, aka phylo-alignment or StatisticalAlignment
(a term coined by JotunHein
), is an approach to sequence alignment with several characteristics:
- Evolutionary models are defined rigorously as continuous-time Markov chains on sequence space
- Stochastic grammars and dynamic programming algorithms are then derived systematically
- Phylogenetic trees, sequence alignments and/or model parameters are imputed or, in a Bayesian framework, co-sampled by MCMC
Phylo-alignment can seem mathematically daunting, because deriving a stochastic grammar systematically from instantaneous mutation rates is not as easy as (say) observing empirically that "setting the gap opening penalty to -11 and the gap extension penalty to -1 gives pretty good results"
However, if the math can be worked out, we get an integrated framework for doing alignments, building phylogenetic trees, predicting exons and other features, measuring rates of mutation events (indels, substitutions...) and reconstructing ancient sequence,
using technology that's not too
much more complicated than the Baum-Welch algorithm
for Pair HMMs.
We (Holmes lab
) have several pieces of software in active development for doing statistical alignment, some more experimental than others.
Other software tools for phylo-alignment include
Links to key papers can be found on the PhylogeneticAlignmentReader
want to read the paper that started it all (often nicknamed "TKF91"):
(OK, there were
several seminal papers before this, e.g. by Bishop and Thompson, Felsenstein, Lawrence Liu et al
... but the TKF91 paper is probably the most influential. See phylogenetic alignment reader
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