segmentmodel.py 121 KB
Newer Older
cmaffeo2's avatar
cmaffeo2 committed
1
import pdb
2
from pathlib import Path
3
import numpy as np
4
import random
5
6
7
from .model.arbdmodel import PointParticle, ParticleType, Group, ArbdModel
from .coords import rotationAboutAxis, quaternion_from_matrix, quaternion_to_matrix
from .model.nonbonded import *
8
from copy import copy, deepcopy
9
from .model.nbPot import nbDnaScheme
10

cmaffeo2's avatar
cmaffeo2 committed
11
12
from scipy.special import erf
import scipy.optimize as opt
13
from scipy import interpolate
cmaffeo2's avatar
cmaffeo2 committed
14

15
16
from .model.CanonicalNucleotideAtoms import canonicalNtFwd, canonicalNtRev, seqComplement
from .model.CanonicalNucleotideAtoms import enmTemplateHC, enmTemplateSQ, enmCorrectionsHC
cmaffeo2's avatar
cmaffeo2 committed
17

cmaffeo2's avatar
cmaffeo2 committed
18
19
from .model.spring_from_lp import k_angle as angle_spring_from_lp

20
# import pdb
21
"""
cmaffeo2's avatar
cmaffeo2 committed
22
TODO:
cmaffeo2's avatar
cmaffeo2 committed
23
 + fix handling of crossovers for atomic representation
cmaffeo2's avatar
cmaffeo2 committed
24
 + map to atomic representation
25
    + add nicks
cmaffeo2's avatar
cmaffeo2 committed
26
    + transform ssDNA nucleotides 
cmaffeo2's avatar
cmaffeo2 committed
27
    - shrink ssDNA
cmaffeo2's avatar
cmaffeo2 committed
28
    + shrink dsDNA backbone
29
    + make orientation continuous
cmaffeo2's avatar
cmaffeo2 committed
30
    + sequence
31
    + handle circular dna
32
 + ensure crossover bead potentials aren't applied twice 
33
 + remove performance bottlenecks
34
 - test for large systems
cmaffeo2's avatar
cmaffeo2 committed
35
 + assign sequence
36
 + ENM
37
38
 - rework Location class 
 - remove recursive calls
39
 - document
40
 - develop unit test suite
41
"""
cmaffeo2's avatar
cmaffeo2 committed
42
43
class CircularDnaError(Exception):
    pass
44

cmaffeo2's avatar
cmaffeo2 committed
45
46
47
class ParticleNotConnectedError(Exception):
    pass

48
49
class Location():
    """ Site for connection within an object """
50
    def __init__(self, container, address, type_, on_fwd_strand = True):
51
        ## TODO: remove cyclic references(?)
52
        self.container = container
cmaffeo2's avatar
cmaffeo2 committed
53
        self.address = address  # represents position along contour length in segment
cmaffeo2's avatar
cmaffeo2 committed
54
        # assert( type_ in ("end3","end5") ) # TODO remove or make conditional
55
        self.on_fwd_strand = on_fwd_strand
56
57
        self.type_ = type_
        self.particle = None
58
        self.connection = None
59
        self.is_3prime_side_of_connection = None
60

61
62
        self.prev_in_strand = None
        self.next_in_strand = None
63
64
        
        self.combine = None     # some locations might be combined in bead model 
65
66
67
68
69
70
71

    def get_connected_location(self):
        if self.connection is None:
            return None
        else:
            return self.connection.other(self)

72
    def set_connection(self, connection, is_3prime_side_of_connection):
73
        self.connection = connection # TODO weakref? 
74
        self.is_3prime_side_of_connection = is_3prime_side_of_connection
75

76
77
78
79
80
81
82
    def get_nt_pos(self):
        try:
            pos = self.container.contour_to_nt_pos(self.address, round_nt=True)
        except:
            if self.address == 0:
                pos = 0
            elif self.address == 1:
83
                pos = self.container.num_nt-1
84
85
86
87
            else:
                raise
        return pos

88
89
90
91
92
93
94
    def __repr__(self):
        if self.on_fwd_strand:
            on_fwd = "on_fwd_strand"
        else:
            on_fwd = "on_rev_strand"
        return "<Location {}.{}[{:.2f},{:d}]>".format( self.container.name, self.type_, self.address, self.on_fwd_strand)
        
