Sequence-based mutation analysis BCKDHA
From Bioinformatikpedia
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 sequences, 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 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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