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The development of novel statistical methods for strain-typing TSEs. - SE1782

This project aims to develop existing methods for the statistical analysis of spatial point and patch distributions in order to improve the techniques currently used to strain type TSEs. Parametric (model-based) and non-parametric (design-based) methods will be considered in the development of a robust and practical technique for the comparative analysis of TSE neuropathology. The work will be carried out at the Universities of Lancaster and Liverpool and the VLA, Weybridge under the supervision of Prof. Diggle and Drs French, Clough and Simmons.

Many important scientific developments in Transmissible Spongiform Encephalopathy (TSE) research have relied on inferences made from studies of strain differentiation; most notably the first studies to record the link between BSE in cattle and new variant CJD in humans. The ability to classify TSE’s into defined strain types is therefore crucial if we are to understand the epidemiology, pathology and diversity of these pathogens.

The most common method currently in use is ‘lesion profiling’, whereby the intensity and distribution of neuropathology is assessed subjectively for a number of defined areas of the brain to produce graphical representations of the ‘score’ in each area. This method was developed over 30 years ago and has a number of problems, which can be addressed using a combination of recently developed statistical techniques and state-of-the-art image analysis technology.

First, much of the subjectivity will be removed by using quantitative rather than qualitative information on the intensity (e.g. number per unit area) and spatial distribution of lesions. This will enable us to provide much more rigorous, precise and powerful methods of typing putative strains. Secondly, the methods proposed will be extended to examine the pathology identified by more recently developed techniques (e.g. PrP staining).

We propose to use material already collected at VLA, Weybridge from mice experiments and ruminant studies to characterise and describe the pathology visible using light microscopy of histological specimens.Understanding the sources of variation in pathology will then enable the development of sampling protocols and statistical methods that are practical, reliable and discriminatory. If successful, this approach could be adopted as standard for the identification and comparison of strain types.
Project Documents
• Final Report : The development of novel statistical methods for strain-typing TSEs   (188k)
Time-Scale and Cost
From: 2003

To: 2004

Cost: £147,537
Contractor / Funded Organisations
University - Liverpool
Animal Health              
Plants and Animals              
Fields of Study
Animal Health