1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 180 181 182 183 184 185 186 187 188 189 190 191 192 193 194 195 196 197 198 199 200 201 202 203 204 205 206 207 208 209 210 211 212 213 214 215 216 217 218 219 220 221 222 223 224 225 226 227 228 229 230 231 232 233 234 235 236 237 238 239 240 241 242 243 244 245 246 247 248 249 250 251 252 253 254 255 256 257 258 259 260 261 262 263 264 265 266 267 268 269 270 271 272 273 274 275 276 277 278 279 280 281 282 283 284 285 286 287 288 289 290 291 292 293 294 295 296 297 298 299 300 301 302 303 304 305 306 307 308 309 310 311 312 313 314 315 316 317 318 319 320 321 322 323 324 325 326 327 328 329 330 331 332 333 334 335 336 337 338 339 340 341 342 343 344 345 346 347 348 349 350 351 352 353 354 355 356 357 358 359 360 361 362 363 364 365 366 367 368 369 370 371 372 373 374 375 376 377 378 379 380 381 382 383 384 385 386 387 388 389 390 391 392 393 394 395 396 397 398 399 400 401 402 403 404 405 406 407 408 409 410 411 412 413 414 415 416 417 418 419 420 421 422 423 424 425 426 427 428 429 430 431 432 433 434 435 436 437 438 439 440 441 442 443 444 445 446 447 448 449 450 451 452 453 454 455 456 457 458 459 460 461 462 463 464 465 466 467 468 469
|
import warnings
from functools import partial
from operator import add
import numpy as np
from ._logging import get_logger
from .parallel import partition, split
from .util import mad
__all__ = ["balance_cooler"]
logger = get_logger(__name__)
class ConvergenceWarning(UserWarning):
pass
def _init(chunk):
return np.copy(chunk["pixels"]["count"])
def _binarize(chunk, data):
data[data != 0] = 1
return data
def _zero_diags(n_diags, chunk, data):
pixels = chunk["pixels"]
mask = np.abs(pixels["bin1_id"] - pixels["bin2_id"]) < n_diags
data[mask] = 0
return data
def _zero_trans(chunk, data):
chrom_ids = chunk["bins"]["chrom"]
pixels = chunk["pixels"]
mask = chrom_ids[pixels["bin1_id"]] != chrom_ids[pixels["bin2_id"]]
data[mask] = 0
return data
def _zero_cis(chunk, data):
chrom_ids = chunk["bins"]["chrom"]
pixels = chunk["pixels"]
mask = chrom_ids[pixels["bin1_id"]] == chrom_ids[pixels["bin2_id"]]
data[mask] = 0
return data
def _timesouterproduct(vec, chunk, data):
pixels = chunk["pixels"]
data = vec[pixels["bin1_id"]] * vec[pixels["bin2_id"]] * data
return data
def _marginalize(chunk, data):
n = len(chunk["bins"]["chrom"])
pixels = chunk["pixels"]
marg = np.bincount(pixels["bin1_id"], weights=data, minlength=n) + np.bincount(
pixels["bin2_id"], weights=data, minlength=n
)
return marg
def _balance_genomewide(
bias,
clr,
spans,
filters,
chunksize,
map,
tol,
max_iters,
rescale_marginals,
use_lock,
):
scale = 1.0
n_bins = len(bias)
for _ in range(max_iters):
marg = (
split(clr, spans=spans, map=map, use_lock=use_lock) # noqa
.prepare(_init)
.pipe(filters)
.pipe(_timesouterproduct, bias)
.pipe(_marginalize)
.reduce(add, np.zeros(n_bins))
)
nzmarg = marg[marg != 0]
if not len(nzmarg):
scale = np.nan
bias[:] = np.nan
var = 0.0
break
marg = marg / nzmarg.mean()
marg[marg == 0] = 1
bias /= marg
var = nzmarg.var()
logger.info(f"variance is {var}")
if var < tol:
break
else:
warnings.warn(
"Iteration limit reached without convergence.", ConvergenceWarning
)
scale = nzmarg.mean()
bias[bias == 0] = np.nan
if rescale_marginals:
bias /= np.sqrt(scale)
return bias, scale, var
def _balance_cisonly(
bias,
clr,
spans,
filters,
chunksize,
map,
tol,
max_iters,
rescale_marginals,
use_lock,
):
chroms = clr.chroms()["name"][:]
chrom_ids = np.arange(len(clr.chroms()))
chrom_offsets = clr._load_dset("indexes/chrom_offset")
bin1_offsets = clr._load_dset("indexes/bin1_offset")
scales = np.ones(len(chrom_ids))
n_bins = len(bias)
for cid, lo, hi in zip(chrom_ids, chrom_offsets[:-1], chrom_offsets[1:]):
