TY - JOUR A1 - Breitenbach, Tim A1 - Helfrich-Förster, Charlotte A1 - Dandekar, Thomas T1 - An effective model of endogenous clocks and external stimuli determining circadian rhythms JF - Scientific Reports N2 - Circadian endogenous clocks of eukaryotic organisms are an established and rapidly developing research field. To investigate and simulate in an effective model the effect of external stimuli on such clocks and their components we developed a software framework for download and simulation. The application is useful to understand the different involved effects in a mathematical simple and effective model. This concerns the effects of Zeitgebers, feedback loops and further modifying components. We start from a known mathematical oscillator model, which is based on experimental molecular findings. This is extended with an effective framework that includes the impact of external stimuli on the circadian oscillations including high dose pharmacological treatment. In particular, the external stimuli framework defines a systematic procedure by input-output-interfaces to couple different oscillators. The framework is validated by providing phase response curves and ranges of entrainment. Furthermore, Aschoffs rule is computationally investigated. It is shown how the external stimuli framework can be used to study biological effects like points of singularity or oscillators integrating different signals at once. The mathematical framework and formalism is generic and allows to study in general the effect of external stimuli on oscillators and other biological processes. For an easy replication of each numerical experiment presented in this work and an easy implementation of the framework the corresponding Mathematica files are fully made available. They can be downloaded at the following link: https://www.biozentrum.uni-wuerzburg.de/bioinfo/computing/circadian/. KW - computational biology and bioinformatics KW - systems biology Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-261655 VL - 11 IS - 1 ER - TY - JOUR A1 - Ampattu, Biju Joseph A1 - Hagmann, Laura A1 - Liang, Chunguang A1 - Dittrich, Marcus A1 - Schlüter, Andreas A1 - Blom, Jochen A1 - Krol, Elizaveta A1 - Goesmann, Alexander A1 - Becker, Anke A1 - Dandekar, Thomas A1 - Müller, Tobias A1 - Schoen, Christoph T1 - Transcriptomic buffering of cryptic genetic variation contributes to meningococcal virulence JF - BMC Genomics N2 - Background: Commensal bacteria like Neisseria meningitidis sometimes cause serious disease. However, genomic comparison of hyperinvasive and apathogenic lineages did not reveal unambiguous hints towards indispensable virulence factors. Here, in a systems biological approach we compared gene expression of the invasive strain MC58 and the carriage strain α522 under different ex vivo conditions mimicking commensal and virulence compartments to assess the strain-specific impact of gene regulation on meningococcal virulence. Results: Despite indistinguishable ex vivo phenotypes, both strains differed in the expression of over 500 genes under infection mimicking conditions. These differences comprised in particular metabolic and information processing genes as well as genes known to be involved in host-damage such as the nitrite reductase and numerous LOS biosynthesis genes. A model based analysis of the transcriptomic differences in human blood suggested ensuing metabolic flux differences in energy, glutamine and cysteine metabolic pathways along with differences in the activation of the stringent response in both strains. In support of the computational findings, experimental analyses revealed differences in cysteine and glutamine auxotrophy in both strains as well as a strain and condition dependent essentiality of the (p)ppGpp synthetase gene relA and of a short non-coding AT-rich repeat element in its promoter region. Conclusions: Our data suggest that meningococcal virulence is linked to transcriptional buffering of cryptic genetic variation in metabolic genes including global stress responses. They further highlight the role of regulatory elements for bacterial virulence and the limitations of model strain approaches when studying such genetically diverse species as N. meningitidis. KW - neisseria meningitidis KW - MITE KW - virulenceregulatory evolution KW - systems biology KW - metabolism KW - cryptic KW - genetic variation KW - stringent response KW - relA Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-157534 VL - 18 IS - 282 ER - TY - JOUR A1 - Naseem, Muhammad A1 - Kunz, Meik A1 - Dandekar, Thomas T1 - Probing the unknowns in cytokinin-mediated immune defense in Arabidopsis with systems biology approaches JF - Bioinformatics and Biology Insights N2 - Plant hormones involving salicylic acid (SA), jasmonic acid (JA), ethylene (Et), and auxin, gibberellins, and abscisic acid (ABA) are known to regulate host immune responses. However, plant hormone cytokinin has the potential to modulate defense signaling including SA and JA. It promotes plant pathogen and herbivore resistance; underlying mechanisms are still unknown. Using systems biology approaches, we unravel hub points of immune interaction mediated by cytokinin signaling in Arabidopsis. High-confidence Arabidopsis protein-protein interactions (PPI) are coupled to changes in cytokinin-mediated gene expression. Nodes of the cellular interactome that are enriched in immune functions also reconstitute sub-networks. Topological analyses and their specific immunological relevance lead to the identification of functional hubs in cellular interactome. We discuss our identified immune hubs in light of an emerging model of cytokinin-mediated immune defense against pathogen infection in plants. KW - plant hormones KW - systems biology KW - interaction networks KW - gene expression KW - cytokinin Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-120199 SN - 1177-9322 VL - 8 ER -