95
96
97
98
99
100
101
102
103
class Connection():
    """ Abstract base class for connection between two elements """
    def __init__(self, A, B, type_ = None):
        assert( isinstance(A,Location) )
        assert( isinstance(B,Location) )
        self.A = A
        self.B = B
        self.type_ = type_
        
104
105
106
107
108
109
110
    def other(self, location):
        if location is self.A:
            return self.B
        elif location is self.B:
            return self.A
        else:
            raise Exception("OutOfBoundsError")
cmaffeo2's avatar
cmaffeo2 committed
111

112
113
114
115
116
117
    def delete(self):
        self.A.container.connections.remove(self)
        self.B.container.connections.remove(self)
        self.A.connection = None
        self.B.connection = None

cmaffeo2's avatar
cmaffeo2 committed
118
119
120
121
    def __repr__(self):
        return "<Connection {}--{}--{}]>".format( self.A, self.type_, self.B )
        

122
        
123
124
125
# class ConnectableElement(Transformable):
class ConnectableElement():
    """ Abstract base class """
cmaffeo2's avatar
cmaffeo2 committed
126
127
128
129
    def __init__(self, connection_locations=None, connections=None):
        if connection_locations is None: connection_locations = []
        if connections is None: connections = []

130
131
        ## TODO decide on names
        self.locations = self.connection_locations = connection_locations
132
133
        self.connections = connections

cmaffeo2's avatar
cmaffeo2 committed
134
    def get_locations(self, type_=None, exclude=()):
135
136
137
138
139
140
141
142
        locs = [l for l in self.connection_locations if (type_ is None or l.type_ == type_) and l.type_ not in exclude]
        counter = dict()
        for l in locs:
            if l in counter:
                counter[l] += 1
            else:
                counter[l] = 1
        assert( np.all( [counter[l] == 1 for l in locs] ) )
143
144
145
146
        return locs

    def get_location_at(self, address, on_fwd_strand=True, new_type="crossover"):
        loc = None
147
        if (self.num_nt == 1):
148
149
150
151
152
153
154
            # import pdb
            # pdb.set_trace()
            ## Assumes that intrahelical connections have been made before crossovers
            for l in self.locations:
                if l.on_fwd_strand == on_fwd_strand and l.connection is None:
                    assert(loc is None)
                    loc = l
cmaffeo2's avatar
cmaffeo2 committed
155
            # assert( loc is not None )
156
157
158
159
160
161
162
163
        else:
            for l in self.locations:
                if l.address == address and l.on_fwd_strand == on_fwd_strand:
                    assert(loc is None)
                    loc = l
        if loc is None:
            loc = Location( self, address=address, type_=new_type, on_fwd_strand=on_fwd_strand )
        return loc
164

cmaffeo2's avatar
cmaffeo2 committed
165
    def get_connections_and_locations(self, connection_type=None, exclude=()):
166
167
        """ Returns a list with each entry of the form:
            connection, location_in_self, location_in_other """
168
        type_ = connection_type
169
170
        ret = []
        for c in self.connections:
171
            if (type_ is None or c.type_ == type_) and c.type_ not in exclude:
172
                if   c.A.container is self:
173
                    ret.append( [c, c.A, c.B] )
174
                elif c.B.container is self:
175
176
                    ret.append( [c, c.B, c.A] )
                else:
177
178
                    import pdb
                    pdb.set_trace()
179
180
181
                    raise Exception("Object contains connection that fails to refer to object")
        return ret

182
    def _connect(self, other, connection, in_3prime_direction=None):
183
184
        ## TODO fix circular references        
        A,B = [connection.A, connection.B]
185
186
187
188
        if in_3prime_direction is not None:
            A.is_3prime_side_of_connection = not in_3prime_direction
            B.is_3prime_side_of_connection = in_3prime_direction
            
189
        A.connection = B.connection = connection
190
191
        self.connections.append(connection)
        other.connections.append(connection)
192
193
194
195
196
197
        l = A.container.locations
        if A not in l: l.append(A)
        l = B.container.locations
        if B not in l: l.append(B)
        

