Roland Eils

Publications of Roland Eils

• Multiparametric image analysis reveals role of Caveolin1 in endosomal progression rather than internalization of EGFR.

  Authors: Hannah Schmidt-Glenewinkel, Eileen Reinz, Svetlana Bulashevska, Joel Beaudouin, Stefan Legewie, Angel Alonso, Roland Eils

  FEBS letters. 04/2012; 586(8):1179-1189.

  Endosomes constitute a central layer in the regulation of growth factor signaling. We applied flow cytometry, confocal microscopy and automated image quantification to define the role of Caveolin1Endosomes constitute a central layer in the regulation of growth factor signaling. We applied flow cytometry, confocal microscopy and automated image quantification to define the role of Caveolin1 (Cav1) in epidermal growth factor (EGF) receptor (i) internalization and (ii) endosomal trafficking. Antisense-downregulation of Cav1 did not affect internalization of EGF:EGFR-complexes from the plasma membrane. Instead, Cav1-knockdown had a profound effect on endosomal trafficking and caused a shift in EGF vesicle distribution towards Rab7-negative compartments at late timepoints. Moreover, image quantification with single-endosome resolution revealed that EGF:Cav1-complexes undergo a maturation pattern reminiscent of late endosomes. Our data suggest a model in which Caveolin1 acts upon EGF endosomes internalized via the Clathrin-pathway and functions at the transition from early to late endosomes.

• Whole-genome analysis of gene expression associates the ubiquitin-proteasome system with the cardiomyopathy phenotype in disease-sensitized congenic mouse strains.

  Authors: Boris T Ivandic, Sergey E Mastitsky, Frank Schönsiegel, Raffi Bekeredjian, Roland Eils, Norbert Frey, Hugo A Katus, Benedikt Brors

  Cardiovascular research. 03/2012; 94(1):87-95.

  Penetrance and phenotypic expressivity of cardiomyopathies are modulated by modifier genes both in model systems and patients. We aimed to dissect the disease-modifying mechanisms by examiningPenetrance and phenotypic expressivity of cardiomyopathies are modulated by modifier genes both in model systems and patients. We aimed to dissect the disease-modifying mechanisms by examining genome-wide gene expression in a new set of mouse (Mus musculus) congenic strains. Mutant alleles of the genes calsarcin-1 (Myoz2), sarcoglycan-delta (Sgcd), and muscle LIM protein (Csrp2) were each transferred onto inbred strain backgrounds C57BL/6, C3H/He, 129S1/Sv, and FVB/N, respectively. At 9-10 weeks of age, left ventricular pump function (fractional shortening, FS) was determined by echocardiography in non-sedated congenic animals. Gene expression was then analysed in myocardial tissue using the Affymetrix Mouse 430.2 microarray platform. Variance stabilization, linear mixed-effects modelling, correlations, gene functional classification, and pathway analysis were conducted using the standard software. Strain background FVB/N appeared to protect against the consequences of gene inactivation. Sgcd-deficient congenics showed normal FS, which was consistent with their hypertrophic cardiomyopathy phenotype. Animals with other allele/background combinations developed an impaired ventricular pump function (FS <65%). Gender did not influence FS significantly, yet it determined the sets of genes that were differentially expressed in mice with low FS. In particular, genes encoding the elements of the ubiquitin-proteasome system (UPS) were strongly correlated with the cardiac impairment (absolute Spearman r≥ 0.7) in both males and females. Gene expression profiling in a novel set of congenic strains revealed an association between the UPS and myocardial contractile function, indicating that the UPS may be an important modifier of phenotypic variability in cardiomyopathies.

• Genome sequencing of pediatric medulloblastoma links catastrophic DNA rearrangements with TP53 mutations.

  Authors: Tobias Rausch, David T W Jones, Marc Zapatka, Adrian M Stütz, Thomas Zichner, Joachim Weischenfeldt, Natalie Jäger, Marc Remke, David Shih, Paul A Northcott [......] Jan J Molenaar, Rogier Versteeg, Marcel Kool, Uri Tabori, David Malkin, Andrey Korshunov, Michael D Taylor, Peter Lichter, Stefan M Pfister, Jan O Korbel

  Cell. 01/2012; 148(1-2):59-71.

