Matches in SemOpenAlex for { <https://semopenalex.org/work/W1996960965> ?p ?o ?g. }
- W1996960965 endingPage "731" @default.
- W1996960965 startingPage "723" @default.
- W1996960965 abstract "Toponome imaging systems (TIS) can yield high-resolution subcellular colocalization images of multiple proteins within single cells and intact tissue sections, giving this technology significant potential for identifying multiplex biomarkers that simultaneously measure several aspects of a cell. The integral role of the microenvironment in malignant progression and the recently appreciated heterogeneity of cancer cells underscore the importance of characterizing complex molecular phenotypes and the large protein network structures of single cells within their preserved anatomical context. Here, we discuss the TIS technique and the potential for developing new sensitive and specific multiplex biomarkers for risk stratification and diagnosis, in addition to its utility for anticancer drug discovery by identifying ‘hub’ proteins that are essential regulators of protein networks. Toponome imaging systems (TIS) can yield high-resolution subcellular colocalization images of multiple proteins within single cells and intact tissue sections, giving this technology significant potential for identifying multiplex biomarkers that simultaneously measure several aspects of a cell. The integral role of the microenvironment in malignant progression and the recently appreciated heterogeneity of cancer cells underscore the importance of characterizing complex molecular phenotypes and the large protein network structures of single cells within their preserved anatomical context. Here, we discuss the TIS technique and the potential for developing new sensitive and specific multiplex biomarkers for risk stratification and diagnosis, in addition to its utility for anticancer drug discovery by identifying ‘hub’ proteins that are essential regulators of protein networks. a protein that is not found, by definition, in any CMPs that comprise a CMP motif within a sample [49]. a measurable cellular component or other substance within an organism used as an indicator of a biological state (e.g., Ki67 in rapidly proliferating cells [47]). See below for more information on multiplex biomarkers. a set of CMPs defined as such on the basis that they all contain at least one or more molecules of the same protein (lead proteins). CMP motifs never contain certain proteins (absent/anti-colocated proteins) and variably contain additional proteins (wild-card proteins) [44]. CMP motifs constitute the first higher order of the hierarchical organization of the toponome. In visualizations of the toponome, each CMP motif is given a unique color code. pattern of protein expression in a given subcellular data point (e.g., a pixel or voxel) within a sample, expressed as a binary sequence; 1 = present, 0 = absent. For example, 00001000111001000100 could be a sequence representation for 20 protein tags [42,44]. a TIS technique that enables the subcellular colocalization of ≥100 proteins by quantification of signal intensity [2]. a protein that interacts with many others in a PPI network, with central importance in cellular functioning due to this aspect. Targeted inhibition of disease-state hub proteins is a novel therapeutic goal. Hub proteins are classified by their ability to bind specific multiple partner proteins either synchronously (party-hub proteins) or asynchronously (date-hub proteins) [62]. a higher order description of the toponome. ‘L’ stands for ‘lead protein’, ‘A’ for ‘absent/anti-colocated protein’, and ‘W’ for ‘wild-card protein’. It constitutes the second higher-order level of the hierarchical organization of the toponome. As an example, AWWALLAAAWLAWWAAAWAA could be a LAW code for 20 protein tags. It is also possible to collect a non-binary generalization of the LAW code from MCEPs [49]. a protein that is by definition present in all CMPs that comprise a CMP motif within a sample. Targeted inhibition of lead proteins has been demonstrated to functionally inhibit a protein network. Therefore, lead proteins are potential therapeutic targets in disease-state phenotypes and are strong candidates for hub proteins (see above). For example, CD13 has been identified as a lead protein in TIS studies; targeted inhibition of CD13 in a rhabdomyosarcoma cell line prevented cells from adopting an exploratory state involved in migration and metastasis, thus the function of a pathological protein network was shown to be dependent on the activity of a TIS-identified lead protein, supporting the