DiSWOP: a novel measure for cell-level protein network analysis in localized proteomics image data.

Motivation: New bioimaging techniques have recently been proposed to visualize the colocation or interaction of several proteins within individual cells, displaying the heterogeneity of neighbouring cells within the same tissue specimen. Such techniques could hold the key to understanding complex biological systems such as the protein interactions involved in cancer. However, there is a need for new algorithmic approaches that analyze the large amounts of multi-tag bioimage data from cancerous and normal tissue specimens to begin to infer protein networks and unravel the cellular heterogeneity at a molecular level.

A novel framework for exploratory analysis of highly variable morphology of migrating epithelial cells.

Migratory cells, for example human retinal epithelial (RPE) cells, exhibit highly variable morphology. This makes it difficult to use traditional methods, such as the landmark based Procrustes analysis or feature based analysis, to quantitatively represent their shapes. We propose a novel framework to generate a low-dimensional representation of highly variable cell shapes.

RAMTaB: robust alignment of multi-tag bioimages.

Background: In recent years, new microscopic imaging techniques have evolved to allow us to visualize several different proteins (or other biomolecules) in a visual field. Analysis of protein co-localization becomes viable because molecules can interact only when they are located close to each other. We present a novel approach to align images in a multi-tag fluorescence image stack.

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.

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(21) per subcellular data point in one single tissue section, we demonstrate an in situ 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).

Protein diffusion and macromolecular crowding in thylakoid membranes.

The photosynthetic light reactions of green plants are mediated by chlorophyll-binding protein complexes located in the thylakoid membranes within the chloroplasts. Thylakoid membranes have a complex structure, with lateral segregation of protein complexes into distinct membrane regions known as the grana and the stroma lamellae. It has long been clear that some protein complexes can diffuse between the grana and the stroma lamellae, and that this movement is important for processes including membrane biogenesis, regulation of light harvesting, and turnover and repair of the photosynthetic complexes.