def partitioned_mds(path1,
path2,
prefix="",
centromere=0,
num_partitions=4,
maxmemory=32000000,
num_threads=3,
alpha=4,
res_ratio=10,
penalty=0.05,
weight=0.05):
"""Partitions structure into substructures and performs MDS"""
#create low-res structures
lowstructure1 = create_low_res_structure(path1, res_ratio)
lowstructure2 = create_low_res_structure(path2, res_ratio)
dt.make_compatible((lowstructure1, lowstructure2))
#get partitions
n = len(lowstructure1.getPoints())
if centromere == 0:
midpoint = int(n / 2)
else:
midpoint = lowstructure1.chrom.getAbsoluteIndex(centromere)
assert num_partitions % 2 == 0
partition_size1 = int(np.ceil(float(midpoint) / (num_partitions / 2)))
partition_size2 = int(np.ceil(float(n - midpoint) / (num_partitions / 2)))
lowpartitions = [
] #low substructures, defined on absolute indices not relative indices
for i in range(int(num_partitions / 2)):
lowpartitions.append(
(i * partition_size1, min(((i + 1) * partition_size1), midpoint)))
for i in range(int(num_partitions / 2)):
lowpartitions.append((midpoint + i * partition_size2,
min((midpoint + (i + 1) * partition_size2),
n - 1)))
lowpartitions = np.array(lowpartitions)
low_contactMat1 = dt.matFromBed(path1, lowstructure1)
low_contactMat2 = dt.matFromBed(path2, lowstructure2)
tad.substructuresFromAbsoluteTads(lowstructure1, lowpartitions)
tad.substructuresFromAbsoluteTads(lowstructure2, lowpartitions)
#create high-res chroms
size1, res1 = dt.basicParamsFromBed(path1)
highChrom1 = dt.ChromParameters(lowstructure1.chrom.minPos,
lowstructure1.chrom.maxPos, res1,
lowstructure1.chrom.name, size1)
size2, res2 = dt.basicParamsFromBed(path2)
highChrom2 = dt.ChromParameters(lowstructure2.chrom.minPos,
lowstructure2.chrom.maxPos, res2,
lowstructure2.chrom.name, size2)
#initialize high-res substructures
high_substructures1 = []
high_substructures2 = []
low_gen_coords = lowstructure1.getGenCoords()
offset1 = 0 #initialize
offset2 = 0
for partition in lowpartitions:
start_gen_coord = low_gen_coords[partition[0]]
end_gen_coord = low_gen_coords[partition[1]]
high_substructure1 = dt.structureFromBed(path1, highChrom1,
start_gen_coord,
end_gen_coord, offset1)
high_substructure2 = dt.structureFromBed(path2, highChrom2,
start_gen_coord,
end_gen_coord, offset2)
high_substructures1.append(high_substructure1)
high_substructures2.append(high_substructure2)
offset1 += (len(high_substructure1.points) - 1) #update
offset2 += (len(high_substructure2.points) - 1) #update
for high_substructure1, high_substructure2 in zip(high_substructures1,
high_substructures2):
dt.make_points_compatible((high_substructure1, high_substructure2))
highstructure1 = dt.Structure([], high_substructures1, highChrom1, 0)
highstructure2 = dt.Structure([], high_substructures2, highChrom2, 0)
infer_structures(low_contactMat1, lowstructure1, low_contactMat2,
lowstructure2, alpha, penalty, num_threads, weight)
print("Low-resolution MDS complete")
highSubstructures1 = pymp.shared.list(highstructure1.structures)
highSubstructures2 = pymp.shared.list(highstructure2.structures)
lowSubstructures1 = pymp.shared.list(lowstructure1.structures)
lowSubstructures2 = pymp.shared.list(lowstructure2.structures)
numSubstructures = len(highstructure1.structures)
num_threads = min(
(num_threads, mp.cpu_count(), numSubstructures)
) #don't exceed number of requested threads, available threads, or structures
with pymp.Parallel(num_threads) as p:
for substructurenum in p.range(numSubstructures):
highSubstructure1 = highSubstructures1[substructurenum]
highSubstructure2 = highSubstructures2[substructurenum]
trueLow1 = lowSubstructures1[substructurenum]
trueLow2 = lowSubstructures2[substructurenum]
#joint MDS
structure_contactMat1 = dt.matFromBed(
path1,
highSubstructure1) #contact matrix for this structure only
structure_contactMat2 = dt.matFromBed(
path2,
highSubstructure2) #contact matrix for this structure only
