Image analysis for high-content screens
Our main research theme is quantifying and mining the rich information present in cellular images to yield biological discoveries. We work on high-throughput projects (100,000–1,000,000 images) probing a variety of biological processes and diseases of interest, with a special interest in psychiatric research, infectious disease, and cancer.
Recent projects include the identification of genetic regulators (glioblastoma differentiation, breast cancer cells' response to heregulin, meiosis) and chemical regulators (leukemic differentiation, mitochondrial function, tuberculosis infection).
Algorithms developed in my group are made readily usable by the scientific community via our user-friendly software, CellProfiler (cellprofiler.org). CellProfiler is versatile, open-source software for quantifying a variety of phenotypes in biological images. Since its release in 2005, it has become well established and widely used. CellProfiler is launched around the world more than 100,000 times annually and cited in more than 800 publications as of September 2013. The software evolves within an active research environment involving dozens of diverse image-based assays, resulting in rich functionality as we continue to improve its capabilities, interface, and support.
High-throughput imaging experiments generate extremely large, multidimensional data sets with quantifiable phenotypic information for every individual cell. We use this rich, latent information to identify patterns resulting from chemical or genetic perturbations to probe the causes and cures for various diseases. For example:
- Predicting how new chemical compounds act in cells
- Identifying and classifying toxicity of compounds destined for clinical trials
- Identifying differences in cell structure between patient cells affected by bipolar disorder or schizophrenia
- Discovering differences among histone deacetylase (HDAC) isoforms, and identifying specific inhibitors against them, which are likely useful against cancer and psychiatric disease
- Identifying gene function from large-scale genome sequencing studies
We developed the Cell Painting assay in order to carry out high-throughput morphological profiling experiments.
In co-cultured cell systems, two or more cell types are grown together in order to maintain more native physiological functions, enabling experiments that test genetic and chemical perturbations in a more realistic environment. We are developing image analysis approaches to extract information from fluorescence microscopy images of these cell systems, enabling experiments in liver regeneration and hepatotoxicity [NSF CAREER project page].
Imaging flow cytometry
Imaging flow cytometry combines the high-throughput nature of flow cytometry with the high-resolution nature of fluorescence microscopy. For each experimental sample, it yields hundreds of thousands of images of individual cells. We are developing methods to mine these large datasets [NSF project page].
Quantifying C. elegans
The worm C. elegans can be robotically prepared and imaged and is an effective model to probe a variety of biological questions that require whole animals rather than isolated cells. We are developing sorely needed C. elegans analysis algorithms and validating them in specific large-scale experiments to identify regulators of fat metabolism and pathogen infection.
Quantifying dynamic phenotypes
Many biological questions can only be investigated by collecting time-lapse movies. We are analyzing these images to identify, for example, novel cell cycle landmarks and motor protein regulators. We are also integrating this data with flow cytometry data to quantify unusual cell cycle outcomes.
Impact on human health
Our CellProfiler software has yielded discoveries in several translational projects, some of which may ultimately have a direct impact on the treatment of disease. For example, CellProfiler has been used to identify several small molecules that are effective in treating particular diseases in mouse models. In some cases, discoveries made using CellProfiler have even led to planning clinical trials in humans, which could directly improve patient outcomes [more details].