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Repeat Composition of CenH3-chromatin and H3K9me2-marked heterochromatin in Sugar Beet (Beta vulgaris)

Teresa Kowar, Falk Zakrzewski, Jiří Macas, Andrea Kobližková, Prisca Viehoever, Bernd Weisshaar, Thomas Schmidt
2016 BMC Plant Biology  
According to CenH3 ChIP-Seq data, additionally to pBV, Ty3-gypsy retrotransposons of the Beetle family constitute the sugar beet centromere, which is in accordance to the statements reported in Zakrzewski  ... 
doi:10.1186/s12870-016-0805-5 pmid:27230558 pmcid:PMC4881148 fatcat:7ffzdrc5rjhqvdhjcwtoc2jkfi

Analysis of a c0t-1 library enables the targeted identification of minisatellite and satellite families in Beta vulgaris

Falk Zakrzewski, Torsten Wenke, Daniela Holtgräwe, Bernd Weisshaar, Thomas Schmidt
2010 BMC Plant Biology  
Acknowledgements Falk Zakrzewski acknowledges a fellowship and financial support of the FAZIT foundation.  ...  Zakrzewski et al. BMC Plant Biology 2010, 10:8 http://www.biomedcentral.com/1471-2229/10/8 Page 6 of 14 Zakrzewski et al.  ...  BMC Plant Biology 2010, 10:8 http://www.biomedcentral.com/1471-2229/10/8 Page 10 of 14 Zakrzewski et al.  ... 
doi:10.1186/1471-2229-10-8 pmid:20064260 pmcid:PMC2820488 fatcat:5fowjhktkrhdxckxdqijrb5np4

Cytosine Methylation of an Ancient Satellite Family in the Wild Beet Beta procumbens

Martin Schmidt, Sarah Hense, André E. Minoche, Juliane C. Dohm, Heinz Himmelbauer, Thomas Schmidt, Falk Zakrzewski
2014 Cytogenetic and Genome Research  
Acknowledgements Falk Zakrzewski acknowledges a fellowship and financial support of the FAZIT foundation.  ...  The start and end positions of the pEV monomer were adopted from Zakrzewski et al. [2011] .  ...  Schmidt /Hense /Minoche /Dohm / Himmelbauer /Schmidt /Zakrzewski Cytogenet Genome Res 2014;143:157-167 DOI: 10.1159/000363485  ... 
doi:10.1159/000363485 pmid:24994030 fatcat:qjgwolq62nfgnfieb6lc7rwfse

Automated detection of the HER2 gene amplification status in Fluorescence in situ hybridization images for the diagnostics of cancer tissues [article]

Falk Zakrzewski, Walter de Back, Martin Weigert, Torsten Wenke, Silke Zeugner, Robert Mantey, Christian Sperling, Katrin Friedrich, Ingo Roeder, Daniela E. Aust, Gustavo Baretton, Pia Hönscheid
2018 bioRxiv   pre-print
AbstractBackgroundThe human epidermal growth factor receptor 2 (HER2) gene amplification status is a crucial marker for evaluating clinical therapies of breast or gastric cancer. Therefore, the detection of HER2 gene amplification status is highly relevant in histopathological diagnostics. Recently, the application of convolutional neural networks (CNNs) has shown large improvements in the automation of classification and object detection in medical image analysis.MethodsHere, we propose a deep
more » ... learning-based pipeline for the detection, localization and classification of interphase nuclei depending on their HER2 gene amplification state in Fluorescence in situ hybridization (FISH) images. Our pipeline combines two RetinaNet-based object localization networks which are trained (1) to detect and classify interphase nuclei into distinct classes normal, low-grade and high-grade and (2) to detect and classify FISH signals into distinct classes HER2 or centromere of chromosome 17 (CEN17). By independently classifying each nucleus twice, the two-step pipeline provides both robustness and interpretability for the automated detection of the HER2 amplification status.ResultsWe demonstrate that the accuracy of this deep learning-based pipeline is on par with that of three pathologists. We demonstrate that our pipeline accurately classifies FISH images on a set of 57 validation images containing several hundreds of nuclei. Consequently, high quality FISH images can now be analyzed at once regarding their image-wide HER2 gene amplification status.ConclusionsThe automatic pipeline is a first step towards assisting pathologists in evaluating the HER2 status of tumors using FISH images, for analyzing FISH images in retrospective studies, and for optimizing the documentation of each tumor sample by automatically annotating and reporting of the HER2 gene amplification specificities.
doi:10.1101/490052 fatcat:chtpw6pv25a5lbqrxqgyvbvhay