  Genomic rearrangements are thought to occur progressively during tumor development. Recent findings, however, suggest an alternative mechanism, involving massive chromosome rearrangements in aGenomic rearrangements are thought to occur progressively during tumor development. Recent findings, however, suggest an alternative mechanism, involving massive chromosome rearrangements in a one-step catastrophic event termed chromothripsis. We report the whole-genome sequencing-based analysis of a Sonic-Hedgehog medulloblastoma (SHH-MB) brain tumor from a patient with a germline TP53 mutation (Li-Fraumeni syndrome), uncovering massive, complex chromosome rearrangements. Integrating TP53 status with microarray and deep sequencing-based DNA rearrangement data in additional patients reveals a striking association between TP53 mutation and chromothripsis in SHH-MBs. Analysis of additional tumor entities substantiates a link between TP53 mutation and chromothripsis, and indicates a context-specific role for p53 in catastrophic DNA rearrangements. Among these, we observed a strong association between somatic TP53 mutations and chromothripsis in acute myeloid leukemia. These findings connect p53 status and chromothripsis in specific tumor types, providing a genetic basis for understanding particularly aggressive subtypes of cancer.

• Multi-parametric analysis and modeling of relationships between mitochondrial morphology and apoptosis.

  Authors: Yara Reis, Marti Bernardo-Faura, Daniela Richter, Thomas Wolf, Benedikt Brors, Anne Hamacher-Brady, Roland Eils, Nathan R Brady

  PloS one. 01/2012; 7(1):e28694.

  Mitochondria exist as a network of interconnected organelles undergoing constant fission and fusion. Current approaches to study mitochondrial morphology are limited by low data sampling coupled withMitochondria exist as a network of interconnected organelles undergoing constant fission and fusion. Current approaches to study mitochondrial morphology are limited by low data sampling coupled with manual identification and classification of complex morphological phenotypes. Here we propose an integrated mechanistic and data-driven modeling approach to analyze heterogeneous, quantified datasets and infer relations between mitochondrial morphology and apoptotic events. We initially performed high-content, multi-parametric measurements of mitochondrial morphological, apoptotic, and energetic states by high-resolution imaging of human breast carcinoma MCF-7 cells. Subsequently, decision tree-based analysis was used to automatically classify networked, fragmented, and swollen mitochondrial subpopulations, at the single-cell level and within cell populations. Our results revealed subtle but significant differences in morphology class distributions in response to various apoptotic stimuli. Furthermore, key mitochondrial functional parameters including mitochondrial membrane potential and Bax activation, were measured under matched conditions. Data-driven fuzzy logic modeling was used to explore the non-linear relationships between mitochondrial morphology and apoptotic signaling, combining morphological and functional data as a single model. Modeling results are in accordance with previous studies, where Bax regulates mitochondrial fragmentation, and mitochondrial morphology influences mitochondrial membrane potential. In summary, we established and validated a platform for mitochondrial morphological and functional analysis that can be readily extended with additional datasets. We further discuss the benefits of a flexible systematic approach for elucidating specific and general relationships between mitochondrial morphology and apoptosis.

• Normalizing for individual cell population context in the analysis of high-content cellular screens.

  Authors: Bettina Knapp, Ilka Rebhan, Anil Kumar, Petr Matula, Narsis A Kiani, Marco Binder, Holger Erfle, Karl Rohr, Roland Eils, Ralf Bartenschlager, Lars Kaderali

  BMC bioinformatics. 12/2011; 12:485.

