Splice AI
Overview
SpliceAI, a 32-layer deep neural network, predicts splicing from a pre-mRNA sequence.
Publication
K. Jaganathan, et al. Predicting splicing from primary sequence with deep learning. Cell, 176 (3) (2019), pp. 535-548 e24
Professional data source
This is a Professional data source and is not available freely. Please contact annotation_support@illumina.com if you would like to obtain it.
VCF File
Example
##fileformat=VCFv4.0
##assembly=GRCh37/hg19
##INFO=<ID=SYMBOL,Number=1,Type=String,Description="HGNC gene symbol">
##INFO=<ID=STRAND,Number=1,Type=String,Description="+ or - depending on whether the gene lies in the positive or negative strand">
##INFO=<ID=TYPE,Number=1,Type=String,Description="E or I depending on whether the variant position is exonic or intronic (GENCODE V24lift37 canonical annotation)">
##INFO=<ID=DIST,Number=1,Type=Integer,Description="Distance between the variant position and the closest splice site (GENCODE V24lift37 canonical annotation)">
##INFO=<ID=DS_AG,Number=1,Type=Float,Description="Delta score (acceptor gain)">
##INFO=<ID=DS_AL,Number=1,Type=Float,Description="Delta score (acceptor loss)">
##INFO=<ID=DS_DG,Number=1,Type=Float,Description="Delta score (donor gain)">
##INFO=<ID=DS_DL,Number=1,Type=Float,Description="Delta score (donor loss)">
##INFO=<ID=DP_AG,Number=1,Type=Integer,Description="Delta position (acceptor gain) relative to the variant position">
##INFO=<ID=DP_AL,Number=1,Type=Integer,Description="Delta position (acceptor loss) relative to the variant position">
##INFO=<ID=DP_DG,Number=1,Type=Integer,Description="Delta position (donor gain) relative to the variant position">
##INFO=<ID=DP_DL,Number=1,Type=Integer,Description="Delta position (donor loss) relative to the variant position">
#CHROM POS ID REF ALT QUAL FILTER INFO
10 92946 . C T . . SYMBOL=TUBB8;STRAND=-;TYPE=E;DIST=-53;DS_AG=0.0000;DS_AL=0.0000;DS_DG=0.0000;DS_DL=0.0000;DP_AG=-26;DP_AL=-10;DP_DG=3;DP_DL=35
10 92946 . C G . . SYMBOL=TUBB8;STRAND=-;TYPE=E;DIST=-53;DS_AG=0.0008;DS_AL=0.0000;DS_DG=0.0003;DS_DL=0.0000;DP_AG=34;DP_AL=-27;DP_DG=35;DP_DL=1
10 92946 . C A . . SYMBOL=TUBB8;STRAND=-;TYPE=E;DIST=-53;DS_AG=0.0004;DS_AL=0.0000;DS_DG=0.0001;DS_DL=0.0000;DP_AG=-10;DP_AL=-48;DP_DG=35;DP_DL=-21
10 92947 . A C . . SYMBOL=TUBB8;STRAND=-;TYPE=E;DIST=-54;DS_AG=0.0002;DS_AL=0.0000;DS_DG=0.0000;DS_DL=0.0000;DP_AG=-49;DP_AL=-11;DP_DG=0;DP_DL=34
10 92947 . A T . . SYMBOL=TUBB8;STRAND=-;TYPE=E;DIST=-54;DS_AG=0.0002;DS_AL=0.0000;DS_DG=0.0000;DS_DL=0.0000;DP_AG=33;DP_AL=-11;DP_DG=-22;DP_DL=34
10 92947 . A G . . SYMBOL=TUBB8;STRAND=-;TYPE=E;DIST=-54;DS_AG=0.0006;DS_AL=0.0000;DS_DG=0.0001;DS_DL=0.0000;DP_AG=33;DP_AL=-11;DP_DG=34;DP_DL=32
Parsing
From the VCF file, we're mainly interested in the following columns:
DS_AG
- Δ score (acceptor gain)DS_AL
- Δ score (acceptor loss)DS_DG
- Δ score (donor gain)DS_DL
- Δ score (donor loss)DP_AG
- Δ position (acceptor gain) relative to the variant positionDP_AL
- Δ position (acceptor loss) relative to the variant positionDP_DG
- Δ position (donor gain) relative to the variant positionDP_DL
- Δ position (donor loss) relative to the variant position
The Splice AI team suggests the following interpretation for the scores:
Range | Confidence | Pathogenicity |
---|---|---|
0 ≤ x < 0.1 | low | likely benign |
0.1 ≤ x ≤ 0.5 | medium | likely pathogenic |
x > 0.5 | high | pathogenic |
Pre-processing
Filtering
Splice AI provides a comprehensive list of entries throughout the genome. However, many of the entries have little value. I.e. observing low splice scores in intergenic regions. Not only do these extra entries require more storage, but the unused content has a negative impact on annotation speed.
As a result, Illumina Connected Annotations filters out all the values in the low confidence tier except for regions within 15 bp of nascent splice sites. For those regions, we found it useful to see if Splice AI predicted an interruption of the splicing mechanism.
Download URL
https://basespace.illumina.com/s/5u6ThOblecrh
JSON Output
"spliceAI":[
{
"hgnc":"BLCAP",
"acceptorGainDistance":-3,
"acceptorGainScore":0.3,
"donorLossDistance":7,
"donorLossScore":0.9
},
{
"hgnc":"NNAT",
"acceptorGainDistance":-1,
"acceptorGainScore":0.2,
"donorGainDistance":-2,
"donorGainScore":0.3
}
]
Field | Type | Notes |
---|---|---|
hgnc | string | HGNC gene symbol |
acceptorGainDistance | int | ± bp from current position |
acceptorGainScore | float | range: 0 - 1.0. 1 decimal place |
acceptorLossDistance | int | ± bp from current position |
acceptorLossScore | float | range: 0 - 1.0. 1 decimal place |
donorGainDistance | int | ± bp from current position |
donorGainScore | float | range: 0 - 1.0. 1 decimal place |
donorLossDistance | int | ± bp from current position |
donorLossScore | float | range: 0 - 1.0. 1 decimal place |