198
199
    # def _find_connections(self, loc):
    #     return [c for c in self.connections if c.A == loc or c.B == loc]
200
201

class SegmentParticle(PointParticle):
cmaffeo2's avatar
cmaffeo2 committed
202
    def __init__(self, type_, position, name="A", **kwargs):
203
        self.name = name
204
        self.contour_position = None
cmaffeo2's avatar
cmaffeo2 committed
205
        PointParticle.__init__(self, type_, position, name=name, **kwargs)
206
207
        self.intrahelical_neighbors = []
        self.other_neighbors = []
cmaffeo2's avatar
cmaffeo2 committed
208
        self.locations = []
209
210
211

    def get_intrahelical_above(self):
        """ Returns bead directly above self """
212
        # assert( len(self.intrahelical_neighbors) <= 2 )
213
214
215
216
217
218
        for b in self.intrahelical_neighbors:
            if b.get_contour_position(self.parent) > self.contour_position:
                return b

    def get_intrahelical_below(self):
        """ Returns bead directly below self """
219
        # assert( len(self.intrahelical_neighbors) <= 2 )
220
221
222
223
        for b in self.intrahelical_neighbors:
            if b.get_contour_position(self.parent) < self.contour_position:
                return b

cmaffeo2's avatar
cmaffeo2 committed
224
    def _neighbor_should_be_added(self,b):
225
226
227
        if type(self.parent) != type(b.parent):
            return True

cmaffeo2's avatar
cmaffeo2 committed
228
229
230
231
        c1 = self.contour_position
        c2 = b.get_contour_position(self.parent)
        if c2 < c1:
            b0 = self.get_intrahelical_below()
232
        else:
cmaffeo2's avatar
cmaffeo2 committed
233
234
235
236
237
238
239
240
241
242
243
244
245
246
247
248
249
            b0 = self.get_intrahelical_above()

        if b0 is not None:            
            c0 = b0.get_contour_position(self.parent)
            if np.abs(c2-c1) < np.abs(c0-c1):
                ## remove b0
                self.intrahelical_neighbors.remove(b0)
                b0.intrahelical_neighbors.remove(self)
                return True
            else:
                return False
        return True
        
    def make_intrahelical_neighbor(self,b):
        add1 = self._neighbor_should_be_added(b)
        add2 = b._neighbor_should_be_added(self)
        if add1 and add2:
250
251
            # assert(len(b.intrahelical_neighbors) <= 1)
            # assert(len(self.intrahelical_neighbors) <= 1)
cmaffeo2's avatar
cmaffeo2 committed
252
253
            self.intrahelical_neighbors.append(b)
            b.intrahelical_neighbors.append(self)
254

cmaffeo2's avatar
cmaffeo2 committed
255
256
257
258
259
260
261
262
263
264
    def get_nt_position(self, seg):
        """ Returns the "address" of the nucleotide relative to seg in
        nucleotides, taking the shortest (intrahelical) contour length route to seg
        """
        if seg == self.parent:
            return seg.contour_to_nt_pos(self.contour_position)
        else:
            pos = self.get_contour_position(seg)
            return seg.contour_to_nt_pos(pos)

265
266
267
268
    def get_contour_position(self,seg):
        if seg == self.parent:
            return self.contour_position
        else:
cmaffeo2's avatar
cmaffeo2 committed
269
270
271
272
273
            cutoff = 30*3
            target_seg = seg

            ## depth-first search
            ## TODO cache distances to nearby locations?
cmaffeo2's avatar
cmaffeo2 committed
274
            def descend_search_tree(seg, contour_in_seg, distance=0, visited_segs=None):
cmaffeo2's avatar
cmaffeo2 committed
275
                nonlocal cutoff
cmaffeo2's avatar
cmaffeo2 committed
276
                if visited_segs is None: visited_segs = []
cmaffeo2's avatar
cmaffeo2 committed
277
278
279
280

                if seg == target_seg:
                    # pdb.set_trace()
                    ## Found a segment in our target
281
282
                    sign = 1 if contour_in_seg == 1 else -1
                    if sign == -1: assert( contour_in_seg == 0 )
cmaffeo2's avatar
cmaffeo2 committed
283
284
                    if distance < cutoff: # TODO: check if this does anything
                        cutoff = distance
285
                    return [[distance, contour_in_seg+sign*seg.nt_pos_to_contour(distance)]], [(seg, contour_in_seg, distance)]
cmaffeo2's avatar
cmaffeo2 committed
286
                if distance > cutoff:
287
                    return None,None
cmaffeo2's avatar
cmaffeo2 committed
288
289
                    
