The core dataset represented in the ALSKP is the largest exome based ALS case/control study to date (Farhan et al., 2018), with 3,864 ALS cases and 7,839 ethnically matched controls. Gene burden testing was used to discover associations of genes with ALS. Using the ALSKP, you can browse these gene-level scores using the “View gene-level associations” search on the home page. The resulting plot shows gene scores plotted by chromosomal location of the gene. The plot may be filtered to show scores based on missense or protein-truncating mutations. Mousing over a point displays the p-value for a gene, and the top genes are also listed in a table below the plot.
|Genome-wide gene-level ALS associations in the ALS Knowledge Portal|
To see full details on variant associations within a gene, click on a gene name in the table, or search for a gene or chromosomal region using the home page search “Explore data on a gene or region”. The resulting table lists all variants found within the gene or region in the ALS exome case-control 2018 study along with their impacts as predicted by the PolyPhen, SIFT, and CADD-Phred algorithms, their minor allele frequencies and allele counts in homozygous and heterozygous cases and controls in the ALS study, and, for comparison, their allele counts and frequencies in the gnomAD databases of exome and whole genome sequences.
ALSKP also offers the Variant Finder tool, which allows you to search the ALS exome case-control 2018 dataset as well as two other ALS GWAS datasets and GWAS studies for psychiatric disorders (described on the ALSKP Data page) for variants that meet specific criteria, such as specified ranges of p-value, odds ratio, allele count, or allele frequency.
The ALSKP is constructed on a software architecture originally developed for the Type 2 Diabetes Knowledge Portal (T2DKP). Since building the T2DKP, we have expanded this architecture in partnership with three other research communities in the cardiometabolic disease space to create Knowledge Portals for cerebrovascular disease (CDKP), cardiovascular disease (CDVKP), and sleep disorders (SDKP). Now, in collaboration with Dr. Sali Farhan of the Neale lab, this platform has been extended into the neurodegenerative disease space with the creation of ALSKP.
We welcome all suggestions, comments, questions, and submission of relevant datasets for the ALSKP. Please contact us at firstname.lastname@example.org!