@misc{HischeLarhlimiSchwarzetal.2012,
  author    = {Hische, Manuela and Larhlimi, Abdelhalim and Schwarz, Franziska and Fischer-Rosinsk{\´y}, Antje and Bobbert, Thomas and Assmann, Anke and Catchpole, Gareth S. and Pfeiffer, Andreas F. H. and Willmitzer, Lothar and Selbig, Joachim and Spranger, Joachim},
  title     = {A distinct metabolic signature predictsdevelopment of fasting plasma glucose},
  series = {Postprints der Universit{\"a}t Potsdam : Mathematisch Naturwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam : Mathematisch Naturwissenschaftliche Reihe},
  number    = {850},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-42740},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-427400},
  pages     = {12},
  year      = {2012},
  abstract  = {Background High blood glucose and diabetes are amongst the conditions causing the greatest losses in years of healthy life worldwide. Therefore, numerous studies aim to identify reliable risk markers for development of impaired glucose metabolism and type 2 diabetes. However, the molecular basis of impaired glucose metabolism is so far insufficiently understood. The development of so called 'omics' approaches in the recent years promises to identify molecular markers and to further understand the molecular basis of impaired glucose metabolism and type 2 diabetes. Although univariate statistical approaches are often applied, we demonstrate here that the application of multivariate statistical approaches is highly recommended to fully capture the complexity of data gained using high-throughput methods. Methods We took blood plasma samples from 172 subjects who participated in the prospective Metabolic Syndrome Berlin Potsdam follow-up study (MESY-BEPO Follow-up). We analysed these samples using Gas Chromatography coupled with Mass Spectrometry (GC-MS), and measured 286 metabolites. Furthermore, fasting glucose levels were measured using standard methods at baseline, and after an average of six years. We did correlation analysis and built linear regression models as well as Random Forest regression models to identify metabolites that predict the development of fasting glucose in our cohort. Results We found a metabolic pattern consisting of nine metabolites that predicted fasting glucose development with an accuracy of 0.47 in tenfold cross-validation using Random Forest regression. We also showed that adding established risk markers did not improve the model accuracy. However, external validation is eventually desirable. Although not all metabolites belonging to the final pattern are identified yet, the pattern directs attention to amino acid metabolism, energy metabolism and redox homeostasis. Conclusions We demonstrate that metabolites identified using a high-throughput method (GC-MS) perform well in predicting the development of fasting plasma glucose over several years. Notably, not single, but a complex pattern of metabolites propels the prediction and therefore reflects the complexity of the underlying molecular mechanisms. This result could only be captured by application of multivariate statistical approaches. Therefore, we highly recommend the usage of statistical methods that seize the complexity of the information given by high-throughput methods.},
  language  = {en}
}
@article{KehrHaebelBlechschmidtSchneideretal.1999,
  author    = {Kehr, Julia and Haebel, Sophie and Blechschmidt-Schneider, Sabine and Willmitzer, Lothar and Steup, Martin and Fisahn, Joachim},
  title     = {Analysis of phloem protein patterns from different organs of Cucurbita maxima Duch. by matrix-assisted laser desorption/ionization time of flight mass spectroscopy combined with sodium dodecyl sufate-polyacryilamide gel electrophoresis},
  year      = {1999},
  language  = {en}
}
@article{DuwenigSteupWillmitzeretal.1997,
  author    = {Duwenig, Elke and Steup, Martin and Willmitzer, Lothar and Kossmann, Jens},
  title     = {Antisense inhibition of cytosolic phosphorylase in potato plants (Solanum tuberosum L.) affects tuber sprouting and flower formation with only little impact on carbohydrate metabolism},
  year      = {1997},
  language  = {en}
}
@article{deAbreueLimaWillmitzerNikoloski2018,
  author    = {de Abreu e Lima, Francisco Anastacio and Willmitzer, Lothar and Nikoloski, Zoran},
  title     = {Classification-driven framework to predict maize hybrid field performance from metabolic profiles of young parental roots},
  series = {PLoS one},
  volume    = {13},
  journal   = {PLoS one},
  number    = {4},
  publisher = {PLoS},
  address   = {San Fransisco},
  issn      = {1932-6203},
  doi       = {10.1371/journal.pone.0196038},
  pages     = {16},
  year      = {2018},