                ret_list = []
290
                hist_list = []
cmaffeo2's avatar
cmaffeo2 committed
291
                ## Find intrahelical locations in seg that we might pass through
292
293
294
295
296
                conn_locs = seg.get_connections_and_locations("intrahelical")
                if isinstance(target_seg, SingleStrandedSegment):
                    tmp = seg.get_connections_and_locations("sscrossover")
                    conn_locs = conn_locs + list(filter(lambda x: x[2].container == target_seg, tmp))
                for c,A,B in conn_locs:
cmaffeo2's avatar
cmaffeo2 committed
297
                    if B.container in visited_segs: continue
298
299
300
                    dx = seg.contour_to_nt_pos( A.address, round_nt=False ) - seg.contour_to_nt_pos( contour_in_seg, round_nt=False)
                    dx = np.abs(dx)
                    results,history = descend_search_tree( B.container, B.address,
cmaffeo2's avatar
cmaffeo2 committed
301
302
303
                                                   distance+dx, visited_segs + [seg] )
                    if results is not None:
                        ret_list.extend( results )
304
305
                        hist_list.extend( history )
                return ret_list,hist_list
cmaffeo2's avatar
cmaffeo2 committed
306

307
            results,history = descend_search_tree(self.parent, self.contour_position)
cmaffeo2's avatar
cmaffeo2 committed
308
309
310
311
312
313
314
315
316
317
318
319
320
321
322
323
324
325
326
            if results is None or len(results) == 0:
                raise Exception("Could not find location in segment") # TODO better error
            return sorted(results,key=lambda x:x[0])[0][1]

            # nt_pos = self.get_nt_position(seg)
            # return seg.nt_pos_to_contour(nt_pos)

    def update_position(self, contour_position):
        self.contour_position = contour_position
        self.position = self.parent.contour_to_position(contour_position)
        if 'orientation_bead' in self.__dict__:
            o = self.orientation_bead
            o.contour_position = contour_position
            orientation = self.parent.contour_to_orientation(contour_position)
            if orientation is None:
                print("WARNING: local_twist is True, but orientation is None; using identity")
                orientation = np.eye(3)
            o.position = self.position + orientation.dot( np.array((Segment.orientation_bond.r0,0,0)) )
            
cmaffeo2's avatar
cmaffeo2 committed
327
328
329
    def __repr__(self):
        return "<SegmentParticle {} on {}[{:.2f}]>".format( self.name, self.parent, self.contour_position)

330
331

## TODO break this class into smaller, better encapsulated pieces
332
333
334
335
336
337
338
339
340
341
342
class Segment(ConnectableElement, Group):

    """ Base class that describes a segment of DNA. When built from
    cadnano models, should not span helices """

    """Define basic particle types"""
    dsDNA_particle = ParticleType("D",
                                  diffusivity = 43.5,
                                  mass = 300,
                                  radius = 3,                 
                              )
cmaffeo2's avatar
cmaffeo2 committed
343
344
345
346
347
    orientation_particle = ParticleType("O",
                                        diffusivity = 100,
                                        mass = 300,
                                        radius = 1,
                                    )
348

cmaffeo2's avatar
cmaffeo2 committed
349
    # orientation_bond = HarmonicBond(10,2)
350
    orientation_bond = HarmonicBond(30,1.5, rRange = (0,500) )
351
352
353
354
355
356
357

    ssDNA_particle = ParticleType("S",
                                  diffusivity = 43.5,
                                  mass = 150,
                                  radius = 3,                 
                              )

358
    def __init__(self, name, num_nt, 
cmaffeo2's avatar
cmaffeo2 committed
359
                 start_position = None,
360
                 end_position = None, 
cmaffeo2's avatar
cmaffeo2 committed
361
362
                 segment_model = None,
                 **kwargs):
363

cmaffeo2's avatar
cmaffeo2 committed
364
365
        if start_position is None: start_position = np.array((0,0,0))

cmaffeo2's avatar
cmaffeo2 committed
366
        Group.__init__(self, name, children=[], **kwargs)
367
        ConnectableElement.__init__(self, connection_locations=[], connections=[])
368

cmaffeo2's avatar
cmaffeo2 committed
369
370
371
        if 'segname' not in kwargs:
            self.segname = name
        # self.resname = name
cmaffeo2's avatar
cmaffeo2 committed
372
373
374
375
376
        self.start_orientation = None
        self.twist_per_nt = 0

        self.beads = [c for c in self.children] # self.beads will not contain orientation beads

377
378
379
        self._bead_model_generation = 0    # TODO: remove?
        self.segment_model = segment_model # TODO: remove?

