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| CSIRO | SOLVE | Issue 7 | May 06 | |
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ARTICLE
IMAGE ANALYSIS:
Software Speeds New Drugs By Youna Angevin-Castro
Automated high-speed screening of the effects of chemical compounds on human cells could significantly accelerate development of new medicines.
In today’s fast-paced world, the capacity of industry to accelerate its processes is paramount to commercial success. This is particularly so in the otherwise long lead-times required for new pharmaceutical products. The impetus to shorten the time it takes to develop new medicines and make them available to patients has opened up a significant line of research by the Biotech Imaging Group at CSIRO Mathematical and Information Sciences (CMIS) in Sydney. Although the use of data to track trends and predict outcomes is a common practice, the high-level quantitative analytics undertaken by CSIRO – through statistical modelling and advanced data analysis – can assist companies in strategic planning and decision-making, effectively improving productivity and reducing unnecessary costs. Benefits extend across a range of business functions, from supply-chain management and financial performance through to research and development, which is where the Biotech Imaging Group is helping the pharmaceuticals industry speed up discovery processes. The group has been working on automated analysis projects to accelerate the screening of chemical compounds to test their candidacy for new drugs. The group is recognised for its expertise in image analysis: the automated extraction of quantitative information from complex images. It has developed a number of software applications for a variety of industries, based on sophisticated mathematics. Drug screening is a critical component of pharmaceutical research and development. The effects of certain compounds on human cells seen under the microscope can provide the initial evidence required to invest in further drug development. However, with a new drug costing up to $1 billion to bring to market, false leads can be extremely costly. CSIRO researcher Dr Pascal Vallotton says millions of compounds are screened by pharmaceutical companies, but only a handful will have the properties being sought. Naturally, companies are keen to quickly identify which compounds these are. Twenty years ago, the discovery of suitable compounds was quite ad hoc, with scientists using educated guesses and manual techniques to test compounds for suitable properties. Today, however, much more automation is possible with high content analysis (HCA). It allows high-speed analysis of cell preparations and the effects on cell structure and morphology. “Fifteen or 20 years ago, many compounds were discovered by chance, but this is no longer adequate,” Dr Vallotton says. The image analysis software developed by the CSIRO Biotech Imaging Group works in a similar way to someone sitting at a microscope, but does everything automatically. “The software extracts measurements from images, such as the number and length of neurites (nerve cell branches), and records changes to these features when compounds are added.” The result is a capacity to screen millions of different compounds at a very rapid rate – quickly identifying those that are potentially beneficial, and preventing unnecessary time and money being invested in inappropriate compounds. Dr Alan Finkel, former chief executive officer of Australian biotechnology instrumentation company Axon Instruments (now part of US company Molecular Devices Corporation), has worked collaboratively with the CSIRO team to develop its ImageXpress™ cellular screening system. Five years ago, Axon introduced a robotic fluorescence microscope which could take tens of thousands of images of tens of thousands of different drugs acting on cell lines so companies could streamline the process of screening compounds to identify potential candidates for further development of medicines. Automated fluorescence microscopes act by detecting DNA, proteins or membrane-bound receptors in cells that have been specifically tagged with fluorescent markers. These markers are subsequently used as reference points for identifying morphological changes in cell samples when pharmaceutical compounds are added. Although Axon had extensive experience in software and database development for this kind of application, it was less experienced in image analysis. They looked to CSIRO for expertise in this area. “In 2000, we were approached by CSIRO to explore the possibility of developing imaging software to assist the analytic capacity of our instruments,” says Dr Finkel, who is now retired from the company. “In the main, drug discovery is a process of massive testing, so any automation must be fast and robust. “Amazingly, this type of image analysis is a very easy task for the human eye. Comparatively, computers struggle badly with image processing. In this instance, we provided the CSIRO team with image sets, along with information about what the expected results should be – and from this, CSIRO scientists developed a set of image-processing algorithms that were accurate and fast, and which we successfully incorporated into our ImageXpress software.” Today, the technology is used in drug screening systems by three of the six major pharmaceutical instrument companies. Last year, German biosciences company Evotec Technologies licensed CSIRO’s software for its high-content screening toolkit. However, the benefits of image analysis are not confined to the pharmaceutical industry. Dr Vallotton says: “The technology CSIRO is developing can be used across a wide variety of applications. The benefits are very broad, and the technology is being used successfully across a number of industries, including mining, metallurgy and agribusiness.” APPLICATION Advances in automated analysis could speed up the screening of chemical compounds BENEFIT Medicines can be created more quickly, without the costs of false leads For further information contact: |
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