Comparative molecular cytogenetic analyses of a major tandemly repeated DNA family and retrotransposon sequences in cultivated jute Corchorus species (Malvaceae)

Rabeya Begum, Falk Zakrzewski, Gerhard Menzel, Beatrice Weber, Sheikh Shamimul Alam, Thomas Schmidt
2013 Annals of Botany  
., 2005; Zakrzewski et al., 2011) .  ...  Repetitive DNA sequences are often strongly methylated at cytosines in different sequence contexts (Zakrzewski et al., 2011) .  ... 
doi:10.1093/aob/mct103 pmid:23666888 pmcid:PMC3690992 fatcat:hilzkvl2gfdjlk2v7cif2sd5su

Whole exome sequencing identifies mTOR and KEAP1 as potential targets for radiosensitization of HNSCC cells refractory to EGFR and β1 integrin inhibition

Erik Klapproth, Ellen Dickreuter, Falk Zakrzewski, Michael Seifert, Andreas Petzold, Andreas Dahl, Evelin Schröck, Barbara Klink, Nils Cordes
2018 OncoTarget  
Copyright: Klapproth et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Intrinsic and acquired resistances are major obstacles in cancer therapy. Genetic characterization is commonly used to identify predictive or prognostic biomarker signatures and potential cancer targets in
more » ... es from therapy-naïve patients. By far less common are such investigations to identify specific, predictive and/or prognostic gene signatures in patients or cancer cells refractory to a specific molecular-targeted intervention. This, however, might have a great value to foster the development of tailored, personalized cancer therapy. Based on our identification of a differential radiosensitization by single and combined β1 integrin (AIIB2) and EGFR (Cetuximab) targeting in more physiological, three-dimensional head and neck squamous cell carcinoma (HNSCC) cell cultures, we performed comparative whole exome sequencing, phosphoproteome analyses and RNAi knockdown screens in responder and nonresponder cell lines. We found a higher rate of gene mutations with putative proteinchanging characteristics in non-responders and different mutational profiles of responders and non-responders. These profiles allow stratification of HNSCC patients and identification of potential targets to address treatment resistance. Consecutively, pharmacological inhibition of mTOR and KEAP1 effectively diminished non-responder insusceptibility to β1 integrin and EGFR targeting for radiosensitization. Our data pinpoint the added value of genetic biomarker identification after selection for cancer subgroup responsiveness to targeted therapies.
doi:10.18632/oncotarget.24266 pmid:29719593 pmcid:PMC5915060 fatcat:2rc6faxo3zconi7ye5tz3cnzx4

Human gastric cancer modelling using organoids

Therese Seidlitz, Sebastian R Merker, Alexander Rothe, Falk Zakrzewski, Cläre von Neubeck, Konrad Grützmann, Ulrich Sommer, Christine Schweitzer, Sebastian Schölch, Heike Uhlemann, Anne-Marlene Gaebler, Kristin Werner (+8 others)
2018 Gut  
doi:10.1136/gutjnl-2017-314549 pmid:29703791 fatcat:db5a2lzev5g2teen7i3vkhwizu

Automated detection of the HER2 gene amplification status in Fluorescence in situ hybridization images for the diagnostics of cancer tissues

Falk Zakrzewski, Walter de Back, Martin Weigert, Torsten Wenke, Silke Zeugner, Robert Mantey, Christian Sperling, Katrin Friedrich, Ingo Roeder, Daniela Aust, Gustavo Baretton, Pia Hönscheid
2019 Scientific Reports  
The human epidermal growth factor receptor 2 (HER2) gene amplification status is a crucial marker for evaluating clinical therapies of breast or gastric cancer. We propose a deep learning-based pipeline for the detection, localization and classification of interphase nuclei depending on their HER2 gene amplification state in Fluorescence in situ hybridization (FISH) images. Our pipeline combines two RetinaNet-based object localization networks which are trained (1) to detect and classify
more » ... ase nuclei into distinct classes normal, low-grade and high-grade and (2) to detect and classify FISH signals into distinct classes HER2 or centromere of chromosome 17 (CEN17). By independently classifying each nucleus twice, the two-step pipeline provides both robustness and interpretability for the automated detection of the HER2 amplification status. The accuracy of our deep learning-based pipeline is on par with that of three pathologists and a set of 57 validation images containing several hundreds of nuclei are accurately classified. The automatic pipeline is a first step towards assisting pathologists in evaluating the HER2 status of tumors using FISH images, for analyzing FISH images in retrospective studies, and for optimizing the documentation of each tumor sample by automatically annotating and reporting of the HER2 gene amplification specificities.
doi:10.1038/s41598-019-44643-z pmid:31160649 pmcid:PMC6546913 fatcat:w2arxuo3fngcxmq3j5xzheh46q

