def roh_poissonhmm(gv,
pos,
phet_roh=0.001,
phet_nonroh=(0.0025, 0.01),
transition=1e-3,
window_size=1000,
min_roh=0,
is_accessible=None,
contig_size=None):
"""Call ROH (runs of homozygosity) in a single individual given a genotype vector.
This function computes the likely ROH using a Poisson HMM model. The chromosome is divided into
equally accessible windows of specified size, then the number of hets observed in each is used
to fit a Poisson HMM. Note this is much faster than `roh_mhmm`, but at the cost of some
resolution.
The model is provided with a probability of observing a het in a ROH (`phet_roh`) and one
or more probabilities of observing a het in a non-ROH, as this probability may not be
constant across the genome (`phet_nonroh`).
Parameters
----------
gv : array_like, int, shape (n_variants, ploidy)
Genotype vector.
pos: array_like, int, shape (n_variants,)
Positions of variants, same 0th dimension as `gv`.
phet_roh: float, optional
Probability of observing a heterozygote in a ROH. Appropriate values
will depend on de novo mutation rate and genotype error rate.
phet_nonroh: tuple of floats, optional
One or more probabilites of observing a heterozygote outside of ROH.
Appropriate values will depend primarily on nucleotide diversity within
the population, but also on mutation rate and genotype error rate.
transition: float, optional
Probability of moving between states. This is based on windows, so a larger window size may
call for a larger transitional probability
window_size: integer, optional
Window size (equally accessible bases) to consider as a potential ROH. Setting this window
too small may result in spurious ROH calls, while too large will result in a lack of
resolution.
min_roh: integer, optional
Minimum size (bp) to condsider as a ROH. Will depend on contig size and recombination rate.
is_accessible: array_like, bool, shape (`contig_size`,), optional
Boolean array for each position in contig describing whether accessible
or not. Although optional, highly recommended so invariant sites are distinguishable from
sites where variation is inaccessible
contig_size: integer, optional
If is_accessible is not available, use this to specify the size of the contig, and assume
all sites are accessible.
Returns
-------
df_roh: DataFrame
Data frame where each row describes a run of homozygosity. Columns are 'start',
'stop', 'length' and 'is_marginal'. Start and stop are 1-based, stop-inclusive.
froh: float
Proportion of genome in a ROH.
Notes
-----
This function requires `pomegranate` (>= 0.9.0) to be installed.
"""
from pomegranate import HiddenMarkovModel, PoissonDistribution
# equally accessbile windows
if is_accessible is None:
if contig_size is None:
raise ValueError(
"If is_accessibile argument is not provided, you must provide contig_size"
)
is_accessible = np.ones((contig_size, ), dtype="bool")
else:
contig_size = is_accessible.size
eqw = equally_accessible_windows(is_accessible, window_size)
ishet = GenotypeVector(gv).is_het()
counts, wins, records = windowed_statistic(pos, ishet, np.sum, windows=eqw)
# heterozygote probabilities
het_px = np.concatenate([(phet_roh, ), phet_nonroh])
# start probabilities (all equal)
start_prob = np.repeat(1 / het_px.size, het_px.size)
# transition between underlying states
transition_mx = _hmm_derive_transition_matrix(transition, het_px.size)
dists = [PoissonDistribution(x * window_size) for x in het_px]
model = HiddenMarkovModel.from_matrix(
transition_probabilities=transition_mx,
distributions=dists,
starts=start_prob)
prediction = np.array(model.predict(counts[:, None]))
df_blocks = tabulate_state_blocks(prediction,
states=list(range(len(het_px))))
df_roh = df_blocks[(df_blocks.state == 0)].reset_index(drop=True)
# adapt the dataframe for ROH
df_roh["start"] = df_roh.start_ridx.apply(lambda y: eqw[y, 0])
df_roh["stop"] = df_roh.stop_lidx.apply(lambda y: eqw[y, 1])
df_roh["length"] = df_roh.stop - df_roh.start
# filter by ROH size
if min_roh > 0:
df_roh = df_roh[df_roh.length >= min_roh]
# compute FROH
froh = df_roh.length.sum() / contig_size
return df_roh[["start", "stop", "length", "is_marginal"]], froh
def roh_mhmm(gv,
pos,
phet_roh=0.001,
phet_nonroh=(0.0025, 0.01),
transition=1e-6,
min_roh=0,
is_accessible=None,
contig_size=None):
"""Call ROH (runs of homozygosity) in a single individual given a genotype vector.