  High-content, high-throughput RNA interference (RNAi) offers unprecedented possibilities to elucidate gene function and involvement in biological processes. Microscopy based screening allowsHigh-content, high-throughput RNA interference (RNAi) offers unprecedented possibilities to elucidate gene function and involvement in biological processes. Microscopy based screening allows phenotypic observations at the level of individual cells. It was recently shown that a cell's population context significantly influences results. However, standard analysis methods for cellular screens do not currently take individual cell data into account unless this is important for the phenotype of interest, i.e. when studying cell morphology. We present a method that normalizes and statistically scores microscopy based RNAi screens, exploiting individual cell information of hundreds of cells per knockdown. Each cell's individual population context is employed in normalization. We present results on two infection screens for hepatitis C and dengue virus, both showing considerable effects on observed phenotypes due to population context. In addition, we show on a non-virus screen that these effects can be found also in RNAi data in the absence of any virus. Using our approach to normalize against these effects we achieve improved performance in comparison to an analysis without this normalization and hit scoring strategy. Furthermore, our approach results in the identification of considerably more significantly enriched pathways in hepatitis C virus replication than using a standard analysis approach. Using a cell-based analysis and normalization for population context, we achieve improved sensitivity and specificity not only on a individual protein level, but especially also on a pathway level. This leads to the identification of new host dependency factors of the hepatitis C and dengue viruses and higher reproducibility of results.

• Corrigendum: autoantibodies against the exocrine pancreas in autoimmune pancreatitis: gene and protein expression profiling and immunoassays identify pancreatic enzymes as a major target of the inflammatory process.

  Authors: J-Matthias Löhr, Ralf Faissner, Dirk Koczan, Peter Bewerunge, Claudio Bassi, Benedikt Brors, Roland Eils, Luca Frulloni, Anette Funk, Walter Halangk [......] Michael Neumaier, Stephanie Nittka, Miklós Sahin-Tóth, Julian Sänger, Sonja Serafini, Martina Schnölzer, Hermann-Josef Thierse, Silke Wandschneider, Giuseppe Zamboni, Günter Klöppel

  The American journal of gastroenterology. 12/2011; 106(12):2209.

• Live-Cell Assays to Identify Regulators of ER-to-Golgi Trafficking.

  Authors: Tautvydas Lisauskas, Petr Matula, Christoph Claas, Susanne Reusing, Stefan Wiemann, Holger Erfle, Lars Lehmann, Peter Fischer, Roland Eils, Karl Rohr, Brian Storrie, Vytaute Starkuviene

  Traffic (Copenhagen, Denmark). 12/2011; 13(3):416-32.

  We applied fluorescence microscopy-based quantitative assays to living cells to identify regulators of endoplasmic reticulum (ER)-to-Golgi trafficking and/or Golgi complex maintenance. We firstWe applied fluorescence microscopy-based quantitative assays to living cells to identify regulators of endoplasmic reticulum (ER)-to-Golgi trafficking and/or Golgi complex maintenance. We first validated an automated procedure to identify factors which influence Golgi-to-ER relocalization of GalT-CFP (β1,4-galactosyltransferase I-cyan fluorescent protein) after brefeldin A (BFA) addition and/or wash-out. We then tested 14 proteins that localize to the ER and/or Golgi complex when overexpressed for a role in ER-to-Golgi trafficking. Nine of them interfered with the rate of BFA-induced redistribution of GalT-CFP from the Golgi complex to the ER, six of them interfered with GalT-CFP redistribution from the ER to a juxtanuclear region (i.e. the Golgi complex) after BFA wash-out and six of them were positive effectors in both assays. Notably, our live-cell approach captures regulator function in ER-to-Golgi trafficking, which was missed in previous fixed cell assays, as well as assigns putative roles for other less characterized proteins. Moreover, we show that our assays can be extended to RNAi and chemical screens.

• Enhancers regulate progression of development in mammalian cells.

  Authors: Anna-Lena Kranz, Roland Eils, Rainer König

  Nucleic acids research. 07/2011; 39(20):8689-702.

