1.1 --- a/grant.txt Sun Apr 12 03:39:30 2009 -0700 1.2 +++ b/grant.txt Sun Apr 12 04:01:58 2009 -0700 1.3 @@ -1,10 +1,12 @@ 1.4 == Specific aims == 1.5 1.6 -Massive new datasets obtained with techniques such as in situ hybridization (ISH) and BAC-transgenics allow the expression levels of many genes at many locations to be compared. Our goal is to develop automated methods to relate spatial variation in gene expression to anatomy. We want to find marker genes for specific anatomical regions, and also to draw new anatomical maps based on gene expression patterns. We have three specific aims: 1.7 - 1.8 -(1) develop an algorithm to screen spatial gene expression data for combinations of marker genes which selectively target anatomical regions 1.9 -(2) develop an algorithm to suggest new ways of carving up a structure into anatomical subregions, based on spatial patterns in gene expression 1.10 -(3) create a 2-D "flat map" dataset of the mouse cerebral cortex that contains a flattened version of the Allen Mouse Brain Atlas ISH data, as well as the boundaries of cortical anatomical areas. Use this dataset to validate the methods developed in (1) and (2). 1.11 +Massive new datasets obtained with techniques such as in situ hybridization (ISH) and BAC-transgenics allow the expression levels of many genes at many locations to be compared. Our goal is to develop automated methods to relate spatial variation in gene expression to anatomy. We want to find marker genes for specific anatomical regions, and also to draw new anatomical maps based on gene expression patterns. We have three specific aims:\\ 1.12 + 1.13 +(1) develop an algorithm to screen spatial gene expression data for combinations of marker genes which selectively target anatomical regions\\ 1.14 + 1.15 +(2) develop an algorithm to suggest new ways of carving up a structure into anatomical subregions, based on spatial patterns in gene expression\\ 1.16 + 1.17 +(3) create a 2-D "flat map" dataset of the mouse cerebral cortex that contains a flattened version of the Allen Mouse Brain Atlas ISH data, as well as the boundaries of cortical anatomical areas. Use this dataset to validate the methods developed in (1) and (2).\\ 1.18 1.19 In addition to validating the usefulness of the algorithms, the application of these methods to cerebral cortex will produce immediate benefits, because there are currently no known genetic markers for many cortical areas. The results of the project will support the development of new ways to selectively target cortical areas, and it will support the development of a method for identifying the cortical areal boundaries present in small tissue samples. 1.20 1.21 @@ -164,7 +166,14 @@ 1.22 \caption{Upper left: $wwc1$. Upper right: $mtif2$. Lower left: wwc1 + mtif2 (each pixel's value on the lower left is the sum of the corresponding pixels in the upper row). Within each picture, the vertical axis roughly corresponds to anterior at the top and posterior at the bottom, and the horizontal axis roughly corresponds to medial at the left and lateral at the right. The red outline is the boundary of region MO. Pixels are colored approximately according to the density of expressing cells underneath each pixel, with red meaning a lot of expression and blue meaning little.} 1.23 \end{figure} 1.24 1.25 - 1.26 +**Correlation** 1.27 +todo 1.28 + 1.29 +**Conditional entropy** 1.30 +todo 1.31 + 1.32 +**Gradient similarity** 1.33 +todo 1.34 1.35 **Geometric and pointwise scoring methods provide complementary information** 1.36 1.37 @@ -191,7 +200,8 @@ 1.38 1.39 1.40 === Aim 1 (and Aim 3) === 1.41 - 1.42 +**Forward stepwise logistic regression** 1.43 +todo 1.44 1.45 1.46 **SVM on all genes at once** 1.47 @@ -283,3 +293,6 @@ 1.48 1.49 Although there is much 2-D organization in anatomy, there are also structures whose shape is fundamentally 3-dimensional. If possible, we would like the method we develop to include a statistical test that warns the user if the assumption of 2-D structure seems to be wrong. 1.50 1.51 + 1.52 + 1.53 +todo: replace aim # bullet pts with #s