Towards Quantitative Spatio-Temporal Gene Expression Measurements in Mice

Abstract

In this project we tried to answer the question whether it is possible to obtain in vivo quantitative spatiotemporal gene expression data of mice, by making use of the GFP protein and Biofluorence Imaging. The research was driven by a more specific question, being whether it is possible to detect if metastasis to the bone has occurred in cancer progression studies, using GFP cancel cell lines, i.e cancer cells that produce Green Fluorescent Proteins (GFP), at a continuous known rate. We tried to give generic answers by researching the following two subquestions. 1.) Is it possible to register a 3D mouse atlas to 2D Bioluminescense or Fluorescence photographs, based on only those photographs? 2.) Can we make qualitative statements on the location of gene expression, after registration with an atlas? The first question is covered in a paper called: 'Atlas Driven Registration of 3D Voxel Data to Multi-view Photographs Based on 3D Distance Maps.' It explains a method to register a 3D piecewise deformable mouse atlas to 2 or more photographic sideviews of a mouse. Based on a distance map that we generated from multiple backprojections of the sideview, we were able to construct an energy function that resembled a 'goodness of fit' of the registration. Comparisons were made with a gold standard and we obtained good results with our method. The second question is covered in a paper called: 'Testing for Spatial Gene Enrichment in C. Elegans Using Chronograms and a 1D Worm Atlas'. In this paper we did not focus on the registration process, because this was a straightforward procedure. With an atlas registered to an expression dataset, we applied different statistical tests to answer the question that given the atlas and the expression profile, the observed expression shows enrichment in a selected organ or not. In this paper we show that we are able to filter highly enriched signals out of our complete dataset. We further discuss the added value of our atlas since it is difficult to validate the obtained results of our tests.