  abstract  = {Maize (Zea mays L.) is a staple food whose production relies on seed stocks that largely comprise hybrid varieties. Therefore, knowledge about the molecular determinants of hybrid performance (HP) in the field can be used to devise better performing hybrids to address the demands for sustainable increase in yield. Here, we propose and test a classification-driven framework that uses metabolic profiles from in vitro grown young roots of parental lines from the Dent x Flint maize heterotic pattern to predict field HP. We identify parental analytes that best predict the metabolic inheritance patterns in 328 hybrids. We then demonstrate that these analytes are also predictive of field HP (0.64 >= r >= 0.79) and discriminate hybrids of good performance (accuracy of 87.50\%). Therefore, our approach provides a cost-effective solution for hybrid selection programs.},
  language  = {en}
}
@article{JuerchottGuoCatchpoleetal.2011,
  author    = {Juerchott, Kathrin and Guo, Ke-Tai and Catchpole, Gareth and Feher, Kristen and Willmitzer, Lothar and Schichor, Christian and Selbig, Joachim},
  title     = {Comparison of metabolite profiles in U87 glioma cells and mesenchymal stem cells},
  series = {Biosystems : journal of biological and information processing sciences},
  volume    = {105},
  journal   = {Biosystems : journal of biological and information processing sciences},
  number    = {2},
  publisher = {Elsevier},
  address   = {Oxford},
  issn      = {0303-2647},
  doi       = {10.1016/j.biosystems.2011.05.005},
  pages     = {130 -- 139},
  year      = {2011},
  abstract  = {Gas chromatography-mass spectrometry (GC-MS) profiles were generated from U87 glioma cells and human mesenchymal stem cells (hMSC). 37 metabolites representing glycolysis intermediates, TCA cycle metabolites, amino acids and lipids were selected for a detailed analysis. The concentrations of these. metabolites were compared and Pearson correlation coefficients were used to calculate the relationship between pairs of metabolites. Metabolite profiles and correlation patterns differ significantly between the two cell lines. These profiles can be considered as a signature of the underlying biochemical system and provide snap-shots of the metabolism in mesenchymal stem cells and tumor cells.},
  language  = {en}
}
@article{SchroederLissoObataetal.2014,
  author    = {Schroeder, Florian and Lisso, Janina and Obata, Toshihiro and Erban, Alexander and Maximova, Eugenia and Giavalisco, Patrick and Kopka, Joachim and Fernie, Alisdair R. and Willmitzer, Lothar and Muessig, Carsten},
  title     = {Consequences of induced brassinosteroid deficiency in Arabidopsis leaves},
  series = {BMC plant biology},
  volume    = {14},
  journal   = {BMC plant biology},
  publisher = {BioMed Central},
  address   = {London},
  issn      = {1471-2229},
  doi       = {10.1186/s12870-014-0309-0},
  pages     = {14},
  year      = {2014},
  abstract  = {Background: The identification of brassinosteroid (BR) deficient and BR insensitive mutants provided conclusive evidence that BR is a potent growth-promoting phytohormone. Arabidopsis mutants are characterized by a compact rosette structure, decreased plant height and reduced root system, delayed development, and reduced fertility. Cell expansion, cell division, and multiple developmental processes depend on BR. The molecular and physiological basis of BR action is diverse. The BR signalling pathway controls the activity of transcription factors, and numerous BR responsive genes have been identified. The analysis of dwarf mutants, however, may to some extent reveal phenotypic changes that are an effect of the altered morphology and physiology. This restriction holds particularly true for the analysis of established organs such as rosette leaves. Results: In this study, the mode of BR action was analysed in established leaves by means of two approaches. First, an inhibitor of BR biosynthesis (brassinazole) was applied to 21-day-old wild-type plants. Secondly, BR complementation of BR deficient plants, namely CPD (constitutive photomorphogenic dwarf)-antisense and cbb1 (cabbage1) mutant plants was stopped after 21 days. BR action in established leaves is associated with stimulated cell expansion, an increase in leaf index, starch accumulation, enhanced CO2 release by the tricarboxylic acid cycle, and increased biomass production. Cell number and protein content were barely affected. Conclusion: Previous analysis of BR promoted growth focused on genomic effects. However, the link between growth and changes in gene expression patterns barely provided clues to the physiological and metabolic basis of growth. Our study analysed comprehensive metabolic data sets of leaves with altered BR levels. The data suggest that BR promoted growth may depend on the increased provision and use of carbohydrates and energy. BR may stimulate both anabolic and catabolic pathways.},
  language  = {en}
}
@article{LisecRoemischMarglNikoloskietal.2011,
  author    = {Lisec, Jan and R{\"o}misch-Margl, Lilla and Nikoloski, Zoran and Piepho, Hans-Peter and Giavalisco, Patrick and Selbig, Joachim and Gierl, Alfons and Willmitzer, Lothar},
  title     = {Corn hybrids display lower metabolite variability and complex metabolite inheritance patterns},
  series = {The plant journal},
  volume    = {68},