infer_structures(structure_contactMat1, highSubstructure1,
structure_contactMat2, highSubstructure2, 2.5,
penalty, num_threads, weight)
transform(trueLow1, highSubstructure1, res_ratio)
transform(trueLow2, highSubstructure2, res_ratio)
highSubstructures1[substructurenum] = highSubstructure1
highSubstructures2[substructurenum] = highSubstructure2
print("MDS performed on structure {} of {}".format(
substructurenum + 1, numSubstructures))
highstructure1.setstructures(highSubstructures1)
highstructure2.setstructures(highSubstructures2)
highstructure1.set_rel_indices()
highstructure2.set_rel_indices()
return highstructure1, highstructure2
def partitionedMDS(path, args):
"""Partitions structure into substructures and performs MDS"""
domainSmoothingParameter = args[0]
minSizeFraction = args[1]
maxmemory = args[2]
num_threads = args[3]
alpha = args[4]
res_ratio = args[5]
alpha2 = args[6]
#create low-res structure
low_chrom = dt.chromFromBed(path)
low_chrom.res *= res_ratio
lowstructure = dt.structureFromBed(path, low_chrom) #low global structure
#get TADs
low_contactMat = dt.matFromBed(path, lowstructure)
low_tad_indices = tad.getDomains(
low_contactMat, lowstructure, domainSmoothingParameter, minSizeFraction
) #low substructures, defined on relative indices not absolute indices
tad.substructuresFromTads(lowstructure, low_tad_indices)
#create high-res chrom
size, res = dt.basicParamsFromBed(path)
highChrom = dt.ChromParameters(lowstructure.chrom.minPos,
lowstructure.chrom.maxPos, res,
lowstructure.chrom.name, size)
highstructure = dt.Structure([], [], highChrom, 0)
high_substructures = []
low_gen_coords = lowstructure.getGenCoords()
offset = 0 #initialize
for td in low_tad_indices:
start_gen_coord = low_gen_coords[td[0]]
end_gen_coord = low_gen_coords[td[1]]
high_substructure = dt.structureFromBed(path, highChrom,
start_gen_coord, end_gen_coord,
offset)
high_substructures.append(high_substructure)
offset += len(high_substructure.points) #update
offset -= 1
highstructure.setstructures(high_substructures)
infer_structure(low_contactMat, lowstructure, alpha, num_threads)
print "Low-resolution MDS complete"
highSubstructures = pymp.shared.list(highstructure.structures)
lowSubstructures = pymp.shared.list(lowstructure.structures)
numSubstructures = len(highstructure.structures)
num_threads = min(
(num_threads, mp.cpu_count(), numSubstructures)
) #don't exceed number of requested threads, available threads, or structures
with pymp.Parallel(num_threads) as p:
for substructurenum in p.range(numSubstructures):
highSubstructure = highSubstructures[substructurenum]
if len(highSubstructure.getPoints()) > 0: #skip empty
trueLow = lowSubstructures[substructurenum]
#perform MDS individually
structure_contactMat = dt.matFromBed(
path,
highSubstructure) #contact matrix for this structure only
infer_structure(structure_contactMat, highSubstructure, alpha2,
num_threads)
#approximate as low resolution
inferredLow = dt.highToLow(highSubstructure, res_ratio)
#rescale
scaling_factor = la.radius_of_gyration(
trueLow) / la.radius_of_gyration(inferredLow)
for i, point in enumerate(inferredLow.points):
if point != 0:
x, y, z = point.pos
inferredLow.points[i].pos = (x * scaling_factor,
y * scaling_factor,
z * scaling_factor)
#recover the transformation for inferred from true low structure
r, t = la.getTransformation(inferredLow, trueLow)
t /= scaling_factor
#transform high structure
highSubstructure.transform(r, t)
highSubstructures[substructurenum] = highSubstructure
print "MDS performed on structure {} of {}".format(
substructurenum + 1, numSubstructures)
highstructure.setstructures(highSubstructures)
return highstructure
def create_high_res_structure(path, lowstructure):
size, res = dt.basicParamsFromBed(path)
highChrom = dt.ChromParameters(lowstructure.chrom.minPos,
lowstructure.chrom.maxPos, res,
lowstructure.chrom.name, size)
return dt.Structure([], [], highChrom, 0)