380
381
382
383
        self.strand_pieces = dict()
        for d in ('fwd','rev'):
            self.strand_pieces[d] = []

384
        self.num_nt = int(num_nt)
385
        if end_position is None:
386
            end_position = np.array((0,0,self.distance_per_nt*num_nt)) + start_position
387
388
389
        self.start_position = start_position
        self.end_position = end_position

cmaffeo2's avatar
cmaffeo2 committed
390
391
392
393
        ## Used to assign cadnano names to beads
        self._generate_bead_callbacks = []
        self._generate_nucleotide_callbacks = []

394
        ## Set up interpolation for positions
395
396
397
398
        self._set_splines_from_ends()

        self.sequence = None

399
400
401
    def __repr__(self):
        return "<{} {}[{:d}]>".format( type(self), self.name, self.num_nt )

cmaffeo2's avatar
cmaffeo2 committed
402
    def set_splines(self, contours, coords):
403
        tck, u = interpolate.splprep( coords.T, u=contours, s=0, k=1)
404
        self.position_spline_params = (tck,u)
405

406
407
    def set_orientation_splines(self, contours, quaternions):
        tck, u = interpolate.splprep( quaternions.T, u=contours, s=0, k=1)
408
409
410
411
412
413
        self.quaternion_spline_params = (tck,u)

    def get_center(self):
        tck, u = self.position_spline_params
        return np.mean(self.contour_to_position(u), axis=0)

414
415
416
    def _get_location_positions(self):
        return [self.contour_to_nt_pos(l.address) for l in self.locations]

cmaffeo2's avatar
cmaffeo2 committed
417
    def insert_dna(self, at_nt: int, num_nt: int, seq=tuple()):
418
419
420
421
422
423
424
425
426
427
428
429
        assert(np.isclose(np.around(num_nt),num_nt))
        if at_nt < 0:
            raise ValueError("Attempted to insert DNA into {} at a negative location".format(self))
        if at_nt > self.num_nt-1:
            raise ValueError("Attempted to insert DNA into {} at beyond the end of the Segment".format(self))
        if num_nt < 0:
            raise ValueError("Attempted to insert DNA a negative amount of DNA into {}".format(self))

        num_nt = np.around(num_nt)
        nt_positions = self._get_location_positions()
        new_nt_positions = [p if p <= at_nt else p+num_nt for p in nt_positions]

cmaffeo2's avatar
cmaffeo2 committed
430
431
        ## TODO: handle sequence

432
433
434
435
436
437
        self.num_nt = self.num_nt+num_nt

        for l,p in zip(self.locations, new_nt_positions):
            l.address = self.nt_pos_to_contour(p)

    def remove_dna(self, first_nt: int, last_nt: int):
cmaffeo2's avatar
cmaffeo2 committed
438
        """ Removes nucleotides between first_nt and last_nt, inclusive """
439
440
441
442
443
444
445
446
447
448
449
450
451
452
453
454
455
456
457
458
459
460
        assert(np.isclose(np.around(first_nt),first_nt))
        assert(np.isclose(np.around(last_nt),last_nt))
        tmp = min((first_nt,last_nt))
        last_nt = max((first_nt,last_nt))
        fist_nt = tmp

        if first_nt < 0 or first_nt > self.num_nt-2:
            raise ValueError("Attempted to remove DNA from {} starting at an invalid location {}".format(self, first_nt))
        if last_nt < 1 or last_nt > self.num_nt-1:
            raise ValueError("Attempted to remove DNA from {} ending at an invalid location {}".format(self, last_nt))
        if first_nt == last_nt:
            return

        first_nt = np.around(first_nt)
        last_nt = np.around(last_nt)

        nt_positions = self._get_location_positions()

        bad_locations = list(filter(lambda p: p >= first_nt and p <= last_nt, nt_positions))
        if len(bad_locations) > 0:
            raise Exception("Attempted to remove DNA containing locations {} from {} between {} and {}".format(bad_locations,self,first_nt,last_nt))

