This article deals with a molecular geometry imaging platform capable of mapping the spatial protein-colocalisation and anti-colocalisation code of large molecular systems at a time. The platform called molecular unlimited systems imaging cycler (MUSIC) robotics was applied to amyotrophic lateral sclerosis (ALS). The detection of ALS specific cells with a corresponding multimolecular geometry in the blood led to therapeutic depletion of these cells and to recovery of the treated patient, obviously because this therapy interferes with pathogenic invasion of these cells into the central nervous system, where they axotomize motor axons. Large scale geometry MUSIC robotics imaging of up to 4.5 × 10 481 power of combinatorial molecular resolution is key to detect these cells and to control depletion therapy for clinical success. These data and new possibilities may argue for clinical application and for a systematic research in the field of molecular geometry of diseases to discover new mathematically defined insight.
Schubert, W. (2010) On the Origin of Cell Function Encoded in the Toponome. Journal of Biotechnology, 149, 252-259. https://doi.org/10.1016/j.jbiotec.2010.03.009
Schubert, W. (2013) Toponomics. In: Dubitzky, W., Wolkenhauer, O., Yokota, H. and Cho, K.-H., Eds., Encyclopedia of Systems Biology, Springer, New York, Heidelberg, 1291-2212.
Schubert, W. (2015) Advances in Toponomics Drug Discovery: Imaging Cycler Microscopy Correctly Predicts a Therapy Method of Amyotrophic Lateral Sclerosis. Cytometry Part A, 87, 696-703. https://doi.org/10.1002/cyto.a.22671
Schubert, W., Gieseler, A., Krusche, A., Serocka, P. and Hillert, R. (2012) Next-Generation Biomarkers Based on 100-Parameter Functional Super-Resolution Microscopy TIS. New Biotechnology, 29, 599-610. https://doi.org/10.1016/j.nbt.2011.12.004
Ostalecki, C., Lee, J.H., Dindorf, J., Collenburg, L., Schierer, S., Simon, B., Schliep, S., Kremmer, E., Schuler, G. and Baur, A.S. (2017) Multiepitope Tissue Analysis Reveals SPPL3-Mediated ADAM10 Activation as a Key Step in the Transformation of Melanocytes. Science Signaling, 10, eaai8288. https://doi.org/10.1126/scisignal.aai8288
Abbott, A. (2006) Mapping Togetherness (Research Highlight). Nature, 443, 609. (Referring to Schubert et al. 2006)
Schubert, W., Bonnekoh, B., Pommer, A.J., Philipsen, L., Boeckelmann, R., Malykh, Y., Gollnick, H., Friedenberger, M., Bode, M. and Dress, A.W. (2006) Analyzing Proteome Topology and Function by Automated Multidimensional Fluorescence Microscopy. Nature Biotechnology, 24, 1270-1278.
Schubert, W. (2006) Exploring Molecular Networks Directly in the Cell. Cytometry A, 69, 109-112. https://doi.org/10.1002/cyto.a.20234
Schubert, W. (2007) A Three Symbol Code for Organized Proteomes Based on Cyclical Imaging of Protein Locations. Cytometry A, 71, 352-360. https://doi.org/10.1002/cyto.a.20281
Schubert, W. (2014) Systematic, Spatial Imaging of Large Multimolecular Assemblies and the Emerging Principles of Supramolecular Order in Biological Systems. Journal of Molecular Recognition, 27, 3-18. https://doi.org/10.1002/jmr.2326
Wickström, M., Larsson, R., Nygren, P. and Gullbo, J. (2011) Aminopeptidase N (CD13) as a Target for Cancer Chemotherapy. Cancer Science, 102, 501-508. https://doi.org/10.1111/j.1349-7006.2010.01826.x
Schubert, W. (1990) Multiple Antigen-Mapping Microscopy of Human Tissue. In: Burger, G., Oberholzer, M., Vooijs, G.P., Eds., Excerpta Medica, Elsevier, Amsterdam, 97-98.
