Menck, Kerstin

[["dc.bibliographiccitation.artnumber","135"],["dc.bibliographiccitation.journal","Frontiers in Oncology"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Bayerlová, Michaela"],["dc.contributor.author","Menck, Kerstin"],["dc.contributor.author","Klemm, Florian"],["dc.contributor.author","Wolff, Alexander"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Bleckmann, Annalen"],["dc.date.accessioned","2019-07-09T11:43:27Z"],["dc.date.available","2019-07-09T11:43:27Z"],["dc.date.issued","2017"],["dc.description.abstract","Breast cancer is a heterogeneous disease and has been classified into five molecular subtypes based on gene expression profiles. Signaling processes linked to different breast cancer molecular subtypes and different clinical outcomes are still poorly understood. Aberrant regulation of Wnt signaling has been implicated in breast cancer progression. In particular Ror1/2 receptors and several other members of the non-canonical Wnt signaling pathway were associated with aggressive breast cancer behavior. However, Wnt signals are mediated via multiple complex pathways, and it is clinically important to determine which particular Wnt cascades, including their domains and targets, are deregulated in poor prognosis breast cancer. To investigate activation and outcome of the Ror2-dependent non-canonical Wnt signaling pathway, we overexpressed the Ror2 receptor in MCF-7 and MDA-MB231 breast cancer cells, stimulated the cells with its ligand Wnt5a, and we knocked-down Ror1 in MDA-MB231 cells. We measured the invasive capacity of perturbed cells to assess phenotypic changes, and mRNA was profiled to quantify gene expression changes. Differentially expressed genes were integrated into a literature-based non-canonical Wnt signaling network. The results were further used in the analysis of an independent dataset of breast cancer patients with metastasis-free survival annotation. Overexpression of the Ror2 receptor, stimulation with Wnt5a, as well as the combination of both perturbations enhanced invasiveness of MCF-7 cells. The expression-responsive targets of Ror2 overexpression in MCF-7 induced a Ror2/Wnt module of the non-canonical Wnt signaling pathway. These targets alter regulation of other pathways involved in cell remodeling processing and cell metabolism. Furthermore, the genes of the Ror2/Wnt module were assessed as a gene signature in patient gene expression data and showed an association with clinical outcome. In summary, results of this study indicate a role of a newly defined Ror2/Wnt module in breast cancer progression and present a link between Ror2 expression and increased cell invasiveness."],["dc.identifier.doi","10.3389/fonc.2017.00135"],["dc.identifier.pmid","28695110"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14538"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58892"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","2234-943X"],["dc.relation.issn","2234-943X"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Ror2 Signaling and Its Relevance in Breast Cancer Progression."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","285"],["dc.bibliographiccitation.journal","Oncology Research and Treatment"],["dc.bibliographiccitation.lastpage","286"],["dc.bibliographiccitation.volume","37"],["dc.contributor.author","Menck, Kerstin"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Scharf, Christian"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Dyck, Lydia"],["dc.contributor.author","Klemm, Florian"],["dc.contributor.author","Binder, Claudia"],["dc.date.accessioned","2018-11-07T09:34:18Z"],["dc.date.available","2018-11-07T09:34:18Z"],["dc.date.issued","2014"],["dc.identifier.isi","000343816900702"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32144"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Karger"],["dc.publisher.place","Basel"],["dc.relation.issn","2296-5262"],["dc.relation.issn","2296-5270"],["dc.title","EMMPRIN/CD147-positive tumor cell microvesicles are pro-invasive and detectable in the blood of cancer patients with metastasis"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","142"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Cells"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Menck, Kerstin"],["dc.contributor.author","Heinrichs, Saskia"],["dc.contributor.author","Baden, Cornelia"],["dc.contributor.author","Bleckmann, Annalen"],["dc.date.accessioned","2021-04-14T08:29:45Z"],["dc.date.available","2021-04-14T08:29:45Z"],["dc.date.issued","2021"],["dc.identifier.doi","10.3390/cells10010142"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82982"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","2073-4409"],["dc.title","The WNT/ROR Pathway in Cancer: From Signaling to Therapeutic