Apply a non-stationary nucleotide model to an alignment with 3 sequences

We load some sample data first and select just 3 sequences.

from cogent3 import get_app

loader = get_app("load_aligned", format_name="fasta", moltype="dna")
select_seqs = get_app("take_named_seqs", "Human", "Rhesus", "Galago")
process = loader + select_seqs
aln = process("data/primate_brca1.fasta")
aln.names

('Rhesus', 'Human', 'Galago')

We analyses these using the general Markov nucleotide, GN, model. Because we analyse just 3 sequences, there is only one possible unrooted tree, hence it is not required to specify the tree in this instance.

gn = get_app("model", "GN")
gn

model(sm='GN', tree=None, unique_trees=False, tree_func=None, name=None,
optimise_motif_probs=False, sm_args=None, lf_args=None, time_het=None,
param_rules=None, opt_args=None, lower=1e-06, upper=50, split_codons=False,
show_progress=False, verbose=False)

We apply this to aln.

fitted = gn(aln)
type(fitted)

cogent3.app.result.model_result

`model_result`

As the output above indicates, fitted is a model_result object.

This object provides an interface for accessing attributes of a fitted model. The representation display (below), a styled table in a jupyter notebook, presents a summary view with the log-likelihood (lnL), number of free parameters (nfp) and whether all matrices satisfied the identifiability conditions diagonal largest in column (DLC) and a unique mapping of Q to P. (For description of these quantities and why they matter see Chang 1996 and Kaehler et al.)

model_result has dictionary behaviour, hence the key column. This will be demonstrated below.

fitted

GN
key	lnL	nfp	DLC	unique_Q
'GN'	-5964.2583	14	True	True

More detail on the fitted model are available via attributes. For instance, display the maximum likelihood estimates via the likelihood function attribute

fitted.lf

GN

log-likelihood = -5964.2583

number of free parameters = 14

Global params
A>C	A>G	A>T	C>A	C>G	C>T	G>A	G>C	G>T	T>A	T>C
1.06	3.19	1.02	1.79	2.33	5.68	9.06	1.11	0.83	1.50	3.56

Edge params
edge	parent	length
Rhesus	root	0.02
Human	root	0.02
Galago	root	0.18

Motif params
A	C	G	T
0.38	0.17	0.21	0.24

fitted.lnL, fitted.nfp

(-5964.258307148503, 14)

fitted.source

'primate_brca1'

The model_result.tree attribute is an “annotated tree”. Maximum likelihood estimates from the model have been assigned to the tree. Of particular significance, the “length” attribute corresponds to the expected number of substitutions (or ENS). For a non-stationary model, like GN, this can be different to the conventional length (Kaehler et al).

fitted.tree, fitted.alignment

(Tree("(Rhesus,Human,Galago);"),
 3 x 2814 dna alignment: Rhesus[TGTGGCACAA...], Human[TGTGGCACAA...], Galago[TGTGGCAAAA...])

We can access the sum of all branch lengths. Either as “ENS” or “paralinear” using the total_length() method.

fitted.total_length(length_as="paralinear")

np.float64(0.9292253552738261)

Fitting a separate nucleotide model to each codon position

Controlled by setting split_codons=True.

gn = get_app("model", "GN", split_codons=True)

fitted = gn(aln)
fitted

GN
key	lnL	nfp	DLC	unique_Q
''	-5867.4461	42	True	True
1	-1955.7571	14
2	-1934.2690	14
3	-1977.4200	14

The model fit statistics, lnL and nfp are now sums of the corresponding values from the fits to the individual positions. The DLC and unique_Q are also a summary across all models. These only achieve the value True when all matrices, from all models, satisfy the condition.

We get access to the likelihood functions of the individual positions via the indicated dict keys.

fitted[3]

LF id: 3

log-likelihood = -1977.4200

number of free parameters = 14

Global params
A>C	A>G	A>T	C>A	C>G	C>T	G>A	G>C	G>T	T>A	T>C
1.75	3.47	2.42	2.37	3.41	16.13	16.85	2.02	1.73	1.93	5.29

Edge params
edge	parent	length
Rhesus	root	0.03
Human	root	0.02
Galago	root	0.18

Motif params
A	C	G	T
0.34	0.14	0.16	0.36