Papers by Andreas Deutsch
Genetic Programming and Evolvable Machines, 2007
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Physical Review Letters, Jul 26, 2002
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Metastatic tumor cell invasion into interstitial tissue is a mechanochemical process that respond... more Metastatic tumor cell invasion into interstitial tissue is a mechanochemical process that responds to tissue cues and further involves proteolytic remodeling of the tumor stroma. How matrix density, tissue guidance and the ability of proteolytic tissue remodeling cooperate and determine decision-making of invading tumor cells in complex-structured three-dimensional (3D) tissue remains unclear. We here developed a collagen-based invasion assay containing a guiding interface of low collagen density adjacent to randomly organized 3D fibrillar lattice and examined the invasion of melanoma cells from multicellular spheroids in response to matrix density, guidance cues and collagenolysis. After 48 hours of culture, two invasion niches developed, (i) sheet-like collective migration along the interface and (ii) single cell- and strand-like invasion into randomly organized 3D matrix. High collagen density impeded migration into the random matrix, whereas migration along a high-density collag...
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submission deadline: April 30, 2008 The field of infectious disease dynamics has come of age duri... more submission deadline: April 30, 2008 The field of infectious disease dynamics has come of age during the last few years. The launch of a new and dedicated journal, with an associated
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Cancers, 2020
Astrocytomas are primary human brain tumors including diffuse or anaplastic astrocytomas that dev... more Astrocytomas are primary human brain tumors including diffuse or anaplastic astrocytomas that develop towards secondary glioblastomas over time. However, only little is known about molecular alterations that drive this progression. We measured multi-omics profiles of patient-matched astrocytoma pairs of initial and recurrent tumors from 22 patients to identify molecular alterations associated with tumor progression. Gene copy number profiles formed three major subcluters, but more than half of the patient-matched astrocytoma pairs differed in their gene copy number profiles like astrocytomas from different patients. Chromosome 10 deletions were not observed for diffuse astrocytomas, but occurred in corresponding recurrent tumors. Gene expression profiles formed three other major subclusters and patient-matched expression profiles were much more heterogeneous than their copy number profiles. Still, recurrent tumors showed a strong tendency to switch to the mesenchymal subtype. The di...
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Cancer development is a multistep process in which cells increase in malignancy through progressi... more Cancer development is a multistep process in which cells increase in malignancy through progressive alterations. The early phase of this process is hardly observable which aggravates an understanding of later tumor development. We shed light on this initial phase with a cell-based stochastic model calibrated with epidemiological data from the tissue scale. Our model allows to estimate the number of tumor cells needed for tumor formation in human tissues based on data on the diagnosed ratios of benign and malignant tumors. We find that the minimal number of cells needed for tumor formation is surprisingly small and largely depends on the tissue type. Our results point towards the existence of tumor-originating niches in which the fate of tumor development is early decided. Our estimate for the human colon agrees well with the size of the stem cell niche in colonic crypts. Our estimates might help to identify the tumor-originating cell type, e.g. our analysis suggests for glioblastoma...
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Nature Communications, 2019
The identity and unique capacity of cancer stem cells (CSC) to drive tumor growth and resistance ... more The identity and unique capacity of cancer stem cells (CSC) to drive tumor growth and resistance have been challenged in brain tumors. Here we report that cells expressing CSC-associated cell membrane markers in Glioblastoma (GBM) do not represent a clonal entity defined by distinct functional properties and transcriptomic profiles, but rather a plastic state that most cancer cells can adopt. We show that phenotypic heterogeneity arises from non-hierarchical, reversible state transitions, instructed by the microenvironment and is predictable by mathematical modeling. Although functional stem cell properties were similar in vitro, accelerated reconstitution of heterogeneity provides a growth advantage in vivo, suggesting that tumorigenic potential is linked to intrinsic plasticity rather than CSC multipotency. The capacity of any given cancer cell to reconstitute tumor heterogeneity cautions against therapies targeting CSC-associated membrane epitopes. Instead inherent cancer cell pl...
