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  1. Book ; Online ; Thesis: Ladder-seq partitions RNA-seq reads by length to improve transcriptome quantification and assembly

    Chakraborty, Shounak [Verfasser] / Canzar, Stefan [Akademischer Betreuer]

    2021  

    Author's details Shounak Chakraborty ; Betreuer: Stefan Canzar
    Keywords Biowissenschaften, Biologie ; Life Science, Biology
    Subject code sg570
    Language English
    Publisher Universitätsbibliothek der Ludwig-Maximilians-Universität
    Publishing place München
    Document type Book ; Online ; Thesis
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  2. Article ; Online: Chromatyping: Reconstructing Nucleosome Profiles from NOMe Sequencing Data.

    Chakraborty, Shounak / Canzar, Stefan / Marschall, Tobias / Schulz, Marcel H

    Journal of computational biology : a journal of computational molecular cell biology

    2020  Volume 27, Issue 3, Page(s) 330–341

    MeSH term(s) Algorithms ; Computational Biology/methods ; CpG Islands ; DNA Methylation ; Epigenesis, Genetic ; Gene Expression Regulation ; Humans ; Markov Chains ; Nucleosomes/genetics ; Promoter Regions, Genetic ; Sequence Analysis, DNA/methods
    Chemical Substances Nucleosomes
    Language English
    Publishing date 2020-02-05
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2030900-4
    ISSN 1557-8666 ; 1066-5277
    ISSN (online) 1557-8666
    ISSN 1066-5277
    DOI 10.1089/cmb.2019.0457
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  3. Article ; Online: Low microsatellite instability: A distinct instability type in gastric cancer?

    Kohlruss, Meike / Chakraborty, Shounak / Hapfelmeier, Alexander / Jesinghaus, Moritz / Slotta-Huspenina, Julia / Novotny, Alexander / Sisic, Leila / Gaida, Matthias M / Ott, Katja / Weichert, Wilko / Pfarr, Nicole / Keller, Gisela

    Journal of cancer research and clinical oncology

    2023  Volume 149, Issue 20, Page(s) 17727–17737

    Abstract: Purpose: We recently showed that low microsatellite instability (MSI-L) is associated with a good response to platinum/5-fluorouracil (5-FU) neoadjuvant chemotherapy (CTx) in gastric cancer. The purpose of this study was to characterize the instability ... ...

    Abstract Purpose: We recently showed that low microsatellite instability (MSI-L) is associated with a good response to platinum/5-fluorouracil (5-FU) neoadjuvant chemotherapy (CTx) in gastric cancer. The purpose of this study was to characterize the instability pattern and to investigate an association of MSI-L tumors with mutations in genes of DNA repair pathways and with total tumor mutation burden (TMB).
    Methods: MSI patterns were compared between 67 MSI high (-H) and 35 MSI-L tumors. Whole-exome sequencing was performed in 34 microsatellite stable (MSS) and 20 MSI-L tumors after or without neoadjuvant CTx.
    Results: Of the 35 MSI-L tumors, 33 tumors had instability at a dinucleotide repeat marker. In the homologous recombination (HR) pathway, 10 of the 34 (29%) MSS and 10 of the 20 (50%) MSI-L tumors showed variants (p = 0.154). In the DNA damage tolerance pathway, 6 of the 34 (18%) MSS and 7 of the 20 (35%) MSI-L tumors had variants (p = 0.194). The HR deficiency score was similar in both tumor groups. TMB was significantly higher in MSI-L compared to MSS tumors after CTx (p = 0.046). In the MSS and MSI-L tumors without CTx no difference was observed (p = 1.00).
    Conclusion: MSI-L due to instability at dinucleotide repeat markers was associated with increased TMB after neoadjuvant CTx treatment, indicating sensitivity to platinum/5-FU CTx. If confirmed in further studies, this could contribute to refined chemotherapeutic options including immune-based strategies for GC patients with MSI-L tumors.
    MeSH term(s) Humans ; Stomach Neoplasms/drug therapy ; Stomach Neoplasms/genetics ; Stomach Neoplasms/pathology ; Microsatellite Instability ; Platinum/therapeutic use ; Fluorouracil/therapeutic use ; Mutation ; Microsatellite Repeats
    Chemical Substances Platinum (49DFR088MY) ; Fluorouracil (U3P01618RT)
    Language English
    Publishing date 2023-10-11
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 134792-5
    ISSN 1432-1335 ; 0171-5216 ; 0084-5353 ; 0943-9382
    ISSN (online) 1432-1335
    ISSN 0171-5216 ; 0084-5353 ; 0943-9382
    DOI 10.1007/s00432-023-05430-6
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  4. Article ; Online: High Concordance of Different Assays in the Determination of Homologous Recombination Deficiency-Associated Genomic Instability in Ovarian Cancer.

