Difference between revisions of "Task 6: Sequence-based mutation analysis"

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Revision as of 16:02, 24 June 2011

Task description

A detailed task description can be found here.

Mutation selection

We selected the following ten mutations:

  • I65T
  • R71H
  • R158Q
  • R261Q
  • T266A
  • P275S
  • T278N
  • P281L
  • G312D
  • R408W

5 of these mutations are associated with our disease phenylketonuria the other 5 not. The 5 disease causing mutations are the most frequent missense/nonsense mutations of people who suffer from phenylketonuria. These numbers were taken from pahDB. However, at this point we are not going to tell which of these are the associated and which are not. We are going to lift this "secret" after our sequence based mutation analysis in order to validate our in silico generated predictions.

To keep our association secret we encrypted the file which contains the disease association for each mutation with the following linux command: "vim -x selected_mutations_and_association.txt"

The encrypted output is as follows:

Encrypted img.png


The decryption can be only performed with the correct password.

Physicochemical properties and changes

I65T

R71H

R158Q

R261Q

T266A

P275S

T278N

P281L

G312D

R408W

Mutations compared to BLOSUM62, PAM(1/250), PSSM and conservation of MSA with all mammalian homologous

BLOSUM 62 matrix

BLOSUM 62 Matrix
BLOSUM62 BCKDHA.gif
The BLOSUM 62 was calculated from blocks of clusters with a sequence identity of 62%. A positive score is given to the more likely substitutions while a negative score is given to the less likely substitutions. Source: [1]

PAM 1/250 matrix

PSSM

MSA with all mammalian homologous

I65T

R71H

R158Q

R261Q

T266A

P275S

T278N

P281L

G312D

R408W

Mutations and secondary structure

Predicted secondary structure

I65T

R71H

R158Q

R261Q

T266A

P275S

T278N

P281L

G312D

R408W

Predicting the effect of mutations with SNAP, SIFT and Polyphen2

SNAP

SIFT

Polyphen2

I65T

R71H

R158Q

R261Q

T266A

P275S

T278N

P281L

G312D

R408W

Discussion