cmaffeo2's avatar
cmaffeo2 committed
461
462
463
464
465
466
467
468
        removed_nt = last_nt-first_nt+1
        new_nt_positions = [p if p <= last_nt else p-removed_nt for p in nt_positions]
        num_nt = self.num_nt-removed_nt

        if self.sequence is not None and len(self.sequence) == self.num_nt:
            self.sequence = [s for s,i in zip(self.sequence,range(self.num_nt)) 
                                if i < first_nt or i > last_nt]
            assert( len(self.sequence) == num_nt )
469

cmaffeo2's avatar
cmaffeo2 committed
470
        self.num_nt = num_nt
471
472
473
474

        for l,p in zip(self.locations, new_nt_positions):
            l.address = self.nt_pos_to_contour(p)

475
476
477
478
479
480
481
482
483
484
485
486
    def __filter_contours(contours, positions, position_filter, contour_filter):
        u = contours
        r = positions

        ## Filter
        ids = list(range(len(u)))
        if contour_filter is not None:
            ids = list(filter(lambda i: contour_filter(u[i]), ids))
        if position_filter is not None:
            ids = list(filter(lambda i: position_filter(r[i,:]), ids))
        return ids

487
    def translate(self, translation_vector, position_filter=None, contour_filter=None):
488
489
490
491
492
493
494
495
        dr = np.array(translation_vector)
        tck, u = self.position_spline_params
        r = self.contour_to_position(u)

        ids = Segment.__filter_contours(u, r, position_filter, contour_filter)

        ## Translate
        r[ids,:] = r[ids,:] + dr[np.newaxis,:]
496
        self.set_splines(u,r)
497
498
499
500
501
502
503
504
505
506
507
508
509
510
511

    def rotate(self, rotation_matrix, about=None, position_filter=None, contour_filter=None):
        tck, u = self.position_spline_params
        r = self.contour_to_position(u)

        ids = Segment.__filter_contours(u, r, position_filter, contour_filter)

        if about is None:
            ## TODO: do this more efficiently
            r[ids,:] = np.array([rotation_matrix.dot(r[i,:]) for i in range(r.shape[0])])
        else:
            dr = np.array(about)
            ## TODO: do this more efficiently
            r[ids,:] = np.array([rotation_matrix.dot(r[i,:]-dr) + dr for  i in range(r.shape[0])])

512
        self.set_splines(u,r)
513
514
515
516

        if self.quaternion_spline_params is not None:
            ## TODO: performance: don't shift between quaternion and matrix representations so much
            tck, u = self.quaternion_spline_params
517
            orientations = [self.contour_to_orientation(v) for v in u]
518
519
520
            for i in ids:
                orientations[i,:] = rotation_matrix.dot(orientations[i])
            quats = [quaternion_from_matrix(o) for o in orientations]
521
            self.set_orientation_splines(u, quats)
522

523
    def _set_splines_from_ends(self):
524
        self.quaternion_spline_params = None
cmaffeo2's avatar
cmaffeo2 committed
525
526
        coords = np.array([self.start_position, self.end_position])
        self.set_splines([0,1], coords)
527

528
529
530
531
532
    def clear_all(self):
        Group.clear_all(self)  # TODO: use super?
        self.beads = []
        for c,loc,other in self.get_connections_and_locations():
            loc.particle = None
533
            other.particle = None
534

535
    def contour_to_nt_pos(self, contour_pos, round_nt=False):
536
        nt = contour_pos*(self.num_nt) - 0.5
537
        if round_nt:
cmaffeo2's avatar
cmaffeo2 committed
538
            assert( np.isclose(np.around(nt),nt) )
539
540
541
            nt = np.around(nt)
        return nt

542
    def nt_pos_to_contour(self,nt_pos):
543
        return (nt_pos+0.5)/(self.num_nt)
544

545
    def contour_to_position(self,s):
546
        p = interpolate.splev( s, self.position_spline_params[0] )
547
548
549
550
        if len(p) > 1: p = np.array(p).T
        return p

    def contour_to_tangent(self,s):
551
        t = interpolate.splev( s, self.position_spline_params[0], der=1 )
552
553
        t = (t / np.linalg.norm(t,axis=0))
        return t.T
554
555
556
        

    def contour_to_orientation(self,s):
557
        assert( isinstance(s,float) or isinstance(s,int) or len(s) == 1 )   # TODO make vectorized version
558