logger.info(chroms[cid])
plo, phi = bin1_offsets[lo], bin1_offsets[hi]
spans = list(partition(plo, phi, chunksize))
scale = 1.0
for _ in range(max_iters):
marg = (
split(clr, spans=spans, map=map, use_lock=use_lock) # noqa
.prepare(_init)
.pipe(filters)
.pipe(_timesouterproduct, bias)
.pipe(_marginalize)
.reduce(add, np.zeros(n_bins))
)
marg = marg[lo:hi]
nzmarg = marg[marg != 0]
if not len(nzmarg):
scale = np.nan
bias[lo:hi] = np.nan
var = 0.0
break
marg = marg / nzmarg.mean()
marg[marg == 0] = 1
bias[lo:hi] /= marg
var = nzmarg.var()
logger.info(f"variance is {var}")
if var < tol:
break
else:
warnings.warn(
"Iteration limit reached without convergence on {}.".format(
chroms[cid]
),
ConvergenceWarning,
)
scale = nzmarg.mean()
b = bias[lo:hi]
b[b == 0] = np.nan
scales[cid] = scale
if rescale_marginals:
bias[lo:hi] /= np.sqrt(scale)
return bias, scales, var
def _balance_transonly(
bias,
clr,
spans,
filters,
chunksize,
map,
tol,
max_iters,
rescale_marginals,
use_lock,
):
scale = 1.0
n_bins = len(bias)
chrom_offsets = clr._load_dset("indexes/chrom_offset")
cweights = 1.0 / np.concatenate(
[
[(1 - (hi - lo) / n_bins)] * (hi - lo)
for lo, hi in zip(chrom_offsets[:-1], chrom_offsets[1:])
]
)
for _ in range(max_iters):
marg = (
split(clr, spans=spans, map=map, use_lock=use_lock) # noqa
.prepare(_init)
.pipe(filters)
.pipe(_zero_cis)
.pipe(_timesouterproduct, bias * cweights)
.pipe(_marginalize)
.reduce(add, np.zeros(n_bins))
)
nzmarg = marg[marg != 0]
if not len(nzmarg):
scale = np.nan
bias[:] = np.nan
var = 0.0
break
marg = marg / nzmarg.mean()
marg[marg == 0] = 1
bias /= marg
var = nzmarg.var()
logger.info(f"variance is {var}")
if var < tol:
break
else:
warnings.warn(
"Iteration limit reached without convergence.", ConvergenceWarning
)
scale = nzmarg.mean()
bias[bias == 0] = np.nan
if rescale_marginals:
bias /= np.sqrt(scale)
return bias, scale, var
def balance_cooler(
clr,
*,
cis_only=False,
trans_only=False,
ignore_diags=2,
mad_max=5,
min_nnz=10,
min_count=0,
blacklist=None,
rescale_marginals=True,
x0=None,
tol=1e-5,
max_iters=200,
chunksize=10_000_000,
map=map,
use_lock=False,
store=False,
store_name="weight",
):
"""
Iterative correction or matrix balancing of a sparse Hi-C contact map in
Cooler HDF5 format.
Parameters
----------
clr : cooler.Cooler
Cooler object
cis_only : bool, optional
Do iterative correction on intra-chromosomal data only.
Inter-chromosomal data is ignored.
trans_only : bool, optional
Do iterative correction on inter-chromosomal data only.
Intra-chromosomal data is ignored.
ignore_diags : int or False, optional
Drop elements occurring on the first ``ignore_diags`` diagonals of the
matrix (including the main diagonal).
chunksize : int or None, optional
Split the contact matrix pixel records into equally sized chunks to
save memory and/or parallelize. Set to ``None`` to use all the pixels
at once.
mad_max : int, optional
Pre-processing bin-level filter. Drop bins whose log marginal sum is
less than ``mad_max`` median absolute deviations below the median log
marginal sum.
min_nnz : int, optional
Pre-processing bin-level filter. Drop bins with fewer nonzero elements
than this value.
min_count : int, optional
Pre-processing bin-level filter. Drop bins with lower marginal sum than
this value.
blacklist : list or 1D array, optional
An explicit list of IDs of bad bins to filter out when performing
balancing.
rescale_marginals : bool, optional
Normalize the balancing weights such that the balanced matrix has rows
/ columns that sum to 1.0. The scale factor is stored in the ``stats``
output dictionary.
map : callable, optional
Map function to dispatch the matrix chunks to workers.
