A new GIS Map Interface for ALFRED: the ALelle FREquency Database R. Gadagkar 1, H. Rajeevan, K.-H. Cheung 1, S. Stein, U. Soundararajan,, J. R. Kidd, A. J. Pakstis,, P. L. Miller 1 and K. K. Kidd Dept. of Genetics and 1 Center for Medical Informatics, Yale University School of Medicine, New Haven, CT, , USA.

Overview ALFRED, the ALlele FREquency Database, is a free, web-accessible, curated compilation of allele frequency data on DNA sequence polymorphisms in anthropologically defined human populations. ALFRED is supported by a grant from the U.S. National Science Foundation to be an international resource for research and teaching in physical anthropology, human population genetics, and any other field that can benefit from easy access to data that are otherwise widely dispersed in the scientific literature.

Recent updates in ALFRED : Over 38,000 frequency tables, and growing Over 450 populations with descriptions and links Over 1300 sites typed for at least one population with links to the molecular definitions. New GIS-based map interface to view populations and frequency data geographically Genotype data for selected polymorphisms. Polymorphic sites ordered by chromosomal position. Standardizing the XML representation of Single Nucleotide Polymorphism (SNP) data - Polymorphism Markup Language (PML)

ALFRED Homepage ALFRED Homepage

GIS-based Map Interface The GIS-based map interface is the newest ALFRED function that enables visualization of genetic data on polymorphism in a geographic context. It enables users to interactively select populations and retrieve data based on geographic locations and also see worldwide and regional clinical patterns of frequencies. Overview What is GIS? GIS: Geographic Information SystemGIS: Geographic Information System ALFRED uses “ArcIMS” (a GIS software package)ALFRED uses “ArcIMS” (a GIS software package) Map images are drawn in response to queriesMap images are drawn in response to queries Data corresponding to features on the image is retrieved by querying the ArcIMS GIS serviceData corresponding to features on the image is retrieved by querying the ArcIMS GIS service The new interface provides an integrated view across spatial and non-spatial data from ALFREDThe new interface provides an integrated view across spatial and non-spatial data from ALFRED

Architecture of the GIS Map Interface

Map Interface Zoom for a more detailed view Triangles represent various populations Select site, sample or population Use directional buttons to navigate the map

Selection of populations based on their location Select a group of populations (draw one or more rectangles in rectangle mode or click on one or more populations in point mode) Optionally click “Zoom In” to zoom into the overall area of interest Information corresponding to the selection is displayed in a tabular format at the bottom of the page

Display frequency data as pie charts Display frequency data at the location of the population/sample Example below displays the distribution of allele frequencies for a TaqMan (C_ _10, rs ) site Population names can be hidden for a clearer view of the pie charts

Genotypes ALFRED now displays genotype information for selected polymorphisms The symbol “G” will appear for a site-population combination when genotype numbers are available Searching with the keyword “Genotype” will retrieve the list of sites with genotype information Click on the “G” to get additional genotype information

Chromosomal Position On the locus information page, the polymorphisms are listed in order following the latest dbSNP build available from NCBI Locus symbol Chromosomal band position Ordered by chromosomal position

ALFRED Data in PML Format Population, Sample information Locus,Polymorphism,Allele information Allele frequency information

ALFRED Population Sample Information in PML Model <pml xmlns:xsi=" "Khoisan" "Khoisan" " The !Kung San are an African tribe located in Southern Africa. Today the !Kung can be found in the region of the Kalahari Desert, primarily in Angola, Namibia, and Botswana. In the literature, the !Kung San may also be known as !Kung, Zhu/twasi and Bushman to name a few...“ ALFRED Population Information ALFRED Sample Information

ALFRED Polymorphism Information in PML Model <pml xmlns:xsi=" + dbSNP rs# and url to dbSNP Allele information Polymorphism information

ALFRED Allele Frequency Information in PML Model "3" "3" + Typing method Allele frequency information for allele_id=“3493” Allele frequency information for allele_id=“3499” Typing_method_id sample_id allele_id”

The ALFRED Team Senior Faculty Kenneth K. Kidd, Ph.D., Professor of Genetics and Psychiatry (ALFRED P.I.) Perry Miller, M.D., Ph.D., Director of Center for Medical Informatics Curators Shannon Stein, B.S., Research Associate Usha Soundararajan, M.S., Research Assistant Programmers Haseena Rajeevan, Ph.D., Systems Programmer Rohit Gadagkar, M.S., Programmer Consultants Andrew J. Pakstis, Ph. D., Research Scientist Judith R. Kidd, Ph. D., Research Scientist Kei-Hoi Cheung, Ph. D., Assistant Professor Supported by the U.S. National Science Foundation