  journal   = {The plant journal},
  number    = {2},
  publisher = {Wiley-Blackwell},
  address   = {Malden},
  issn      = {0960-7412},
  doi       = {10.1111/j.1365-313X.2011.04689.x},
  pages     = {326 -- 336},
  year      = {2011},
  abstract  = {We conducted a comparative analysis of the root metabolome of six parental maize inbred lines and their 14 corresponding hybrids showing fresh weight heterosis. We demonstrated that the metabolic profiles not only exhibit distinct features for each hybrid line compared with its parental lines, but also separate reciprocal hybrids. Reconstructed metabolic networks, based on robust correlations between metabolic profiles, display a higher network density in most hybrids as compared with the corresponding inbred lines. With respect to metabolite level inheritance, additive, dominant and overdominant patterns are observed with no specific overrepresentation. Despite the observed complexity of the inheritance pattern, for the majority of metabolites the variance observed in all 14 hybrids is lower compared with inbred lines. Deviations of metabolite levels from the average levels of the hybrids correlate negatively with biomass, which could be applied for developing predictors of hybrid performance based on characteristics of metabolite patterns.},
  language  = {en}
}
@article{FeherLisecRoemischMargletal.2014,
  author    = {Feher, Kristen and Lisec, Jan and Roemisch-Margl, Lilla and Selbig, Joachim and Gierl, Alfons and Piepho, Hans-Peter and Nikoloski, Zoran and Willmitzer, Lothar},
  title     = {Deducing hybrid performance from parental metabolic profiles of young primary roots of maize by using a multivariate diallel approach},
  series = {PLoS one},
  volume    = {9},
  journal   = {PLoS one},
  number    = {1},
  publisher = {PLoS},
  address   = {San Fransisco},
  issn      = {1932-6203},
  doi       = {10.1371/journal.pone.0085435},
  pages     = {9},
  year      = {2014},
  language  = {en}
}
@article{MeyerWituckaWallBecheretal.2012,
  author    = {Meyer, Rhonda C. and Witucka-Wall, Hanna and Becher, Martina and Blacha, Anna Maria and Boudichevskaia, Anastassia and D{\"o}rmann, Peter and Fiehn, Oliver and Friedel, Svetlana and von Korff, Maria and Lisec, Jan and Melzer, Michael and Repsilber, Dirk and Schmidt, Renate and Scholz, Matthias and Selbig, Joachim and Willmitzer, Lothar and Altmann, Thomas},
  title     = {Heterosis manifestation during early Arabidopsis seedling development is characterized by intermediate gene expression and enhanced metabolic activity in the hybrids},
  series = {The plant journal},
  volume    = {71},
  journal   = {The plant journal},
  number    = {4},
  publisher = {Wiley-Blackwell},
  address   = {Hoboken},
  issn      = {0960-7412},
  doi       = {10.1111/j.1365-313X.2012.05021.x},
  pages     = {669 -- 683},
  year      = {2012},
  abstract  = {Heterosis-associated cellular and molecular processes were analyzed in seeds and seedlings of Arabidopsis thaliana accessions Col-0 and C24 and their heterotic hybrids. Microscopic examination revealed no advantages in terms of hybrid mature embryo organ sizes or cell numbers. Increased cotyledon sizes were detectable 4 days after sowing. Growth heterosis results from elevated cell sizes and numbers, and is well established at 10 days after sowing. The relative growth rates of hybrid seedlings were most enhanced between 3 and 4 days after sowing. Global metabolite profiling and targeted fatty acid analysis revealed maternal inheritance patterns for a large proportion of metabolites in the very early stages. During developmental progression, the distribution shifts to dominant, intermediate and heterotic patterns, with most changes occurring between 4 and 6 days after sowing. The highest incidence of heterotic patterns coincides with establishment of size differences at 4 days after sowing. In contrast, overall transcript patterns at 4, 6 and 10 days after sowing are characterized by intermediate to dominant patterns, with parental transcript levels showing the largest differences. Overall, the results suggest that, during early developmental stages, intermediate gene expression and higher metabolic activity in the hybrids compared to the parents lead to better resource efficiency, and therefore enhanced performance in the hybrids.},
  language  = {en}
}
@article{LisecSteinfathMeyeretal.2009,
  author    = {Lisec, Jan and Steinfath, Matthias and Meyer, Rhonda C. and Selbig, Joachim and Melchinger, Albrecht E. and Willmitzer, Lothar and Altmann, Thomas},
  title     = {Identification of heterotic metabolite QTL in Arabidopsis thaliana RIL and IL populations},
  issn      = {0960-7412},
  doi       = {10.1111/j.1365-313X.2009.03910.x},
  year      = {2009},