Default is the builtin ``map``, but alternatives include parallel map
implementations from a multiprocessing pool.
x0 : 1D array, optional
Initial weight vector to use. Default is to start with ones(n_bins).
tol : float, optional
Convergence criterion is the variance of the marginal (row/col) sum
vector.
max_iters : int, optional
Iteration limit.
store : bool, optional
Whether to store the results in the file when finished. Default is
False.
store_name : str, optional
Name of the column of the bin table to save to. Default name is
'weight'.
Returns
-------
bias : 1D array, whose shape is the number of bins in ``h5``.
Vector of bin bias weights to normalize the observed contact map.
Dropped bins will be assigned the value NaN.
N[i, j] = O[i, j] * bias[i] * bias[j]
stats : dict
Summary of parameters used to perform balancing and the average
magnitude of the corrected matrix's marginal sum at convergence.
"""
# Divide the number of elements into non-overlapping chunks
nnz = clr.info["nnz"]
if chunksize is None:
chunksize = nnz
spans = [(0, nnz)]
else:
edges = np.arange(0, nnz + chunksize, chunksize)
spans = list(zip(edges[:-1], edges[1:]))
# List of pre-marginalization data transformations
base_filters = []
if cis_only:
base_filters.append(_zero_trans)
if ignore_diags:
base_filters.append(partial(_zero_diags, ignore_diags))
# Initialize the bias weights
n_bins = clr.info["nbins"]
if x0 is not None:
bias = x0
bias[np.isnan(bias)] = 0
else:
bias = np.ones(n_bins, dtype=float)
# Drop bins with too few nonzeros from bias
if min_nnz > 0:
filters = [_binarize] + base_filters
marg_nnz = (
split(clr, spans=spans, map=map, use_lock=use_lock) # noqa
.prepare(_init)
.pipe(filters)
.pipe(_marginalize)
.reduce(add, np.zeros(n_bins))
)
bias[marg_nnz < min_nnz] = 0
filters = base_filters
marg = (
split(clr, spans=spans, map=map, use_lock=use_lock) # noqa
.prepare(_init)
.pipe(filters)
.pipe(_marginalize)
.reduce(add, np.zeros(n_bins))
)
# Drop bins with too few total counts from bias
if min_count:
bias[marg < min_count] = 0
# MAD-max filter on the marginals
if mad_max > 0:
offsets = clr._load_dset("indexes/chrom_offset")
for lo, hi in zip(offsets[:-1], offsets[1:]):
c_marg = marg[lo:hi]
marg[lo:hi] /= np.median(c_marg[c_marg > 0])
logNzMarg = np.log(marg[marg > 0])
med_logNzMarg = np.median(logNzMarg)
dev_logNzMarg = mad(logNzMarg)
cutoff = np.exp(med_logNzMarg - mad_max * dev_logNzMarg)
bias[marg < cutoff] = 0
# Filter out pre-determined bad bins
if blacklist is not None:
bias[blacklist] = 0
# Do balancing
if cis_only:
bias, scale, var = _balance_cisonly(
bias,
clr,
spans,
base_filters,
chunksize,
map,
tol,
max_iters,
rescale_marginals,
use_lock,
)
elif trans_only:
bias, scale, var = _balance_transonly(
bias,
clr,
spans,
base_filters,
chunksize,
map,
tol,
max_iters,
rescale_marginals,
use_lock,
)
else:
bias, scale, var = _balance_genomewide(
bias,
clr,
spans,
base_filters,
chunksize,
map,
tol,
max_iters,
rescale_marginals,
use_lock,
)
stats = {
"tol": tol,
"min_nnz": min_nnz,
"min_count": min_count,
"mad_max": mad_max,
"cis_only": cis_only,
"ignore_diags": ignore_diags,
"scale": scale,
"converged": var < tol,
"var": var,
"divisive_weights": False,
}
if store:
with clr.open("r+") as grp:
if store_name in grp["bins"]:
del grp["bins"][store_name]
h5opts = {"compression": "gzip", "compression_opts": 6}
grp["bins"].create_dataset(store_name, data=bias, **h5opts)
grp["bins"][store_name].attrs.update(stats)
return bias, stats
iterative_correction = balance_cooler # alias
|