This function computes the likely ROH using a Multinomial HMM model. There are 3
observable states at each position in a chromosome/contig: 0 = Hom, 1 = Het,
2 = inaccessible (i.e., unobserved).
The model is provided with a probability of observing a het in a ROH (`phet_roh`) and one
or more probabilities of observing a het in a non-ROH, as this probability may not be
constant across the genome (`phet_nonroh`).
Parameters
----------
gv : array_like, int, shape (n_variants, ploidy)
Genotype vector.
pos: array_like, int, shape (n_variants,)
Positions of variants, same 0th dimension as `gv`.
phet_roh: float, optional
Probability of observing a heterozygote in a ROH. Appropriate values
will depend on de novo mutation rate and genotype error rate.
phet_nonroh: tuple of floats, optional
One or more probabilites of observing a heterozygote outside of ROH.
Appropriate values will depend primarily on nucleotide diversity within
the population, but also on mutation rate and genotype error rate.
transition: float, optional
Probability of moving between states.
min_roh: integer, optional
Minimum size (bp) to condsider as a ROH. Will depend on contig size
and recombination rate.
is_accessible: array_like, bool, shape (`contig_size`,), optional
Boolean array for each position in contig describing whether accessible
or not.
contig_size: int, optional
If is_accessible not known/not provided, allows specification of
total length of contig.
Returns
-------
df_roh: DataFrame
Data frame where each row describes a run of homozygosity. Columns are 'start',
'stop', 'length' and 'is_marginal'. Start and stop are 1-based, stop-inclusive.
froh: float
Proportion of genome in a ROH.
Notes
-----
This function requires `hmmlearn <http://hmmlearn.readthedocs.io/en/latest/>`_ to be
installed.
This function currently requires around 4GB memory for a contig size of ~50Mbp.
"""
from hmmlearn import hmm
# setup inputs
if isinstance(phet_nonroh, float):
phet_nonroh = phet_nonroh,
gv = GenotypeVector(gv)
pos = asarray_ndim(pos, 1)
check_dim0_aligned(gv, pos)
is_accessible = asarray_ndim(is_accessible, 1, dtype=bool)
# heterozygote probabilities
het_px = np.concatenate([(phet_roh, ), phet_nonroh])
# start probabilities (all equal)
start_prob = np.repeat(1 / het_px.size, het_px.size)
# transition between underlying states
transition_mx = _hmm_derive_transition_matrix(transition, het_px.size)
# probability of inaccessible
if is_accessible is None:
if contig_size is None:
raise ValueError(
"If is_accessibile argument is not provided, you must provide contig_size"
)
p_accessible = 1.0
else:
p_accessible = is_accessible.mean()
contig_size = is_accessible.size
emission_mx = _mhmm_derive_emission_matrix(het_px, p_accessible)
# initialize HMM
roh_hmm = hmm.MultinomialHMM(n_components=het_px.size)
roh_hmm.n_symbols_ = 3
roh_hmm.startprob_ = start_prob
roh_hmm.transmat_ = transition_mx
roh_hmm.emissionprob_ = emission_mx
# locate heterozygous calls
is_het = gv.is_het()
# predict ROH state
pred, obs = _mhmm_predict_roh_state(roh_hmm, is_het, pos, is_accessible,
contig_size)
# find ROH windows
df_blocks = tabulate_state_blocks(pred, states=list(range(len(het_px))))
df_roh = df_blocks[(df_blocks.state == 0)].reset_index(drop=True)
# adapt the dataframe for ROH
for col in 'state', 'support', 'start_lidx', 'stop_ridx', 'size_max':
del df_roh[col]
df_roh.rename(columns={
'start_ridx': 'start',
'stop_lidx': 'stop',
'size_min': 'length'
},
inplace=True)
# make coordinates 1-based
df_roh['start'] = df_roh['start'] + 1
df_roh['stop'] = df_roh['stop'] + 1
# filter by ROH size
if min_roh > 0:
df_roh = df_roh[df_roh.length >= min_roh]
# compute FROH
froh = df_roh.length.sum() / contig_size
return df_roh, froh