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Cell Painting and Morphology

Explore cell biology with broad strokes.

Overview

Cell Painting is an unbiased, image-based profiling method that is changing the process of drug discovery in the biotech and pharmaceutical industries, but it is inaccessible to smaller institutions because it requires high-content imaging, the generation of large datasets enabled by high-throughput automation, and a combination of expertise in cell biology, microscopy, automation, and data science.

Cell Painting requires a significant financial investment in order to support the needed equipment and personnel with the expertise to execute these assays. Our Cell Painting Assay Service provides customers who are interested in exploring this game-changing methodology, but are not ready to fully invest, a more gradual approach to evaluating the technology. It also provides customers who have already made the investment a viable option to contract out their work when deadlines are quickly approaching.

Cell Painting Assay

Key Benefits

  • Shorter timelines because it requires little assay design/development.
  • Straightforward assay preparation and the use of a palette of dyes reduces data variability. 
  • Highly sensitive to differences in cell phenotypes.

Key Challenges

  • Due to its high sensitivity, technical artifacts and additional noise are often and unknowingly detected as the disease profile, leading to issues downstream.
  • The amount of data curse of dimensionality’ can be difficult to overcome.
  • Can be difficult to interpret results.

Cell Painting Can Be Used Throughout Drug Discovery

Quality Control

The technique is highly sensitive to changes in phenotypes that may be useful for detecting assay instability.

Assay Development

Cell Painting can be used to discover phenotypic differences between a disease model and a healthy cell model. If differences are found, then it can potentially be used as the readout of a screening campaign.

Mechanism of Action (MOA)

Image profiles generated by Cell Painting are clustered by similarities in the phenotypic readouts. The close clustering of a novel compound with unknown MOA to that with compounds that have a known MOA suggest that they share a common or similar MOA.

How It Works

Cell Painting is an image-based, phenotypic profiling method that uses morphological features extracted from images of cells stained with a set of fluorescent dyes that llabel a generic set of cell organelles and components (see table and images below). Unlike screening, there is not a pre-defined phenotype being identified in Cell Painting; rather, it is an unbiased approach that aims to cluster similar phenotypic profiles together to attribute phenotypic fingerprints to specific conditions.

Cell Painting Table
Cell Painting Assay 2
cytochalasin comp

Feature Extraction and Clustering

Features are then extracted from each condition tested. An example of this is shown in the data shown below, where k-means clustering was used to find 9 distinct clusters with unique phenotypic profiles that could then be compared against known compounds to suggest potential MOA.

clusters

Unique Questions. Unique Solutions.