Biomedical Engineering Reference
In-Depth Information
3.4.3 Genome-Wide Annotation of
-Barrel Membrane Proteins
b
The methods developed for discriminating
-barrel membrane proteins have been
applied to detect such proteins in genomic sequences. Zhai and Saier [
58
] devel-
oped a
b
-barrel finder program based on secondary structure, hydropathy and
amphipathicity parameters and used it for identifying TMBs in
Escherichia coli
genome. Berven et al. [
59
] proposed a program for identifying TMBs using two
factors (1) C-terminal pattern typical of many integral
b
b
-barrel proteins and (2)
b
integral
-barrel score based on the extent to which the sequence contains stretches
of amino acids typical of transmembrane
b
-strands. Bigelow et al. [
60
] introduced a
profile-based HMM for discriminating TMBs and suggested the probable TMBs in
genomic sequences of 72 Gram-negative bacteria. The average occurrence of
TMBs in genomes is predicted to be about 3%. Gromiha et al. [
61
] proposed a
new approach for detecting TMBs in genomic sequences and the TMB finding
pipeline is given below (Fig.
2
). It includes the identification procedure using the
residue pair preferences between TMBs and globular proteins and that between
TMBs and TMH proteins [
44
] as well as elimination methods, which includes
shorter sequences, TMH proteins using the program SOSUI [
17
], TMH and globu-
lar proteins that have more than 70% sequence identity and 80% coverage with
known sequences and structures in Uniprot [
62
] and PDB [
6
], respectively, using
the program, BLAST [
63
]. Further a database, TMBETA-GENOME has been
developed for annotated TMBs in 275 genomic sequences, and it is available at
http://tmbeta-genome.cbrc.jp/annotation/
[
64
]. Recently, Tsirigos et al. [
65
] devel-
oped a comprehensive database of integral
-barrel outer membrane proteins from
Gram-negative bacteria, OMPdb, which contains 67,766 proteins, which are classi-
fied into 85 families, based on structural and functional criteria. It has cross-
references to other databases, references to the literature, and annotation for
sequence features, such as transmembrane segments and signal peptides.
Furthermore, OMPdb has the facility to browse the available data as well as to
submit advance text searches and run BLAST queries against the database of protein
sequences or domain searches against the collection of profile HMMs that represent the
domain organization of each family. The database is available at
http://bioinformatics.
biol.uoa.gr/OMPdb
.
b
3.5 Prediction of Membrane Spanning
b
-Strand Segments
Several statistical methods and machine-learning techniques have been proposed
for predicting the membrane spanning segments of TMBs. As mentioned in the
previous section, the performance of machine-learning techniques is better than that
with statistical and knowledge-based methods. In addition, the inclusion of align-
ment profiles improved the accuracy significantly.