The genome of the recently domesticated crop plant sugar beet (Beta vulgaris)

Juliane C. Dohm, André E. Minoche, Daniela Holtgräwe, Salvador Capella-Gutiérrez, Falk Zakrzewski, Hakim Tafer, Oliver Rupp, Thomas Rosleff Sörensen, Ralf Stracke, Richard Reinhardt, Alexander Goesmann, Thomas Kraft (+7 others)
2013 Nature  
Sugar beet (Beta vulgaris ssp. vulgaris) is an important crop of temperate climates which provides nearly 30% of the world's annual sugar production and is a source for bioethanol and animal feed. The species belongs to the order of Caryophylalles, is diploid with 2n 5 18 chromosomes, has an estimated genome size of 714-758 megabases 1 and shares an ancient genome triplication with other eudicot plants 2 . Leafy beets have been cultivated since Roman times, but sugar beet is one of the most
more » ... ntly domesticated crops. It arose in the late eighteenth century when lines accumulating sugar in the storage root were selected from crosses made with chard and fodder beet 3 . Here we present a reference genome sequence for sugar beet as the first non-rosid, non-asterid eudicot genome, advancing comparative genomics and phylogenetic reconstructions. The genome sequence comprises 567 megabases, of which 85% could be assigned to chromosomes. The assembly covers a large proportion of the repetitive sequence content that was estimated 4 to be 63%. We predicted 27,421 protein-coding genes supported by transcript data and annotated them on the basis of sequence homology. Phylogenetic analyses provided evidence for the separation of Caryophyllales before the split of asterids and rosids, and revealed lineage-specific gene family expansions and losses. We sequenced spinach (Spinacia oleracea), another Caryophyllales species, and validated features that separate this clade from rosids and asterids. Intraspecific genomic variation was analysed based on the genome sequences of sea beet (Beta vulgaris ssp. maritima; progenitor of all beet crops) and four additional sugar beet accessions. We identified seven million variant positions in the reference genome, and also large regions of low variability, indicating artificial selection. The sugar beet genome sequence enables the identification of genes affecting agronomically relevant traits, supports molecular breeding and maximizes the plant's potential in energy biotechnology. During the last 200 years of sugar beet breeding, the sugar content has increased from 8% to 18% in today's cultivars. Breeding has also actively selected for traits like resistance to viral and fungal diseases, improved taproot yield, monogermy of the seed and bolting resistance.
doi:10.1038/nature12817 pmid:24352233 fatcat:dmr3jgfzz5dbbe6dwmwonpx6g4

An interpretable automated detection system for FISH-based HER2 oncogene amplification testing in histo-pathological routine images of breast and gastric cancer diagnostics [article]

Sarah Schmell and Falk Zakrzewski and Walter de Back and Martin Weigert and Uwe Schmidt and Torsten Wenke and Silke Zeugner and Robert Mantey and Christian Sperling and Ingo Roeder and Pia Hoenscheid and Daniela Aust and Gustavo Baretton
2020 arXiv   pre-print
FISH slides were produced and digitized as described in Zakrzewski et al. (2019) .  ...  The nucleus-and FISH image-wide HER2 amplification status is inferred via different ratios ( Figure 1A .3 and 5) and thresholds as mentioned in Zakrzewski et al. (2019) .  ... 
arXiv:2005.12066v1 fatcat:ogdtlss3wffcpngcnrxzxemsca

Recommendations on test datasets for evaluating AI solutions in pathology [article]

André Homeyer, Christian Geißler, Lars Ole Schwen, Falk Zakrzewski, Theodore Evans, Klaus Strohmenger, Max Westphal, Roman David Bülow, Michaela Kargl, Aray Karjauv, Isidre Munné-Bertran, Carl Orge Retzlaff (+18 others)
2022 arXiv   pre-print
Artificial intelligence (AI) solutions that automatically extract information from digital histology images have shown great promise for improving pathological diagnosis. Prior to routine use, it is important to evaluate their predictive performance and obtain regulatory approval. This assessment requires appropriate test datasets. However, compiling such datasets is challenging and specific recommendations are missing. A committee of various stakeholders, including commercial AI developers,
more » ... hologists, and researchers, discussed key aspects and conducted extensive literature reviews on test datasets in pathology. Here, we summarize the results and derive general recommendations for the collection of test datasets. We address several questions: Which and how many images are needed? How to deal with low-prevalence subsets? How can potential bias be detected? How should datasets be reported? What are the regulatory requirements in different countries? The recommendations are intended to help AI developers demonstrate the utility of their products and to help regulatory agencies and end users verify reported performance measures. Further research is needed to formulate criteria for sufficiently representative test datasets so that AI solutions can operate with less user intervention and better support diagnostic workflows in the future.
arXiv:2204.14226v1 fatcat:dlevgcz2cneqdlmu746xgxy44e

