Difference between revisions of "Sequence-based mutation analysis BCKDHA"
From Bioinformatikpedia
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+ | [[File:Betteralignment_BCKDHA.png | thumb |right| Multiple Alignment of the homologous sequences of BCKDHA with CLUSTALW]] |
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With this 25 results and the BCKDHA-sequence we made a multiple alignment by using CLUSTALW. |
With this 25 results and the BCKDHA-sequence we made a multiple alignment by using CLUSTALW. |
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The alignment with all mammalian homologous was quite bad because of the sequences "Q6ZSA3" and "E2RPW4". These two sequences are much longer than the other one. |
The alignment with all mammalian homologous was quite bad because of the sequences "Q6ZSA3" and "E2RPW4". These two sequences are much longer than the other one. |
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− | So we removed those sequences and realigned the other sequences. |
+ | So we removed those sequences and realigned the other sequences. |
− | [[File:Betteralignment_BCKDHA.png | thumb |right| Multiple Alignment of the homologous sequences of BCKDHA with CLUSTALW]] |
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==SNAP== |
==SNAP== |
Revision as of 23:27, 22 June 2011
Subset of mutations
Reference amino acid | Mutated amino acid | Secondary Structure | |||||
---|---|---|---|---|---|---|---|
Position | Residue | Properties | Structure | Residue | Properties | Structure | |
29 | G | tiny, small | E | charged, polar | C | ||
125 | Q | acidic, polar | E | charged, polar | C | ||
166 | Y | hydrophobic, aromatic, polar | N | acidic, polar, small | H | ||
249 | G | tiny, small | S | polar, small, tiny, hydroxylic | H | ||
264 | C | sulphur containing, hydrophobic, tiny, small, polar | W | hydrophobic, aromatic, polar | E | ||
265 | R | charged, positive (basic), polar | W | hydrophobic, aromatic, polar | E | ||
326 | I | aliphatic, hydrophobic | T | hydroxylic, hydrophobic, small, polar | E | ||
361 | I | aliphatic, hydrophobic | V | aliphatic, hydrophobic, small | H | ||
409 | F | aromatic, hydrophobic | C | sulphur containing, hydrophobic, tiny, small, polar | C | ||
438 | Y | hydrophobic, aromatic, polar | N | acidic, polar, small | C |
Position | AA1/AA2 | BLOSUM62 | PAM1 | PAM250 | |||
---|---|---|---|---|---|---|---|
score | worst | score | worst | score | worst | ||
29 | G/E | -2 | -4 (I, L) | 7 | 0 (I, W, Y) | 9 | 2 (W) |
125 | Q/E | 2 | -3 (C, F, I) | 27 | 0 (F, W, Y) | 7 | 1 (C, F, W) |
166 | Y/N | -2 | -3 (D, G, P) | 3 | 0 (R, D, Q, G, K, M, P) | 2 | 1 (A, R, D, Q, E, G, K, P) |
249 | G/S | 0 | -4 (I, L) | 21 | 0 (I, W, Y) | 11 | 2 (W) |
264 | C/W | -2 | -4 (E) | 0 | 0 (N, D, Q, E, G, L, K, M, F, W) | 1 | 1 (R, N, D, Q, E, L, K, M, F, W) |
265 | R/W | -3 | -3 (W, V, F, I, C) | 8 | 0 (D, E, G, Y) | 7 | 1 (F) |
326 | I/T | -1 | -4 (G) | 7 | 0 (G, A, P, W) | 4 | 1 (W) |
361 | I/V | 3 | -4 (G) | 33 | 0 (G, H, P, W) | 9 | 1 (W) |
409 | F/C | -2 | -4 (P) | 0 | 0 (D, C, Q, E, K, P, V) | 1 | 1 (R, D, C, Q, E, G, K, P) |
438 | Y/N | -2 | -3 (D, G, P) | 3 | 0 (R, D, Q, G, K, M, P) | 2 | 1 (A, R, D, Q, E, G, K, P) |
Annotation: H = helix, E = beta-sheet, C = coil
PSSM
PsiBlast was run using the following command: blastpgp -i sequence.fasta -j 5 -d /data/blast/nr/nr -C profile.ckp
Multiple Sequence Alignment
To find the homologue sequences to BCKDHA we used BLAST. It found 250 homologous and 25 of them are mammals.
