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C ritical Assessment of Genome Interpretation

Annotate all missense

Challenge: Annotate all missense

Dataset description: public

Variant data: public

Dataset availability: public

Last updated: 7 May 2018

This challenge will tentatively close at 8:00 PM PST (Pacific Standard Time) on 9 May 2018.

Download answer key and predictions: registered users only, limited by CAGI Data Use Agreement. The answer key and predictions are accessible to registered users only, and their use is limited by the CAGI Data Use agreement . Please log in to access the file.

Presentations from the CAGI 5 conference: registered users only, limited by CAGI Data Use Agreement. Presentations are accessible to registered users only, and their use is limited by the CAGI Data Use Agreement. Please log in to access the file.

Summary

dbNSFP describes 81,084,849 possible protein-altering variants in the human genome. The challenge is to predict the functional effect of every such variant. For the vast majority of these missense and nonsense variants, the functional impact is not currently known, but experimental and clinical evidence are accruing rapidly. Rather than drawing upon a single discrete dataset as typical with CAGI, predictions will be assessed by comparing with experimental or clinical annotations made available after the prediction submission date, on an ongoing basis. If predictors assent, predictions will also incorporated into dbNSFP.

Background

Currently, dozens of in silico methods for predicting the deleteriousness of a variant are available. In many cases, different methods may give opposite predictions for the same variant. dbNSFP is a database of human nonsynonymous single nucleotide variants (nsSNVs) and their functional predictions and annotations (Liu et al., 2011, 2013; Liu et al., 2016). It compiles 20 functional prediction scores and 6 conservation scores, as well as other related information including allele frequencies observed in different large datasets, various gene IDs from different databases, functional descriptions of genes, gene expression and gene interaction information.

Prediction challenge

A list of all possible nsSNVs based on the human reference sequence was created from dbNSFP (Liu et al., 2011, 2013; Liu et al., 2016). Predictors are asked to predict the functional effect predict each coding SNV.

Since the vast majority of these nsSNVs do not have experimental information, this challenge will assess in silico predictions with new experimental or clinical annotations as they appear in literature or databases. We anticipate making evaluations at the time of each CAGI experiment, approximately once a year.

Test File Format

chr: Chromosome number
pos(1-based): Physical position on the chromosome as to hg38 (1-based coordinate). For mitochondrial SNV, this position refers to the rCRS (GenBank: NC_012920).
Ref: Reference nucleotide allele (as on the + strand)
Alt: Alternative nucleotide allele (as on the + strand)
aaref: Reference amino acid. "X" if the variant is a stop-loss
aaalt: Alternative amino acid. "X" if the variant is a stop-gain
hg19_chr: Chromosome as to hg19, "." means missing
hg19_pos(1-based): Physical position on the chromosome as to hg19 (1-based coordinate). For mitochondrial SNV, this position refers to a YRI sequence (GenBank: AF347015)
hg18_chr: Chromosome as to hg18, "." means missing 1
hg18_pos(1-based): Physical position on the chromosome as to hg18 (1-based coordinate). For mitochondrial SNV, this position refers to a YRI sequence (GenBank: AF347015)
Genename: Gene name; if the nsSNV can be assigned to multiple genes, gene names are separated by ";"
Cds_strand: Coding sequence (CDS) strand (+ or -)
Refcodon: Reference codon
Codonpos: Position on the codon (1, 2 or 3)
Ensembl_geneid: Ensembl gene id
Ensembl_transcriptid: Ensembl transcript ids (Multiple entries separated by ";")
Ensembl_proteinid: Ensembl protein ids. Multiple entries separated by ";", corresponding to Ensembl_transcriptids
AA: Amino acid position with respect to protein. Multiple entires separated by “;”, corresponding to Ensembl proteinid.

Prediction submission format

The prediction submission is a tab-delimited text file. Organizers provide a file template, which should be used for submission. In addition, a validation script is provided, and predictors should check the correctness of the format before submitting their predictions.

In the submitted file, each row must include the following tab-separated fields:

chr: chromosome number
pos(1-based): physical position on the chromosome as to hg38 (1-based coordinate). For mitochondrial SNV, this position refers to the rCRS (GenBank: NC_012920).
ref: reference nucleotide allele (as on the + strand)
alt: alternative nucleotide allele (as on the + strand)
Prediction Score: Annotation score for each SNV from 0 (benign) to 1 (deleterious)
SD: standard deviation of the prediction in column 5 indicating confidence
Pred: Based on the score in column 19, indicate whether the SNV is "D(amaging)" , "T(olerated)" or "U(known)"
Comments: optional brief comment on the basis of the prediction in column

In the file, cells in columns 5-8 are marked with a "*". Submit your predictions by replacing the "*" with your value. No empty cells are allowed in the submission. You must submit predictions and standard deviation for all the variants; if you are not confident in a prediction for a variant, enter an appropriate large standard error for the prediction. Optionally, enter a brief comment on the basis of the prediction. If you do not enter a comment on a prediction, leave the "*" in those cells. Please make sure you follow the submission guidelines strictly.

In addition, your submission must include a detailed description of the method used to make the predictions, similar in style to the Methods section in a scientific article. This information will be submitted as a separate file.

If predictors assent, predictions will also be incorporated into dbNSFP. This must be explicitly specified in the document describing the method.

Given the large file that needs to be submitted for this challenge, submit your predictions and detailed description of the method by dropping the appropriate files into the Box upload widget on this page. The file submitted will go into a write-only folder for this challenge. Please name the files with group ID, submission ID and the date.

Submit File to Annotate all missense Challenge CAGI5 Submission Folder (disabled)

References

Liu X, Jian X, Boerwinkle E. 2011. dbNSFP: A lightweight database of human nonsynonymous snps and their functional predictions. Hum Mutat 32:894-899. PMCID:PMC3145015. doi:10.1002/humu.21517

Liu X, Jian X, Boerwinkle E. 2013. dbNSFP v2.0: A database of human non-synonymous SNVs and their functional predictions and annotations. Hum Mutat 34:E2393-2402. PMCID:PMC4109890. doi:10.1002/humu.22376

Liu X, Wu C, Li C, Boerwinkle E. 2016. dbNSFP v3.0: A one-stop database of functional predictions and annotations for human nonsynonymous and splice-site SNVs. Hum Mutat 37:235-241. PMCID:PMC4752381. doi:10.1002/humu.22932

Download dataset

Devided by chromosomes: 5-dbNSFP3.4a_per_chr.zip (633.79 MB)

All chromosomes in one file: dbNSFP3.4a_all_variant_subset.zip (633.79 MB)

Download submission template extract: This submission validation script is available only to registered users. Please log in to access the file.

Download submission validation script: This submission validation script is available only to registered users. Please log in to access the file.

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