Targeted capture-based NGS is superior to multiplex PCR-based NGS for hereditary BRCA1 and BRCA2 gene analysis in FFPE tumor samples

Falk Zakrzewski, Laura Gieldon, Andreas Rump, Michael Seifert, Konrad Grützmann, Alexander Krüger, Sina Loos, Silke Zeugner, Karl Hackmann, Joseph Porrmann, Johannes Wagner, Karin Kast (+5 others)
2019 BMC Cancer  
With the introduction of Olaparib treatment for BRCA-deficient recurrent ovarian cancer, testing for somatic and/or germline mutations in BRCA1/2 genes in tumor tissues became essential for treatment decisions. In most cases only formalin-fixed paraffin-embedded (FFPE) samples, containing fragmented and chemically modified DNA of minor quality, are available. Thus, multiplex PCR-based sequencing is most commonly applied in routine molecular testing, which is predominantly focused on the
more » ... cation of known hot spot mutations in oncogenes. Methods: We compared the overall performance of an adjusted targeted capture-based enrichment protocol and a multiplex PCR-based approach for calling of pathogenic SNVs and InDels using DNA extracted from 13 FFPE tissue samples. We further applied both strategies to seven blood samples and five matched FFPE tumor tissues of patients with known germline exon-spanning deletions and gene-wide duplications in BRCA1/2 to evaluate CNV detection based solely on panel NGS data. Finally, we analyzed DNA from FFPE tissues of 11 index patients from families suspected of having hereditary breast and ovarian cancer, of whom no blood samples were available for testing, in order to identify underlying pathogenic germline BRCA1/2 mutations. Results: The multiplex PCR-based protocol produced inhomogeneous coverage among targets of each sample and between samples as well as sporadic amplicon drop out, leading to insufficiently or non-covered nucleotides, which subsequently hindered variant detection. This protocol further led to detection of PCR-artifacts that could easily have been misinterpreted as pathogenic mutations. No such limitations were observed by application of an adjusted targeted capture-based protocol, which allowed for CNV calling with 86% sensitivity and 100% specificity. All pathogenic CNVs were confirmed in the five matched FFPE tumor samples from patients carrying known pathogenic germline mutations and we additionally identified somatic loss of the second allele in BRCA1/2. Furthermore we detected pathogenic BRCA1/2 variants in four the eleven FFPE samples from patients of whom no blood was available for analysis. Conclusions: We demonstrate that an adjusted targeted capture-based enrichment protocol is superior to commonly applied multiplex PCR-based protocols for reliable BRCA1/2 variant detection, including CNV-detection, using FFPE tumor samples.
doi:10.1186/s12885-019-5584-6 fatcat:fpnqvsk4fbavfjxu5g2gd2qkdy

New Books

2000 Physics today  
ADAM FALK Popularizations Absolute Zero and the Conquest of Cold. T. Shachtman.  ...  Zakrzewski, eds. Springer-Verlag, New York, 2000. 312 pp. $54.00 hc ISBN 0-387-98895-5 Strings, Conformal Fields, and M-The- ory. Graduate Texts in Contemporary Physics. 2nd edition. M. Kaku.  ... 
doi:10.1063/1.2405486 fatcat:nebgywmetjhabdl67gd57jedfy

Page 305 of Journal of Mass Spectrometry Vol. 36, Issue 3 [page]

2001 Journal of Mass Spectrometry  
Biol. 1988; 201: 601 gomery JA, Raghavachari K, Al-Laham MA, Zakrzewski VG, Wess J, Nanavati S, Vogel Z, Maggio R.  ...  Acta 1970; 221: 165 Falk M, Sidhu P, Walter JA. Nat. Toxins 1998; 6: 159 Acknowledgements Kang YK. Prog. Biophys. Mol.  ... 

Page 56 of National Union Catalog Vol. 33, Issue [page]

1963 National Union Catalog  
. ; 1, Polish literature-Addresses, essays, lectures, L Pollak, Roman, 1886- I, Zakrzewski, Bogdan, ed.  ...  Editor: L, F, Manheim. 1, Tterature—Peycholgy —Perlod 1, Manheim, Roem Falk, Cc ice On Literature and Psycho! m. Mover Language Association of America. General PN 49.  ... 
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