    Pfarr, Nicole / von Schwarzenberg, Karin / Zocholl, Dario / Merkelbach-Bruse, Sabine / Siemanowski, Janna / Mayr, Eva-Maria / Herold, Sylvia / Kleo, Karsten / Heukamp, Lukas C / Willing, Eva-Maria / Menzel, Michael / Lehmann, Ulrich / Bartels, Stephan / Chakraborty, Shounak / Baretton, Gustavo / Demes, Melanie C / Döring, Claudia / Kazdal, Daniel / Budczies, Jan /
    Rad, Roland / Wild, Peter / Christinat, Yann / McKee, Thomas / Schirmacher, Peter / Horst, David / Büttner, Reinhard / Stenzinger, Albrecht / Sehouli, Jalid / Vollbrecht, Claudia / Hummel, Michael / Braicu, Elena I / Weichert, Wilko

    JCO precision oncology

    2024  Volume 8, Page(s) e2300348

    Abstract: Purpose: Poly(ADP-ribose) polymerase inhibitors (PARPi) have shown promising clinical results in the treatment of ovarian cancer. Analysis of biomarker subgroups consistently revealed higher benefits for patients with homologous recombination deficiency ...

    Abstract Purpose: Poly(ADP-ribose) polymerase inhibitors (PARPi) have shown promising clinical results in the treatment of ovarian cancer. Analysis of biomarker subgroups consistently revealed higher benefits for patients with homologous recombination deficiency (HRD). The test that is most often used for the detection of HRD in clinical studies is the Myriad myChoice assay. However, other assays can also be used to assess biomarkers, which are indicative of HRD, genomic instability (GI), and
    Methods: DNA from HGSOC samples was extracted from formalin-fixed paraffin-embedded tissue blocks of cases previously run with the Myriad myChoice assay, and GI was measured by multiple molecular assays (CytoSNP, AmoyDx, Illumina TSO500 HRD, OncoScan, NOGGO GISv1, QIAseq HRD Panel and whole genome sequencing), applying different bioinformatics algorithms.
    Results: Application of different assays to assess GI, including Myriad myChoice, revealed high concordance of the generated scores ranging from very substantial to nearly perfect fit, depending on the assay and bioinformatics pipelines applied. Interlaboratory comparison of assays also showed high concordance of GI scores.
    Conclusion: Assays for GI assessment not only show a high concordance with each other but also in correlation with Myriad myChoice. Thus, almost all of the assays included here can be used effectively to assess HRD-associated GI in the clinical setting. This is important as PARPi treatment on the basis of these tests is compliant with European Medicines Agency approvals, which are methodologically not test-bound.
    MeSH term(s) Humans ; Female ; BRCA1 Protein/genetics ; Mutation ; BRCA2 Protein/genetics ; Ovarian Neoplasms/diagnosis ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/drug therapy ; Genomic Instability/genetics ; Homologous Recombination/genetics
    Chemical Substances BRCA1 protein, human ; BRCA1 Protein ; BRCA2 protein, human ; BRCA2 Protein
    Language English
    Publishing date 2024-03-21
    Publishing country United States
    Document type Journal Article
    ISSN 2473-4284
    ISSN (online) 2473-4284
    DOI 10.1200/PO.23.00348
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  5. Article ; Online: Partitioning RNAs by length improves transcriptome reconstruction from short-read RNA-seq data.

    Ringeling, Francisca Rojas / Chakraborty, Shounak / Vissers, Caroline / Reiman, Derek / Patel, Akshay M / Lee, Ki-Heon / Hong, Ari / Park, Chan-Woo / Reska, Tim / Gagneur, Julien / Chang, Hyeshik / Spletter, Maria L / Yoon, Ki-Jun / Ming, Guo-Li / Song, Hongjun / Canzar, Stefan

    Nature biotechnology

    2022  Volume 40, Issue 5, Page(s) 741–750

    Abstract: The accuracy of methods for assembling transcripts from short-read RNA sequencing data is limited by the lack of long-range information. Here we introduce Ladder-seq, an approach that separates transcripts according to their lengths before sequencing and ...

