Toponome

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The toponome is the spatial network code of proteins and other biomolecules in morphologically intact cells and tissues. [1] It is mapped and decoded by imaging cycler microscopy (ICM) in situ able to co-map many thousand supermolecules in one sample (tissue section or cell sample at high subcellular resolution). The term "toponome" is derived from the ancient Greek nouns "topos" (τόπος; place, position) and "nomos" (νόμος; law), and the term "toponomics" refers to the study of the toponome. It was introduced by Walter Schubert in 2003. [2] It addresses the fact that the network of biomolecules in cells and tissues follows topological rules enabling coordinated actions. For example, the cell surface toponome provides the spatial protein interaction code for the execution of a cell movement, a "code of conduct". [2] [3] [4] This is intrinsically dependent on the specific spatial arrangement of similar and dissimilar compositions of supermolecules (compositional periodicity) with a specific spatial order along a cell surface membrane. This spatial order is periodically repeated when the cell tries to enter the exploratory state from the spherical state (spatial periodicity). [5] This spatial toponome code is hierarchically organized with lead biomolecule(s), anti-colocated (absent) biomolecule(s) [2] [3] and wildcard molecules which are variably associated with the lead biomolecule(s). It has been shown that inhibition of lead molecule(s) in a surface membrane leads to disassembly of the corresponding biomolecular network and loss of function. [3] [4]

Spatial network graph in which the vertices or edges are spatial elements associated with geometric objects

A spatial network is a graph in which the vertices or edges are spatial elements associated with geometric objects, i.e. the nodes are located in a space equipped with a certain metric. The simplest mathematical realization is a lattice or a random geometric graph, where nodes are distributed uniformly at random over a two-dimensional plane; a pair of nodes are connected if the Euclidean distance is smaller than a given neighborhood radius. Transportation and mobility networks, Internet, mobile phone networks, power grids, social and contact networks and neural networks are all examples where the underlying space is relevant and where the graph's topology alone does not contain all the information. Characterizing and understanding the structure, resilience and the evolution of spatial networks is crucial for many different fields ranging from urbanism to epidemiology.

Protein biological molecule consisting of chains of amino acid residues

Proteins are large biomolecules, or macromolecules, consisting of one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific three-dimensional structure that determines its activity.

Biomolecule molecule that is produced by a living organism

A biomolecule or biological molecule is a loosely used term for molecules and ions that are present in organisms, essential to some typically biological process such as cell division, morphogenesis, or development. Biomolecules include large macromolecules such as proteins, carbohydrates, lipids, and nucleic acids, as well as small molecules such as primary metabolites, secondary metabolites, and natural products. A more general name for this class of material is biological materials. Biomolecules are usually endogenous but may also be exogenous. For example, pharmaceutical drugs may be natural products or semisynthetic (biopharmaceuticals) or they may be totally synthetic.

Citations

  1. Schubert, W (2013). "Toponomics" in Dubitzky, Wolkenhauer, Cho, Yokota. Encyclopedia of Systems Biology. Springer New York. pp. 2191–2212. ISBN   978-1-4419-9862-0.
  2. 1 2 3 Schubert, W (2003). "Topological Proteomics, Toponomics, MELK-Technology". Advances in Biochemical Engineering/Biotechnology. 83: 189–209. doi:10.1007/3-540-36459-5_8.
  3. 1 2 3 Schubert, Walter; Bonnekoh, Bernd; Pommer, Ansgar J; Philipsen, Lars; Böckelmann, Raik; Malykh, Yanina; Gollnick, Harald; Friedenberger, Manuela; Bode, Marcus; Dress, Andreas W M (1 October 2006). "Analyzing proteome topology and function by automated multidimensional fluorescence microscopy". Nature Biotechnology. 24 (10): 1270–1278. doi:10.1038/nbt1250. PMID   17013374.
  4. 1 2 Schubert, Walter (15 September 2010). "On the origin of cell functions encoded in the toponome". Journal of Biotechnology. 149 (4): 252–259. doi:10.1016/j.jbiotec.2010.03.009.
  5. Schubert, Walter (January 2014). "Systematic, spatial imaging of large multimolecular assemblies and the emerging principles of supramolecular order in biological systems". Journal of Molecular Recognition. 27 (1): 3–18. doi:10.1002/jmr.2326. PMC   4283051 Lock-green.svg.

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Toponomics is a discipline in systems biology, molecular cell biology, and histology. It concerns the study of the toponome of organisms. The toponome is the spatial network code of proteins and other biomolecules in morphologically intact cells and tissues. The terms toponome and toponomics were introduced by Walter Schubert in 2003 based on observations with imaging cycler microscopes (ICM). The term “toponome” is derived from the ancient Greek nouns “topos” and “nomos”. Hence the term toponomics is descriptive term addressing the fact that the spatial network of biomolecules in cells follows topological rules enabling coordinated actions. This spatial organization is directly revealed by imaging cycler microscopy with parameter- and dimension-unlimited functional resolution. The resulting toponome structures are hierarchically organized and can be described by a three symbol code. Toponomics is the field of study that has at its goal to decode the complete toponome in health and disease – the next big challenge in human biotechnology after having decoded the human genome.

An imaging cycler microscope (ICM) is a fully automated (epi)fluorescence microscope which overcomes the spectral resolution limit resulting in parameter- and dimension-unlimited fluorescence imaging. The principle and robotic device was described by Walter Schubert in 1997 and has been further developed with his co-workers within the human toponome project. The ICM runs robotically controlled repetitive incubation-imaging-bleaching cycles with dye-conjugated probe libraries recognizing target structures in situ. This results in the transmission of a randomly large number of distinct biological informations by re-using the same fluorescence channel after bleaching for the transmission of another biological information using the same dye which is conjugated to another specific probe, a.s.o. Thereby noise-reduced quasi-multichannel fluorescence images with reproducible physical, geometrical, and biophysical stabilities are generated. The resulting power of combinatorial molecular discrimination (PCMD) per data point is given by 65,536k, where 65,536 is the number of grey value levels, and k is the number of co-mapped biomolecules and/or subdomains per biomolecule(s). High PCMD has been shown for k = 100, and in principle can be expanded for much higher numbers of k. In contrast to traditional multichannel–few-parameter fluorescence microscopy high PCMDs in an ICM lead to high functional and spatial resolution. Systematic ICM analysis of biological systems reveals the supramolecular segregation law that describes the principle of order of large, hierarchically organized biomolecular networks in situ (toponome). The ICM is the core technology for the systematic mapping of the complete protein network code in tissues. The original ICM method includes any modification of the bleaching step. Corresponding modifications have been reported for antibody retrieval and chemical dye-quenching debated recently. The Toponome Imaging Systems (TIS) and multi-epitope-ligand cartographs (MELC) represent different stages of the ICM technological development. Imaging cycler microscopy received the American ISAC best paper award in 2008 for the three symbol code of organized proteomes.