  abstract  = {Two mapping populations of a cross between the Arabidopsis thaliana accessions Col-0 and C24 were cultivated and analyzed with respect to the levels of 181 metabolites to elucidate the biological phenomenon of heterosis at the metabolic level. The relative mid-parent heterosis in the F-1 hybrids was <20\% for most metabolic traits. The first mapping population consisting of 369 recombinant inbred lines (RILs) and their test cross progeny with both parents allowed us to determine the position and effect of 147 quantitative trait loci (QTL) for metabolite absolute mid-parent heterosis (aMPH). Furthermore, we identified 153 and 83 QTL for augmented additive (Z(1)) and dominance effects (Z(2)), respectively. We identified putative candidate genes for these QTL using the ARACYC database (http://www.arabidopsis.org/ biocyc), and calculated the average degree of dominance, which was within the dominance and over-dominance range for most metabolites. Analyzing a second population of 41 introgression lines (ILs) and their test crosses with the recurrent parent, we identified 634 significant differences in metabolite levels. Nine per cent of these effects were classified as over-dominant, according to the mode of inheritance. A comparison of both approaches suggested epistasis as a major contributor to metabolite heterosis in Arabidopsis. A linear combination of metabolite levels was shown to significantly correlate with biomass heterosis (r = 0.62).},
  language  = {en}
}
@misc{GaertnerSteinfathAndorfetal.2009,
  author    = {G{\"a}rtner, Tanja and Steinfath, Matthias and Andorf, Sandra and Lisec, Jan and Meyer, Rhonda C. and Altmann, Thomas and Willmitzer, Lothar and Selbig, Joachim},
  title     = {Improved heterosis prediction by combining information on DNA- and metabolic markers},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-45132},
  year      = {2009},
  abstract  = {Background: Hybrids represent a cornerstone in the success story of breeding programs. The fundamental principle underlying this success is the phenomenon of hybrid vigour, or heterosis. It describes an advantage of the offspring as compared to the two parental lines with respect to parameters such as growth and resistance against abiotic or biotic stress. Dominance, overdominance or epistasis based models are commonly used explanations. Conclusion/Significance: The heterosis level is clearly a function of the combination of the parents used for offspring production. This results in a major challenge for plant breeders, as usually several thousand combinations of parents have to be tested for identifying the best combinations. Thus, any approach to reliably predict heterosis levels based on properties of the parental lines would be highly beneficial for plant breeding. Methodology/Principal Findings: Recently, genetic data have been used to predict heterosis. Here we show that a combination of parental genetic and metabolic markers, identified via feature selection and minimum-description-length based regression methods, significantly improves the prediction of biomass heterosis in resulting offspring. These findings will help furthering our understanding of the molecular basis of heterosis, revealing, for instance, the presence of nonlinear genotype-phenotype relationships. In addition, we describe a possible approach for accelerated selection in plant breeding.},
  language  = {en}
}
@article{LorberthRitteWillmitzeretal.1998,
  author    = {Lorberth, Ruth and Ritte, Gerhard and Willmitzer, Lothar and Kossmann, Jens},
  title     = {Inhibition of a starch-granule-bound protein leads to modified starch and repression of cold sweetening},
  year      = {1998},
  language  = {en}
}
@article{ToepferCaldanaGrimbsetal.2013,
  author    = {T{\"o}pfer, Nadine and Caldana, Camila and Grimbs, Sergio and Willmitzer, Lothar and Fernie, Alisdair R. and Nikoloski, Zoran},
  title     = {Integration of genome-scale modeling and transcript profiling reveals metabolic pathways underlying light and temperature acclimation in arabidopsis},
  series = {The plant cell},
  volume    = {25},
  journal   = {The plant cell},
  number    = {4},
  publisher = {American Society of Plant Physiologists},
  address   = {Rockville},
  issn      = {1040-4651},
  doi       = {10.1105/tpc.112.108852},
  pages     = {1197 -- 1211},
  year      = {2013},
  abstract  = {Understanding metabolic acclimation of plants to challenging environmental conditions is essential for dissecting the role of metabolic pathways in growth and survival. As stresses involve simultaneous physiological alterations across all levels of cellular organization, a comprehensive characterization of the role of metabolic pathways in acclimation necessitates integration of genome-scale models with high-throughput data. Here, we present an integrative optimization-based approach, which, by coupling a plant metabolic network model and transcriptomics data, can predict the metabolic pathways affected in a single, carefully controlled experiment. Moreover, we propose three optimization-based indices that characterize different aspects of metabolic pathway behavior in the context of the entire metabolic network. We demonstrate that the proposed approach and indices facilitate quantitative comparisons and characterization of the plant metabolic response under eight different light and/or temperature conditions. The predictions of the metabolic functions involved in metabolic acclimation of Arabidopsis thaliana to the changing conditions are in line with experimental evidence and result in a hypothesis about the role of homocysteine-to-Cys interconversion and Asn biosynthesis. The approach can also be used to reveal the role of particular metabolic pathways in other scenarios, while taking into consideration the entirety of characterized plant metabolism.},
