def estimate_clock_model(params):
"""
implementing treetime clock
"""
if assure_tree(params, tmp_dir='clock_model_tmp'):
return 1
dates = utils.parse_dates(params.dates, date_col=params.date_column, name_col=params.name_column)
if len(dates)==0:
return 1
outdir = get_outdir(params, '_clock')
###########################################################################
### READ IN VCF
###########################################################################
#sets ref and fixed_pi to None if not VCF
aln, ref, fixed_pi = read_if_vcf(params)
is_vcf = True if ref is not None else False
###########################################################################
### ESTIMATE ROOT (if requested) AND DETERMINE TEMPORAL SIGNAL
###########################################################################
if params.aln is None and params.sequence_length is None:
print("one of arguments '--aln' and '--sequence-length' is required.", file=sys.stderr)
return 1
basename = get_basename(params, outdir)
try:
myTree = TreeTime(dates=dates, tree=params.tree, aln=aln, gtr='JC69',
verbose=params.verbose, seq_len=params.sequence_length,
ref=ref)
except TreeTimeError as e:
print("\nTreeTime setup failed. Please see above for error messages and/or rerun with --verbose 4\n")
raise e
myTree.tip_slack=params.tip_slack
if params.clock_filter:
n_bad = [n.name for n in myTree.tree.get_terminals() if n.bad_branch]
myTree.clock_filter(n_iqd=params.clock_filter, reroot=params.reroot or 'least-squares')
n_bad_after = [n.name for n in myTree.tree.get_terminals() if n.bad_branch]
if len(n_bad_after)>len(n_bad):
print("The following leaves don't follow a loose clock and "
"will be ignored in rate estimation:\n\t"
+"\n\t".join(set(n_bad_after).difference(n_bad)))
if not params.keep_root:
# reroot to optimal root, this assigns clock_model to myTree
if params.covariation: # this requires branch length estimates
myTree.run(root="least-squares", max_iter=0,
use_covariation=params.covariation)
try:
res = myTree.reroot(params.reroot,
force_positive=not params.allow_negative_rate)
except TreeTimeError as e:
print("ERROR: unknown root or rooting mechanism!")
raise e
myTree.get_clock_model(covariation=params.covariation)
else:
myTree.get_clock_model(covariation=params.covariation)
d2d = utils.DateConversion.from_regression(myTree.clock_model)
print('\n',d2d)
print(fill('The R^2 value indicates the fraction of variation in'
'root-to-tip distance explained by the sampling times.'
'Higher values corresponds more clock-like behavior (max 1.0).')+'\n')
print(fill('The rate is the slope of the best fit of the date to'
'the root-to-tip distance and provides an estimate of'
'the substitution rate. The rate needs to be positive!'
'Negative rates suggest an inappropriate root.')+'\n')
print('\nThe estimated rate and tree correspond to a root date:')
if params.covariation:
reg = myTree.clock_model
dp = np.array([reg['intercept']/reg['slope']**2,-1./reg['slope']])
droot = np.sqrt(reg['cov'][:2,:2].dot(dp).dot(dp))
print('\n--- root-date:\t %3.2f +/- %1.2f (one std-dev)\n\n'%(-d2d.intercept/d2d.clock_rate, droot))
else:
print('\n--- root-date:\t %3.2f\n\n'%(-d2d.intercept/d2d.clock_rate))
if not params.keep_root:
# write rerooted tree to file
outtree_name = basename+'rerooted.newick'
Phylo.write(myTree.tree, outtree_name, 'newick')
print("--- re-rooted tree written to \n\t%s\n"%outtree_name)
table_fname = basename+'rtt.csv'
with open(table_fname, 'w') as ofile:
ofile.write("#name, date, root-to-tip distance\n")
ofile.write("#Dates of nodes that didn't have a specified date are inferred from the root-to-tip regression.\n")