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Bioinformatics and biology insights, 2017
Many normal and cancerous cell lines exhibit a stable composition of cells in distinct states whi... more Many normal and cancerous cell lines exhibit a stable composition of cells in distinct states which can, e.g., be defined on the basis of cell surface markers. There is evidence that such an equilibrium is associated with stochastic transitions between distinct states. Quantifying these transitions has the potential to better understand cell lineage compositions. We introduce CellTrans, an R package to quantify stochastic cell state transitions from cell state proportion data from fluorescence-activated cell sorting and flow cytometry experiments. The R package is based on a mathematical model in which cell state alterations occur due to stochastic transitions between distinct cell states whose rates only depend on the current state of a cell. CellTrans is an automated tool for estimating the underlying transition probabilities from appropriately prepared data. We point out potential analytical challenges in the quantification of these cell transitions and explain how CellTrans hand...
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Molecular Cancer Therapeutics, 2017
Tumor cells—even if nonauxotrophic—are often highly sensitive to arginine deficiency. We hypothes... more Tumor cells—even if nonauxotrophic—are often highly sensitive to arginine deficiency. We hypothesized that arginine deprivation therapy (ADT) if combined with irradiation could be a new treatment strategy for glioblastoma (GBM) patients because systemic ADT is independent of local penetration and diffusion limitations. A proof-of-principle in vitro study was performed with ADT being mimicked by application of recombinant human arginase or arginine-free diets. ADT inhibited two-dimensional (2-D) growth and cell-cycle progression, and reduced growth recovery after completion of treatment in four different GBM cell line models. Cells were less susceptible to ADT alone in the presence of citrulline and in a three-dimensional (3-D) environment. Migration and 3-D invasion were not unfavorably affected. However, ADT caused a significant radiosensitization that was more pronounced in a GBM cell model with p53 loss of function as compared with its p53-wildtype counterpart. The synergistic ef...
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PLOS Computational Biology, 2015
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ACM Transactions on Modeling and Computer Simulation, 2016
Multipotent differentiation, where cells adopt one of several cell fates, is a determinate and or... more Multipotent differentiation, where cells adopt one of several cell fates, is a determinate and orchestrated procedure that often incorporates stochastic mechanisms in order to diversify cell types. How these stochastic phenomena interact to govern cell fate is poorly understood. Nonetheless, cell fate decision-making procedure is mainly regulated through the activation of differentiation waves and associated signaling pathways. In the current work, we focus on the Notch/Delta signaling pathway, which is not only known to trigger such waves but also is used to achieve the principle of lateral inhibition (i.e., a competition for exclusive fates through cross-signaling between neighboring cells). Such a process ensures unambiguous stochastic decisions influenced by intrinsic noise sources, such as those found in the regulation of signaling pathways, and extrinsic stochastic fluctuations attributed to microenvironmental factors. However, the effect of intrinsic and extrinsic noise on ce...
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Computational Fluid and Solid Mechanics 2003#R##N#Proceedings Second MIT Conference on Compurational Fluid and Solid Mechanics June 17–20, 2003, 2003
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Lecture Notes in Computer Science, 2004
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Lecture Notes in Computer Science, 2005
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Lecture Notes in Computer Science, 2008
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Interface focus, Jan 6, 2012
Formation of spatial patterns of cells is a recurring theme in biology and often depends on regul... more Formation of spatial patterns of cells is a recurring theme in biology and often depends on regulated cell motility. Motility of the rod-shaped cells of the bacterium Myxococcus xanthus depends on two motility machineries, type IV pili (giving rise to S-motility) and the gliding motility apparatus (giving rise to A-motility). Cell motility is regulated by occasional reversals. Moving M. xanthus cells can organize into spreading colonies or spore-filled fruiting bodies, depending on their nutritional status. To ultimately understand these two pattern-formation processes and the contributions by the two motility machineries, as well as the cell reversal machinery, we analyse spatial self-organization in three M. xanthus strains: (i) a mutant that moves unidirectionally without reversing by the A-motility system only, (ii) a unidirectional mutant that is also equipped with the S-motility system, and (iii) the wild-type that, in addition to the two motility systems, occasionally reverse...
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Selected Topics in Cancer Modeling
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Physical Review Letters, 1997
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Physical Review Letters, 2002
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Papers by Andreas Deutsch