Schubert, W. (1992) Antigenic Determinants of T Iymphocyte Alpha/Beta Receptor and Other Leukocyte Surface Proteins as Differential Markers of Skeletal Muscle Regeneration: Detection of Spatially and Timely Restricted Patterns by MAM Microscopy. European Journal of Cell Biology, 58, 395-410.
Dress, A., Lokot, T., Schubert, W. and Serocka, P. (2008) Two Theorems about Similarity Maps. Annals of Combinatorics, 12, 279-290. https://doi.org/10.1007/s00026-008-0351-4
Goyal, N.A. and Mozaffar, T. (2014) Experimental Trials in Amyotrophic Lateral Sclerosis: A Review of Recently Completed, Ongoing and Planned Trials Using Existing and Novel Drugs. Expert Opinion on Investigational Drugs, 23, 1541-1551. https://doi.org/10.1517/13543784.2014.933807
Schubert, W., Masters, C.L. and Beyreuther, K. (1993) APP + T Lymphocytes Selectively Sorted to Endomysial Tubes in Polymyositis Displace NCAM-Expressing Muscle Fibers. European Journal of Cell Biology, 62, 333-342.
Moisse, K., Mepham, J., Volkening, K., Welch, I., Hill, T. and Strong, M.J. (2009) Cytosolic TDP-43 Expression Following Axotomy Is Associated with Caspase 3 Activation in NFL-/-Mice: Support for a Role for TDP-43 in the Physiological Response to Neuronal Injury. Brain Research, 1296, 176-186. https://doi.org/10.1016/j.brainres.2009.07.023
Barysenka, A., Dress, A.W. and Schubert, W. (2010) An Information Theoretic Thresholding Method for Detecting Protein Colocalizations in Stacks of Fluorescence Images. Journal of Biotechnology, 149, 127-131. https://doi.org/10.1016/j.jbiotec.2010.01.009
Schubert, W., Gieseler, A., Krusche, A. and Hillert, R. (2009) Toponome Mapping in Prostate Cancer: Detection of 2000 Protein Clusters in a Single Tissue Section and Cell Type Specific Annotation by Using a Three Symbol Code. Journal of Proteome Research, 8, 2696-2707. https://doi.org/10.1021/pr800944f
Schubert, W., Friedenberger, M., Bode, M., Krusche, A. and Hillert, R. (2008) Functional Architecture of the Cell Nucleus: Towards Comprehensive Toponome Reference Maps of Apoptosis. Biochimica et Biophysica Acta, 1783, 2080-2088. https://doi.org/10.1016/j.bbamcr.2008.07.019
Bode, M., Irmler, M., Friedenberger, M., May, C., Jung, K., Stephan, C., Meyer, H.E., Lach, C., Hillert, R., Krusche, A., Beckers, J., Marcus, K. and Schubert, W. (2008) Interlocking Transcriptomics, Proteomics and Toponomics Technologies for Brain Tissue Analysis in Murine Hippocamapus. Proteomics, 8, 1170-1178. https://doi.org/10.1002/pmic.200700742
Bhattacharya, S., Mathew, G., Ruban, E., Epstein, D.B., Krusche, A., Hillert, R., Schubert, W. and Khan, M. (2010) Toponome Imaging System: In Situ Protein Network Mapping in Normal and Cancerous Colon from the Same Patient Reveals More than Five-Thousand Cancer Specific Protein Clusters and Their Subcellular Annotation by Using a Three Symbol Code. Journal of Proteome Research, 9, 6112-6125. https://doi.org/10.1021/pr100157p
Friedenberger, M., Bode, M., Krusche, A. and Schubert, W. (2007) Fluorescence Detection of Protein Clusters in Individual Cells and Tissue Sections by Using Toponome Imaging System (TIS): Sample Preparation and Measuring Procedures. Nature Protocols, 2, 2285-2294. https://doi.org/10.1038/nprot.2007.320
Hillert, R., Gieseler, A., Krusche, A., Humme, D., Röwert-Huber, H.J., Sterry, W., Walden, P. and Schubert, W. (2016) Large Molecular Systems Landscape Uncovers T Cell Trapping in Human Skin Cancer. Scientific Reports, 6, Article No. 19012. https://doi.org/10.1038/srep19012