Publications

906 Publications visible to you, out of a total of 906

Abstract (Expand)

We describe a Rudin-Osher-Fatemi (ROF) filter based segmentation approach for whole tissue samples, combining floating intensity thresholding and rule-based feature detection. Method is validated against manual counts and compared with two commercial software kits (Tissue Studio 64, Definiens AG, and Halo, Indica Labs) and a straightforward machine-learning approach in a set of 50 test images. Further, the novel method and both commercial packages are applied to a set of 44 whole tissue sections. Outputs are compared with gene expression data available for the same tissue samples. Finally, the ROF based method is applied to 44 expert-specified tumor subregions for testing selection and subsampling strategies. Our method is deterministic, fully automated, externally repeatable, independent on training data and -- in difference to most commercial software kits -- completely documented. Among all tested methods, the novel approach is best correlated with manual count (0.9297). Automated detection of evaluation subregions proved to be fully reliable. Subsampling within tumor subregions is possible with results almost identical to full sampling. Comparison with gene expression data obtained for the same tissue samples reveals only moderate to low correlation levels, thus indicating that image morphometry constitutes an independent source of information about antibody-polarized macrophage occurence and distribution.

Authors: Marcus Wagner, René Hänsel, Sarah Reinke, Julia Richter, Michael Altenbuchinger, Ulf-Dietrich Braumann, Rainer Spang, Markus Löffler, Wolfram Klapper

Date Published: No date defined

Publication Type: Not specified

Human Diseases: diffuse large B-cell lymphoma

Abstract (Expand)

It is generally accepted that epigenetic modifications, such as DNA and histone methylations, affect transcription and that a gene’s transcription feeds back on its epigenetic profile. Depending on the epigenetic modification, positive and negative feedback loops have been described. Here, we study whether such interrelation are mandatory and how transcription factor networks affect it. We apply self-organizing map machine learning to a published data set on the specification and differentiation of murine intestinal stem cells in order to provide an integrative view of gene transcription and DNA, as well as histone methylation during this process. We show that, although gain/loss of H3K4me3 at a gene promoter is generally considered to be associated with its increased/decreased transcriptional activity, such an interrelation is not mandatory, i.e., changes of the modification level do not necessarily affect transcription. Similar considerations hold for H3K27me3. In addition, even strong changes in the transcription of a gene do not necessarily affect its H3K4me3 and H3K27me3 modification profile. We provide a mechanistic explanation of these phenomena that is based on a model of epigenetic regulation of transcription. Thereby, the analyzed data suggest a broad variance in gene specific regulation of histone methylation and support the assumption of an independent regulation of transcription by histone methylation and transcription factor networks. The results provide insights into basic principles of the specification of tissue stem cells and highlight open questions about a mechanistic modeling of this process.

Authors: T. Thalheim, Lydia Hopp, Hans Binder, G. Aust, J. Galle

Date Published: No date defined

Publication Type: Not specified

Abstract

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Authors: B. Kampe, U. Hahn

Date Published: No date defined

Publication Type: Proceedings

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Authors: A. Lagemann, Reinhold Haux, Alfred Winter

Date Published: No date defined

Publication Type: Misc

Abstract (Expand)

Molecular mechanisms of lower grade (II- III) diffuse gliomas (LGG) are still poorly understood, mainly because of their heterogeneity. They split into astrocytoma- (IDH-A) and oligodendro-glioma-like (IDH-O) tumors both carrying mutations(s) at the Isocitrate dehydrogenase (IDH) gene and into IDH wild type (IDH-wt) gliomas of glioblastoma-resemblance. We generated de-tailed maps of the transcriptomes and DNA-methylomes revealing that cell functions divide into three major archeotypic hallmarks: (i) increased proliferation in IDH-wt and, to a less degree, IDH-O, (ii) increased inflammation in IDH-A and IDH-wt, and (iii) the loss of synaptic transmis-sion in all subtypes. Immunogenic properties of IDH-A are diverse partly resembling signatures observed in grade IV mesenchymal glioblastomas or in grade I pilocytic astrocytomas. We ana-lyzed details of coregulation between gene expression and DNA-methylation and of the immu-nogenic micro-environment presumably driving tumor development and treatment resistance. Our transcriptome and methylome maps support personalized, case-by-case views to decipher the heterogeneity of glioma states in terms of data portraits. Thereby molecular cartography provides a graphical coordinate system, which links gene-level information with glioma sub-types, their phenotypes and clinical context.

Authors: Hans Binder, Maria Schmidt, Lydia Hopp, Arsen Arakelyan, Henry Löffler-Wirth

Date Published: No date defined

Publication Type: Journal article

Human Diseases: brain glioma

Abstract (Expand)

BACKGROUND: The growing interest in the secondary use of electronic health record (EHR) data has increased the number of new data integration and data sharing infrastructures. The present work has been developed in the context of the German Medical Informatics Initiative, where 29 university hospitals agreed to the usage of the Health Level Seven Fast Healthcare Interoperability Resources (FHIR) standard for their newly established data integration centers. This standard is optimized to describe and exchange medical data but less suitable for standard statistical analysis which mostly requires tabular data formats. OBJECTIVES: The objective of this work is to establish a tool that makes FHIR data accessible for standard statistical analysis by providing means to retrieve and transform data from a FHIR server. The tool should be implemented in a programming environment known to most data analysts and offer functions with variable degrees of flexibility and automation catering to users with different levels of FHIR expertise. METHODS: We propose the fhircrackr framework, which allows downloading and flattening FHIR resources for data analysis. The framework supports different download and authentication protocols and gives the user full control over the data that is extracted from the FHIR resources and transformed into tables. We implemented it using the programming language R [1] and published it under the GPL-3 open source license. RESULTS: The framework was successfully applied to both publicly available test data and real-world data from several ongoing studies. While the processing of larger real-world data sets puts a considerable burden on computation time and memory consumption, those challenges can be attenuated with a number of suitable measures like parallelization and temporary storage mechanisms. CONCLUSION: The fhircrackr R package provides an open source solution within an environment that is familiar to most data scientists and helps overcome the practical challenges that still hamper the usage of EHR data for research.

Authors: J. Palm, F. A. Meineke, J. Przybilla, T. Peschel

Date Published: 25th Jan 2023

Publication Type: Journal article

Abstract (Expand)

We describe the creation of GRASCCO, a novel German-language corpus composed of some 60 clinical documents with more than.43,000 tokens. GRASCCO is a synthetic corpus resulting from a series of alienation steps to obfuscate privacy-sensitive information contained in real clinical documents, the true origin of all GRASCCO texts. Therefore, it is publicly shareable without any legal restrictions We also explore whether this corpus still represents common clinical language use by comparison with a real (non-shareable) clinical corpus we developed as a contribution to the Medical Informatics Initiative in Germany (MII) within the SMITH consortium. We find evidence that such a claim can indeed be made.

Editor:

Date Published: 17th Aug 2022

Publication Type: InProceedings

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