  During development and differentiation of an organism, accurate gene regulation is central for cells to maintain and balance their differentiation processes. Transcriptional interactions betweenDuring development and differentiation of an organism, accurate gene regulation is central for cells to maintain and balance their differentiation processes. Transcriptional interactions between cis-acting DNA elements such as promoters and enhancers are the basis for precise and balanced transcriptional regulation. We identified modules of combinations of binding sites in proximal and distal regulatory regions upstream of all transcription start sites (TSSs) in silico and applied these modules to gene expression time-series of mouse embryonic development and differentiation of human stem cells. In addition to tissue-specific regulation controlled by combinations of transcription factors (TFs) binding at promoters, we observed that in particular the combination of TFs binding at promoters together with TFs binding at the respective enhancers regulate highly specifically temporal progression during development: whereas 40% of TFs were specific for time intervals, 79% of TF pairs and even 97% of promoter-enhancer modules showed specificity for single time intervals of the human stem cells. Predominantly SP1 and E2F contributed to temporal specificity at promoters and the forkhead (FOX) family of TFs at enhancer regions. Altogether, we characterized three classes of TFs: with binding sites being enriched at the TSS (like SP1), depleted at the TSS (like FOX), and rather uniformly distributed.

• Proteomic bronchiolitis obliterans syndrome risk monitoring in lung transplant recipients.

  Authors: Thomas Wolf, Tonio Oumeraci, Jens Gottlieb, Andreas Pich, Benedikt Brors, Roland Eils, Axel Haverich, Brigitte Schlegelberger, Tobias Welte, Marc Zapatka, Nils von Neuhoff

  Transplantation. 06/2011; 92(4):477-85.

  Obliterative bronchiolitis poses a primary obstacle for long-term survival of lung transplant recipients and manifests clinically as bronchiolitis obliterans syndrome (BOS). Establishing a molecularObliterative bronchiolitis poses a primary obstacle for long-term survival of lung transplant recipients and manifests clinically as bronchiolitis obliterans syndrome (BOS). Establishing a molecular level screening method to detect BOS-related proteome changes before its diagnosis by forced expiratory volume surrogate marker criteria was the main objective of this study. Bronchoalveolar lavage was performed in 82 lung transplant recipients (48/34 with/without known BOS development) at different time points between 12 and 48 months after lung transplantation. A mass spectrometry-based method was devised to generate bronchoalveolar lavage fluid proteome profiles that were screened for BOS-specific alterations. Statistically significant marker peptides and proteins were identified and validated by in-gel digestion, tandem mass spectrometric sequencing, and quantitative immunoassays. Among the panel of statistically significant markers were Clara cell protein, calgranulin A, human neutrophil peptides, and the antimicrobial agent histatin. To assess their clinical relevance, a highly sensitive and specific classifier model was developed. Positive BOS classification by monitoring of seven polypeptides correlated strongly with a significant decrease in BOS-free time. Thus, it was possible to detect high-risk patients early on in the pathogenetic process. Monitoring the bronchoalveolar lavage fluid levels of seven polypeptides detected by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry allows a reliable prediction of early BOS using a Random Forest decision tree-based classifier model. The high accuracy of this robust model and its synergistic potential in combination with established forced expiratory volume-based diagnostics could make it an effective tool to supplement the current diagnostic regime after multicentric validation.

• Negative feedback in the bone morphogenetic protein 4 (BMP4) synexpression group governs its dynamic signaling range and canalizes development.

  Authors: Malte Paulsen, Stefan Legewie, Roland Eils, Emil Karaulanov, Christof Niehrs

  Proceedings of the National Academy of Sciences of the United States of America. 06/2011; 108(25):10202-7.

  What makes embryogenesis a robust and canalized process is an important question in developmental biology. A bone morphogenetic protein (BMP) morphogen gradient plays a key role in embryonicWhat makes embryogenesis a robust and canalized process is an important question in developmental biology. A bone morphogenetic protein (BMP) morphogen gradient plays a key role in embryonic development, and we are beginning to understand how the self-regulating properties of its signaling circuitry ensure robust embryonic patterning. An unexplored question is why the BMP signaling circuit is organized as a modular synexpression group, with a prevalence of feedback inhibitors. Here, we provide evidence from direct experimentation and mathematical modeling that the synexpressed feedback inhibitors BAMBI, SMAD6, and SMAD7 (i) expand the dynamic BMP signaling range essential for proper embryonic patterning and (ii) reduce interindividual phenotypic and molecular variability in Xenopus embryos. Thereby, negative feedback linearizes signaling responses and confers robust patterning, thus promoting canalized development. The presence of negative feedback inhibitors in other growth factor synexpression groups suggests that these properties may constitute a general principle.

