Top hits: fast first-round annotation
To address these immediate questions, WGAViewer offers a fast (around 0.5-2.0 second per SNP, depending on web and CPU speed) first-round annotation procedure.
As an illustration for this function we load the pre-annotation example dataset by clicking on menu “File->Open an example dataset” and select “Pre-annotation dataset” “CHAVI_SETPOINT_SCIENCE.wr”. Click on menu “Tools->Top hits”, an annotation dialog will present itself (Figure 3.3.1-1). In this fast annotation process, using the latest genome build and coordinates available at the time of the annotation, WGAViewer will search for any known transcripts and exons located within an adjustable upstream and downstream region. WGAViewer will also annotate each SNP for their consequence type from the following 14 categories:
ESSENTIAL_SPLICE_SITE, STOP_GAINED, STOP_LOST, FRAMESHIFT_CODING, NON_SYNONYMOUS_CODING, SPLICE_SITE, SYNONYMOUS_CODING, REGULATION_REGION, 5PRIME_UTR, 3PRIME_UTR, INTRONIC, UPSTREAM, DOWNSTREAM, INTERGENIC.
Figure 3.3.1-1. Parameters of first-round annotation for top hits.
This process is based on an annotated and updated physical location so the accuracy of the annotation can be ensured even if the MAP file, which has been used to generate the input .wr file for WGAViewer, is from an out-of-date genome build. This policy also applies for all the following annotation procedures.
Figure 3.3.1-2 shows the results of this fast first-round annotation using data on host control of HIV-1 viral load. As shown from this figure, most of the hits among the top 20 are on chromosome 6 and clustered in MHC region. The first hit, rs2395029, is non-synonymous coding in gene HCP5. The second hit, rs9264942, is classified as intergenic but only 35Kbp upstream to HLA-C gene. This first-round annotation provides a very brief but explicit insight into the top hits. But one also has the option to skip this step and directly enter into the next stage by un-checking the “Perform a brief annotation for gene context” box in Figure 3.3.1-1.
Figure 3.3.1-2. Results of first-round annotation for top hits. (Click to enlarge)
Click on the blue hyperlink of each hit will bring up a resource menu for top hits (Figure 3.3.1-3). Click on the resource entries (for example, dbSNP) to visit the webpage for the hit in the relevant public databases, or click on “Annotate” to perform individual comprehensive annotation, as we will discuss in the following section.
Figure 3.3.1-3. Resource menu for top hits
Likewise, click on the blue hyperlink of each gene will bring up a resource menu for the closest genes (Figure 3.3.1-4).
Figure 3.3.1-4. Resource menu for the closest gene