  language  = {en}
}
@article{RoessnerLuedemannBrustetal.2001,
  author    = {Roessner, Ute and Luedemann, A. and Brust, D. and Fiehn, Oliver and Linke, Thomas and Willmitzer, Lothar and Fernie, Alisdair R.},
  title     = {Metabolic profiling allows comprehensive phenotyping of genetically or environmentally modified plant systems},
  issn      = {1040-4651},
  year      = {2001},
  language  = {en}
}
@article{CatchpolePlatzerWeikertetal.2011,
  author    = {Catchpole, Gareth and Platzer, Alexander and Weikert, Cornelia and Kempkensteffen, Carsten and Johannsen, Manfred and Krause, Hans and Jung, Klaus and Miller, Kurt and Willmitzer, Lothar and Selbig, Joachim and Weikert, Steffen},
  title     = {Metabolic profiling reveals key metabolic features of renal cell carcinoma},
  series = {Journal of cellular and molecular medicine : a journal of translational medicine},
  volume    = {15},
  journal   = {Journal of cellular and molecular medicine : a journal of translational medicine},
  number    = {1},
  publisher = {Wiley-Blackwell},
  address   = {Malden},
  issn      = {1582-1838},
  doi       = {10.1111/j.1582-4934.2009.00939.x},
  pages     = {109 -- 118},
  year      = {2011},
  abstract  = {Recent evidence suggests that metabolic changes play a pivotal role in the biology of cancer and in particular renal cell carcinoma (RCC). Here, a global metabolite profiling approach was applied to characterize the metabolite pool of RCC and normal renal tissue. Advanced decision tree models were applied to characterize the metabolic signature of RCC and to explore features of metastasized tumours. The findings were validated in a second independent dataset. Vitamin E derivates and metabolites of glucose, fatty acid, and inositol phosphate metabolism determined the metabolic profile of RCC. alpha-tocopherol, hippuric acid, myoinositol, fructose-1-phosphate and glucose-1-phosphate contributed most to the tumour/normal discrimination and all showed pronounced concentration changes in RCC. The identified metabolic profile was characterized by a low recognition error of only 5\% for tumour versus normal samples. Data on metastasized tumours suggested a key role for metabolic pathways involving arachidonic acid, free fatty acids, proline, uracil and the tricarboxylic acid cycle. These results illustrate the potential of mass spectroscopy based metabolomics in conjunction with sophisticated data analysis methods to uncover the metabolic phenotype of cancer. Differentially regulated metabolites, such as vitamin E compounds, hippuric acid and myoinositol, provide leads for the characterization of novel pathways in RCC.},
  language  = {en}
}
@misc{SteinfathGaertnerLisecetal.2009,
  author    = {Steinfath, Matthias and G{\"a}rtner, Tanja and Lisec, Jan and Meyer, Rhonda C. and Altmann, Thomas and Willmitzer, Lothar and Selbig, Joachim},
  title     = {Prediction of hybrid biomass in Arabidopsis thaliana by selected parental SNP and metabolic markers},
  series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  number    = {1324},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-43111},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-431115},
  pages     = {9},
  year      = {2009},
  abstract  = {A recombinant inbred line (RIL) population, derived from two Arabidopsis thaliana accessions, and the corresponding testcrosses with these two original accessions were used for the development and validation of machine learning models to predict the biomass of hybrids. Genetic and metabolic information of the RILs served as predictors. Feature selection reduced the number of variables (genetic and metabolic markers) in the models by more than 80\% without impairing the predictive power. Thus, potential biomarkers have been revealed. Metabolites were shown to bear information on inherited macroscopic phenotypes. This proof of concept could be interesting for breeders. The example population exhibits substantial mid-parent biomass heterosis. The results of feature selection could therefore be used to shed light on the origin of heterosis. In this respect, mainly dominance effects were detected.},
  language  = {en}
}
@article{SteinfathGaertnerLisecetal.2009,
  author    = {Steinfath, Matthias and G{\"a}rtner, Tanja and Lisec, Jan and Meyer, Rhonda Christiane and Altmann, Thomas and Willmitzer, Lothar and Selbig, Joachim},
  title     = {Prediction of hybrid biomass in Arabidopsis thaliana by selected parental SNP and metabolic markers},
