Toponome imaging system: multiplex biomarkers in oncology

Evans, Robert G.; Naidu, Babu; Rajpoot, Nasir M.; Epstein, D. B. A.; Khan, Michael

doi:10.1016/j.molmed.2012.10.003

Cited by 9 publications

(6 citation statements)

References 82 publications

(178 reference statements)

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“…an automated molecular fluorescence tagging and imaging system that yields subcellular colocalization of more than 100 proteins through sequential episodes of tag binding/bleaching to an intact cell or tissue section [38]. Therefore, this novel technology holds promise for developing a new generation of multiplex biomarkers.…”

Section: New Techniquesmentioning

confidence: 99%

“…The integral role of the microenvironment in malignant progression and the recently appreciated heterogeneity of cancer cells stress the importance of characterizing complex molecular phenotypes and the large protein network structures of single cells within their anatomical context. However, the technology requires optimization to improve the reproducibility and accuracy of image analysis, as well as further validation of findings using complementary techniques [38]. …”

Section: New Techniquesmentioning

confidence: 99%

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New Trends of Emerging Technologies in Digital Pathology

et al. 2016

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The future paradigm of pathology will be digital. Instead of conventional microscopy, a pathologist will perform a diagnosis through interacting with images on computer screens and performing quantitative analysis. The fourth generation of virtual slide telepathology systems, so-called virtual microscopy and whole-slide imaging (WSI), has allowed for the storage and fast dissemination of image data in pathology and other biomedical areas. These novel digital imaging modalities encompass high-resolution scanning of tissue slides and derived technologies, including automatic digitization and computational processing of whole microscopic slides. Moreover, automated image analysis with WSI can extract specific diagnostic features of diseases and quantify individual components of these features to support diagnoses and provide informative clinical measures of disease. Therefore, the challenge is to apply information technology and image analysis methods to exploit the new and emerging digital pathology technologies effectively in order to process and model all the data and information contained in WSI. The final objective is to support the complex workflow from specimen receipt to anatomic pathology report transmission, that is, to improve diagnosis both in terms of pathologists' efficiency and with new information. This article reviews the main concerns about and novel methods of digital pathology discussed at the latest workshop in the field carried out within the European project AIDPATH (Academia and Industry Collaboration for Digital Pathology).

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Section: New Techniquesmentioning

confidence: 99%

Section: New Techniquesmentioning

confidence: 99%

New Trends of Emerging Technologies in Digital Pathology

et al. 2016

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“…These oligonucleotides are complimentary to genes on the array and allow the measurement of particular gene expression profiles with high sensitivity. This array is unable to predict and analyze unknown genes, as their sequences need to be known for the manufacture of the [219] PSA [220] Cyclooxygenasearachidonic acid metabolites [221] 2000 cell surface protein cluster in cancer [222] Ovarian BRCA1 BRCA2 mutations [223] CpG-island hypermethylation (BRCA1) [224] Prostasin [225] HE4 [226] Ca125 [227] Eosinophil-derived neurotoxin and COOHterminal osteopontin [228] Breast BRCA1 BRCA2 mutations [223] CpG-island hypermethylation (BRCA1, E-cadherin, TMS1 and estrogen receptor) [229] EpCAM, CD45 [230] Pancreatic Palladin mutation [231] BNC1 ADAMTS1 methylation [232] A1-antitrypsin Apolipoprotein A1 [233] Gastric PTEN mutation [234] CpG-island hypermethylation (hMLH1 and p14ARF) [235] miR-1, miR20a, miR-27a, miR-34 and miR-423-5p expression [236] Hepatocellular RASSF1A, SSBP2 and B4GALT1 hypermethylation [237] AFP-L3 [238] Colorectal CpG-island hypermethylation, hypermethylation of miRNAs (miR-124a) [239] p53 expression [239], EGFR-related KRAS [240], c-MET, b-catenin [241] CEA [242] Smaller number of combinational molecular phenotype cluster in cancer [167] Some of these biomarkers are currently in clinical practice. AFP: Alpha feto-protein; CEA: Carcino-embryonic antigen; PSA: Prostate specific antigen.…”

