Toponome Imaging System: <i>In Situ</i> 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
Sayantan Bhattacharya
George Mathew
Ernie Ruban
David B. A. Epstein
Andreas Krusche
Reyk Hillert
Walter Schubert
Michael Khan
10.1021/pr100157p.s013
https://acs.figshare.com/articles/dataset/Toponome_Imaging_System_i_In_Situ_i_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/2707978
In a proof of principle study, we have applied an automated fluorescence toponome imaging system (TIS) to examine whether TIS can find protein network structures, distinguishing cancerous from normal colon tissue present in a surgical sample from the same patient. By using a three symbol code and a power of combinatorial molecular discrimination (PCMD) of 2<sup>21</sup> per subcellular data point in one single tissue section, we demonstrate an <i>in situ</i> protein network structure, visualized as a mosaic of 6813 protein clusters (combinatorial molecular phenotype or CMPs), in the cancerous part of the colon. By contrast, in the histologically normal colon, TIS identifies nearly 5 times the number of protein clusters as compared to the cancerous part (32 009). By subcellular visualization procedures, we found that many cell surface membrane molecules were closely associated with the cell cytoskeleton as unique CMPs in the normal part of the colon, while the same molecules were disassembled in the cancerous part, suggesting the presence of dysfunctional cytoskeleton−membrane complexes. As expected, glandular and stromal cell signatures were found, but interestingly also found were potentially TIS signatures identifying a very restricted subset of cells expressing several putative stem cell markers, all restricted to the cancerous tissue. The detection of these signatures is based on the extreme searching depth, high degree of dimensionality, and subcellular resolution capacity of TIS. These findings provide the technological rationale for the feasibility of a complete colon cancer toponome to be established by massive parallel high throughput/high content TIS mapping.
2010-12-03 00:00:00
Symbol CodeIn
Situ Protein Network Mapping
protein network structures
Cancerous Colon
fluorescence toponome imaging system
protein network structure
CMP
Subcellular Annotation
tissue section
symbol code
cell cytoskeleton
PCMD
Same Patient
colon tissue
Toponome Imaging System
stromal cell signatures
Protein Clusters
colon cancer toponome
principle study
protein clusters
subcellular visualization procedures
subcellular data point
cell markers
subcellular resolution capacity
TIS signatures
5 times
cell surface membrane molecules
6813 protein clusters