Description
The gnomAD Proportion Expression Across Transcript Scores (pext) (pext) track set displays isoform expression levels across 53
tissues, based on 11,706 tissue samples from the Genotype Tissue Expression (GTEx) v7 dataset.
The gnomAD pext tracks provide a comprehensive view of the expression of exons across a
gene using the proportion expression across transcripts, or pext metric, a
transcript-level annotation metric that quantifies isoform expression for variants. This metric
was calculated by annotating each variant with the expression of all possible consequences across
all transcripts for each tissue and normalizing the expression of the annotation to the total
expression of the gene, which can be interpreted as a measure of the proportion of the total
transcriptional output from a gene that would be affected by the variant annotation in question.
Each of the subtracks shows the pext metric for a specific tissue, except the gnomAD
pext Mean Proportion subtrack that shows the average pext metrics calculated from the 53 GTEx
tissues.
Display Conventions and Configuration
The pext graphs display the mean expression at each base position for protein-coding (CDS) regions.
While UTRs do have expression in transcriptome datasets, this information is not included
for the visualization. The details page shows calculated sample percentages for the range of
sequence within the browser window.
Methods
The pext values are derived from isoform quantifications using the RSEM tool. Detailed information about
development and commands to create these files can be found here. Pext values were downloaded
from the gnomAD website
and transformed into bigWigs, one per tissue. For the full list of UCSC specific steps, please
see the "gnomAD PEXT scores" section of the
hg19 makedoc from our GitHub repository.
Note that isoform quantification tools can be imprecise, especially for longer genes with many
annotated isoforms. Regions with low pext values might be enriched for annotation errors (ie. there
may be edge cases for which an exon that is established to be critical for gene function may appear
unexpressed with pext). Also note that the GTEx dataset is postmortem adult tissue, and thus
the possibility that an exon may be development-specific or may be expressed in tissues not
represented in GTEx can not be dismissed.
Data Access
The raw data can be explored interactively with the Table Browser, or
the Data Integrator. For automated access, this track, like all
others, is available via our API.
The data can also be found directly from the gnomAD downloads page.
Please refer to our
mailing list archives
for questions and example queries, or our
Data Access FAQ
for more information.
More information about using and understanding the gnomAD data can be found in the
gnomAD FAQ site.
Credits
Thanks to the Genome Aggregation
Database Consortium for making these data available, Nick Watts for developing this track on
the gnomAD Browser, and Anna Benet-Pagès and Chris Lee for building this track on the UCSC Genome
Browser. The data are released under the ODC Open Database License
(ODbL) as described here.
References
Lek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E, Fennell T, O'Donnell-Luria AH, Ware JS, Hill
AJ, Cummings BB et al.
Analysis of protein-coding genetic variation in 60,706 humans.
Nature. 2016 Aug 18;536(7616):285-91.
PMID: 27535533; PMC: PMC5018207
Karczewski KJ, Francioli LC, Tiao G, Cummings BB, Alföldi J, Wang Q, Collins RL, Laricchia KM,
Ganna A, Birnbaum DP et al.
The mutational constraint spectrum quantified from variation in 141,456 humans.
Nature. 2020 May;581(7809):434-443.
PMID: 32461654; PMC: PMC7334197
Collins RL, Brand H, Karczewski KJ, Zhao X, Alföldi J, Francioli LC, Khera AV, Lowther C,
Gauthier LD, Wang H et al.
A structural variation reference for medical and population genetics.
Nature. 2020 May;581(7809):444-451.
PMID: 32461652; PMC: PMC7334194
Cummings BB, Karczewski KJ, Kosmicki JA, Seaby EG, Watts NA, Singer-Berk M, Mudge JM, Karjalainen J,
Satterstrom FK, O'Donnell-Luria AH et al.
Transcript expression-aware annotation improves rare variant interpretation.
Nature. 2020 May;581(7809):452-458.
PMID: 32461655; PMC: PMC7334198
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