Section: Genomicsmentioning

confidence: 99%

Extracting biomarkers of commitment to cancer development: potential role of vibrational spectroscopy in systems biology

Theophilou

Paraskevaidi

Lima

et al. 2015

Expert Review of Molecular Diagnostics

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The complex processes driving cancer have so far impeded the discovery of dichotomous biomarkers associated with its initiation and progression. Reductionist approaches utilizing 'omics' technologies have met some success in identifying molecular alterations associated with carcinogenesis. Systems biology is an emerging science that combines high-throughput investigation techniques to define the dynamic interplay between regulatory biological systems in response to internal and external cues. Vibrational spectroscopy has the potential to play an integral role within systems biology research approaches. It is capable of examining global models of carcinogenesis by scrutinizing chemical bond alterations within molecules. The application of infrared or Raman spectroscopic approaches coupled with computational analysis under the systems biology umbrella can assist the transition of biomarker research from the molecular level to the system level. The comprehensive representation of carcinogenesis as a multilevel biological process will inevitably revolutionize cancer-related healthcare by personalizing risk prediction and prevention.

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“…Current research surprisingly showed that toponome fingerprinting of peripheral human blood lymphocytes is able to detect progressive neurological disease 5 years prior to its clinical onset (Schubert W, to be published), and that a monogenetic disease can be successfully treated by conversion of the genotype specific toponome code into a normal one by using a small non‐toxic drug (Ruonala M. et al ., personal communication). Together, these technological, biological, and clinical validations show that the IC approach is able to unravel subcellular disease mechanisms and to find novel drug targets and biomarkers directly at the target sites of disease inside human tissue from biopsies and/or surgical material (Evans et al ., ).…”

Section: Imaging Cyclers Can Break the Spectral Resolution Limit And mentioning

confidence: 99%

Systematic, spatial imaging of large multimolecular assemblies and the emerging principles of supramolecular order in biological systems

Schubert¹

2013

J. Mol. Recognit.

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Understanding biological systems at the level of their relational (emergent) molecular properties in functional protein networks relies on imaging methods, able to spatially resolve a tissue or a cell as a giant, non-random, topologically defined collection of interacting supermolecules executing myriads of subcellular mechanisms. Here, the development and findings of parameter-unlimited functional super-resolution microscopy are described—a technology based on the fluorescence imaging cycler (IC) principle capable of co-mapping thousands of distinct biomolecular assemblies at high spatial resolution and differentiation (<40 nm distances). It is shown that the subcellular and transcellular features of such supermolecules can be described at the compositional and constitutional levels; that the spatial connection, relational stoichiometry, and topology of supermolecules generate hitherto unrecognized functional self-segmentation of biological tissues; that hierarchical features, common to thousands of simultaneously imaged supermolecules, can be identified; and how the resulting supramolecular order relates to spatial coding of cellular functionalities in biological systems. A large body of observations with IC molecular systems microscopy collected over 20 years have disclosed principles governed by a law of supramolecular segregation of cellular functionalities. This pervades phenomena, such as exceptional orderliness, functional selectivity, combinatorial and spatial periodicity, and hierarchical organization of large molecular systems, across all species investigated so far. This insight is based on the high degree of specificity, selectivity, and sensitivity of molecular recognition processes for fluorescence imaging beyond the spectral resolution limit, using probe libraries controlled by ICs. © 2013 The Authors. Journal of Molecular Recognition published by John Wiley & Sons, Ltd.

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Toponome imaging system: multiplex biomarkers in oncology

Cited by 9 publications

References 82 publications

New Trends of Emerging Technologies in Digital Pathology

New Trends of Emerging Technologies in Digital Pathology

Extracting biomarkers of commitment to cancer development: potential role of vibrational spectroscopy in systems biology

Systematic, spatial imaging of large multimolecular assemblies and the emerging principles of supramolecular order in biological systems

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