Our AACDS web application allows users to retrieve AACDS classifications and the relevant information of variants or variants in genes of interest. The web interface is organized into three major components:
(1) Variant query. (2) Gene query, and (3) AACDS-based genome analysis.
The search for the first two interfaces can be performed in two distinct methods: (1) single entry query, or (2) batch query. The third one, AACDS-based genome analysis, requires an input file.
Users can search for the AACDS classification of their variant of interest, by providing some search parameters.
The website outputs a variant summary page, which reports the AACDS category of the variant and its relevant information, along with any additional variant data. Note that all the deleterious and conservation scores reported here are the original scores used in their corresponding papers; i.e., we did not perform any re-scaling of the scores.
Users can retrieve a list of variants within a gene whose variants’ characteristics match the user’s interest. If a particular AACDS class is specified, the website returns all SNPs that belong to the searching AACDS category. If any of the four features (high deleterious count, has gene-trait association, has gene-disease-association, and has variant-disease association) are specified, a list of variants whose characteristics are compatible with the searching feature is returned. The summary table provides a short description (11 attributes) of the variants; users can also download the complete table (37 attributes) through the “download” button. Exported file types include .csv and .txt.
For this search feature, we aim to provide the overall statistics for a set of SNPs found in an individual’s genome. Users can perform the AACDS-based genome analysis on two levels: (1) Whole genome statistics and (2) Gene-by-gene statistics.
In either case, the schema classifies SNPs into several groups, based on the assigned AACDS classes. The results can be ranked by gene names or by AACDS groups.
Our original paper describes the AACDS as an 8-level category (variant categories 1, 2A, 2B, 3A, 3B, 4, 5, and 6). However, many SNPs cannot be exclusively defined into one class, therefore, a maximum of 12 classes are reported in this implementation to represent all distinct conditions possible when joining multiple assigned AACDS categories together; e.g. a variant can be in class 1/2B, 1/3B, or 1/2B/3B, etc.
In addition to the number of variants within each AACDS class, the tabular output also presents the average (and the standard deviation) for all six deleterious scores, three conservation scores, and two population-specific minor allele frequencies. Note that the raw scores for the first five deleterious predictors were re-scaled to [0, 1] for comparison purposes; a score closer to 1 represents a stronger (deleterious) effect of a variant. A MutationAssessor score of > 3.5 designates high functional impact, hence “deleterious”.
For each of the above analyses, a batch search is possible if users provide a .txt file (tab delimited) with the following formats:
Query by DNA coordinates
Chr:10 26781257 T A
Chr:10 26781257 T C
Chr:10 26781257 T GColumn legend:
1=chromosome
2=coordinate (hg19)
3=reference nucleotide
4=alternate nucleotideQuery by gene names or UniProt accessions
Gene:AACS 8 G S
Gene:GOT1 413 Q H
Gene:NT5C2 515 K Q
Or
Uniprot:Q8IZY2 2000 N K
Uniprot:Q86UK0 2000 T A
Uniprot:O95477 2000 L RColumn legend:
1=gene name or Uniprot accession
2=amino acid residue number (Uniprot numbering)
3=reference amino acid
4=alternate amino acid
Gene:HSD3B2 1
Gene:ABCA12 1
Gene:SH3BP2 1
Or
Uniprot:Q86V21 4
Uniprot:P01011 2B
Uniprot:Q9NY61 4Column legend:
1=gene name or Uniprot accession
2=AACDS category (1, 2A, 2B, 3A, 3B, 4, 5, or 6)
10 26781257 T A
10 26781257 T C
10 26781257 T GColumn legend:
1=chromosome
2=coordinate (hg19)
3=reference nucleotide
4=alternate nucleotide