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Quantitative Biology

ISSN 2095-4689

ISSN 2095-4697(Online)

CN 10-1028/TM

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Quant. Biol.    2013, Vol. 1 Issue (1) : 91-100    https://doi.org/10.1007/s40484-013-0011-5
REVIEW
Computational neuroanatomy and co-expression of genes in the adult mouse brain, analysis tools for the Allen Brain Atlas
Pascal Grange1,1(), Michael Hawrylycz2, and Partha P. Mitra1
1. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, NY 11724, USA
2. Allen Institute for Brain Science, Washington, WA 98103, USA
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Abstract

We review quantitative methods and software developed to analyze genome-scale, brain-wide spatially-mapped gene-expression data. We expose new methods based on the underlying high-dimensional geometry of voxel space and gene space, and on simulations of the distribution of co-expression networks of a given size. We apply them to the Allen Atlas of the adult mouse brain, and to the co-expression network of a set of genes related to nicotine addiction retrieved from the NicSNP database. The computational methods are implemented in BrainGeneExpressionAnalysis (BGEA), a Matlab toolbox available for download.
Corresponding Author(s): Pascal Grange   
Issue Date: 05 March 2013
 Cite this article:   
Pascal Grange,Michael Hawrylycz,and Partha P. Mitra. Computational neuroanatomy and co-expression of genes in the adult mouse brain, analysis tools for the Allen Brain Atlas[J]. Quant. Biol., 2013, 1(1): 91-100.
 URL:  
https://academic.hep.com.cn/qb/EN/10.1007/s40484-013-0011-5
https://academic.hep.com.cn/qb/EN/Y2013/V1/I1/91
Fig.1  Caption. Monte Carlo analysis of the graph underlying the co-expression matrix of 288 genes from the NicSNP database. Average and maximum size of connected components as a function of the threshold on co-expression.
Fig.2  Caption. The flowchart of computational analysis of the collective neuroanatomical properties of a set of genes in the BrainGeneExpressionAnalysis toolbox. The steps marked as random extractions and computations are described in supplementary materials S2 and S3.
Fig.3  Caption. A toy model with 9 genes, and only three distinct values of co-expression, 0, 0.6 and 0.9, for simplicity. Before any thresholding procedure is applied (on the left-hand side of the figure), there is one connected component. The average and maximum size of connected components are both 9. The graph on the right-hand side is obtained by a thresholding procedure at a threshold of 0.6. There are three connected components, the maximal size is 4, and the average size is 3.
Fig.4  Caption. One of the connected components of the co-expression network, at co-expression threshold 0.9. It is better-fitted to the striatum (STR) than more than 99% of the set of three genes drawn from the coronal Allen Atlas of the adult mouse brain. The symbols for other brain regions read as follows: Basic= ‘basic cell groups’, CTX= cortex, OLF= olfactory areas, HIP= hippocampal region, RHP= retrohippocampal region, PAL= pallidum, TH= thalamus, HY= hypothalamus, MB= midbrain, P= pons, MY= medulla, CB= cerebellum.
Fig.5  Caption. Sorted correlation coefficients between expression energies evaluated from sagittal and coronal sections in the left hemisphere of the mouse brain.
Fig.6  Caption. (A) Sorted elements of the upper-diagonal part of the co-expression matrix of the coronal atlas, Catlas.

(B) Maximal-intensity projection of the expression energy of Atp6v0c.

(C) Maximal-intensity projection of the expression energy of Atp2a2. The pair of genes (Atp6v0c, Atp2a2) has the highest co-expression in the coronal atlas, 0.9781.

Fig.7  Caption Cumulative distribution function of the upper-diagonal entries of the co-expression matrix of 288 genes (the special co-expression network Cset of the flowchart of Figure 1) from the NicSNP database, for which mouse orthologs are found in the Allen Atlas of the adult mouse brain. As the red curve (or CDFset) sits above the simulated average of the simulated mean of CDFs (or<CDF>) of co-expression networks of 288 genes, at low values of the threshold, the special set as a whole appears to be less co-expressed than expected by chance.
Fig.8  Caption. Monte Carlo analysis of the graph underlying the co-expression matrix of 288 genes from the NicSNP database. Estimated probabilities for the average and maximum size of connected components to be larger than in random sets of genes of the same size.
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