This is the reverse of what is asked in http://biostar.stackexchange.com/questions/6297/genomic-change-to-aa-change
I have a list of Gene names and related amino acid changes that I am looking for and would like to know the genomic co-ordinates of the SNP locations causing these. What is the best way to get to this?
I wrote a tool named backlocate for this job .
This tool is available in my experimental package http://code.google.com/p/variationtoolkit/.
example:
echo -e "NOTCH2\tM1T\nEIF4G1\tD240Y" |\
backlocate -f /path/to/hg19.fa
#User.Gene AA1 petide.pos.1 AA2 knownGene.name knownGene.strand knownGene.AA index0.in.rna codon base.in.rna chromosome index0.in.genomic exon
##uc001eik.2
NOTCH2 M 1 T uc001eik.2 - M 0 ATG A chr1 120612019 Exon 1
NOTCH2 M 1 T uc001eik.2 - M 1 ATG T chr1 120612018 Exon 1
NOTCH2 M 1 T uc001eik.2 - M 2 ATG G chr1 120612017 Exon 1
##uc001eil.2
NOTCH2 M 1 T uc001eil.2 - M 0 ATG A chr1 120612019 Exon 1
NOTCH2 M 1 T uc001eil.2 - M 1 ATG T chr1 120612018 Exon 1
NOTCH2 M 1 T uc001eil.2 - M 2 ATG G chr1 120612017 Exon 1
##uc001eim.3
NOTCH2 M 1 T uc001eim.3 - M 0 ATG A chr1 120548116 Exon 2
NOTCH2 M 1 T uc001eim.3 - M 1 ATG T chr1 120548115 Exon 2
NOTCH2 M 1 T uc001eim.3 - M 2 ATG G chr1 120548114 Exon 2
##Warning ref aminod acid for uc003fnp.2 [240] is not the same (I/D)
EIF4G1 D 240 Y uc003fnp.2 + I 717 ATC A chr3 184039089 Exon 10
EIF4G1 D 240 Y uc003fnp.2 + I 718 ATC T chr3 184039090 Exon 10
EIF4G1 D 240 Y uc003fnp.2 + I 719 ATC C chr3 184039091 Exon 10
##Warning ref aminod acid for uc003fnu.3 [240] is not the same (I/D)
EIF4G1 D 240 Y uc003fnu.3 + I 717 ATC A chr3 184039089 Exon 9
EIF4G1 D 240 Y uc003fnu.3 + I 718 ATC T chr3 184039090 Exon 9
EIF4G1 D 240 Y uc003fnu.3 + I 719 ATC C chr3 184039091 Exon 9
##Warning ref aminod acid for uc003fnq.2 [240] is not the same (V/D)
EIF4G1 D 240 Y uc003fnq.2 + V 717 GTA G chr3 184039350 Exon 7
EIF4G1 D 240 Y uc003fnq.2 + V 718 GTA T chr3 184039351 Exon 7
EIF4G1 D 240 Y uc003fnq.2 + V 719 GTA A chr3 184039352 Exon 7
##Warning ref aminod acid for uc003fnr.2 [240] is not the same (L/D)
EIF4G1 D 240 Y uc003fnr.2 + L 717 CTC C chr3 184039581 Exon 6
EIF4G1 D 240 Y uc003fnr.2 + L 718 CTC T chr3 184039582 Exon 6
EIF4G1 D 240 Y uc003fnr.2 + L 719 CTC C chr3 184039583 Exon 6
##Warning ref aminod acid for uc003fny.3 [240] is not the same (T/D)
EIF4G1 D 240 Y uc003fny.3 + T 717 ACC A chr3 184039677 Exon 3
EIF4G1 D 240 Y uc003fny.3 + T 718 ACC C chr3 184039678 Exon 3
EIF4G1 D 240 Y uc003fny.3 + T 719 ACC C chr3 184039679 Exon 3
##uc010hxx.2
EIF4G1 D 240 Y uc010hxx.2 + D 717 GAT G chr3 184038780 Exon 10
EIF4G1 D 240 Y uc010hxx.2 + D 718 GAT A chr3 184039069 Exon 11
EIF4G1 D 240 Y uc010hxx.2 + D 719 GAT T chr3 184039070 Exon 11
##Warning ref aminod acid for uc003fns.2 [240] is not the same (L/D)
EIF4G1 D 240 Y uc003fns.2 + L 717 CTC C chr3 184039209 Exon 10
EIF4G1 D 240 Y uc003fns.2 + L 718 CTC T chr3 184039210 Exon 10
EIF4G1 D 240 Y uc003fns.2 + L 719 CTC C chr3 184039211 Exon 10
Hi Pierre,
Is this tool still available on the link you have pointed out? I could not download anything following this "How to Install the Variation toolkit" (https://code.google.com/p/variationtoolkit/wiki/HowToInstall) instructions. I need to use your backlocate tool. Thanks!
To anyone who is still trying to use this, best thing I could do to get this to compile was to follow the instructions here: https://github.com/lindenb/jvarkit/wiki/BackLocate (use standalone=yes instruction) Worked on my macOS Sierra, and on CentOS.
http://bioinformatics.mdanderson.org/main/Transvar
Introduction
TransVar is a reverse annotator for inferring genomic characterization(s) of mutations (e.g., chr3:178936091 G/A) from protein or cDNA annotation(s) (e.g., PIK3CA p.E545K or PIK3CA c.1633G>A). It is designed for resolving ambiguous mutation origins, arising from alternative splicing.