ID | Accession | Entry name |
---|---|---|
sp | P11178 | ODBA_BOVIN |
sp | P12694 | ODBA_HUMAN |
sp | Q8HXY4 | ODBA_MACFA |
sp | P50136 | ODBA_MOUSE |
sp | A5A6H9 | ODBA_PANTR |
sp | P11960 | ODBA_RAT |
tr | Q6ZSA3 | Q6ZSA3_HUMAN |
tr | E7ESE6 | E7ESE6_HUMAN |
tr | B2R8A9 | B2R8A9_HUMAN |
tr | Q658P7 | Q658P7_HUMAN |
tr | E7EW46 | E7EW46_HUMAN |
tr | B4DP47 | B4DP47_HUMAN |
tr | Q59EI3 | Q59EI3_HUMAN |
tr | F1N5F2 | F1N5F2_BOVIN |
tr | B1PK12 | B1PK12_PIG |
tr | E2RPW4 | E2RPW4_CANFA |
tr | B2LSM3 | B2LSM3_SHEEP |
tr | F1RHA0 | F1RHA0_PIG |
tr | F1PI86 | F1PI86_CANFA |
tr | D2HMT3 | D2HMT3_AILME |
tr | Q2TBT9 | Q2TBT9_BOVIN |
tr | Q3U3J1 | Q3U3J1_MOUSE |
tr | Q99L69 | Q99L69_MOUSE |
tr | Q5EB89 | Q5EB89_RAT |
tr | B1WBN3 | B1WBN3_RAT |
With this 25 results and the BCKDHA-sequence we made a multiple alignment by using CLUSTALW. The alignment with all mammalian homologous was quite bad because of the sequences "Q6ZSA3" and "E2RPW4". These two sequences are much longer than the other one. So we removed those sequences and realigned the other sequences.
SNAP
To run SNAP we used the command:
snapfun -i BCKDHA.fasta -m mutations.txt -o SNAP.out
nsSNP | Prediction | Reliability Index | Expected Accuracy |
---|---|---|---|
G29E | Neutral | 0 | 53% |
Q125E | Non-neutral | 1 | 63% |
Y166N | Non-neutral | 2 | 70% |
G249S | Neutral | 1 | 60% |
C264W | Non-neutral | 4 | 82% |
R265W | Non-neutral | 4 | 82% |
I326T | Non-neutral | 3 | 78% |
I361V | Neutral | 4 | 85% |
F409C | Non-neutral | 4 | 82% |
Y438N | Non-neutral | 4 | 82% |
SIFT
Polyphen2
Position | AA1/AA2 | HumDiv | HumVar | ||||||
---|---|---|---|---|---|---|---|---|---|
prediction | Score | Sensitivity | Specificity | prediction | Score | Sensitivity | Specificity | ||
29 | G/E | benign | 0.025 | 0.96 | 0.80 | benign | 0.018 | 0.96 | 0.52 |
125 | Q/E | possibly damaging | 0.759 | 0.85 | 0.93 | benign | 0.285 | 0.87 | 0.75 |
166 | Y/N | probably damaging | 0.997 | 0.40 | 0.98 | probably damaging | 0.964 | 0.59 | 0.93 |
249 | G/S | benign | 0.145 | 0.93 | 0.86 | benign | 0.292 | 0.86 | 0.75 |
264 | C/W | probably damaging | 1.000 | 0.00 | 1.00 | probably damaging | 1.000 | 0.00 | 1.00 |
265 | R/W | probably damaging | 1.000 | 0.00 | 1.00 | probably damaging | 1.000 | 0.00 | 1.00 |
326 | I/T | probably damaging | 0.997 | 0.40 | 0.98 | probably damaging | 0.998 | 0.16 | 0.99 |
361 | I/V | benign | 0.039 | 0.95 | 0.82 | benign | 0.178 | 0.89 | 0.70 |
409 | F/C | probably damaging | 0.998 | 0.27 | 0.99 | probably damaging | 0.939 | 0.64 | 0.92 |
438 | Y/N | probably damaging | 1.000 | 0.00 | 1.00 | probably damaging | 0.987 | 0.49 | 0.96 |
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