for n in myTree.tree.get_terminals():
if hasattr(n, "raw_date_constraint") and (n.raw_date_constraint is not None):
if np.isscalar(n.raw_date_constraint):
tmp_str = str(n.raw_date_constraint)
elif len(n.raw_date_constraint):
tmp_str = str(n.raw_date_constraint[0])+'-'+str(n.raw_date_constraint[1])
else:
tmp_str = ''
ofile.write("%s, %s, %f\n"%(n.name, tmp_str, n.dist2root))
else:
ofile.write("%s, %f, %f\n"%(n.name, d2d.numdate_from_dist2root(n.dist2root), n.dist2root))
for n in myTree.tree.get_nonterminals(order='preorder'):
ofile.write("%s, %f, %f\n"%(n.name, d2d.numdate_from_dist2root(n.dist2root), n.dist2root))
print("--- wrote dates and root-to-tip distances to \n\t%s\n"%table_fname)
###########################################################################
### PLOT AND SAVE RESULT
###########################################################################
plot_rtt(myTree, outdir+params.plot_rtt)
return 0
def estimate_clock_model(params):
"""
implementing treetime clock
"""
if assure_tree(params, tmp_dir='clock_model_tmp'):
return 1
dates = utils.parse_dates(params.dates)
if len(dates)==0:
return 1
outdir = get_outdir(params, '_clock')
###########################################################################
### READ IN VCF
###########################################################################
#sets ref and fixed_pi to None if not VCF
aln, ref, fixed_pi = read_if_vcf(params)
is_vcf = True if ref is not None else False
###########################################################################
### ESTIMATE ROOT (if requested) AND DETERMINE TEMPORAL SIGNAL
###########################################################################
if params.aln is None and params.sequence_length is None:
print("one of arguments '--aln' and '--sequence-length' is required.", file=sys.stderr)
return 1
basename = get_basename(params, outdir)
myTree = TreeTime(dates=dates, tree=params.tree, aln=aln, gtr='JC69',
verbose=params.verbose, seq_len=params.sequence_length,
ref=ref)
myTree.tip_slack=params.tip_slack
if myTree.tree is None:
print("ERROR: tree loading failed. exiting...")
return 1
if params.clock_filter:
n_bad = [n.name for n in myTree.tree.get_terminals() if n.bad_branch]
myTree.clock_filter(n_iqd=params.clock_filter, reroot=params.reroot or 'least-squares')
n_bad_after = [n.name for n in myTree.tree.get_terminals() if n.bad_branch]
if len(n_bad_after)>len(n_bad):
print("The following leaves don't follow a loose clock and "
"will be ignored in rate estimation:\n\t"
+"\n\t".join(set(n_bad_after).difference(n_bad)))
if not params.keep_root:
# reroot to optimal root, this assigns clock_model to myTree
if params.covariation: # this requires branch length estimates
myTree.run(root="least-squares", max_iter=0,
use_covariation=params.covariation)
res = myTree.reroot(params.reroot,
force_positive=not params.allow_negative_rate)
myTree.get_clock_model(covariation=params.covariation)
if res==ttconf.ERROR:
print("ERROR: unknown root or rooting mechanism!\n"
"\tvalid choices are 'least-squares', 'ML', and 'ML-rough'")
return 1
else:
myTree.get_clock_model(covariation=params.covariation)
d2d = utils.DateConversion.from_regression(myTree.clock_model)
print('\n',d2d)
print('The R^2 value indicates the fraction of variation in'
'\nroot-to-tip distance explained by the sampling times.'
'\nHigher values corresponds more clock-like behavior (max 1.0).')
print('\nThe rate is the slope of the best fit of the date to'
'\nthe root-to-tip distance and provides an estimate of'
'\nthe substitution rate. The rate needs to be positive!'