TransVar has the following features:
Citation: Zhou W, Chen T, Chong Z, Rohrdanz MA, Melott JM, Wakefield C, Zeng J, Weinstein JN, Meric-Bernstam F, Mills GB, Chen K. TransVar: a multi-level variant annotator for precision genomics. Nature Methods. In Press.
Have you tried the Ensembl REST API?
To convert from protein coordinates http://beta.rest.ensembl.org/documentation/info/assembly_translation
To convert from transcript coordinates
You'd need to get the Ensembl protein or transcript IDs, which you can get easily using BioMart (tutorial on BioMart here
Then, for your query, BRAF.p.V600E:c.1799T>A, input
From protein
http://beta.rest.ensembl.org/map/translation/ENSP00000288602/600..600?content-type=application/json
Output
{"mappings":[{"seq_region_name":"7","gap":0,"coord_system":"chromosome","strand":-1,"rank":0,"end":140453135,"start":140453137}]
From transcript
http://beta.rest.ensembl.org/map/cds/ENST00000288602/1799?content-type=application/json
{"mappings":[{"seq_region_name":"7","gap":0,"coord_system":"chromosome","strand":-1,"rank":0,"end":140453136,"start":140453136}]}
I like the idea of being able to use ensembl, but is there any way to get the nucleotide as well!
My example variant was:
VAR_031436 Q9NXK6 MPRG_HUMAN p.Ile24Thr
Which I need nucleotide and chromosome-coordinate for, and this is the corresponding link which gives me chr-location, but not the corresponding nucleotide change (am assuming it would be just one possible nucleotide combination of reference and alternate, so there is no ambiguity and one-one correspondence)
http://beta.rest.ensembl.org/map/translation/ENSP00000343877/24..24?content-type=application/json
Any thoughts?
You can get this using the Ensembl VEP. http://www.ensembl.org/info/docs/tools/vep/index.html.
Use the annotation you have there, selecting HGVS annotation as your input file format. This will tell you the location you hit, the nucleotide/codon change, the gene/transcript/protein sequence it hits.
Emily, thanks for pointing that! I was able to format my data to HGVS and use VEP to obtain coordinate and codon. However, some do not get any output via VEP!! ENSP00000256339:p.Val1597Ala returns a blank in VEP. Though it works just fine in polyphen2! http://genetics.bwh.harvard.edu/ggi/pph2/3a7d3e9d7dc0c940e1b608c62ba2c28296dcfe2b/1771738.html
Hi. I think the issue here is that we don't have a Valine annotated at position 1597 in ENSP00000256339. We have that position as a Proline (http://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000133958;r=14:93799565-94173618;t=ENST00000256339). I put in the input ENSP00000256339:p.Pro1597Ala instead and got four hits. Perhaps this is the wrong protein ID?
To convert from transcript coordinates you'd need to get the Ensembl protein or transcript IDs, which you can get easily using BioMart (tutorial on BioMart here
@Emily_Ensembl I think you forgot to include the link to the BioMart tutorial on how to go from genomic coordinate to transcript ID. Can you post it here? Thanks.
You can find the 3 b.p. codon which encodes the amino acid, but you need more information if you want single base pair resolution...
Can I use it if I don't know the amino acid position of the protein? I addition, as far as I understand, gene name and mutation info (either of the form c.123G>T or IVS4+1G>T) are not enough in order to deduce a specific genomic location as there may be more than a single transcript. Am I wrong?
f I don't know the amino acid position of the protein? you could loop over all the positions of the protein. "are not enough in order to deduce a specific genomic location as there may be more than a single transcript": of course. Furthermore, the very same protein can be encoded by two mRNA.
Albeit built for mapping protein sequence intervals, my script "protein2genome.pl" can do this. It ships with the variant annotation tool CooVar.
Here is how it works. First you need a GFF or a GTF file with the coordinates of your genes. To test your specific example, I created a GTF file that contains only the first isoform of the BRAF gene, but you could also work with GFF/GTF files containing all human genes and isoforms or containing genes from any other organism. Then you can run protein2genome.pl like this:
echo "ENST00000288602 . . 600 600 . . . ID=V600E" | perl protein2genome.pl BRAF-001.gtf
Produces the output:
7 . . 140453135 140453137 . - . ID=V600E(ENST00000288602);segment=1of1;p_start=600;p_end=600
Explanation: I am basically piping a GFF-compliant input line specifying the ID of the transcript and the position of the protein sequence change into the script. The script then outputs the mapped genomic coordinates (chromosome 7, codon start=140453135, codon-end=140453137).
A more detailed explanation of input and output formats can be found here.
I would say this script is more useful for non-model organisms, because for model organisms with associated databases you have other possibilities to do that (see other answers in this thread, for example the Ensembl REST API which is quite neat).
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version 2.3.6
Here is an example of what I was talking about: BRAF.p.V600E:c.1799T>A
Given just this information, is there a way I can get to the genomic coordinates. I guess there is the CDS position, can this direct us to the genomic location?
Here is an example of what I was talking about: BRAF.p.V600E:c.1799T>A Given just this information, is there a way I can get to the genomic coordinates. I guess there is the CDS position, does this help?