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Combining HT-RNAi or Compound Screens with High Content Assays
Richer Datasets Offer Higher Patho-Physiological Relevance
Ever since starting its landmark time lapse video-microscopy screen for
cell division genes in C. elegans (Gönczy et al.,
2000, Nature 408:331; Sönnichsen et
al.,
2005, Nature
434: 462), Cenix
has led the industry in applying the principles of high content (HC)
biology
to HT-RNAi in systems from worms to human cells.
Until recently, large scale studies, whether they were screens of
compound libraries or genomes, favored the use of single parameter
readouts such as those enabled by conventional plate readers.
This
choice reflected both the industry's widespread emphasis on maximizing
analysis
throughputs, and the limited availability of readout technologies
allowing the long-sought combination of high throughput (HT) with high
content (HC).
In fact, this limitation has begun to fade in recent years, as HT/HC
readout instrumentation has shown significant progress. Beyond several
emerging technologies enabling multiplexed homogeneous assays, Cenix
has particularly focused its efforts on the development and HT/HC
application of automated microscopy-based assays. Indeed, since
this approach allows the mining of subcellular localisation data and
other in situ information, it
arguably offers the strongest, widest potential for rich,
multi-parameter analyses. Such advanced capabilities require an optimal
combination of cutting-edge microscopy hardware for fast, yet flawless
image acquisition, with sofisticated computing hardware and software
for HT data management, storage and automated image analysis.
The task of accurately converting complex microscopy images
into a series of quantitative numeric measurements is particularly
challenging and represents one of the most active areas of new
technology development today. For this reason, Cenix has complemented
its own strengths in high performance computing and bio-informatics by
exploring a wide range of specialized third party solutions, both
academic and commercial, to secure the broadest, most powerful
capabilities in this area.
 As a result, Cenix
has partnered with Munich-based Definiens
AG to
integrate its Definiens XD™ image analysis technology into Cenix's
HT/HC-RNAi research offerings. Based on Definiens Cognition Network
Technology
developed originally
for satellite imagery, Definiens XD™ offers a very wide range of
object-oriented analysis methods to build fully-customizable algorithms
applicable to microscopy images, overcoming many limitations common to
most other packages which use pixel-based paradigms.
With these tools and capabilities in place, Cenix can offer cutting
edge capabilities for the development and implementation of
multiplexed cell-based assays allowing multi-parameter
analyses within single screening runs.
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