'\nNegative rates suggest an inappropriate root.\n')
print('\nThe estimated rate and tree correspond to a root date:')
if params.covariation:
reg = myTree.clock_model
dp = np.array([reg['intercept']/reg['slope']**2,-1./reg['slope']])
droot = np.sqrt(reg['cov'][:2,:2].dot(dp).dot(dp))
print('\n--- root-date:\t %3.2f +/- %1.2f (one std-dev)\n\n'%(-d2d.intercept/d2d.clock_rate, droot))
else:
print('\n--- root-date:\t %3.2f\n\n'%(-d2d.intercept/d2d.clock_rate))
if not params.keep_root:
# write rerooted tree to file
outtree_name = basename+'rerooted.newick'
Phylo.write(myTree.tree, outtree_name, 'newick')
print("--- re-rooted tree written to \n\t%s\n"%outtree_name)
table_fname = basename+'rtt.csv'
with open(table_fname, 'w') as ofile:
ofile.write("#name, date, root-to-tip distance\n")
ofile.write("#Dates of nodes that didn't have a specified date are inferred from the root-to-tip regression.\n")
for n in myTree.tree.get_terminals():
if hasattr(n, "raw_date_constraint") and (n.raw_date_constraint is not None):
if np.isscalar(n.raw_date_constraint):
tmp_str = str(n.raw_date_constraint)
elif len(n.raw_date_constraint):
tmp_str = str(n.raw_date_constraint[0])+'-'+str(n.raw_date_constraint[1])
else:
tmp_str = ''
ofile.write("%s, %s, %f\n"%(n.name, tmp_str, n.dist2root))
else:
ofile.write("%s, %f, %f\n"%(n.name, d2d.numdate_from_dist2root(n.dist2root), n.dist2root))
for n in myTree.tree.get_nonterminals(order='preorder'):
ofile.write("%s, %f, %f\n"%(n.name, d2d.numdate_from_dist2root(n.dist2root), n.dist2root))
print("--- wrote dates and root-to-tip distances to \n\t%s\n"%table_fname)
###########################################################################
### PLOT AND SAVE RESULT
###########################################################################
plot_rtt(myTree, outdir+params.plot_rtt)
return 0
def timetree(params):
"""
implementeing treetime tree
"""
if params.relax is None:
relaxed_clock_params = None
elif params.relax==[]:
relaxed_clock_params=True
elif len(params.relax)==2:
relaxed_clock_params={'slack':params.relax[0], 'coupling':params.relax[1]}
dates = utils.parse_dates(params.dates, date_col=params.date_column, name_col=params.name_column)
if len(dates)==0:
print("No valid dates -- exiting.")
return 1
if assure_tree(params, tmp_dir='timetree_tmp'):
print("No tree -- exiting.")
return 1
outdir = get_outdir(params, '_treetime')
gtr = create_gtr(params)
infer_gtr = params.gtr=='infer'
###########################################################################
### READ IN VCF
###########################################################################
#sets ref and fixed_pi to None if not VCF
aln, ref, fixed_pi = read_if_vcf(params)
is_vcf = True if ref is not None else False
branch_length_mode = params.branch_length_mode
#variable-site-only trees can have big branch lengths, the auto setting won't work.
if is_vcf or (params.aln and params.sequence_length):
if branch_length_mode == 'auto':
branch_length_mode = 'joint'
###########################################################################
### SET-UP and RUN
###########################################################################
if params.aln is None and params.sequence_length is None:
print("one of arguments '--aln' and '--sequence-length' is required.", file=sys.stderr)
return 1
myTree = TreeTime(dates=dates, tree=params.tree, ref=ref,
aln=aln, gtr=gtr, seq_len=params.sequence_length,
verbose=params.verbose, fill_overhangs=not params.keep_overhangs)
myTree.tip_slack=params.tip_slack
if not myTree.one_mutation:
print("TreeTime setup failed, exiting")
return 1
# coalescent model options
try:
coalescent = float(params.coalescent)
if coalescent<10*myTree.one_mutation:
coalescent = None
except:
if params.coalescent in ['opt', 'const', 'skyline']:
coalescent = params.coalescent
else:
print("unknown coalescent model specification, has to be either "
"a float, 'opt', 'const' or 'skyline' -- exiting")
return 1
# determine whether confidence intervals are to be computed and how the
# uncertainty in the rate estimate should be treated
calc_confidence = params.confidence
if params.clock_std_dev:
vary_rate = params.clock_std_dev if calc_confidence else False
elif params.confidence and params.covariation:
vary_rate = True
elif params.confidence:
