TY - JOUR A1 - Langenhan, Jennifer A1 - Jaeger, Carsten A1 - Baum, K. A1 - Simon, M. A1 - Lisec, Jan T1 - A Flexible Tool to Correct Superimposed Mass Isotopologue Distributions in GC‐APCI‐MS Flux Experiments N2 - The investigation of metabolic fluxes and metabolite distributions within cells by means of tracer molecules is a valuable tool to unravel the complexity of biological systems. Technological advances in mass spectrometry (MS) technology such as atmospheric pressure chemical ionization (APCI) coupled with high resolution (HR), not only allows for highly sensitive analyses but also broadens the usefulness of tracer‐based experiments, as interesting signals can be annotated de novo when not yet present in a compound library. However, several effects in the APCI ion source, i.e., fragmentation and rearrangement, lead to superimposed mass isotopologue distributions (MID) within the mass spectra, which need to be corrected during data evaluation as they will impair enrichment calculation otherwise. Here, we present and evaluate a novel software tool to automatically perform such corrections. We discuss the different effects, explain the implemented algorithm, and show its application on several experimental datasets. This adjustable tool is available as an R package from CRAN. KW - Mass Spectrometry KW - Isotopologue Distribution KW - Metabolic Flux KW - R package PY - 2022 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-547318 DO - https://doi.org/10.3390/metabo12050408 VL - 12 IS - 5 SP - 1 EP - 10 PB - MDPI AN - OPUS4-54731 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Lisec, Jan A1 - Kobelt, D. A1 - Walther, W. A1 - Mokrizkij, M. A1 - Grötzinger, C. A1 - Jaeger, Carsten A1 - Baum, K. A1 - Simon, M. A1 - Wolf, J. A1 - Beindorf, N. A1 - Brenner, W. A1 - Stein, U. T1 - Systematic Identification of MACC1-Driven Metabolic Networks in Colorectal Cancer N2 - MACC1 is a prognostic and predictive metastasis biomarker for more than 20 solid Cancer entities. However, its role in cancer metabolism is not sufficiently explored. Here, we report on how MACC1 impacts the use of glucose, glutamine, lactate, pyruvate and fatty acids and show the comprehensive analysis of MACC1-driven metabolic networks. We analyzed concentrationdependent changes in nutrient use, nutrient depletion, metabolic tracing employing 13C-labeled substrates, and in vivo studies. We found that MACC1 permits numerous effects on cancer metabolism. Most of those effects increased nutrient uptake. Furthermore, MACC1 alters metabolic pathways by affecting metabolite production or turnover from metabolic substrates. MACC1 supports use of glucose, glutamine and pyruvate via their increased depletion or altered distribution within metabolic pathways. In summary, we demonstrate that MACC1 is an important regulator of metabolism in cancer cells. KW - Mass Spectroscopy KW - Metabolomics KW - Cancer PY - 2021 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-533526 DO - https://doi.org/10.3390/cancers13050978 VL - 13 IS - 5 SP - 1 EP - 22 PB - MDPI Journal Cancers AN - OPUS4-53352 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Tjaden, B. A1 - Baum, K. A1 - Marquardt, V. A1 - Simon, M. A1 - Trajkovic-Arsic, M. A1 - Kouril, T. A1 - Siebers, B. A1 - Lisec, Jan A1 - Siveke, J. T. A1 - Schulte, J. H. A1 - Benary, U. A1 - Remke, M. A1 - Wolf, J. A1 - Schramm, A. T1 - MYCN-induced metabolic rewiring creates novel therapeutic vulnerabilities in neuroblastoma N2 - MYCN is a transcription factor that is aberrantly expressed in many tumor types and is often correlated with poor patient prognosis. Recently, several lines of evidence pointed to the fact that oncogenic activation of MYC family proteins is concomitant with reprogramming of tumor cells to cope with an enhanced need for metabolites during cell growth. These adaptions are driven by the ability of MYC proteins to act as transcriptional amplifiers in a tissue-of-origin specific manner. Here, we describe the effects of MYCN overexpression on metabolic reprogramming in neuroblastoma cells. Ectopic expression of MYCN induced a glycolytic switch that was concomitant with enhanced sensitivity towards 2-deoxyglucose, an inhibitor of glycolysis. Moreover, global metabolic profiling revealed extensive alterations in the cellular metabolome resulting from overexpression of MYCN. Limited supply with either of the two main carbon sources, glucose or glutamine, resulted in distinct shifts in steady-state metabolite levels and significant changes in glutathione metabolism. Interestingly, interference with glutamine-glutamate conversion preferentially blocked proliferation of MYCN overexpressing cells, when glutamine levels were reduced. Thus, our study uncovered MYCN induction and nutrient levels as important metabolic master switches in neuroblastoma cells and identified critical nodes that restrict tumor cell proliferation. KW - Mass-spectrometry KW - Tumor metabolism KW - MYCN PY - 2018 DO - https://doi.org/10.1101/423756 SP - 1 EP - 21 PB - Cold Spring Harbor Laboratory CY - Cold Spring Harbor, NY AN - OPUS4-46815 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Homberg, U. A1 - Baum, D. A1 - Prohaska, S. A1 - Kalbe, Ute A1 - Witt, K. J. T1 - Automatic extraction and analysis of realistic pore structures from muCT data for pore space characterization of graded soil N2 - We present image-based methods to extract and analyze the pore structure of graded soil from CT scans. To assess and characterize realistic pore structures of graded soil, we process data of hetero disperse granulär material acquired via high-resolut ion CT. Real soil material configures a pore space with irregulär formations and complex arrangements. In Order to derive parameters of the pore space, a compact representation of the complex pore structure and efficient analysis methods are required. For this purpose, we propose mathematical definitions of the pore structure elements like pore centers, pore paths, pore constrictions, and pore bodies. These definitions are based on the distance map given on the Segmentation of the soil material into particles andpore space. For the extraction of the deftned structure elements, we present two image-basedprocessing pipelines that use the correspondence between our distance-based definition of pore structure elements and a Voronoi decomposition of the pore space. From the extractedpore centers andpore paths, we construct a graph and encode the distance Information on it. This graph, which we call the pore graph, is a compact 3d-representation of the topology of the pore space and provides a good basis to apply efficient graph-based methods for quantification as well as visualization and exploration of the spatial relationships and Connectivity of the pore space. T2 - ICSE6 - 6th International conference on scour and erosion CY - Paris, France DA - 27.08.2012 KW - Microtomography KW - Image analysis KW - Pore structure KW - Pore constriction KW - Suffosion KW - Graded soil PY - 2012 IS - ICSE6-181 SP - 345 EP - 352 AN - OPUS4-26965 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -