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from collections import defaultdict
import numpy as np
from . import config as ttconf
from .seq_utils import alphabets, profile_maps, alphabet_synonyms
from .gtr import GTR
class GTR_site_specific(GTR):
"""
Defines General-Time-Reversible model of character evolution that
allows for different models at different sites in the alignment
"""
def __init__(self, seq_len=1, approximate=True, **kwargs):
"""constructor for site specfic GTR models
Parameters
----------
seq_len : int, optional
number of sites, determines dimensions of frequency vectors etc
approximate : bool, optional
use linear interpolation for exponentiated matrices to speed up calcuations
**kwargs
Description
"""
self.seq_len=seq_len
self.approximate = approximate
super(GTR_site_specific, self).__init__(**kwargs)
self.is_site_specific=True
@property
def Q(self):
"""function that return the product of the transition matrix
and the equilibrium frequencies to obtain the rate matrix
of the GTR model
"""
tmp = np.einsum('ia,ij->ija', self.Pi, self.W)
diag_vals = np.sum(tmp, axis=0)
for x in range(tmp.shape[-1]):
np.fill_diagonal(tmp[:,:,x], -diag_vals[:,x])
return tmp
def assign_rates(self, mu=1.0, pi=None, W=None):
"""
Overwrite the GTR model given the provided data
Parameters
----------
mu : float
Substitution rate
W : nxn matrix
Substitution matrix
pi : n vector
Equilibrium frequencies
"""
if not np.isscalar(mu) and pi is not None and len(pi.shape)==2:
if mu.shape[0]!=pi.shape[1]:
raise ValueError("GTR_site_specific: length of rate vector (got {}) and equilibrium frequency vector (got {}) must match!".format(mu.shape[0], pi.shape[1]))
n = len(self.alphabet)
if np.isscalar(mu):
self._mu = mu*np.ones(self.seq_len)
else:
self._mu = np.copy(mu)
self.seq_len = mu.shape[0]
if pi is not None and pi.shape[0]==n and len(pi.shape)==2:
self.seq_len = pi.shape[1]
Pi = np.copy(pi)
else:
if pi is not None:
if len(pi)==n:
Pi = np.repeat([pi], self.seq_len, axis=0).T
else:
raise ValueError("GTR_site_specific: length of equilibrium frequency vector (got {}) does not match alphabet length {}".format(len(pi), n))
else:
Pi = np.ones(shape=(n,self.seq_len))
self._Pi = Pi/np.sum(Pi, axis=0)
if W is None or W.shape!=(n,n):
if (W is not None) and W.shape!=(n,n):
raise ValueError("GTR_site_specific: Size of substitution matrix (got {}) does not match alphabet length {}".format(W.shape, n))
W = np.ones((n,n))
np.fill_diagonal(W, 0.0)
np.fill_diagonal(W, - W.sum(axis=0))
else:
W=0.5*(np.copy(W)+np.copy(W).T)
np.fill_diagonal(W,0)
average_rate = np.einsum('ia,ij,ja',self.Pi, W, self.Pi)/self.seq_len
# average_rate = W.dot(avg_pi).dot(avg_pi)
self._W = W/average_rate
self._mu *=average_rate
self.is_site_specific=True
self._eig()
self._make_expQt_interpolator()
@classmethod
def random(cls, L=1, avg_mu=1.0, alphabet='nuc', pi_dirichlet_alpha=1,
W_dirichlet_alpha=3.0, mu_gamma_alpha=3.0, rng=None):
"""
Creates a random GTR model
Parameters
----------
L : int, optional
number of sites for which to generate a model
avg_mu : float
Substitution rate
alphabet : str
Alphabet name (should be standard: 'nuc', 'nuc_gap', 'aa', 'aa_gap')
pi_dirichlet_alpha : float, optional
parameter of dirichlet distribution
W_dirichlet_alpha : float, optional
parameter of dirichlet distribution
mu_gamma_alpha : float, optional
parameter of dirichlet distribution
Returns
-------
GTR_site_specific
model with randomly sampled frequencies
"""
if rng is None:
rng = np.random.default_rng()
alphabet=alphabets[alphabet]
gtr = cls(alphabet=alphabet, seq_len=L)
n = gtr.alphabet.shape[0]
# Dirichlet distribution == l_1 normalized vector of samples of the Gamma distribution
if pi_dirichlet_alpha:
pi = 1.0*rng.gamma(pi_dirichlet_alpha, size=(n,L))
else:
pi = np.ones((n,L))
pi /= pi.sum(axis=0)
if W_dirichlet_alpha:
tmp = 1.0*rng.gamma(W_dirichlet_alpha, size=(n,n))
else:
tmp = np.ones((n,n))
tmp = np.tril(tmp,k=-1)
W = tmp + tmp.T
if mu_gamma_alpha:
mu = rng.gamma(mu_gamma_alpha, size=(L,))
else:
mu = np.ones(L)
gtr.assign_rates(mu=mu, pi=pi, W=W)
gtr.mu *= avg_mu/np.mean(gtr.average_rate())
return gtr
@classmethod
def custom(cls, mu=1.0, pi=None, W=None, **kwargs):
"""
Create a GTR model by specifying the matrix explicitly
Parameters
----------
mu : float
Substitution rate
W : nxn matrix
Substitution matrix
pi : n vector
Equilibrium frequencies
**kwargs:
Key word arguments to be passed to the constructor
Keyword Args
------------
alphabet : str
Specify alphabet when applicable. If the alphabet specification is
required, but no alphabet is specified, the nucleotide alphabet will be used as
default.
"""
gtr = cls(**kwargs)
gtr.assign_rates(mu=mu, pi=pi, W=W)
return gtr
@classmethod
def infer(cls, sub_ija, T_ia, root_state, pc=1.0,
gap_limit=0.01, Nit=30, dp=1e-5, **kwargs):
r"""
Infer a GTR model by specifying the number of transitions and time spent in each
character. The basic equation that is being solved is
:math:`n_{ij} = pi_i W_{ij} T_j`
where :math:`n_{ij}` are the transitions, :math:`pi_i` are the equilibrium
state frequencies, :math:`W_{ij}` is the "substitution attempt matrix",
while :math:`T_i` is the time on the tree spent in character state
:math:`i`. To regularize the process, we add pseudocounts and also need
to account for the fact that the root of the tree is in a particular
state. the modified equation is
:math:`n_{ij} + pc = pi_i W_{ij} (T_j+pc+root\_state)`
Parameters
----------
nija : nxn matrix
The number of times a change in character state is observed
between state j and i at position a
Tia :n vector
The time spent in each character state at position a
root_state : np.array
probability that site a is in state i.
pc : float
Pseudocounts, this determines the lower cutoff on the rate when
no substitutions are observed
**kwargs:
Key word arguments to be passed
Keyword Args
------------
alphabet : str
Specify alphabet when applicable. If the alphabet specification
is required, but no alphabet is specified, the nucleotide alphabet will be used as default.
"""
from scipy import linalg as LA
gtr = cls(**kwargs)
gtr.logger("GTR: model inference ",1)
q = len(gtr.alphabet)
L = sub_ija.shape[-1]
n_iter = 0
n_ija = np.copy(sub_ija)
n_ija[range(q),range(q),:] = 0
n_ij = n_ija.sum(axis=-1)
m_ia = np.sum(n_ija,axis=1) + root_state + pc
n_a = n_ija.sum(axis=1).sum(axis=0) + pc
Lambda = np.sum(root_state,axis=0) + q*pc
p_ia_old=np.zeros((q,L))
p_ia = np.ones((q,L))/q
mu_a = np.ones(L)
W_ij = np.ones((q,q)) - np.eye(q)
while (LA.norm(p_ia_old-p_ia)>dp) and n_iter<Nit:
gtr.logger(' '.join(map(str, ['GTR inference iteration',n_iter,'change:',LA.norm(p_ia_old-p_ia)])), 3)
n_iter += 1
p_ia_old = np.copy(p_ia)
S_ij = np.einsum('a,ia,ja',mu_a, p_ia, T_ia)
W_ij = (n_ij + n_ij.T + pc)/(S_ij + S_ij.T + pc)
avg_pi = p_ia.mean(axis=-1)
average_rate = W_ij.dot(avg_pi).dot(avg_pi) # crude approx, will be fixed in assign rates
W_ij = W_ij/average_rate
mu_a *=average_rate
p_ia = m_ia/(mu_a*np.dot(W_ij,T_ia)+Lambda)
p_ia = p_ia/p_ia.sum(axis=0)
mu_a = n_a/(pc+np.einsum('ia,ij,ja->a', p_ia, W_ij, T_ia))
if n_iter >= Nit:
gtr.logger('WARNING: maximum number of iterations has been reached in GTR inference',3, warn=True)
if LA.norm(p_ia_old-p_ia) > dp:
gtr.logger('the iterative scheme has not converged',3,warn=True)
if gtr.gap_index is not None:
for p in range(p_ia.shape[-1]):
if p_ia[gtr.gap_index,p]<gap_limit:
gtr.logger('The model allows for gaps which are estimated to occur at a low fraction of %1.3e'%p_ia[gtr.gap_index,p]+
'\n\t\tthis can potentially result in artifacts.'+
'\n\t\tgap fraction will be set to %1.4f'%gap_limit,4,warn=True)
p_ia[gtr.gap_index,p] = gap_limit
p_ia[:,p] /= p_ia[:,p].sum()
gtr.assign_rates(mu=mu_a, W=W_ij, pi=p_ia)
return gtr
def _eig(self):
eigvals, vec, vec_inv = [], [], []
for pi in range(self.seq_len):
if len(self.W.shape)>2:
W = np.copy(self.W[:,:,pi])
np.fill_diagonal(W, 0)
elif pi==0:
np.fill_diagonal(self.W, 0)
W=self.W
ev, evec, evec_inv = self._eig_single_site(W,self.Pi[:,pi])
eigvals.append(ev)
vec.append(evec)
vec_inv.append(evec_inv)
self.eigenvals = np.array(eigvals).T
self.v = np.swapaxes(vec,0,-1)
self.v_inv = np.swapaxes(vec_inv, 0,-1)
def _make_expQt_interpolator(self):
"""Function that evaluates the exponentiated substitution matrix at multiple
time points and constructs a linear interpolation object
"""
self.rate_scale = self.average_rate().mean()
t_grid = (1.0/self.rate_scale)*np.concatenate((np.linspace(0,.1,11)[:-1],
np.linspace(.1,1,21)[:-1],
np.linspace(1,5,21)[:-1],
np.linspace(5,10,11)))
stacked_expQT = np.stack([self._expQt(t) for t in t_grid], axis=0)
from scipy.interpolate import interp1d
self.expQt_interpolator = interp1d(t_grid, stacked_expQT, axis=0,
assume_sorted=True, copy=False, kind='linear')
def _expQt(self, t):
"""Raw numerical matrix exponentiation using the diagonalized matrix.