• RIP: the regulatory interaction predictor--a machine learning-based approach for predicting target genes of transcription factors.

  Authors: Tobias Bauer, Roland Eils, Rainer König

  Bioinformatics (Oxford, England). 06/2011; 27(16):2239-47.

  Understanding transcriptional gene regulation is essential for studying cellular systems. Identifying genome-wide targets of transcription factors (TFs) provides the basis to discover the involvementUnderstanding transcriptional gene regulation is essential for studying cellular systems. Identifying genome-wide targets of transcription factors (TFs) provides the basis to discover the involvement of TFs and TF cooperativeness in cellular systems and pathogenesis. We present the regulatory interaction predictor (RIP), a machine learning approach that inferred 73 923 regulatory interactions (RIs) for 301 human TFs and 11 263 target genes with considerably good quality and 4516 RIs with very high quality. The inference of RIs is independent of any specific condition. Our approach employs support vector machines (SVMs) trained on a set of experimentally proven RIs from a public repository (TRANSFAC). Features of RIs for the learning process are based on a correlation meta-analysis of 4064 gene expression profiles from 76 studies, in silico predictions of transcription factor binding sites (TFBSs) and combinations of these employing knowledge about co-regulation of genes by a common TF (TF-module). The trained SVMs were applied to infer new RIs for a large set of TFs and genes. In a case study, we employed the inferred RIs to analyze an independent microarray dataset. We identified key TFs regulating the transcriptional response upon interferon alpha stimulation of monocytes, most prominently interferon-stimulated gene factor 3 (ISGF3). Furthermore, predicted TF-modules were highly associated to their functionally related pathways. Descriptors of gene expression, TFBS predictions, experimentally verified binding information and statistical combination of this enabled inferring RIs on a genome-wide scale for human genes with considerably good precision serving as a good basis for expression profiling studies. r.koenig@dkfz.de Supplementary data are available at Bioinformatics online.

• Herpesviral replication compartments move and coalesce at nuclear speckles to enhance export of viral late mRNA.

  Authors: Lynne Chang, William J Godinez, Il-Han Kim, Marco Tektonidis, Primal de Lanerolle, Roland Eils, Karl Rohr, David M Knipe

  Proceedings of the National Academy of Sciences of the United States of America. 05/2011; 108(21):E136-44.

  The role of the intranuclear movement of chromatin in gene expression is not well-understood. Herpes simplex virus forms replication compartments (RCs) in infected cell nuclei as sites of viral DNAThe role of the intranuclear movement of chromatin in gene expression is not well-understood. Herpes simplex virus forms replication compartments (RCs) in infected cell nuclei as sites of viral DNA replication and late gene transcription. These structures develop from small compartments that grow in size, move, and coalesce. Quantitative analysis of RC trajectories, derived from 4D images, shows that most RCs move by directed motion. Directed movement is impaired in the presence of actin and myosin inhibitors as well as a transcription inhibitor. In addition, RCs coalesce at and reorganize nuclear speckles. Lastly, distinct effects of actin and myosin inhibitors on viral gene expression suggest that RC movement is not required for transcription, but rather, movement results in the bridging of transcriptionally active RCs with nuclear speckles to form structures that enhance export of viral late mRNAs.

• Nonrigid registration of 2-D and 3-D dynamic cell nuclei images for improved classification of subcellular particle motion.

  Authors: Il-Han Kim, Yi-Chun M Chen, David L Spector, Roland Eils, Karl Rohr

  IEEE transactions on image processing : a publication of the IEEE Signal Processing Society. 04/2011; 20(4):1011-22.

