Cytomics in characterizing Toponomes: Towards the biological code of the cell

Schubert, Walter

doi:10.1002/cyto.a.20203

Cited by 22 publications

(18 citation statements)

References 28 publications

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“…In addition, the identification of proteins by conventional immunohistochemistry cannot be quantified, a further limitation of this conventional approach, which can now be overcome by the MELC data mining process. Even more valuable and unique, the MELC technology also allows identifying molecular networks not only by protein colocalization motifs but also the absence of proteins, the so-called anticolocalization code (10). Thus, we went on and investigated if all T cells are increased in the colorectal cancer mucosa.…”

Section: Resultsmentioning

confidence: 99%

“…For visualization of CMP motifs of interest, the ''Topolyzer'' (MelTec GmbH & Co. KG) was used. This software package allows to visualize CMP motifs of interest as tables, boxplots, toponome maps (10), and on the level of fluorescence and binarized images. Colocalization maps were constructed by superimposing a set of illumination-adjusted colorized fluorescence images, with a distinct color and transparency each.…”

Section: Melc Technologymentioning

confidence: 99%

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Systematic High-Content Proteomic Analysis Reveals Substantial Immunologic Changes in Colorectal Cancer

Berndt

Philipsen²,

Bartsch³

et al. 2008

Cancer Research

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The immune system is a significant determinant of epithelial tumorigenesis, but its role in colorectal cancer pathogenesis is not well understood. The function of the immune system depends upon the integrity of the protein network environment, and thus, we performed MELC immunofluorescence microscopy focusing on the lamina propria. By analyzing structurally intact tissues from colorectal cancer, ulcerative colitis, and healthy colonic mucosa, we used this unique and novel highly multiplexed robotic-imaging technology, which allows visualizing dozens of proteins simultaneously, and explored the toponome in colorectal cancer mucosa for the first time. We identified 1,930 motifs that distinguish control from colorectal cancer tissue. In colorectal cancer, the number of activated T cells is increased, explained by a lack of bax, caspase-3, and caspase-8. Whereas CD4 + CD25 + T cells are decreased and are, other than in ulcerative colitis, not activated, cytotoxic T cells are significantly increased in colorectal cancer. Furthermore, the number of activated human lymphocyte antigen (HLA)-DR + T-cells is increased in colorectal cancer, pointing to an altered antigen presentation. In colorectal cancer, CD3 + CD29 + expression and assembly of the LFA-1 and LFA-3 receptor are differentially changed, indicating a distinct regulation of T-cell adhesion in colorectal cancer. We also identified increased numbers of natural killer and CD44 + cells in the colorectal cancer mucosa and nuclear factor-KB as regulator of apoptosis in these cell populations. High-content proteomic analysis showed that colorectal cancer induces a tremendous modification of protein expression profiles in the lamina propria. Thus, topological proteomic analysis may help to unravel the role of the adaptive immune system in colorectal cancer and aid the development of new antitumor immunotherapy approaches.

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Section: Resultsmentioning

confidence: 99%

Section: Melc Technologymentioning

confidence: 99%

Systematic High-Content Proteomic Analysis Reveals Substantial Immunologic Changes in Colorectal Cancer

Berndt

Philipsen²,

Bartsch³

et al. 2008

Cancer Research

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“…This software package allows visualization of CMP motifs of interest as tables, boxplots (10 -12), and in a given tissue sample, by superimposing these CMP motifs on the corresponding biological structures to create toponome maps (13). In addition, the Topolyzer allows visualization of the fluorescence and binarized images for a given CMP motif.…”

Section: Data Of Interest Visualizationmentioning

confidence: 99%

“…In addition, the identification of proteins by conventional IHC cannot be quantified, a further limitation of this conventional approach, which can now be overcome by the MELC data mining process. Even more valuable and unique, the MELC technology also allows for the identification of molecular networks not only by protein colocalization motifs, but also by the absence of proteins, the so-called anticolocalization code (13).…”

Section: Multidimensional Analysis Of Protein Locations In Inflamed Cmentioning

confidence: 99%

Proteomic Analysis of the Inflamed Intestinal Mucosa Reveals Distinctive Immune Response Profiles in Crohn’s Disease and Ulcerative Colitis