    Abstract The accuracy of methods for assembling transcripts from short-read RNA sequencing data is limited by the lack of long-range information. Here we introduce Ladder-seq, an approach that separates transcripts according to their lengths before sequencing and uses the additional information to improve the quantification and assembly of transcripts. Using simulated data, we show that a kallisto algorithm extended to process Ladder-seq data quantifies transcripts of complex genes with substantially higher accuracy than conventional kallisto. For reference-based assembly, a tailored scheme based on the StringTie2 algorithm reconstructs a single transcript with 30.8% higher precision than its conventional counterpart and is more than 30% more sensitive for complex genes. For de novo assembly, a similar scheme based on the Trinity algorithm correctly assembles 78% more transcripts than conventional Trinity while improving precision by 78%. In experimental data, Ladder-seq reveals 40% more genes harboring isoform switches compared to conventional RNA sequencing and unveils widespread changes in isoform usage upon m
    MeSH term(s) Gene Expression Profiling/methods ; High-Throughput Nucleotide Sequencing/methods ; Protein Isoforms ; RNA ; RNA-Seq ; Sequence Analysis, RNA/methods ; Transcriptome/genetics
    Chemical Substances Protein Isoforms ; RNA (63231-63-0)
    Language English
    Publishing date 2022-01-10
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1311932-1
    ISSN 1546-1696 ; 1087-0156
    ISSN (online) 1546-1696
    ISSN 1087-0156
    DOI 10.1038/s41587-021-01136-7
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    In stock of ZB MED Cologne/Königswinter

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  6. Article ; Online: An integrated cellular and molecular model of gastric neuroendocrine cancer evolution highlights therapeutic targets.

    Griger, Joscha / Widholz, Sebastian A / Jesinghaus, Moritz / de Andrade Krätzig, Niklas / Lange, Sebastian / Engleitner, Thomas / Montero, Juan José / Zhigalova, Ekaterina / Öllinger, Rupert / Suresh, Veveeyan / Winkler, Wiebke / Lier, Svenja / Baranov, Olga / Trozzo, Riccardo / Ben Khaled, Najib / Chakraborty, Shounak / Yu, Jiakun / Konukiewitz, Björn / Steiger, Katja /
    Pfarr, Nicole / Rajput, Ashish / Sailer, David / Keller, Gisela / Schirmacher, Peter / Röcken, Christoph / Fagerstedt, Klaus W / Mayerle, Julia / Schmidt-Supprian, Marc / Schneider, Günter / Weichert, Wilko / Calado, Dinis P / Sommermann, Thomas / Klöppel, Günter / Rajewsky, Klaus / Saur, Dieter / Rad, Roland

    Cancer cell

    2023  Volume 41, Issue 7, Page(s) 1327–1344.e10

    Abstract: Gastric neuroendocrine carcinomas (G-NEC) are aggressive malignancies with poorly understood biology and a lack of disease models. Here, we use genome sequencing to characterize the genomic landscapes of human G-NEC and its histologic variants. We ... ...

    Abstract Gastric neuroendocrine carcinomas (G-NEC) are aggressive malignancies with poorly understood biology and a lack of disease models. Here, we use genome sequencing to characterize the genomic landscapes of human G-NEC and its histologic variants. We identify global and subtype-specific alterations and expose hitherto unappreciated gains of MYC family members in a large part of cases. Genetic engineering and lineage tracing in mice delineate a model of G-NEC evolution, which defines MYC as a critical driver and positions the cancer cell of origin to the neuroendocrine compartment. MYC-driven tumors have pronounced metastatic competence and display defined signaling addictions, as revealed by large-scale genetic and pharmacologic screening of cell lines and organoid resources. We create global maps of G-NEC dependencies, highlight critical vulnerabilities, and validate therapeutic targets, including candidates for clinical drug repurposing. Our study gives comprehensive insights into G-NEC biology.
    MeSH term(s) Humans ; Animals ; Mice ; Carcinoma, Neuroendocrine/drug therapy ; Carcinoma, Neuroendocrine/genetics ; Carcinoma, Neuroendocrine/metabolism ; Stomach Neoplasms/drug therapy ; Stomach Neoplasms/genetics ; Stomach Neoplasms/metabolism ; Models, Molecular ; Neuroendocrine Tumors/drug therapy ; Neuroendocrine Tumors/genetics
    Language English
    Publishing date 2023-06-22
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2078448-X
    ISSN 1878-3686 ; 1535-6108
    ISSN (online) 1878-3686
    ISSN 1535-6108
    DOI 10.1016/j.ccell.2023.06.001
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