This is the computational bottleneck in many simulations.
Parameters
----------
t : float
time
Returns
-------
np.array
stack of matrices for each site
"""
eLambdaT = np.exp(t*self.mu*self.eigenvals)
return np.einsum('jia,ja,kja->ika', self.v, eLambdaT, self.v_inv)
def expQt(self, t):
if t*self.rate_scale<10 and self.approximate:
return self.expQt_interpolator(t)
else:
return self._expQt(t)
def prop_t_compressed(self, seq_pair, multiplicity, t, return_log=False):
print("NOT IMPEMENTED")
def propagate_profile(self, profile, t, return_log=False):
"""
Compute the probability of the sequence state of the parent
at time (t+t0, backwards), given the sequence state of the
child (profile) at time t0.
Parameters
----------
profile : numpy.array
Sequence profile. Shape = (L, a),
where L - sequence length, a - alphabet size.
t : double
Time to propagate
return_log: bool
If True, return log-probability
Returns
-------
`
res : np.array
Profile of the sequence after time t in the past.
Shape = (L, a), where L - sequence length, a - alphabet size.
"""
Qt = self.expQt(t)
res = np.einsum('ai,ija->aj', profile, Qt)
return np.log(np.maximum(ttconf.TINY_NUMBER,res)) if return_log else np.maximum(0,res)
def evolve(self, profile, t, return_log=False):
"""
Compute the probability of the sequence state of the child
at time t later, given the parent profile.
Parameters
----------
profile : numpy.array
Sequence profile. Shape = (L, a),
where L - sequence length, a - alphabet size.
t : double
Time to propagate
return_log: bool
If True, return log-probability
Returns
-------
res : np.array
Profile of the sequence after time t in the future.
Shape = (L, a), where L - sequence length, a - alphabet size.
"""
Qt = self.expQt(t)
res = np.einsum('ai,jia->aj', profile, Qt)
return np.log(res) if return_log else res
def prob_t(self, seq_p, seq_ch, t, pattern_multiplicity = None,
return_log=False, ignore_gaps=True):
"""
Compute the probability to observe seq_ch (child sequence) after time t starting from seq_p
(parent sequence).
Parameters
----------
seq_p : character array
Parent sequence
seq_c : character array
Child sequence
t : double
Time (branch len) separating the profiles.
pattern_multiplicity : numpy array
If sequences are reduced by combining identical alignment patterns,
these multplicities need to be accounted for when counting the number
of mutations across a branch. If None, all pattern are assumed to
occur exactly once.
return_log : bool
It True, return log-probability.
Returns
-------
prob : np.array
Resulting probability
"""
if t<0:
logP = -ttconf.BIG_NUMBER
else:
tmp_eQT = self.expQt(t)
bad_indices=(tmp_eQT==0)
logQt = np.log(tmp_eQT + ttconf.TINY_NUMBER*(bad_indices))
logQt[np.isnan(logQt) | np.isinf(logQt) | bad_indices] = -ttconf.BIG_NUMBER
seq_indices_c = np.zeros(len(seq_ch), dtype=int)
seq_indices_p = np.zeros(len(seq_p), dtype=int)
for ai, a in enumerate(self.alphabet):
seq_indices_p[seq_p==a] = ai
seq_indices_c[seq_ch==a] = ai
if len(logQt.shape)==2:
logP = np.sum(logQt[seq_indices_p, seq_indices_c]*pattern_multiplicity)
else:
logP = np.sum(logQt[seq_indices_p, seq_indices_c, np.arange(len(seq_ch))]*pattern_multiplicity)
return logP if return_log else np.exp(logP)
def average_rate(self):
if self.Pi.shape[1]>1:
return np.einsum('a,ia,ij,ja->a',self.mu, self.Pi, self.W, self.Pi)
else:
return self.mu*np.einsum('ia,ij,ja->a',self.Pi, self.W, self.Pi)
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