print(fill("Outside of covariation aware mode TreeTime cannot estimate confidence intervals "
"without specified standard deviation of the clock rate.Please specify '--clock-std-dev' "
"or rerun with '--covariation'. Will proceed without confidence estimation"))
vary_rate = False
calc_confidence = False
else:
vary_rate = False
# RUN
root = None if params.keep_root else params.reroot
try:
success = myTree.run(root=root, relaxed_clock=relaxed_clock_params,
resolve_polytomies=(not params.keep_polytomies),
Tc=coalescent, max_iter=params.max_iter,
fixed_clock_rate=params.clock_rate,
n_iqd=params.clock_filter,
time_marginal="assign" if calc_confidence else False,
vary_rate = vary_rate,
branch_length_mode = branch_length_mode,
reconstruct_tip_states=params.reconstruct_tip_states,
fixed_pi=fixed_pi,
use_covariation = params.covariation, n_points=params.n_skyline)
except TreeTimeError as e:
print("\nTreeTime run FAILED: please check above for errors and/or rerun with --verbose 4.\n")
raise e
###########################################################################
### OUTPUT and saving of results
###########################################################################
if infer_gtr:
fname = outdir+'sequence_evolution_model.txt'
with open(fname, 'w') as ofile:
ofile.write(str(myTree.gtr)+'\n')
print('\nInferred sequence evolution model (saved as %s):'%fname)
print(myTree.gtr)
fname = outdir+'molecular_clock.txt'
with open(fname, 'w') as ofile:
ofile.write(str(myTree.date2dist)+'\n')
print('\nInferred sequence evolution model (saved as %s):'%fname)
print(myTree.date2dist)
basename = get_basename(params, outdir)
if coalescent in ['skyline', 'opt', 'const']:
print("Inferred coalescent model")
if coalescent=='skyline':
print_save_plot_skyline(myTree, plot=basename+'skyline.pdf', save=basename+'skyline.tsv', screen=True)
else:
Tc = myTree.merger_model.Tc.y[0]
print(" --T_c: \t %1.2e \toptimized inverse merger rate in units of substitutions"%Tc)
print(" --T_c: \t %1.2e \toptimized inverse merger rate in years"%(Tc/myTree.date2dist.clock_rate))
print(" --N_e: \t %1.2e \tcorresponding 'effective population size' assuming 50 gen/year\n"%(Tc/myTree.date2dist.clock_rate*50))
# plot
import matplotlib.pyplot as plt
from .treetime import plot_vs_years
leaf_count = myTree.tree.count_terminals()
label_func = lambda x: (x.name if x.is_terminal() and ((leaf_count<30
and (not params.no_tip_labels))
or params.tip_labels) else '')
plot_vs_years(myTree, show_confidence=False, label_func=label_func,
confidence=0.9 if calc_confidence else None)
tree_fname = (outdir + params.plot_tree)
plt.savefig(tree_fname)
print("--- saved tree as \n\t %s\n"%tree_fname)
plot_rtt(myTree, outdir + params.plot_rtt)
if params.relax:
fname = outdir+'substitution_rates.tsv'
print("--- wrote branch specific rates to\n\t %s\n"%fname)
with open(fname, 'w') as fh:
fh.write("#node\tclock_length\tmutation_length\trate\tfold_change\n")
for n in myTree.tree.find_clades(order="preorder"):
if n==myTree.tree.root:
continue
g = n.branch_length_interpolator.gamma
fh.write("%s\t%1.3e\t%1.3e\t%1.3e\t%1.2f\n"%(n.name, n.clock_length, n.mutation_length, myTree.date2dist.clock_rate*g, g))
export_sequences_and_tree(myTree, basename, is_vcf, params.zero_based,
timetree=True, confidence=calc_confidence,
reconstruct_tip_states=params.reconstruct_tip_states)
return 0
def timetree(params):
"""
implementeing treetime tree
"""
if params.relax is None:
relaxed_clock_params = None
elif params.relax==[]:
relaxed_clock_params=True
elif len(params.relax)==2:
relaxed_clock_params={'slack':params.relax[0], 'coupling':params.relax[1]}
dates = utils.parse_dates(params.dates)
if len(dates)==0:
print("No valid dates -- exiting.")
return 1
if assure_tree(params, tmp_dir='timetree_tmp'):
print("No tree -- exiting.")
return 1
outdir = get_outdir(params, '_treetime')
gtr = create_gtr(params)
infer_gtr = params.gtr=='infer'
###########################################################################
### READ IN VCF
###########################################################################
#sets ref and fixed_pi to None if not VCF
aln, ref, fixed_pi = read_if_vcf(params)
is_vcf = True if ref is not None else False
branch_length_mode = params.branch_length_mode
#variable-site-only trees can have big branch lengths, the auto setting won't work.