  series = {Theoretical and applied genetics : TAG ; international journal of plant breeding research},
  volume    = {120},
  journal   = {Theoretical and applied genetics : TAG ; international journal of plant breeding research},
  publisher = {Springer},
  address   = {Berlin},
  issn      = {0040-5752},
  doi       = {10.1007/s00122-009-1191-2},
  pages     = {239 -- 247},
  year      = {2009},
  abstract  = {A recombinant inbred line (RIL) population, derived from two Arabidopsis thaliana accessions, and the corresponding testcrosses with these two original accessions were used for the development and validation of machine learning models to predict the biomass of hybrids. Genetic and metabolic information of the RILs served as predictors. Feature selection reduced the number of variables (genetic and metabolic markers) in the models by more than 80\% without impairing the predictive power. Thus, potential biomarkers have been revealed. Metabolites were shown to bear information on inherited macroscopic phenotypes. This proof of concept could be interesting for breeders. The example population exhibits substantial mid-parent biomass heterosis. The results of feature selection could therefore be used to shed light on the origin of heterosis. In this respect, mainly dominance effects were detected.},
  language  = {en}
}
@article{MeyerKustererLisecetal.2009,
  author    = {Meyer, Rhonda Christiane and Kusterer, Barbara and Lisec, Jan and Steinfath, Matthias and Becher, Martina and Scharr, Hanno and Melchinger, Albrecht E. and Selbig, Joachim and Schurr, Ulrich and Willmitzer, Lothar and Altmann, Thomas},
  title     = {QTL analysis of early stage heterosis for biomass in Arabidopsis},
  series = {Theoretical and applied genetics},
  volume    = {129},
  journal   = {Theoretical and applied genetics},
  number    = {2},
  publisher = {Springer Nature},
  address   = {Berlin},
  issn      = {1432-2242},
  doi       = {10.1007/s00122-009-1074-6},
  pages     = {227 -- 237},
  year      = {2009},
  abstract  = {The main objective of this study was to identify genomic regions involved in biomass heterosis using QTL, generation means, and mode-of-inheritance classification analyses. In a modified North Carolina Design III we backcrossed 429 recombinant inbred line and 140 introgression line populations to the two parental accessions, C24 and Col-0, whose F 1 hybrid exhibited 44\% heterosis for biomass. Mid-parent heterosis in the RILs ranged from -31 to 99\% for dry weight and from -58 to 143\% for leaf area. We detected ten genomic positions involved in biomass heterosis at an early developmental stage, individually explaining between 2.4 and 15.7\% of the phenotypic variation. While overdominant gene action was prevalent in heterotic QTL, our results suggest that a combination of dominance, overdominance and epistasis is involved in biomass heterosis in this Arabidopsis cross.},
  language  = {en}
}
@misc{MeyerKustererLisecetal.2009,
  author    = {Meyer, Rhonda Christiane and Kusterer, Barbara and Lisec, Jan and Steinfath, Matthias and Becher, Martina and Scharr, Hanno and Melchinger, Albrecht E. and Selbig, Joachim and Schurr, Ulrich and Willmitzer, Lothar and Altmann, Thomas},
  title     = {QTL analysis of early stage heterosis for biomass in Arabidopsis},
  series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  number    = {1330},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-43127},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-431272},
  pages     = {11},
  year      = {2009},
  abstract  = {The main objective of this study was to identify genomic regions involved in biomass heterosis using QTL, generation means, and mode-of-inheritance classification analyses. In a modified North Carolina Design III we backcrossed 429 recombinant inbred line and 140 introgression line populations to the two parental accessions, C24 and Col-0, whose F 1 hybrid exhibited 44\% heterosis for biomass. Mid-parent heterosis in the RILs ranged from -31 to 99\% for dry weight and from -58 to 143\% for leaf area. We detected ten genomic positions involved in biomass heterosis at an early developmental stage, individually explaining between 2.4 and 15.7\% of the phenotypic variation. While overdominant gene action was prevalent in heterotic QTL, our results suggest that a combination of dominance, overdominance and epistasis is involved in biomass heterosis in this Arabidopsis cross.},
  language  = {en}
}
@misc{SzymanskiJozefczukNikoloskietal.2009,
  author    = {Szymanski, Jedrzej and Jozefczuk, Szymon and Nikoloski, Zoran and Selbig, Joachim and Nikiforova, Victoria and Catchpole, Gareth and Willmitzer, Lothar},
  title     = {Stability of metabolic correlations under changing environmental conditions in Escherichia coli : a systems approach},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-45253},
  year      = {2009},