hypothesis that lead proteins are central organizers in a protein network [44]. alternative image analysis strategy using gray-value levels of protein expression signal intensity without a binarization step. A high-dimensional intensity vector is constructed and a pseudocolor image is painted whereby the color of two pixels is similar if their corresponding high-dimensional intensity vector is located close by, and vice versa [55,56]. TIS technology can measure up to 100 biomarkers simultaneously within a single cell [2]. Combinatorial analysis of this information (such as CMPs, LAW codes, or MCEPs) is a ‘multiplex’ biomarker assay that yields highly ordered complex signatures of cells, as compared with conventional multiplex biomarkers that examine only approximately five substances. Therefore, TIS multiplex biomarkers should provide highly sensitive and specific diagnostic and prognostic information, based upon their ability to reveal greater levels of complexity. the number of possible different combinations of n different proteins detectable in a given subcellular location, such as a pixel (2D picture element) or a voxel (3D volume element). When protein expression data is binarized (i.e., marked as either present or absent), the PCMD of TIS with n different proteins is 2n. In fSR TIS examining co-expression of at least 100 proteins there is a PCMD of 2100 [2]. In approaches where protein expression data are scaled rather than binarized (e.g., the MCEP approach), the PCMD increases manifoldly. alignment of images in a TIS image stack is a key step for discovering novel protein complexes and functional protein networks. RAMTaB is based on a block-based method for aligning images that may have been displaced during the automated image capture process. The algorithm estimates sub-pixel shifts to two decimal places and yields a confidence measure regarding the success of registration. RAMTaB software is freely available for download [46]. ‘subset surprisology’ refers to the observation that the number of pixels, subcellular locations, or cells whose intensities for various proteins/molecules are simultaneously high with respect to corresponding thresholds is surprisingly large. In the TIS-SIM approach [2] (which omits a binarization step), 8 bits, or potentially 16 bits, are used to describe pixel intensity per protein instead of 1 bit (present/absent) to generate the pixel protein profiles (PPPs). ‘Lasagne’ software enables an investigator to highlight a pixel location and reveal all other pixels with similar PPPs [57]. the preserved subcellular protein network architecture of an intact individual cell. ‘Toponome’ is a fusion of the Greek words ‘topos’ (place, position) and ‘nomos’ (law) [2,42]. an automated molecular fluorescence-tagging and imaging system that yields subcellular colocation of >100 proteins (fSR TIS, see above) through sequential episodes of tag binding/bleaching to an intact cell or tissue section. 2D or 3D representations of the toponome can be constructed from TIS data sets [2,42,44,45]. the application of a TIS as a systems biology tool, as when studying protein networks in homeostatic or diseased states. It reveals rules governing the organization of protein network architecture. Two novel hierarchical levels of protein network organization have been revealed by TIS studies, CMP motifs, and LAW codes (see above) [2,42]. an online open access data sharing tool for multimodal visualization and exploration of multivariate bioimages. WHIDE reduces the complexity of the data and yields molecular co-expression patterns/phenotypes (MCEPs) giving a pseudocolored toponomic information map. Available online via the BioIMAX website (http://ani.cebitec.uni-bielefeld.de/BioIMAX/) [55,58]. a protein that is variably present across CMPs that constitute a single CMP motif within a sample [49]." @default.
- W1996960965 created "2016-06-24" @default.
- W1996960965 creator A5022852434 @default.
- W1996960965 creator A5027146712 @default.
- W1996960965 creator A5031687662 @default.
- W1996960965 creator A5059252783 @default.
- W1996960965 creator A5069179055 @default.
- W1996960965 date "2012-12-01" @default.
- W1996960965 modified "2023-10-03" @default.
- W1996960965 title "Toponome imaging system: multiplex biomarkers in oncology" @default.
- W1996960965 cites W1535415765 @default.
- W1996960965 cites W1599833391 @default.
- W1996960965 cites W1767380958 @default.
- W1996960965 cites W1935467915 @default.
- W1996960965 cites W1964302896 @default.
- W1996960965 cites W1965256905 @default.
- W1996960965 cites W1966127055 @default.