  The observed motion of subcellular particles in fluorescence microscopy image sequences of live cells is generally a superposition of the motion and deformation of the cell and the motion of theThe observed motion of subcellular particles in fluorescence microscopy image sequences of live cells is generally a superposition of the motion and deformation of the cell and the motion of the particles. Decoupling the two types of movements to enable accurate classification of the particle motion requires the application of registration algorithms. We have developed an intensity-based approach for nonrigid registration of multichannel microscopy image sequences of cell nuclei. First, based on 3-D synthetic images we demonstrate that cell nucleus deformations change the observed motion types of particles and that our approach allows to recover the original motion. Second, we have successfully applied our approach to register 2-D and 3-D real microscopy image sequences. A quantitative experimental comparison with previous approaches for nonrigid registration of cell microscopy has also been performed.

• Comparative transcriptome profiling of amyloid precursor protein family members in the adult cortex.

  Authors: Dorothee Aydin, Mikhail A Filippov, Jakob-Andreas Tschäpe, Norbert Gretz, Marco Prinz, Roland Eils, Benedikt Brors, Ulrike C Müller

  BMC genomics. 03/2011; 12:160.

  The β-amyloid precursor protein (APP) and the related β-amyloid precursor-like proteins (APLPs) undergo complex proteolytic processing giving rise to several fragments. Whereas it is well establishedThe β-amyloid precursor protein (APP) and the related β-amyloid precursor-like proteins (APLPs) undergo complex proteolytic processing giving rise to several fragments. Whereas it is well established that Aβ accumulation is a central trigger for Alzheimer's disease, the physiological role of APP family members and their diverse proteolytic products is still largely unknown. The secreted APPsα ectodomain has been shown to be involved in neuroprotection and synaptic plasticity. The γ-secretase-generated APP intracellular domain (AICD) functions as a transcriptional regulator in heterologous reporter assays although its role for endogenous gene regulation has remained controversial. To gain further insight into the molecular changes associated with knockout phenotypes and to elucidate the physiological functions of APP family members including their proposed role as transcriptional regulators, we performed DNA microarray transcriptome profiling of prefrontal cortex of adult wild-type (WT), APP knockout (APP-/-), APLP2 knockout (APLP2-/-) and APPsα knockin mice (APPα/α) expressing solely the secreted APPsα ectodomain. Biological pathways affected by the lack of APP family members included neurogenesis, transcription, and kinase activity. Comparative analysis of transcriptome changes between mutant and wild-type mice, followed by qPCR validation, identified co-regulated gene sets. Interestingly, these included heat shock proteins and plasticity-related genes that were both down-regulated in knockout cortices. In contrast, we failed to detect significant differences in expression of previously proposed AICD target genes including Bace1, Kai1, Gsk3b, p53, Tip60, and Vglut2. Only Egfr was slightly up-regulated in APLP2-/- mice. Comparison of APP-/- and APPα/α with wild-type mice revealed a high proportion of co-regulated genes indicating an important role of the C-terminus for cellular signaling. Finally, comparison of APLP2-/- on different genetic backgrounds revealed that background-related transcriptome changes may dominate over changes due to the knockout of a single gene. Shared transcriptome profiles corroborated closely related physiological functions of APP family members in the adult central nervous system. As expression of proposed AICD target genes was not altered in adult cortex, this may indicate that these genes are not affected by lack of APP under resting conditions or only in a small subset of cells.

• Artesunate activates mitochondrial apoptosis in breast cancer cells via iron-catalyzed lysosomal reactive oxygen species production.

  Authors: Anne Hamacher-Brady, Henning A Stein, Simon Turschner, Ina Toegel, Rodrigo Mora, Nina Jennewein, Thomas Efferth, Roland Eils, Nathan R Brady

  The Journal of biological chemistry. 02/2011; 286(8):6587-601.