Intervention"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Onkologie"],["dc.bibliographiccitation.volume","36"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Leha, Andreas"],["dc.contributor.author","Artmann, Stephan"],["dc.contributor.author","Menck, Kerstin"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Klemm, E."],["dc.date.accessioned","2018-11-07T09:19:06Z"],["dc.date.available","2018-11-07T09:19:06Z"],["dc.date.issued","2013"],["dc.identifier.isi","000326360900431"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/28557"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Karger"],["dc.publisher.place","Basel"],["dc.title","Identification of prognostic miRNAs in breast cancer through profiling of tumor educated macrophages"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","143"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Molecular Cell Biology"],["dc.bibliographiccitation.lastpage","153"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Menck, Kerstin"],["dc.contributor.author","Scharf, Christian"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Dyck, Lydia"],["dc.contributor.author","Rost, Ulrike"],["dc.contributor.author","Wenzel, Dirk"],["dc.contributor.author","Dhople, Vishnu M."],["dc.contributor.author","Siam, Laila"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Klemm, Florian"],["dc.date.accessioned","2018-11-07T09:58:48Z"],["dc.date.available","2018-11-07T09:58:48Z"],["dc.date.issued","2015"],["dc.description.abstract","Tumor cells secrete not only a variety of soluble factors, but also extracellular vesicles that are known to support the establishment of a favorable tumor niche by influencing the surrounding stroma cells. Here we show that tumor-derived microvesicles (T-MV) also directly influence the tumor cells by enhancing their invasion in a both autologousand heterologous manner. Neither the respective vesicle-free supernatant nor MV from benign mammary cells mediate invasion. Uptake of T-MV is essential for the proinvasive effect. We further identify the highly glycosylated form of the extracellular matrix metalloproteinase inducer (EMMPRIN) as a marker for proinvasive MV. EMMPRIN is also present at high levels on MV from metastatic breast cancer patients in vivo. Anti-EMMPRIN strategies, such as MV deglycosylation, gene knockdown, and specific blocking peptides, inhibit MV-induced invasion. Interestingly, the effect of EMMPRIN-bearing MV is not mediated by matrix metalloproteinases but by activation of the p38/MAPK signaling pathway in the tumor cells. In conclusion, T-MV stimulate cancer cell invasion via a direct feedback mechanism dependent on highly glycosylated EMMPRIN."],["dc.description.sponsorship","Deutsche Krebshilfe [109615]; DFG [BI 703/3-2]; eBIO MetastaSys (BMBF)"],["dc.identifier.doi","10.1093/jmcb/mju047"],["dc.identifier.isi","000355232100006"],["dc.identifier.pmid","25503107"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13819"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37445"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","1759-4685"],["dc.relation.issn","1674-2788"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0"],["dc.title","Tumor-derived microvesicles mediate human breast cancer invasion through differentially glycosylated EMMPRIN"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","15482"],["dc.bibliographiccitation.issue","17"],["dc.bibliographiccitation.journal","Oncotarget"],["dc.bibliographiccitation.lastpage","15493"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Rietkötter, Eva"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Bayerlová, Michaela"],["dc.contributor.author","Menck, Kerstin"],["dc.contributor.author","Chuang, Han-Ning"],["dc.contributor.author","Wenske, Britta"],["dc.contributor.author","Schwartz, Hila"],["dc.contributor.author","Erez, Neta"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.contributor.author","Pukrop, Tobias"],["dc.date.accessioned","2019-07-09T11:42:37Z"],["dc.date.available","2019-07-09T11:42:37Z"],["dc.date.issued","2015-06-20"],["dc.description.abstract","The mononuclear phagocytic system is categorized in three major groups: monocyte-derived cells (MCs), dendritic cells and resident macrophages. During breast cancer progression the colony stimulating factor 1 (CSF-1) can reprogram MCs into tumor-promoting macrophages in the primary tumor. However, the effect of CSF-1 during colonization of the brain parenchyma is largely unknown. Thus, we analyzed the outcome of anti-CSF-1 treatment on the resident macrophage population of the brain, the microglia, in comparison to MCs, alone and in different in vitro co-culture models. Our results underline the addiction of MCs to CSF-1 while surprisingly, microglia were not affected. Furthermore, in contrast to the brain, the bone marrow did not express the alternative ligand, IL-34. Yet treatment with IL-34 and co-culture with carcinoma cells partially rescued the anti-CSF-1 effects on MCs. Further, MC-induced invasion was significantly reduced by anti-CSF-1 treatment while microglia-induced invasion was reduced to a lower extend. Moreover, analysis of lung and breast cancer brain metastasis revealed significant differences of CSF-1 and CSF-1R expression. Taken together, our findings demonstrate not only differences of anti-CSF-1 treatment on MCs and microglia