Using mathematical modelling to optimise work flow in the Sanger Mouse Genetics Project

A problem presented at the UK MMSG NC3Rs Study Group 2013.

Presented by:
Mr James Bussell (Research Support Facility, Wellcome Trust Sanger Institute)
Dr Chris Lelliott (Mouse Genetics Project, Wellcome Trust Sanger Institute)
Ms Jennifer Salisbury (Research Support Facility, The Wellcome Trust Sanger Institute)
Dr Jacqui White (Phenotyping, Wellcome Trust Sanger Institute)
N Bussell, CJ Lelliott, S Naire, JS Salisbury, J Tindall, H Wardle-Jones, K White

Problem Description

In recent years, the generation and phenotypic analysis of genetically modified mice was been increasing at breakneck pace around the world. Allied to this, a number of consortia operating under the banner of the International Mouse Phenotyping Consortium (IMPC) have the goal to produce and phenotype mice with null alleles for all coding genes (Ayadi et al. 2012; Ramirez-Solis et al. 2012). The Sanger Mouse Genetics Project (MGP) is one of the world leaders in this field and operates well established large-scale and high-throughput screening (HTS) pipeline for the generation, expansion, phenotyping and export of colonies of genetically-modified mice. This entails the coordination of several steps and teams to enable the delivery of mice for downstream applications. So far the MGP has phenotyped over 500 lines of mice and generated and exported many more, making it one of the largest non-commercial mouse breeding facilities in the UK. Due to the complexity and scale of the project, inefficiencies exist in our processes which will increase the number of surplus mice, extend the transit time of colonies through the pipeline and result in the suboptimal use of space within the facility.

We have already refined data generation and analysis to maximize the value of results from the animals used in our pipeline (Karp et al. 2012). To our knowledge however, mathematical modelling has not been applied to the workflows of biological in vivo HTS projects, presumably due to the intrinsic variability of model organisms. Optimization of the pipeline will generate significant benefits from the 3Rs perspective, as well as improving resource usage and distribution. Given the global scale of phenotyping efforts and the increasing use of high-throughput animal screens, lessons learned from the optimisation process for the MGP will have wide-ranging benefits for animal usage and welfare around the world.

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Study Group Report

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