SPSmart: adapting population based SNP genotype databases for fast and comprehensive web access

Abstract

Background: In the last five years large online resources of human variability have appeared, notably HapMap, Perlegen and the CEPH foundation. These databases of genotypes with population information act as catalogues of human diversity, and are widely used as reference sources for population genetics studies. Although many useful conclusions may be extracted by querying databases individually, the lack of flexibility for combining data from within and between each database does not allow the calculation of key population variability statistics.

Results: We have developed a novel tool for accessing and combining large-scale genomic databases of single nucleotide polymorphisms (SNPs) in widespread use in human population genetics: SPSmart (SNPs for Population Studies). A fast pipeline creates and maintains a data mart from the most commonly accessed databases of genotypes containing population information: data is mined, summarized into the standard statistical reference indices, and stored into a relational database that currently handles as many as 4 x 10(9) genotypes and that can be easily extended to new database initiatives. We have also built a web interface to the data mart that allows the browsing of underlying data indexed by population and the combining of populations, allowing intuitive and straightforward comparison of population groups. All the information served is optimized for web display, and most of the computations are already pre-processed in the data mart to speed up the data browsing and any computational treatment requested.

Conclusion: In practice, SPSmart allows populations to be combined into user-defined groups, while multiple databases can be accessed and compared in a few simple steps from a single query. It performs the queries rapidly and gives straightforward graphical summaries of SNP population variability through visual inspection of allele frequencies outlined in standard pie-chart format. In addition, full numerical description of the data is output in statistical results panels that include common population genetics metrics such as heterozygosity, Fst and In.

Figure 1

Flowchart of processes implemented in SPSmart. The underlying SPSmart processing engine is capable of dealing with virtually any database that contains genotypes grouped by populations. Any dataset is summarized into common populational statistical indexes, and then combined with dbSNP additional information in order to improve the online data browsing experience.

Figure 2

Finding discrepancies among databases. SNP rs6824418 data from Perlegen and HapMap indicating discrepant allele frequency estimates for populations EUA and CEU (European American and CEPH European respectively).

Figure 3

Comparing similar populations in different databases. SNP rs2789823 data from Perlegen and HapMap illustrating a fixed difference SNP that shows the degree of European:African admixture in the African American population sample of Perlegen (AFA) compared to the HapMap African population: the Yoruba of Ibadan, Nigeria (YRI).

Figure 4

Inspecting a chromosome region. Using a chromosome region search to find an alternative SNP marker with improved quality flanking sequence in the same linkage disequilibrium block (rs10012227 as a better substitute for rs4698702).