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The availability of the assembled mouse genome makes possible, for the first time, an alignment and comparison of two large vertebrate genomes. We have investigated different strategies of alignment for the subsequent analysis of conservation of genomes that are effective for different quality assemblies. These strategies were applied to the comparison of the working draft of the human genome with the Mouse Genome Sequencing Consortium assembly, as well as other intermediate mouse assemblies. Our methods are fast and the resulting alignments exhibit a high degree of sensitivity, covering more than 90 percent of known coding exons in the human genome. We have obtained such coverage while preserving specificity. With a view towards the end user, we have developed a suite of tools and websites for automatically aligning, and subsequently browsing and working with whole genome comparisons. We describe the use of these tools to identify conserved non-coding regions between the human and mouse genomes, some of which have not been identified by other methods.

Information in the cortex is thought to be represented by the joint activity of neurons. Here we describe how fundamental questions about neural representation can be cast in terms of the topological structure of population activity. A new method, based on the concept of persistent homology, is introduced and applied to the study of population activity in primary visual cortex (V1). We found that the topological structure of activity patterns when the cortex is spontaneously active is similar to those evoked by natural image stimulation and consistent with the topology of a two sphere. We discuss how this structure could emerge from the functional organization of orientation and spatial frequency maps and their mutual relationship. Our findings extend prior results on the relationship between spontaneous and evoked activity in V1 and illustrates how computational topology can help tackle elementary questions about the representation of information in the nervous system.