but also in the CSF-1 receptor and ligand expression in brain and bone marrow as well as in brain metastasis."],["dc.identifier.doi","10.18632/oncotarget.3855"],["dc.identifier.fs","618466"],["dc.identifier.pmid","26098772"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13609"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58709"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1949-2553"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.subject.mesh","Animals"],["dc.subject.mesh","Antibodies, Monoclonal"],["dc.subject.mesh","Brain"],["dc.subject.mesh","Brain Neoplasms"],["dc.subject.mesh","Breast Neoplasms"],["dc.subject.mesh","Cell Line, Tumor"],["dc.subject.mesh","Cell Movement"],["dc.subject.mesh","Cell Proliferation"],["dc.subject.mesh","Female"],["dc.subject.mesh","Humans"],["dc.subject.mesh","Interleukin-1"],["dc.subject.mesh","MCF-7 Cells"],["dc.subject.mesh","Macrophage Colony-Stimulating Factor"],["dc.subject.mesh","Macrophages"],["dc.subject.mesh","Mice"],["dc.subject.mesh","Mice, Inbred BALB C"],["dc.subject.mesh","Microglia"],["dc.subject.mesh","Monocytes"],["dc.subject.mesh","Neoplasm Invasiveness"],["dc.subject.mesh","Receptor, Macrophage Colony-Stimulating Factor"],["dc.title","Anti-CSF-1 treatment is effective to prevent carcinoma invasion induced by monocyte-derived cells but scarcely by microglia."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","395"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Experimental & Clinical Cancer Research"],["dc.bibliographiccitation.volume","40"],["dc.contributor.author","Menck, Kerstin"],["dc.contributor.author","Heinrichs, Saskia"],["dc.contributor.author","Wlochowitz, Darius"],["dc.contributor.author","Sitte, Maren"],["dc.contributor.author","Noeding, Helen"],["dc.contributor.author","Janshoff, Andreas"],["dc.contributor.author","Treiber, Hannes"],["dc.contributor.author","Ruhwedel, Torben"],["dc.contributor.author","Schatlo, Bawarjan"],["dc.contributor.author","von der Brelie, Christian"],["dc.contributor.author","Wiemann, Stefan"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Bleckmann, Annalen"],["dc.date.accessioned","2022-02-01T10:31:31Z"],["dc.date.accessioned","2022-08-18T12:32:54Z"],["dc.date.available","2022-02-01T10:31:31Z"],["dc.date.available","2022-08-18T12:32:54Z"],["dc.date.issued","2021-12-15"],["dc.date.updated","2022-07-29T12:18:08Z"],["dc.description.abstract","Abstract\r\n \r\n Background\r\n Breast cancer has been associated with activation of the WNT signaling pathway, although no driver mutations in WNT genes have been found yet. Instead, a high expression of the alternative WNT receptor ROR2 was observed, in particular in breast cancer brain metastases. However, its respective ligand and downstream signaling in this context remained unknown.\r\n \r\n \r\n Methods\r\n We modulated the expression of ROR2 in human breast cancer cells and characterized their gene and protein expression by RNA-Seq, qRT-PCR, immunoblots and reverse phase protein array (RPPA) combined with network analyses to understand the molecular basis of ROR2 signaling in breast cancer. Using co-immunoprecipitations, we verified the interaction of ROR2 with the identified ligand, WNT11. The functional consequences of WNT11/ROR2 signaling for tumor cell aggressiveness were assessed by microscopy, impedance sensing as well as viability and invasion assays. To evaluate the translational significance of our findings, we performed gene set enrichment, expression and survival analyses on human breast cancer brain metastases.\r\n \r\n \r\n Results\r\n We found ROR2 to be highly expressed in aggressive breast tumors and associated with worse metastasis-free survival. ROR2 overexpression induced a BRCAness-like phenotype in a cell-context specific manner and rendered cells resistant to PARP inhibition. High levels of ROR2 were furthermore associated with defects in cell morphology and cell-cell-contacts leading to increased tumor invasiveness. On a molecular level, ROR2 overexpression upregulated several non-canonical WNT ligands, in particular WNT11. Co-immunoprecipitation confirmed that WNT11 indeed interacts with the cysteine-rich domain of ROR2 and triggers its invasion-promoting signaling via RHO/ROCK. Knockdown of WNT11 reversed the pro-invasive phenotype and the cellular changes in ROR2-overexpressing cells.\r\n \r\n \r\n Conclusions\r\n Taken together, our study revealed a novel auto-stimulatory loop in which ROR2 triggers the expression of its own ligand, WNT11, resulting in enhanced tumor invasion associated with breast cancer metastasis."],["dc.identifier.citation","Journal of Experimental & Clinical Cancer Research. 