedrich
A1  - Horneff, Gerd
A1  - Klein, Ariane
A1  - Peitz, Joachim
A1  - Schmidt, Nadine
A1  - Bielack, Stefan
A1  - Groß-Wieltsch, Ute
A1  - Classen, Carl F.
A1  - Klasen, Jessica
A1  - Deutz, Peter
A1  - Kamitz, Dirk
A1  - Lassy, Lisa
A1  - Tenbrock, Klaus
A1  - Wagner, Norbert
A1  - Bernbeck, Benedikt
A1  - Brummel, Bastian
A1  - Lara-Villacanas, Eusebia
A1  - Münstermann, Esther
A1  - Schneider, Dominik T.
A1  - Tietsch, Nadine
A1  - Westkemper, Marco
A1  - Weiß, Michael
A1  - Kramm, Christof
A1  - Kühnle, Ingrid
A1  - Kullmann, Silke
A1  - Girschick, Hermann
A1  - Specker, Christof
A1  - Vinnemeier-Laubenthal, Elisabeth
A1  - Haenicke, Henriette
A1  - Schulz, Claudia
A1  - Schweigerer, Lothar
A1  - Müller, Thomas G.
A1  - Stiefel, Martina
A1  - Belohradsky, Bernd H.
A1  - Soetedjo, Veronika
A1  - Kindle, Gerhard
A1  - Grimbacher, Bodo
T1  - The German national registry of primary immunodeficiencies (2012-2017)
JF  - Frontiers in Immunology
N2  - Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. 

Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. 

Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1-25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0-88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE-syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%-subcutaneous; 29%-intravenous; 1%-unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. 

Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment.
KW  - registry for primary immunodeficiency
KW  - primary immunodeficiency (PID)
KW  - German PID-NET registry
KW  - PID prevalence
KW  - European Society for Immunodeficiencies (ESID)
KW  - IgG substitution therapy
KW  - CVID
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226629
VL  - 10
ER  -