  abstract  = {Background: Biological systems adapt to changing environments by reorganizing their cellula r and physiological program with metabolites representing one important response level. Different stresses lead to both conserved and specific responses on the metabolite level which should be reflected in the underl ying metabolic network. Methodology/Principal Findings: Starting from experimental data obtained by a GC-MS based high-throughput metabolic profiling technology we here develop an approach that: (1) extracts network representations from metabolic conditiondependent data by using pairwise correlations, (2) determines the sets of stable and condition-dependent correlations based on a combination of statistical significance and homogeneity tests, and (3) can identify metabolites related to the stress response, which goes beyond simple ob servation s about the changes of metabolic concentrations. The approach was tested with Escherichia colias a model organism observed under four different environmental stress conditions (cold stress, heat stress, oxidative stress, lactose diau xie) and control unperturbed conditions. By constructing the stable network component, which displays a scale free topology and small-world characteristics, we demonstrated that: (1) metabolite hubs in this reconstructed correlation networks are significantly enriched for those contained in biochemical networks such as EcoCyc, (2) particular components of the stable network are enriched for functionally related biochemical path ways, and (3) ind ependently of the response scale, based on their importance in the reorganization of the cor relation network a set of metabolites can be identified which represent hypothetical candidates for adjusting to a stress-specific response. Conclusions/Significance: Network-based tools allowed the identification of stress-dependent and general metabolic correlation networks. This correlation-network-ba sed approach does not rely on major changes in concentration to identify metabolites important for st ress adaptation, but rather on the changes in network properties with respect to metabolites. This should represent a useful complementary technique in addition to more classical approaches.},
  language  = {en}
}
@article{MettlerMuehlhausHemmeetal.2014,
  author    = {Mettler, Tabea and M{\"u}hlhaus, Timo and Hemme, Dorothea and Sch{\"o}ttler, Mark Aurel and Rupprecht, Jens and Idoine, Adam and Veyel, Daniel and Pal, Sunil Kumar and Yaneva-Roder, Liliya and Winck, Flavia Vischi and Sommer, Frederik and Vosloh, Daniel and Seiwert, Bettina and Erban, Alexander and Burgos, Asdrubal and Arvidsson, Samuel Janne and Schoenfelder, Stephanie and Arnold, Anne and Guenther, Manuela and Krause, Ursula and Lohse, Marc and Kopka, Joachim and Nikoloski, Zoran and M{\"u}ller-R{\"o}ber, Bernd and Willmitzer, Lothar and Bock, Ralph and Schroda, Michael and Stitt, Mark},
  title     = {Systems analysis of the response of photosynthesis, metabolism, and growth to an increase in irradiance in the photosynthetic model organism chlamydomonas reinhardtii},
  series = {The plant cell},
  volume    = {26},
  journal   = {The plant cell},
  number    = {6},
  publisher = {American Society of Plant Physiologists},
  address   = {Rockville},
  issn      = {1040-4651},
  doi       = {10.1105/tpc.114.124537},
  pages     = {2310 -- 2350},
  year      = {2014},
  abstract  = {We investigated the systems response of metabolism and growth after an increase in irradiance in the nonsaturating range in the algal model Chlamydomonas reinhardtii. In a three-step process, photosynthesis and the levels of metabolites increased immediately, growth increased after 10 to 15 min, and transcript and protein abundance responded by 40 and 120 to 240 min, respectively. In the first phase, starch and metabolites provided a transient buffer for carbon until growth increased. This uncouples photosynthesis from growth in a fluctuating light environment. In the first and second phases, rising metabolite levels and increased polysome loading drove an increase in fluxes. Most Calvin-Benson cycle (CBC) enzymes were substrate-limited in vivo, and strikingly, many were present at higher concentrations than their substrates, explaining how rising metabolite levels stimulate CBC flux. Rubisco, fructose-1,6-biosphosphatase, and seduheptulose-1,7-bisphosphatase were close to substrate saturation in vivo, and flux was increased by posttranslational activation. In the third phase, changes in abundance of particular proteins, including increases in plastidial ATP synthase and some CBC enzymes, relieved potential bottlenecks and readjusted protein allocation between different processes. Despite reasonable overall agreement between changes in transcript and protein abundance (R-2 = 0.24), many proteins, including those in photosynthesis, changed independently of transcript abundance.},
  language  = {en}
}
@article{BrotmanLandauPninietal.2012,
  author    = {Brotman, Yariv and Landau, Udi and Pnini, Smadar and Lisec, Jan and Balazadeh, Salma and M{\"u}ller-R{\"o}ber, Bernd and Zilberstein, Aviah and Willmitzer, Lothar and Chet, Ilan and Viterbo, Ada},
