Task 6: MSUD - Sequence-based mutation analysis

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Revision as of 12:52, 16 June 2012 by Wagnerr (talk | contribs) (Comparison)

Sequence-based mutation analysis

task description

For this Task the group that reviewed our page last week was to chose 10 SNP's on which we can work on. We assume we don't know which of the SNP's cause MSUP or affects the protein structure or function. As we haven't received any message from the group which reviewed our page last week by thursday, we've decided to chose the 10 SNP's by ourselves: L17F, M82I,Q125E, I213T, C258Y, T310R, A328T, I361V, R429H, N404S

Comparison of wild type AA and mutant AA

Physiological properties<ref>http://en.wikipedia.org/wiki/Amino_acid</ref> and predicted secondary structure element (reprof with pssm)

Positionwt-AAwt propertiesmutant-AAmutant propertiesexpected effect on proteinsec-struct-element( reprof )
17L-Hydrophobic side chain, non-polar, charge: neutralFHydrophobic side chain, non-polar, charge: neutral-L
82MHydrophobic side chain, non-polar, charge: neutralIHydrophobic side chain, non-polar, charge: neutral-E
125Qpolar, charge: neutralEpolar, charge: negative+L
213IHydrophobic side chain, non-polar, charge: neutralTpolar, charge: neutral+H
258Cpolar, charge: neutralYpolar, charge: neutral-L
310Tpolar, charge: neutralRpolar, charge: positive+H
328Anon-polar, charge: neutralTpolar, charge: neutral-E
361IHydrophobic side chain, non-polar, charge: neutralVnon-polar, charge: neutral-H
404Npolar, charge: neutralSpolar, charge: neutral-L
429Rpolar, charge: positiveHpolar, charge: positive( 10% ) negative( 90% )+H

Blosum62, PAM1, PAM250 scores

The scores for an aminoacid change in the matrices Blosum and PAM should give another hint, whether the substitution has an effect on the resulting protein or not. The higher the X in BlosumX, the shorter is the evolutionary context of sequences it is calculated for, while in PAMX the opposite is the case.calculated for sequences

Positionwt-AAmutant-AABlosum62-Score<ref>http://www.uky.edu/Classes/BIO/520/BIO520WWW/blosum62.htm</ref> is PAM1-Score<ref>http://www.icp.ucl.ac.be/~opperd/private/pam1.html</ref>PAM250-Score<ref>http://www.icp.ucl.ac.be/~opperd/private/pam250.html</ref>
17LF01313
82MI152
125QE2277
213IT-274
258CY-234
310TR-125
328AT-13211
361IV1339
404NS1205
429RH0106

3D-Structure

PSI-BLAST - PSSM

the command we used to create the PSSM-file, and the file itsself can be found in the journal

The underlying database is big_db.

Results:

poswt-AAmut-AApssm-scorepssm percent wtpssm percent mut
17LF1319
82MI1286
125QE-1970
213IT-2412
258CY-4290
310TR-3600
328AT25912
361IV26313
429RH-1261
404NS21916

Tools

Polyphen2

Results:

SNPpolyphen-scoresensitivityspecificitydescription
L17F0.9950.680.97PROBABLY DAMAGING
M82I0.4680.890.90POSSIBLY DAMAGING
Q125E0.5440.880.91POSSIBLY DAMAGING
I213T0.6440.870.91POSSIBLY DAMAGING
C258Y1.0000.001.00PROBABLY DAMAGING
T310R1.0000.001.00PROBABLY DAMAGING
A328T0.9990.140.99PROBABLY DAMAGING
I361V0.3860.900.89BENIGN
N404S0.0001.001.00BENIGN
R429H0.0020.990.30BENIGN

Snap/Snap2

SNPsnap-predsnap-relsnap-expected-accsnap2-predsnap2-relsnap2-expected-acc
L17FNeutral378%Neutral682%
M82INeutral485%Neutral472%
Q125ENon-neutral163%Non-neutral471%
I213TNeutral378%Non-neutral680%
C258YNon-neutral270%Non-neutral680%
T310RNon-neutral163%Non-neutral680%
A328TNeutral485%Neutral157%
I361VNeutral589%Neutral893%
N404SNeutral794%Neutral997%
R429HNeutral692%Neutral472%

SIFT

SNPsift-predictionsift-scoresift-conservationsequences represented at pos
L17FAFFECT PROTEIN FUNCTION0.004.321
M82Ibe TOLERATED0.263.1217
Q125EAFFECT PROTEIN FUNCTION0.023.0219
I213Tbe TOLERATED0.223.0219
C258YAFFECT PROTEIN FUNCTION0.023.0219
T310RAFFECT PROTEIN FUNCTION0.013.0219
A328Tbe TOLERATED1.003.0219
I361Vbe TOLERATED0.063.0219
N404Sbe TOLERATED0.993.0219
R429HAFFECT PROTEIN FUNCTION0.033.2115

Comparison

thumb Venn-Diagram of the SNPs predicted from Polyphen, SIFT and SNAP that are assumed to have a negative effect on protein functionality.

References

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