Multiplex Cytological Profiling Assay to Measure Diverse Cellular States

Computational methods for image-based profiling are under active development, but their success hinges on assays that can capture a wide range of phenotypes. We have developed a multiplex cytological profiling assay that “paints the cell” with as many fluorescent markers as possible without compromising our ability to extract rich, quantitative profiles in high throughput. The assay detects seven major cellular components. In a pilot screen of bioactive compounds, the assay detected a range of cellular phenotypes and it clustered compounds with similar annotated protein targets or chemical structure based on cytological profiles. The results demonstrate that the assay captures subtle patterns in the combination of morphological labels, thereby detecting the effects of chemical compounds even though their targets are not stained directly. This image-based assay provides an unbiased approach to characterize compound- and disease-associated cell states to support future probe discovery

An image analysis toolbox for high-throughput C. elegans assays

We present a toolbox for high-throughput screening of image-based Caenorhabditis elegans phenotypes. The image analysis algorithms measure morphological phenotypes in individual worms and are effective for a variety of assays and imaging systems. This WormToolbox is available through the open-source CellProfiler project and enables objective scoring of whole-worm high-throughput image-based assays of C. elegans for the study of diverse biological pathways that are relevant to human disease.National Institutes of Health (U.S.) (U54 EB005149

Top-k spatial joins of probabilistic objects

Abstract — Probabilistic data have recently become popular in applications such as scientific and geospatial databases. For images and other spatial datasets, probabilistic values can capture the uncertainty in extent and class of the objects in the images. Relating one such dataset to another by spatial joins is an important operation for data management systems. We consider probabilistic spatial join (PSJ) queries, which rank the results according to a score that incorporates both the uncertainties associated with the objects and the distances between them. We present algorithms for two kinds of PSJ queries: Threshold PSJ queries, which return all pairs that score above a given threshold, and top-k PSJ queries, which return the k top-scoring pairs. For threshold PSJ queries, we propose a plane sweep algorithm that, because it exploits the special structure of the problem, runs in O(n (log n + k)) time, where n is the number of points and k is the number of results. We extend the algorithms to 2-D data and to top-k PSJ queries. To further speed up top-k PSJ queries, we develop a scheduling technique that estimates the scores at the level of blocks, then hands the blocks to the plane sweep algorithm. By finding high-scoring pairs early, the scheduling allows a large portion of the datasets to be pruned. Experiments demonstrate speed-ups of two orders of magnitude. I

Thresholding by mixture models.

<p>Mixture models derive a threshold from two density functions (one for the background, one for the foreground) fitted to the distribution of intensities in the image. Units are arbitrary. Original image from project described in Moffat et al. <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000603#pcbi.1000603-Moffat1" target="_blank">[80]</a>.</p

Speeding Up Whole-Genome Alignment by Indexing Frequency Vectors

Motivation: Many biological applications require the comparison of large genome strings. Current techniques suffer from high computational and I/O costs