if is_vcf or (params.aln and params.sequence_length):
if branch_length_mode == 'auto':
branch_length_mode = 'joint'
###########################################################################
### SET-UP and RUN
###########################################################################
if params.aln is None and params.sequence_length is None:
print("one of arguments '--aln' and '--sequence-length' is required.", file=sys.stderr)
return 1
myTree = TreeTime(dates=dates, tree=params.tree, ref=ref,
aln=aln, gtr=gtr, seq_len=params.sequence_length,
verbose=params.verbose)
myTree.tip_slack=params.tip_slack
if not myTree.one_mutation:
print("TreeTime setup failed, exiting")
return 1
# coalescent model options
try:
coalescent = float(params.coalescent)
if coalescent<10*myTree.one_mutation:
coalescent = None
except:
if params.coalescent in ['opt', 'const', 'skyline']:
coalescent = params.coalescent
else:
print("unknown coalescent model specification, has to be either "
"a float, 'opt', 'const' or 'skyline' -- exiting")
return 1
# determine whether confidence intervals are to be computed and how the
# uncertainty in the rate estimate should be treated
calc_confidence = params.confidence
if params.clock_std_dev:
vary_rate = params.clock_std_dev if calc_confidence else False
elif params.confidence and params.covariation:
vary_rate = True
elif params.confidence:
print("\nOutside of covariance aware mode TreeTime cannot estimate confidence intervals "
"without specified standard deviation of the clock rate Please specify '--clock-std-dev' "
"or rerun with '--covariance'. Will proceed without confidence estimation")
vary_rate = False
calc_confidence = False
else:
vary_rate = False
# RUN
root = None if params.keep_root else params.reroot
success = myTree.run(root=root, relaxed_clock=relaxed_clock_params,
resolve_polytomies=(not params.keep_polytomies),
Tc=coalescent, max_iter=params.max_iter,
fixed_clock_rate=params.clock_rate,
n_iqd=params.clock_filter,
time_marginal="assign" if calc_confidence else False,
vary_rate = vary_rate,
branch_length_mode = branch_length_mode,
fixed_pi=fixed_pi,
use_covariation = params.covariation)
if success==ttconf.ERROR: # if TreeTime.run failed, exit
print("\nTreeTime run FAILED: please check above for errors and/or rerun with --verbose 4.\n")
return 1
###########################################################################
### OUTPUT and saving of results
###########################################################################
if infer_gtr:
print('\nInferred GTR model:')
print(myTree.gtr)
print(myTree.date2dist)
basename = get_basename(params, outdir)
if coalescent in ['skyline', 'opt', 'const']:
print("Inferred coalescent model")
if coalescent=='skyline':
print_save_plot_skyline(myTree, plot=basename+'skyline.pdf', save=basename+'skyline.tsv', screen=True)
else:
Tc = myTree.merger_model.Tc.y[0]
print(" --T_c: \t %1.2e \toptimized inverse merger rate in units of substitutions"%Tc)
print(" --T_c: \t %1.2e \toptimized inverse merger rate in years"%(Tc/myTree.date2dist.clock_rate))
print(" --N_e: \t %1.2e \tcorresponding 'effective population size' assuming 50 gen/year\n"%(Tc/myTree.date2dist.clock_rate*50))
# plot
import matplotlib.pyplot as plt
from .treetime import plot_vs_years
leaf_count = myTree.tree.count_terminals()
label_func = lambda x: (x.name if x.is_terminal() and ((leaf_count<30
and (not params.no_tip_labels))
or params.tip_labels) else '')
plot_vs_years(myTree, show_confidence=False, label_func=label_func,
confidence=0.9 if params.confidence else None)
tree_fname = (outdir + params.plot_tree)
plt.savefig(tree_fname)
print("--- saved tree as \n\t %s\n"%tree_fname)
plot_rtt(myTree, outdir + params.plot_rtt)
if params.relax:
fname = outdir+'substitution_rates.tsv'
print("--- wrote branch specific rates to\n\t %s\n"%fname)
with open(fname, 'w') as fh:
fh.write("#node\tclock_length\tmutation_length\trate\tfold_change\n")
for n in myTree.tree.find_clades(order="preorder"):
if n==myTree.tree.root:
continue
g = n.branch_length_interpolator.gamma
fh.write("%s\t%1.3e\t%1.3e\t%1.3e\t%1.2f\n"%(n.name, n.clock_length, n.mutation_length, myTree.date2dist.clock_rate*g, g))
export_sequences_and_tree(myTree, basename, is_vcf, params.zero_based,
timetree=True, confidence=calc_confidence)
return 0