PMID- 23080114
OWN - NLM
STAT- MEDLINE
DCOM- 20130729
LR  - 20220316
IS  - 1367-4811 (Electronic)
IS  - 1367-4803 (Linking)
VI  - 28
IP  - 24
DP  - 2012 Dec 15
TI  - Discriminative modelling of context-specific amino acid substitution 
      probabilities.
PG  - 3240-7
LID - 10.1093/bioinformatics/bts622 [doi]
AB  - MOTIVATION: Protein sequence searching and alignment are fundamental tools of 
      modern biology. Alignments are assessed using their similarity scores, 
      essentially the sum of substitution matrix scores over all pairs of aligned amino 
      acids. We previously proposed a generative probabilistic method that yields 
      scores that take the sequence context around each aligned residue into account. 
      This method showed drastically improved sensitivity and alignment quality 
      compared with standard substitution matrix-based alignment. RESULTS: Here, we 
      develop an alternative discriminative approach to predict sequence 
      context-specific substitution scores. We applied our approach to compute 
      context-specific sequence profiles for Basic Local Alignment Search Tool (BLAST) 
      and compared the new tool (CS-BLASTdis) to BLAST and the previous 
      context-specific version (CS-BLASTgen). On a dataset filtered to 20% maximum 
      sequence identity, CS-BLASTdisis was 51% more sensitive than BLAST and 17% more 
      sensitive than CS-BLASTgenin, detecting remote homologues at 10% false discovery 
      rate. At 30% maximum sequence identity, its alignments contain 21 and 12% more 
      correct residue pairs than those of BLAST and CS-BLASTgen, respectively. Clear 
      improvements are also seen when the approach is combined with PSI-BLAST and 
      HHblits. We believe the context-specific approach should replace substitution 
      matrices wherever sensitivity and alignment quality are critical.
FAU - Angermuller, Christof
AU  - Angermuller C
AD  - Gene Center Munich and Department of Biochemistry, Ludwig-Maximilians-Universtat 
      Munchen, 81377 Munich, Germany.
FAU - Biegert, Andreas
AU  - Biegert A
FAU - Soding, Johannes
AU  - Soding J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121017
PL  - England
TA  - Bioinformatics
JT  - Bioinformatics (Oxford, England)
JID - 9808944
SB  - IM
MH  - Algorithms
MH  - *Amino Acid Substitution
MH  - Models, Statistical
MH  - Probability
MH  - Sequence Alignment/*methods
MH  - *Sequence Analysis, Protein
MH  - *Software
EDAT- 2012/10/20 06:00
MHDA- 2013/07/31 06:00
CRDT- 2012/10/20 06:00
PHST- 2012/10/20 06:00 [entrez]
PHST- 2012/10/20 06:00 [pubmed]
PHST- 2013/07/31 06:00 [medline]
AID - bts622 [pii]
AID - 10.1093/bioinformatics/bts622 [doi]
PST - ppublish
SO  - Bioinformatics. 2012 Dec 15;28(24):3240-7. doi: 10.1093/bioinformatics/bts622. 
      Epub 2012 Oct 17.