2021 Dec 15;40(1):395"],["dc.identifier.doi","10.1186/s13046-021-02187-z"],["dc.identifier.pii","2187"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/98882"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112913"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-517"],["dc.publisher","BioMed Central"],["dc.relation.eissn","1756-9966"],["dc.rights.holder","The Author(s)"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject","Breast cancer"],["dc.subject","Metastasis"],["dc.subject","ROR2"],["dc.subject","WNT11"],["dc.subject","BRCAness"],["dc.subject","Network analysis"],["dc.title","WNT11/ROR2 signaling is associated with tumor invasion and poor survival in breast cancer"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","309"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Clinical & Experimental Metastasis"],["dc.bibliographiccitation.lastpage","323"],["dc.bibliographiccitation.volume","33"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Conradi, Lena-Christin"],["dc.contributor.author","Menck, Kerstin"],["dc.contributor.author","Schmick, Nadine Annette"],["dc.contributor.author","Schubert, Antonia"],["dc.contributor.author","Rietkoetter, Eva"],["dc.contributor.author","Arackal, Jetcy"],["dc.contributor.author","Middel, Peter"],["dc.contributor.author","Schambony, Alexandra"],["dc.contributor.author","Liersch, Torsten"],["dc.contributor.author","Homayounfar, Kia"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Klemm, Florian"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Pukrop, Tobias"],["dc.date.accessioned","2018-11-07T10:16:24Z"],["dc.date.available","2018-11-07T10:16:24Z"],["dc.date.issued","2016"],["dc.description.abstract","Liver metastasis development in breast cancer patients is common and confers a poor prognosis. So far, the prognostic significance of surgical resection and clinical relevance of biomarker analysis in metastatic tissue have barely been investigated. We previously demonstrated an impact of WNT signaling in breast cancer brain metastasis. This study aimed to investigate the value of established prognostic markers and WNT signaling components in liver metastases. Overall N = 34 breast cancer liver metastases (with matched primaries in 19/34 cases) were included in this retrospective study. Primaries and metastatic samples were analyzed for their expression of the estrogen (ER) and progesterone receptor, HER-2, Ki67, and various WNT signaling-components by immunohistochemistry. Furthermore, beta-catenin-dependent and -independent WNT scores were generated and analyzed for their prognostic value. Additionally, the influence of the alternative WNT receptor ROR on signaling and invasiveness was analyzed in vitro. ER positivity (HR 0.09, 95 % CI 0.01-0.56) and high Ki67 (HR 3.68, 95 % CI 1.12-12.06) in the primaries had prognostic impact. However, only Ki67 remained prognostic in the metastatic tissue (HR 2.46, 95 % CI 1.11-5.44). Additionally, the beta-catenin-independent WNT score correlated with reduced overall survival only in the metastasized situation (HR 2.19, 95 % CI 1.02-4.69, p = 0.0391). This is in line with the in vitro results of the alternative WNT receptors ROR1 and ROR2, which foster invasion. In breast cancer, the value of prognostic markers established in primary tumors cannot directly be translated to metastases. Our results revealed beta-catenin-independent WNT signaling to be associated with poor prognosis in patients with breast cancer liver metastasis."],["dc.identifier.doi","10.1007/s10585-016-9780-3"],["dc.identifier.isi","000373005900002"],["dc.identifier.pmid","26862065"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13177"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/41033"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","1573-7276"],["dc.relation.issn","0262-0898"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","beta-catenin-independent WNT signaling and Ki67 in contrast to the estrogen receptor status are prognostic and associated with poor prognosis in breast cancer liver metastases"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","42"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Genome Medicine"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Chereda, Hryhorii"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Menck, Kerstin"],["dc.contributor.author","Perera-Bel, Júlia"],["dc.contributor.author","Stegmaier, Philip"],["dc.contributor.author","Auer, Florian"],["dc.contributor.author","Kramer, Frank"],["dc.contributor.author","Leha, Andreas"],["dc.contributor.author","Beißbarth, Tim"],["dc.date.accessioned","2021-04-14T08:28:07Z"],["dc.date.accessioned","2022-08-18T12:39:45Z"],["dc.date.available","2021-04-14T08:28:07Z"],["dc.date.available","2022-08-18T12:39:45Z"],["dc.date.issued","2021-03-11"],["dc.date.updated","2022-07-29T12:18:05Z"],["dc.description.abstract","Abstract\r\n \r\n Background\r\n Contemporary deep learning approaches show cutting-edge performance in a variety of complex prediction tasks. Nonetheless, the application of deep learning in healthcare remains limited since deep learning methods are often considered as non-interpretable black-box models. However, the machine learning community made recent elaborations on interpretability methods explaining data point-specific decisions of deep learning techniques. We believe that such explanations can assist the need in personalized precision medicine decisions via explaining patient-specific predictions.