Cell cycle dependence of protein subcellular location inferred from static, asynchronous images

Abstract

Protein subcellular location is one of the most important determinants of protein function during cellular processes. Changes in protein behavior during the cell cycle are expected to be involved in cellular reprogramming during disease and development, and there is therefore a critical need to understand cell-cycle dependent variation in protein localization which may be related to aberrant pathway activity. With this goal, it would be useful to have an automated method that can be applied on a proteomic scale to identify candidate proteins showing cell-cycle dependent variation of location. Fluorescence microscopy, and especially automated, high-throughput microscopy, can provide images for tens of thousands of fluorescently-tagged proteins for this purpose. Previous work on analysis of cell cycle variation has traditionally relied on obtaining time-series images over an entire cell cycle; these methods are not applicable to the single time point images that are much easier to obtain on a large scale. Hence a method that can infer cell cycle-dependence of proteins from asynchronous, static cell images would be preferable. In this work, we demonstrate such a method that can associate protein pattern variation in static images with cell cycle progression. We additionally show that a one-dimensional parameterization of cell cycle progression and protein feature pattern is sufficient to infer association between localization and cell cycle.

Segmentation, tracking and cell cycle analysis of live-cell imaging data with Cell-ACDC

“…Automated approaches do not achieve the close-to-perfect accuracy required for many questions and thus still require manual inspection and correction. While tools have been previously developed for automatic lineage tree construction [13][14][15][16][17][18] they are specific for symmetrically dividing cells or require a dedicated fluorescent marker for the cell cycle stage inference.…”

Dual Channel Colocalization for Cell Cycle Analysis Using 3D Confocal Microscopy

“…cancer [1], [2]. Getting a better understanding of changes in the cell cycle before and after drug treatment is important for discovering new effective drugs.…”

Classification of cell cycle phases in 3D confocal microscopy using PCNA and chromocenter features

“…Accurate measurement of cell cycle progression is useful for understanding disease processes such as cancer and high-throughput anti-cancer drug screening studies [1,3,9,20,25]. Quantifying changes in the cell cycle phases between untreated and treated cells offer a promising screening approach for discovering active compounds for new effective drug development.…”