1. How do I use this database?
HEX is designed to provide genetic variability data on a phenotypically characterized set of individuals; specifically, people who have aged without neurodegeneration. For example, a researcher may want to consult HEX if (s)he has candidate variants from a sequencing experiment in a neurodegenerative disease kindred. HEX can be used to help filter these candidate variants by looking to see if they are present in the HEX cohort, allowing for a more confident interpretation.
If a researcher finds a candidate variant in a family with early onset AD but no known causative mutation, then (s)he might look for that variant in the genome aggregation database gnomAD. If the variant is in gnomAD, one might be inclined to interpret it as benign with respect to AD. However, the variant in gnomAD could have come from a person with AD, as this information is unavailable to the researcher, or it could have come from a 30-year-old donor at high risk of developing AD in the future. Searching for the variant in HEX will allow the researcher to make this determination with greater confidence, because HEX includes only data from elderly people without evidence of neurodegenerative disease.
2. What search terms can I use?
You may search HEX in several different ways: 1) by genomic region of interest, 2) by a specific gene (using gene symbol), 3) by transcript ID, or 4) by rsID.
3. Why does the total number of alleles not add up to 936 (i.e. 468 people x 2 alleles per person)?
In some instances sequences and/or variants may not have passed quality control and for this reason have not been included in the final HEX count.
4. Why are some variants in introns? I thought exome sequencing only captured exons?
Due to the techniques used, sequence data from adjacent introns may be collected in addition to exonic regions. These regions have been included in the database because some of them have high quality data and relevant impacts on protein expression (e.g., splice sites).
5. Which genome assembly does HEX use as a reference?
HEX uses GRCh37/hg19 as the reference genome assembly.
6. What is the ethnicity/geographic origin of the samples in HEX? Does the database annotate variants with this information?
Samples originate from brain banks across the United Kingdom and the United States. All samples were reported as Caucasian. HEX does not annotate variants with ethnicity/geographic origin information.
7. How do I cite the database in my publication?
When citing this database, please use the following format: HEX Database (www.alzforum.org/exomes/hex). Alzforum. Date of Access. You may also cite the bioRχiv manuscript (Guerreiro et al., 2018).
8. How do I report a data error or bug in the database?
We welcome your feedback! Please contact us at firstname.lastname@example.org.
9. How can I see which exon my variant of interest is located in?
You may add columns to the table using the Modify Table drop down menu located in the upper right corner. Additional columns include exon, gene name, average sample read depth, and transcript ID. Columns can also be removed from the display for easier viewing.
10. Will HEX be updated?
Yes! HEX will be updated periodically as more samples/data become available.