Berndt

Bartsch²,

Philipsen³

et al. 2007

The Journal of Immunology

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Although Crohn’s disease (CrD) and ulcerative colitis (UC) share several clinical features, the mechanisms of tissue injury differ. Because the global cellular function depends upon the protein network environment as a whole, we explored changes in the distribution and association of mucosal proteins to define key events involved in disease pathogenesis. Endoscopic biopsies were taken from CrD, UC, and control colonic mucosa, and Multi-Epitope-Ligand-Cartographie immunofluorescence microscopy with 32 different Abs was performed. Multi-Epitope-Ligand-Cartographie is a novel, highly multiplexed robotic imaging technology which allows integrating cell biology and biomathematical tools to visualize dozens of proteins simultaneously in a structurally intact cell or tissue. In CrD, the number of CD3+CD45RA+ naive T cells was markedly increased, but only activated memory, but not naive, T cells expressed decreased levels of Bax, active caspase-3 or -8. In UC, only CD4+ T cells coexpressing NF-κB were caspase-8 and poly(ADP-ribose)-polymerase positive. Furthermore, the number of CD4+CD25+ T cells was elevated only in UC, whereas in CrD and controls, the number of these cells was similar. By using hub analysis, we also identified that the colocalization pattern with NF-κB+ and poly(ADP-ribose)-polymerase+ as base motifs distinguished CrD from UC. High-content proteomic analysis of the intestinal mucosa demonstrated for the first time that different T cell populations within the intestinal mucosa express proteins translating distinct biological functions in each form of inflammatory bowel disease. Thus, topological proteomic analysis may help to unravel the pathogenesis of inflammatory bowel disease by defining distinct immunopathogenic profiles in CrD and UC.

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“…It does not only include the methods for high-content analysis of a great number of individual cells in a cellular system but also the concept of analysis of these data. The potential of cytomics is on one hand in single cell analysis in combination with a number of technologies (slide based cytometry (SBC), 9,10), toponomics (11,12), spectral imaging (13), proteomics (14)] and applications [drug discovery (15,16), predictive medicine (7,17), clinical diagnosis, translational medicine, human cytome project (18,19), cardiovascular disease, autoimmune disease (20), oncology (21,22), and microbiology (23)]. On the other hand, it is the (mathematical) top-down approach to systems biology.…”

mentioning

confidence: 99%

Cytomics and nanobioengineering

Pierzchalski¹,

Robitzki²,

Mittag³

et al. 2008

Cytometry Part B Clinical

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The finding that an individual's genome differs as much as by many million variants from that of the human reference assembly diminished the great enthusiasm that every disease could be predicted based on nucleotide polymorphisms. Even individual cells of an organ may be specifically equipped to perform specific tasks and that the information of individual cells in a cell system is key information to understand function or dysfunction. Therefore, cytomics received great attention during the last years as it allows to quantitatively and qualitatively analyzing great number of individual cells, cell constituents, and of their intracellular and functional interactions in a cellular system and also giving the concept of analysis of these data.Exhaustive data extraction from multiparametric assays and multiple tests are the prerequisite for prediction of drug toxicity. Cytomics, as novel approach for unsupervised data analysis give a chance to find the most predictive parameters, which describe best the toxicity of a chemical. Cytomics is intrinsically connected to drug development and drug discovery.Focused on small structures, nanobioengineering is the ideal partner of cytomics, the systems biological discipline for cell population analysis. Realizing the idea ''from the molecule to the patient'' develops and offers chemical compounds, proteins, and other biomolecules, cells as well as tissues as instruments and products for a wide variety of biotechnological and biomedical applications.The integrative nanobioengineering combining different disciplines of nanotechnology will promote the development of innovative therapies and diagnostic methods. It can improve the precision of the measurements with focus on single cell analysis. By nanobioengineering and whole body imaging techniques, cytomics covers the field from molecules through bacterial cells, eukaryotic tissues, and organs to small animal live analysis. Toxicological testing and medical drug development are currently strongly broadening. It harbors the promise to substantially impact on various fields of biomedicine, drug discovery, and predictive medicine.As the number of scientific data is rising exponentially, new data analysis tools and strategies like cytomics and nanobioengineering take a lead and get closer to application. Bionanoengineering may strongly support the quantitative data supply, thus strengthening the rationale for cytomics approach. q

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Cytomics in characterizing Toponomes: Towards the biological code of the cell

Cited by 22 publications

References 28 publications

Systematic High-Content Proteomic Analysis Reveals Substantial Immunologic Changes in Colorectal Cancer

Systematic High-Content Proteomic Analysis Reveals Substantial Immunologic Changes in Colorectal Cancer

Proteomic Analysis of the Inflamed Intestinal Mucosa Reveals Distinctive Immune Response Profiles in Crohn’s Disease and Ulcerative Colitis

Cytomics and nanobioengineering

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