\r\n \r\n \r\n Methods\r\n Layer-wise Relevance Propagation (LRP) is a technique to explain decisions of deep learning methods. It is widely used to interpret Convolutional Neural Networks (CNNs) applied on image data. Recently, CNNs started to extend towards non-Euclidean domains like graphs. Molecular networks are commonly represented as graphs detailing interactions between molecules. Gene expression data can be assigned to the vertices of these graphs. In other words, gene expression data can be structured by utilizing molecular network information as prior knowledge. Graph-CNNs can be applied to structured gene expression data, for example, to predict metastatic events in breast cancer. Therefore, there is a need for explanations showing which part of a molecular network is relevant for predicting an event, e.g., distant metastasis in cancer, for each individual patient.\r\n \r\n \r\n Results\r\n We extended the procedure of LRP to make it available for Graph-CNN and tested its applicability on a large breast cancer dataset. We present Graph Layer-wise Relevance Propagation (GLRP) as a new method to explain the decisions made by Graph-CNNs. We demonstrate a sanity check of the developed GLRP on a hand-written digits dataset and then apply the method on gene expression data. We show that GLRP provides patient-specific molecular subnetworks that largely agree with clinical knowledge and identify common as well as novel, and potentially druggable, drivers of tumor progression.\r\n \r\n \r\n Conclusions\r\n The developed method could be potentially highly useful on interpreting classification results in the context of different omics data and prior knowledge molecular networks on the individual patient level, as for example in precision medicine approaches or a molecular tumor board."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2021"],["dc.identifier.citation","Genome Medicine. 2021 Mar 11;13(1):42"],["dc.identifier.doi","10.1186/s13073-021-00845-7"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17744"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82506"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112973"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","BioMed Central"],["dc.relation.eissn","1756-994X"],["dc.rights","CC BY 4.0"],["dc.rights.holder","The Author(s)"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject","Gene expression data"],["dc.subject","Explainable AI"],["dc.subject","Personalized medicine"],["dc.subject","Precision medicine"],["dc.subject","Classification of cancer"],["dc.subject","Deep learning"],["dc.subject","Prior knowledge"],["dc.subject","Molecular networks"],["dc.title","Explaining decisions of graph convolutional neural networks: patient-specific molecular subnetworks responsible for metastasis prediction in breast cancer"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e55057"],["dc.bibliographiccitation.issue","119"],["dc.bibliographiccitation.journal","Journal of Visualized Experiments"],["dc.contributor.author","Menck, Kerstin"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Schulz, Matthias"],["dc.contributor.author","Ries, Lena"],["dc.contributor.author","Binder, Claudia"],["dc.date.accessioned","2018-11-07T10:28:42Z"],["dc.date.available","2018-11-07T10:28:42Z"],["dc.date.issued","2017"],["dc.description.abstract","The release of extracellular vesicles (EVs) including small endosomal-derived exosomes (Exos, diameter < 100 nm) and large plasma membrane-derived microvesicles (MVs, diameter > 100 nm) is a fundamental cellular process that occurs in all living cells. These vesicles transport proteins, lipids and nucleic acids specific for their cell of origin and in vitro studies have highlighted their importance as mediators of intercellular communication. EVs have been successfully isolated from various body fluids and especially EVs in blood have been identified as promising biomarkers for cancer or infectious diseases. In order to allow the study of MV subpopulations in blood, we present a protocol for the standardized isolation and characterization of MVs from peripheral blood samples. MVs are pelleted from EDTA-anticoagulated plasma samples by differential centrifugation and typically possess a diameter of 100 - 600 nm. Due to their larger size, they can easily be studied by flow cytometry, a technique that is routinely used in clinical diagnostics and available in most laboratories. Several examples for quality control assays of the isolated MVs will be given and markers that can be used for the discrimination of different MV subpopulations in blood will be presented."],["dc.identifier.doi","10.3791/55057"],["dc.identifier.isi","000397847200045"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43486"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Journal Of Visualized Experiments"],["dc.relation.issn","1940-087X"],["dc.title","Isolation and Characterization of Microvesicles from Peripheral Blood"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]