XRATE is a program for prototyping
phylogenetic hidden Markov models
A hidden Markov model (HMM) is a statistical Markov model in which the system being modeled is assumed to be a Markov process — call it X — with unobservable ("''hidden''") states. As part of the definition, HMM requires that there be an obs ...
and
stochastic context-free grammar Grammar theory to model symbol strings originated from work in computational linguistics aiming to understand the structure of natural languages. Probabilistic context free grammars (PCFGs) have been applied in probabilistic modeling of RNA structur ...
s. It is used to discover patterns of evolutionary conservation in
sequence alignment
In bioinformatics, a sequence alignment is a way of arranging the sequences of DNA, RNA, or protein to identify regions of similarity that may be a consequence of functional, structural, or evolutionary relationships between the sequences. Alig ...
s. The program can be used to estimate parameters for such models from "training" alignment data, or to apply the parameterized model so as to annotate new alignments. The program allows specification of a variety of
models of DNA sequence evolution which may be arbitrarily organized using
formal grammars.
As an example of how XRATE is used, consider a protein-coding
gene consisting of
exons
An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequence ...
interspersed with
introns. The exons contain triplets of nucleotides (
codons
The genetic code is the set of rules used by living cells to translate information encoded within genetic material ( DNA or RNA sequences of nucleotide triplets, or codons) into proteins. Translation is accomplished by the ribosome, which links ...
) that are translated by
ribosomes
Ribosomes ( ) are macromolecular machines, found within all cells, that perform biological protein synthesis (mRNA translation). Ribosomes link amino acids together in the order specified by the codons of messenger RNA (mRNA) molecules to f ...
according to the
genetic code, and consequently are under
selection pressure (since any mutation may affect the translated
amino acid sequence). In contrast, the introns are under fewer selective constraints and tend to evolve faster. These varying pressures show up clearly in
multiple alignments.
The sequential layout of introns and exons can be described using
grammar theory (from linguistics) and each of their distinct evolutionary signatures modeled as a
continuous-time Markov process
A continuous-time Markov chain (CTMC) is a continuous stochastic process in which, for each state, the process will change state according to an exponential random variable and then move to a different state as specified by the probabilities of ...
.
XRATE allows the user to specify such models in a configuration file and estimate their parameters (evolutionary rates, length distributions of exons and introns, etc.) directly from alignment data, using the
Expectation-maximization algorithm.
XRATE can be downloaded as part of th
DART software package It accepts input files in
Stockholm format
Stockholm format is a multiple sequence alignment format used by Pfam, Rfam anDfam to disseminate protein, RNA and DNA sequence alignments. The alignment editorRaleehtml" ;"title=",;()[">,;()[aBb.-_--supports pseudoknot and further structure marku ...
.
References
{{Reflist
External links
XRATE homepagean
file format
Bioinformatics software