Difference between revisions of "Task 6: MSUD - Sequence-based mutation analysis"
(→PSI-BLAST - PSSM) |
|||
Line 105: | Line 105: | ||
<tr><td>R429H</td><td>AFFECT PROTEIN FUNCTION</td><td>0.03</td><td>3.21</td><td>15</td></tr> |
<tr><td>R429H</td><td>AFFECT PROTEIN FUNCTION</td><td>0.03</td><td>3.21</td><td>15</td></tr> |
||
</table> |
</table> |
||
+ | |||
+ | === Comparison === |
||
+ | [[File:PolyPhen_SIFT_SNAP_VennDiagram.png|Thumb]] |
||
= References = |
= References = |
Revision as of 12:49, 16 June 2012
Contents
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)
Position | wt-AA | wt properties | mutant-AA | mutant properties | expected effect on protein | sec-struct-element( reprof ) |
17 | L | -Hydrophobic side chain, non-polar, charge: neutral | F | Hydrophobic side chain, non-polar, charge: neutral | - | L |
82 | M | Hydrophobic side chain, non-polar, charge: neutral | I | Hydrophobic side chain, non-polar, charge: neutral | - | E |
125 | Q | polar, charge: neutral | E | polar, charge: negative | + | L |
213 | I | Hydrophobic side chain, non-polar, charge: neutral | T | polar, charge: neutral | + | H |
258 | C | polar, charge: neutral | Y | polar, charge: neutral | - | L |
310 | T | polar, charge: neutral | R | polar, charge: positive | + | H |
328 | A | non-polar, charge: neutral | T | polar, charge: neutral | - | E |
361 | I | Hydrophobic side chain, non-polar, charge: neutral | V | non-polar, charge: neutral | - | H |
404 | N | polar, charge: neutral | S | polar, charge: neutral | - | L |
429 | R | polar, charge: positive | H | polar, 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
Position | wt-AA | mutant-AA | Blosum62-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> |
17 | L | F | 0 | 13 | 13 |
82 | M | I | 1 | 5 | 2 |
125 | Q | E | 2 | 27 | 7 |
213 | I | T | -2 | 7 | 4 |
258 | C | Y | -2 | 3 | 4 |
310 | T | R | -1 | 2 | 5 |
328 | A | T | -1 | 32 | 11 |
361 | I | V | 1 | 33 | 9 |
404 | N | S | 1 | 20 | 5 |
429 | R | H | 0 | 10 | 6 |
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:
pos | wt-AA | mut-AA | pssm-score | pssm percent wt | pssm percent mut |
17 | L | F | 1 | 31 | 9 |
82 | M | I | 1 | 28 | 6 |
125 | Q | E | -1 | 97 | 0 |
213 | I | T | -2 | 41 | 2 |
258 | C | Y | -4 | 29 | 0 |
310 | T | R | -3 | 60 | 0 |
328 | A | T | 2 | 59 | 12 |
361 | I | V | 2 | 63 | 13 |
429 | R | H | -1 | 26 | 1 |
404 | N | S | 2 | 19 | 16 |
Tools
Polyphen2
Results:
SNP | polyphen-score | sensitivity | specificity | description |
L17F | 0.995 | 0.68 | 0.97 | PROBABLY DAMAGING |
M82I | 0.468 | 0.89 | 0.90 | POSSIBLY DAMAGING |
Q125E | 0.544 | 0.88 | 0.91 | POSSIBLY DAMAGING |
I213T | 0.644 | 0.87 | 0.91 | POSSIBLY DAMAGING |
C258Y | 1.000 | 0.00 | 1.00 | PROBABLY DAMAGING |
T310R | 1.000 | 0.00 | 1.00 | PROBABLY DAMAGING |
A328T | 0.999 | 0.14 | 0.99 | PROBABLY DAMAGING |
I361V | 0.386 | 0.90 | 0.89 | BENIGN |
N404S | 0.000 | 1.00 | 1.00 | BENIGN |
R429H | 0.002 | 0.99 | 0.30 | BENIGN |
Snap/Snap2
SNP | snap-pred | snap-rel | snap-expected-acc | snap2-pred | snap2-rel | snap2-expected-acc |
L17F | Neutral | 3 | 78% | Neutral | 6 | 82% |
M82I | Neutral | 4 | 85% | Neutral | 4 | 72% |
Q125E | Non-neutral | 1 | 63% | Non-neutral | 4 | 71% |
I213T | Neutral | 3 | 78% | Non-neutral | 6 | 80% |
C258Y | Non-neutral | 2 | 70% | Non-neutral | 6 | 80% |
T310R | Non-neutral | 1 | 63% | Non-neutral | 6 | 80% |
A328T | Neutral | 4 | 85% | Neutral | 1 | 57% |
I361V | Neutral | 5 | 89% | Neutral | 8 | 93% |
N404S | Neutral | 7 | 94% | Neutral | 9 | 97% |
R429H | Neutral | 6 | 92% | Neutral | 4 | 72% |
SIFT
SNP | sift-prediction | sift-score | sift-conservation | sequences represented at pos |
L17F | AFFECT PROTEIN FUNCTION | 0.00 | 4.32 | 1 |
M82I | be TOLERATED | 0.26 | 3.12 | 17 |
Q125E | AFFECT PROTEIN FUNCTION | 0.02 | 3.02 | 19 |
I213T | be TOLERATED | 0.22 | 3.02 | 19 |
C258Y | AFFECT PROTEIN FUNCTION | 0.02 | 3.02 | 19 |
T310R | AFFECT PROTEIN FUNCTION | 0.01 | 3.02 | 19 |
A328T | be TOLERATED | 1.00 | 3.02 | 19 |
I361V | be TOLERATED | 0.06 | 3.02 | 19 |
N404S | be TOLERATED | 0.99 | 3.02 | 19 |
R429H | AFFECT PROTEIN FUNCTION | 0.03 | 3.21 | 15 |
Comparison
References
<references />