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INTRODUCTION
Comparing genomic sequences across related species is a fruitful source of biological insight. Functional elements such as exons tend to exhibit significant sequence similarity due to purifying selection, whereas regions that are not functional tend to be neutrally evolving and thus less conserved. The first step in comparing genomic sequences is to align them--to map the letters of the sequences to each other. After an alignment is computed, visualization frameworks become essential to enable users to interact with the sequence and conservation data, especially in the context of longer DNA sequences or whole genomes. Visualization frameworks should be easy to understand by a biologist and provide insight into the mutations that a particular genomic locus has undergone.
The VISTA portal is a comprehensive comparative genomics resource that provides biomedical scientists with a single unified framework to generate and download multiple sequence alignments, visualize the results in the context of existing annotations and analyze comparative results in search for important sequence signals in alignments. The VISTA suite of programs has been in development and continued use since 2000 (1-4). It was originally developed for the alignment and comparative analysis of long genomic sequences and later was expanded to pair-wise and multiple alignment of vertebrate genomes. VISTA has popularized the visualization of the level of conservation in the format of a continuous curve based on the conservation in a sliding window. This concept proved to be extremely successful due to the easy interpretation of the resulting plots.
VISTA was built through a close collaboration between computational and biological scientists, resulting in a product that is robust, efficient and powerful, yet simple to use for a person without extensive computer experience, as is illustrated by more than 1000 citations to the various VISTA-associated tools (according to http://scholar.google.com).
In the last 2 years the VISTA portal has seen many significant improvements. In addition to updating the whole genome alignments, computed using recent assemblies of vertebrate, insect, plant and microbial genomes, we have added significant new functionality and resources to the Genome Browser and other tools, including: 
A novel multiple whole genome alignment algorithm.
A new server for whole-genome alignment of bacterial genomes.
Base-pair level visualization ability within the VISTA browser.
Visual access to the results of the prediction of potential deleteriousness of non-synonymous Single Nucleotide Polymorphisms (SNPs) by the algorithm PolyPhen (5).
A novel conservation track, Rank-VISTA, to show the statistical significance of conserved regions computed by the Gumby algorithm (6).
Whole-genome rVISTA, that allows for evaluation of which conserved transcription factor binding sites (TFBS) are over-represented in a group of genes.