  title     = {The LysM Receptor-Like Kinase LysM RLK1 is required to activate defense and abiotic-stress responses induced by overexpression of fungal chitinases in arabidopsis plants},
  series = {Molecular plant},
  volume    = {5},
  journal   = {Molecular plant},
  number    = {5},
  publisher = {Oxford Univ. Press},
  address   = {Oxford},
  issn      = {1674-2052},
  doi       = {10.1093/mp/sss021},
  pages     = {1113 -- 1124},
  year      = {2012},
  abstract  = {Application of crab shell chitin or pentamer chitin oligosaccharide to Arabidopsis seedlings increased tolerance to salinity in wild-type but not in knockout mutants of the LysM Receptor-Like Kinase1 (CERK1/LysM RLK1) gene, known to play a critical role in signaling defense responses induced by exogenous chitin. Arabidopsis plants overexpressing the endochitinase chit36 and hexoaminidase excy1 genes from the fungus Trichoderma asperelleoides T203 showed increased tolerance to salinity, heavy-metal stresses, and Botrytis cinerea infection. Resistant lines, overexpressing fungal chitinases at different levels, were outcrossed to lysm rlk1 mutants. Independent homozygous hybrids lost resistance to biotic and abiotic stresses, despite enhanced chitinase activity. Expression analysis of 270 stress-related genes, including those induced by reactive oxygen species (ROS) and chitin, revealed constant up-regulation (at least twofold) of 10 genes in the chitinase-overexpressing line and an additional 76 salt-induced genes whose expression was not elevated in the lysm rlk1 knockout mutant or the hybrids harboring the mutation. These findings elucidate that chitin-induced signaling mediated by LysM RLK1 receptor is not limited to biotic stress response but also encompasses abiotic-stress signaling and can be conveyed by ectopic expression of chitinases in plants.},
  language  = {en}
}
@article{deAbreueLimaLiWenetal.2018,
  author    = {de Abreu e Lima, Francisco Anastacio and Li, Kun and Wen, Weiwei and Yan, Jianbing and Nikoloski, Zoran and Willmitzer, Lothar and Brotman, Yariv},
  title     = {Unraveling lipid metabolism in maize with time-resolved multi-omics data},
  series = {The plant journal},
  volume    = {93},
  journal   = {The plant journal},
  number    = {6},
  publisher = {Wiley},
  address   = {Hoboken},
  issn      = {0960-7412},
  doi       = {10.1111/tpj.13833},
  pages     = {1102 -- 1115},
  year      = {2018},
  abstract  = {Maize is the cereal crop with the highest production worldwide, and its oil is a key energy resource. Improving the quantity and quality of maize oil requires a better understanding of lipid metabolism. To predict the function of maize genes involved in lipid biosynthesis, we assembled transcriptomic and lipidomic data sets from leaves of B73 and the high-oil line By804 in two distinct time-series experiments. The integrative analysis based on high-dimensional regularized regression yielded lipid-transcript associations indirectly validated by Gene Ontology and promoter motif enrichment analyses. The co-localization of lipid-transcript associations using the genetic mapping of lipid traits in leaves and seedlings of a B73 x By804 recombinant inbred line population uncovered 323 genes involved in the metabolism of phospholipids, galactolipids, sulfolipids and glycerolipids. The resulting association network further supported the involvement of 50 gene candidates in modulating levels of representatives from multiple acyl-lipid classes. Therefore, the proposed approach provides high-confidence candidates for experimental testing in maize and model plant species.},
  language  = {en}
}
@article{TenenboimSmirnovaWillmitzeretal.2014,
  author    = {Tenenboim, Hezi and Smirnova, Julia and Willmitzer, Lothar and Steup, Martin and Brotman, Yariv},
  title     = {VMP1-deficient Chlamydomonas exhibits severely aberrant cell morphology and disrupted cytokinesies},
  series = {BMC plant biology},
  volume    = {14},
  journal   = {BMC plant biology},
  publisher = {BioMed Central},
  address   = {London},
  issn      = {1471-2229},
  doi       = {10.1186/1471-2229-14-121},
  pages     = {13},
  year      = {2014},
  abstract  = {Background: The versatile Vacuole Membrane Protein 1 (VMP1) has been previously investigated in six species. It has been shown to be essential in macroautophagy, where it takes part in autophagy initiation. In addition, VMP1 has been implicated in organellar biogenesis; endo-, exo- and phagocytosis, and protein secretion; apoptosis; and cell adhesion. These roles underly its proven involvement in pancreatitis, diabetes and cancer in humans. Results: In this study we analyzed a VMP1 homologue from the green alga Chlamydomonas reinhardtii. CrVMP1 knockdown lines showed severe phenotypes, mainly affecting cell division as well as the morphology of cells and organelles. We also provide several pieces of evidence for its involvement in macroautophagy.},
  language  = {en}
}