Conservation Score Of Amino Acid Positions In Human Proteins

Question

[Khader Shameer]

I am currently looking at few amino acid positions in human proteins and I would like to get a conservation score with respect to the position for a particular analysis. Please let me know if you have used any pre-computed database or tool/method that can be used to generate such a score. I have set of protein sequence, their corresponding positions at the moment. Conceptually I can use a pipeline of BLAST search followed by alignment and subsequent parsing to find the conservation scores, but I would like to know if this is already implemented as a standard tool by someone else.

I know about the tool CONSURF, which is an interesting tool for residue specific score, but it is more geared towards protein structure derived sequence and not available for whole Uniprot data. Another tool that I am aware of is the PSIC which is being discussed in another question by Tim. AFAIK, PSIC is not available as stand-alone program for download.

[Bilouweb]

As I understand, you want a program where you give a multiple alignment and a position in input and you want the conservation score in output, am I right ?

[Khader Shameer]

@bilouweb: I have edited my question accordingly. I only have sequences at the moment - I am yet to proceed with the alignment.

[olga.botvinnik]

Did you get this working? If you're using human vs everyone else data, do you mind posting it?

[gongjing.rss]

Hi, Khader, I know it has been a long time. Have you found any (pre-calculated) resources on amino acid conservation score?

Answer 1

[Bilouweb]

I have a stand alone program (MstatX) which measures the conservation at all positions in a multiple alignment of proteins (with gaps represented by '-').

Conservation can be calculated by a weighted entropy score or by a trident score (Valdar).

It is written in C++ so it can be compiled on any plateform.

But it is not related to a database, you have to generate the multiple alignments before.

If you are interested, you can get the last version from github : https://github.com/gcollet/MstatX

If you don't know git, just ask me, I will give you the sources.

[Bilouweb]

If you think of upgrades to this program, like other conservation measures or other multiple alignment format, feel fre to ask, I will try to implement new features.

[Khader Shameer]

Hi Biouweb: Can you tell me the details of the calculation implemented in MstatX ?

[Hari]

Hi i am trying to install the Mstatx but i get an installation error,i am using a Linux open suse.I get a 'make error'please guide me

Answer 2

[Sean Davis]

You might look at the SIFT tool. It can take as input the genomic position and associated variant. It can also be downloaded directly. A quick scan of the methods for SIFT may tell you if it is appropriate.

If you are interested in the conservation scores associated with the nucleotide positions of the amino acid position, that is easily obtained by the UCSC Table Browser.

[Khader Shameer]

Thanks Sean, I checked SIFT- it doesn't provide a score for all residues in a protein. My residues of interest are not just confined to SNPs. Also, SIFT score is more of a way to comprehend effect of mutation on protein and not as such a conservation score.

Answer 3

[Hari]

You can try Clustal x which i used for calculation of conservation score,you can download the tool and do the alignment for your sequences,once you have the MSA , select the sequence from the MSA you want and click on quality -> save column scores to file,this will give the score of all the residues of your sequence.

Answer 4

[Jose Manuel Duarte]

I've found that the AL2CO tool is quite good for this. If you have the MSA already it will calculate the conservation scores with all kinds of methods and you can adjust parameters like gap treatment, sequence weighting, scoring matrix and so on.

Answer 5

[mg0010]

Try software ResCons. It is a cross-OS platform software.Available for download from https://github.com/ManavalanG/ResCons/releases. You could probably modify it to suit your needs.