Variant Function Prediction

Question

[User 1933]

Basically, I would like to know what are some variant function/effect predictor ?

I already know SIFT and Polyphen and mutationassessor. I was curious if there is any other that I have missed.

Answer 1

[mdm-two]

Other potential candidates:

Gemini: GEMINI: integrative exploration of genetic variation and genome annotations

http://quinlanlab.org/pdf/Gemini-Quinlan-Stroke-UVA.pdf

PLoS Comput Biol. 2013 Jul;9(7):e1003153. doi: 10.1371/journal.pcbi.1003153. Epub 2013 Jul 18.

GERP (integrated in Ensembl VEP?): http://www.nature.com/ng/journal/v46/n4/full/ng.2932.html

Condel (Custom integration in Ensembl VEP) computes a weighed average of the scores (WAS) of five known computational tools aimed at classifying missense mutations as likely deleterious or likely neutral.The tools included in Condel are SIFT, Polyphen2, MAPP, LogR Pfam E-value (implemented ad hoc following the instructions at Clifford, R. J., Edmonson, M. N., Nguyen, C., and Buetow, K. H. (2004). Large-scale analysis of non-synonymous coding region single nucleotide polymorphisms. Bioinformatics 20, 1006-1014) and Mutation Assessor.

ActiveDriver - enriched protein signalling sites, domains, regulatory motifs/post-trans-modification: http://individual.utoronto.ca/reimand/ActiveDriver/

VAAST - probabilistic disease-gene finder (Variant Annotation, Analysis & Search Tool): http://www.yandell-lab.org/software/vaast.html

http://www.yandell-lab.org/software/VAAST_Users_Guide.pdf

http://genome.cshlp.org/content/early/2011/06/22/gr.123158.111.full.pdf

FunSeq - Annotation of Noncoding Variants: http://funseq.gersteinlab.org/

http://www.sciencemag.org/content/342/6154/1235587.full

SNPnexus - noncoding regulatory or conserved: http://snp-nexus.org/

http://bioinformatics.oxfordjournals.org/cgi/reprint/25/5/655

GMCC reports supporting annotations for the specified genomic region. The particular strength of the GMCC is it works in genomic space, not simply in spliced transcript space as some similar tools do. Within gene features, GMCC can report on the effects on splice site, UTR and coding regions in all isoforms affected by the mutation. Website: http://cbio.mskcc.org/gmcc

TransFIC improves the assessment of the functional impact of tumor nsSNVs by taking into account the basal tolerance of genes to high impacting functional variants in the human population.

Poster: http://bg.upf.edu/blog/2012/11/transfic-and-oncodrivefm-tools-for-the-analysis-of-cancer-sequencing-data/

Publication: http://genomemedicine.com/content/pdf/gm390.pdf

SciPhy

Home: http://www.broadinstitute.org/genome_bio/siphy/

Pub: http://bioinformatics.oxfordjournals.org/cgi/content/full/25/12/i54

Docs: http://www.broadinstitute.org/genome_bio/siphy/documentation.html

Pathogenic-or-Not-Pipeline (PON-P): http://bioinf.uta.fi/PON-P/

http://onlinelibrary.wiley.com/doi/10.1002/humu.22102/abstract

[abhishekniroula7]

PON-P server has been shut down. A new version PON-P2 is now available http://structure.bmc.lu.se/PON-P2/.

Answer 2

[Emily]

You're looking for a variant effect predictor? I would suggest the Variant Effect Predictor.

[User 1933]

that is same as SIFT and Polyphen 2

[Emily]

Yes, those are available options.

Answer 3

[Jorge Amigo]

as a good starting point, you may find ANNOVAR's list of functional annotations very interesting: SIFT, PolyPhen, PhyloP, LRT, MutationTaster, MutationAssessor, FATHMM, SiPhy, GERP++, MetaSVM and MetaLR, and the recently published CADD C score.

Answer 4

[Pablo]

You can use most of the annotations proposed at the same time with SnpEff/SnpSift + dbNSFP

http://snpeff.sourceforge.net/SnpSift.html#dbNSFP

You have the following scores form dbNSFP:

$ zcat dbNSFP2.4.txt.gz | head -n 1 | tr "\t" "\n"
...
SLR_test_statistic 
codonpos
fold-degenerate
Ancestral_allele
Ensembl_geneid
Ensembl_transcriptid
aapos
aapos_SIFT
aapos_FATHMM
SIFT_score
SIFT_converted_rankscore
SIFT_pred
Polyphen2_HDIV_score
Polyphen2_HDIV_rankscore
Polyphen2_HDIV_pred
Polyphen2_HVAR_score
Polyphen2_HVAR_rankscore
Polyphen2_HVAR_pred
LRT_score
LRT_converted_rankscore
LRT_pred
MutationTaster_score
MutationTaster_converted_rankscore
MutationTaster_pred
MutationAssessor_score
MutationAssessor_rankscore
MutationAssessor_pred
FATHMM_score
FATHMM_rankscore
FATHMM_pred
RadialSVM_score
RadialSVM_rankscore
RadialSVM_pred
LR_score
LR_rankscore
LR_pred
Reliability_index
CADD_raw
CADD_raw_rankscore
CADD_phred
GERP++_NR
GERP++_RS
GERP++_RS_rankscore
phyloP46way_primate
phyloP46way_primate_rankscore
phyloP46way_placental
phyloP46way_placental_rankscore
phyloP100way_vertebrate
phyloP100way_vertebrate_rankscore
phastCons46way_primate
phastCons46way_primate_rankscore
phastCons46way_placental
phastCons46way_placental_rankscore
phastCons100way_vertebrate
phastCons100way_vertebrate_rankscore
SiPhy_29way_pi
SiPhy_29way_logOdds
SiPhy_29way_logOdds_rankscore
LRT_Omega
UniSNP_ids
1000Gp1_AC
1000Gp1_AF
1000Gp1_AFR_AC
1000Gp1_AFR_AF
1000Gp1_EUR_AC
1000Gp1_EUR_AF
1000Gp1_AMR_AC
1000Gp1_AMR_AF
1000Gp1_ASN_AC
1000Gp1_ASN_AF
ESP6500_AA_AF
ESP6500_EA_AF

Answer 5

[Naga]

You can also use MutationTaster and Provean

[User 1933]

seems they don't work with hg19 - but thank you in any case

[Naga]

GRCh37 and h19 are same. So, PROVEAN should work.

Answer 6

[christopher medway]

I am going to throw HaploReg into the ring. It is a great tool to explore the potential effects of non-coding variants.

[le.marcorin]

I am using Haploreg to study some non-coding regions but I 'm having problems understanding those values in the 'Regulatory motifs altered' area in the end of the page. Could you help me? I already read the paper from Kheradpour and Kellis, 2013, but it didn't help

Answer 7

[Noushin N]

you can also use bioinformatics tools CHASM and VEST via CRAVAT webserver: http://www.cravat.us