- W1996960965 cites W1967350125 @default.
- W1996960965 cites W1971353685 @default.
- W1996960965 cites W1972034516 @default.
- W1996960965 cites W1973671404 @default.
- W1996960965 cites W1979426842 @default.
- W1996960965 cites W1979520135 @default.
- W1996960965 cites W1983450521 @default.
- W1996960965 cites W1984984201 @default.
- W1996960965 cites W1985373839 @default.
- W1996960965 cites W1987966760 @default.
- W1996960965 cites W1989891384 @default.
- W1996960965 cites W1993182928 @default.
- W1996960965 cites W1993419086 @default.
- W1996960965 cites W1995168398 @default.
- W1996960965 cites W1996713544 @default.
- W1996960965 cites W1998203484 @default.
- W1996960965 cites W2004212298 @default.
- W1996960965 cites W2004399853 @default.
- W1996960965 cites W2004801541 @default.
- W1996960965 cites W2006891306 @default.
- W1996960965 cites W2017409194 @default.
- W1996960965 cites W2018312170 @default.
- W1996960965 cites W2019921780 @default.
- W1996960965 cites W2027316963 @default.
- W1996960965 cites W2030424208 @default.
- W1996960965 cites W2039537951 @default.
- W1996960965 cites W2040529285 @default.
- W1996960965 cites W2042027949 @default.
- W1996960965 cites W2043772256 @default.
- W1996960965 cites W2045000546 @default.
- W1996960965 cites W2045800415 @default.
- W1996960965 cites W2047664743 @default.
- W1996960965 cites W2047834789 @default.
- W1996960965 cites W2052926310 @default.
- W1996960965 cites W2054978317 @default.
- W1996960965 cites W2057776163 @default.
- W1996960965 cites W2058569154 @default.
- W1996960965 cites W2061078277 @default.
- W1996960965 cites W2064110396 @default.
- W1996960965 cites W2064696266 @default.
- W1996960965 cites W2065709676 @default.
- W1996960965 cites W2072627901 @default.
- W1996960965 cites W2074947364 @default.
- W1996960965 cites W2075446367 @default.
- W1996960965 cites W2085971602 @default.
- W1996960965 cites W2089956125 @default.
- W1996960965 cites W2091881579 @default.
- W1996960965 cites W2104101394 @default.
- W1996960965 cites W2114319457 @default.
- W1996960965 cites W2115886860 @default.
- W1996960965 cites W2118104220 @default.
- W1996960965 cites W2118282875 @default.
- W1996960965 cites W2119001643 @default.
- W1996960965 cites W2119884047 @default.
- W1996960965 cites W2123697007 @default.
- W1996960965 cites W2124812362 @default.
- W1996960965 cites W2126379430 @default.
- W1996960965 cites W2129336819 @default.
- W1996960965 cites W2132346826 @default.
- W1996960965 cites W2133569234 @default.
- W1996960965 cites W2137888576 @default.
- W1996960965 cites W2141350366 @default.
- W1996960965 cites W2141392622 @default.
- W1996960965 cites W2143468862 @default.
- W1996960965 cites W2152064969 @default.
- W1996960965 cites W2158423544 @default.
- W1996960965 cites W2161983416 @default.
- W1996960965 cites W2167233646 @default.
- W1996960965 cites W2275907327 @default.
- W1996960965 cites W2416621186 @default.
- W1996960965 cites W2920241073 @default.
- W1996960965 cites W4236667318 @default.
- W1996960965 doi "https://doi.org/10.1016/j.molmed.2012.10.003" @default.
- W1996960965 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23122853" @default.
- W1996960965 hasPublicationYear "2012" @default.
- W1996960965 type Work @default.
- W1996960965 sameAs 1996960965 @default.
- W1996960965 citedByCount "11" @default.
- W1996960965 countsByYear W19969609652013 @default.
- W1996960965 countsByYear W19969609652014 @default.
- W1996960965 countsByYear W19969609652015 @default.