Bioinformatics Algorithms: Techniques and Applications

subject to �
Dij ∈Pmn
xij ≥ 1, where Pmn ∈ I.
ACKNOWLEDGMENTS 487
To account for the noise in the experimental data, a set of linear programs is
constructed in a probabilistic fashion, where the probability of including an LP constraint
in Equation 21.12 equals the probability with which the corresponding protein–
protein interaction is assumed to be correct. The LP-score for a domain pair Dij is
then averaged over all LP programs. An additional randomization experiment is used
to compute p-values and prevent overprediction of interactions between frequently
occurring domain pairs. Guimaraes at al. [26] demonstrated that the PE method outperforms
the EM and DPEA methods (Fig. 21.11).
GLOSSARY
Coevolution Coordinated evolution. It is generally agreed that proteins that interact
with each other or have similar function undergo coordinated evolution.
Gene fusion A pair of genes in one genome is fused together into a single gene in
another genome.
HMMer HMMer is a freely distributable implementation of profile HMM (hidden
Markov model) software for protein sequence analysis. It uses profile HMMs to do
sensitive database searching using statistical descriptions of a sequence family’s
consensus.
iPfam iPfam is a resource that describes domain–domain interactions that are observed
in PDB crystal structures.
Ortholog Two genes from two different species are said to be orthologs if they
evolved directly from a single gene in the last common ancestor.
PDB The protein data bank (PDB) is a central repository for 3D structural data of
proteins and nucleic acids. The data, typically obtained by X-ray crystallography
or NMR spectroscopy, are submitted by biologists and biochemists from around
the world, released into the public domain, and can be accessed for free.
Pfam Pfam is a large collection of multiple sequence alignments and hidden Markov
models covering many common protein domains and families.
Phylogenetic profile A phylogenetic profile for a protein is a vector of 1s and 0s
representing the presence or absence of that protein in a reference set organisms.
Distance matrix A matrix containing the evolutionary distances of organisms or
proteins in a family.
ACKNOWLEDGMENTS
This work was funded by the intramural research program of the National Library of
Medicine, National Institutes of Health.