  The antimalarial agent artesunate (ART) activates programmed cell death (PCD) in cancer cells in a manner dependent on the presence of iron and the generation of reactive oxygen species. In malariaThe antimalarial agent artesunate (ART) activates programmed cell death (PCD) in cancer cells in a manner dependent on the presence of iron and the generation of reactive oxygen species. In malaria parasites, ART cytotoxicity originates from interactions with heme-derived iron within the food vacuole. The analogous digestive compartment of mammalian cells, the lysosome, similarly contains high levels of redox-active iron and in response to specific stimuli can initiate mitochondrial apoptosis. We thus investigated the role of lysosomes in ART-induced PCD and determined that in MCF-7 breast cancer cells ART activates lysosome-dependent mitochondrial outer membrane permeabilization. ART impacted endolysosomal and autophagosomal compartments, inhibiting autophagosome turnover and causing perinuclear clustering of autophagosomes, early and late endosomes, and lysosomes. Lysosomal iron chelation blocked all measured parameters of ART-induced PCD, whereas lysosomal iron loading enhanced death, thus identifying lysosomal iron as the lethal source of reactive oxygen species upstream of mitochondrial outer membrane permeabilization. Moreover, lysosomal inhibitors chloroquine and bafilomycin A1 reduced ART-activated PCD, evidencing a requirement for lysosomal function during PCD signaling. ART killing did not involve activation of the BH3-only protein, Bid, yet ART enhanced TNF-mediated Bid cleavage. We additionally demonstrated the lysosomal PCD pathway in T47D and MDA-MB-231 breast cancer cells. Importantly, non-tumorigenic MCF-10A cells resisted ART-induced PCD. Together, our data suggest that ART triggers PCD via engagement of distinct, interconnected PCD pathways, with hierarchical signaling from lysosomes to mitochondria, suggesting a potential clinical use of ART for targeting lysosomes in cancer treatment.

• Bronchoalveolar lavage fluid of lung cancer patients: mapping the uncharted waters using proteomics technology.

  Authors: Tonio Oumeraci, Bernd Schmidt, Thomas Wolf, Marc Zapatka, Andreas Pich, Benedikt Brors, Roland Eils, Michael Fleischhacker, Brigitte Schlegelberger, Nils von Neuhoff

  Lung cancer (Amsterdam, Netherlands). 02/2011; 72(1):136-8.

  The search for proteome-level markers of non-small cell lung cancer (NSCLC) has been mainly limited to serum or cell line screening approaches up to this point. We would like to demonstrate by thisThe search for proteome-level markers of non-small cell lung cancer (NSCLC) has been mainly limited to serum or cell line screening approaches up to this point. We would like to demonstrate by this proof-of-principle study investigating bronchoalveolar lavage fluid samples from a cohort of NSCLC and control patients, that this readily available biofluid might be a more suitable source for discovering clinically usable NSCLC biomarkers.

• Reconstructing the Stochastic Evolution Diagram of Dynamic Complex Systems.

  Authors: Navid Bazzazzadeh, Benedikt Brors, Roland Eils

  Proceedings of the Twenty-Fifth AAAI Conference on Artificial Intelligence, AAAI 2011, San Francisco, California, USA, August 7-11, 2011; 01/2011

• Quantification of frap experiments in live cell image sequences by combining segmentation and registration.

  Authors: Il-Han Kim, Catharina Cadmus, Andrea C. Pfeifer, Ursula Klingmüller, Roland Eils, Karl Rohr

  Proceedings of the 8th IEEE International Symposium on Biomedical Imaging: From Nano to Macro, ISBI 2011, March 30 - April 2, 2011, Chicago, Illinois, USA; 01/2011

• Nonrigid Registration of 2-D and 3-D Dynamic Cell Nuclei Images for Improved Classification of Subcellular Particle Motion.

  Authors: Il-Han Kim, Yi-Chun Chen, David L. Spector, Roland Eils, Karl Rohr

  IEEE Transactions on Image Processing. 01/2011; 20:1011-1022.

• Tracking multiple particles in fluorescence microscopy images via probabilistic data association.

  Authors: William J. Godinez, Marko Lampe, Roland Eils, Barbara Müller, Karl Rohr

  Proceedings of the 8th IEEE International Symposium on Biomedical Imaging: From Nano to Macro, ISBI 2011, March 30 - April 2, 2011, Chicago, Illinois, USA; 01/2011