559
560
561
562
563
        if self.quaternion_spline_params is None:
            axis = self.contour_to_tangent(s)
            axis = axis / np.linalg.norm(axis)
            rotAxis = np.cross(axis,np.array((0,0,1)))
            rotAxisL = np.linalg.norm(rotAxis)
564
            zAxis = np.array((0,0,1))
565
566

            if rotAxisL > 0.001:
567
568
569
                theta = np.arcsin(rotAxisL) * 180/np.pi
                if axis.dot(zAxis) < 0: theta = 180-theta
                orientation0 = rotationAboutAxis( rotAxis/rotAxisL, theta, normalizeAxis=False ).T
570
            else:
571
572
                orientation0 = np.eye(3) if axis.dot(zAxis) > 0 else \
                               rotationAboutAxis( np.array((1,0,0)), 180, normalizeAxis=False )
573
574
575
            if self.start_orientation is not None:
                orientation0 = orientation0.dot(self.start_orientation)

576
577
578
            orientation = rotationAboutAxis( axis, self.twist_per_nt*self.contour_to_nt_pos(s), normalizeAxis=False )
            orientation = orientation.dot(orientation0)
        else:
579
            q = interpolate.splev( s, self.quaternion_spline_params[0] )
580
581
            if len(q) > 1: q = np.array(q).T # TODO: is this needed?
            orientation = quaternion_to_matrix(q)
582

583
        return orientation
584

cmaffeo2's avatar
cmaffeo2 committed
585
    def get_contour_sorted_connections_and_locations(self,type_):
cmaffeo2's avatar
cmaffeo2 committed
586
        sort_fn = lambda c: c[1].address
cmaffeo2's avatar
cmaffeo2 committed
587
        cl = self.get_connections_and_locations(type_)
cmaffeo2's avatar
cmaffeo2 committed
588
        return sorted(cl, key=sort_fn)
589
590
591
    
    def randomize_unset_sequence(self):
        bases = list(seqComplement.keys())
592
        # bases = ['T']        ## FOR DEBUG
593
        if self.sequence is None:
594
            self.sequence = [random.choice(bases) for i in range(self.num_nt)]
595
        else:
596
            assert(len(self.sequence) == self.num_nt) # TODO move
597
598
599
            for i in range(len(self.sequence)):
                if self.sequence[i] is None:
                    self.sequence[i] = random.choice(bases)
600

cmaffeo2's avatar
cmaffeo2 committed
601
602
603
    def _get_num_beads(self, max_basepairs_per_bead, max_nucleotides_per_bead ):
        raise NotImplementedError

604
    def _generate_one_bead(self, contour_position, nts):
605
606
        raise NotImplementedError

cmaffeo2's avatar
cmaffeo2 committed
607
    def _generate_atomic_nucleotide(self, contour_position, is_fwd, seq, scale, strand_segment):
cmaffeo2's avatar
cmaffeo2 committed
608
609
610
611
612
        """ Seq should include modifications like 5T, T3 Tsinglet; direction matters too """

        # print("Generating nucleotide at {}".format(contour_position))
        
        pos = self.contour_to_position(contour_position)
613
        orientation = self.contour_to_orientation(contour_position)
cmaffeo2's avatar
cmaffeo2 committed
614

615
616
617
618
619
620
621
622
623
624
625
626
627
628
629
630
631
632
        """ deleteme
        ## TODO: move this code (?)
        if orientation is None:
            import pdb
            pdb.set_trace()
            axis = self.contour_to_tangent(contour_position)
            angleVec = np.array([1,0,0])
            if axis.dot(angleVec) > 0.9: angleVec = np.array([0,1,0])
            angleVec = angleVec - angleVec.dot(axis)*axis
            angleVec = angleVec/np.linalg.norm(angleVec)
            y = np.cross(axis,angleVec)
            orientation = np.array([angleVec,y,axis]).T
            ## TODO: improve placement of ssDNA
            # rot = rotationAboutAxis( axis, contour_position*self.twist_per_nt*self.num_nt, normalizeAxis=True )
            # orientation = rot.dot(orientation)
        else:
            orientation = orientation                            
        """
cmaffeo2's avatar
cmaffeo2 committed
633
        key = seq
634
635
        nt_dict = canonicalNtFwd if is_fwd else canonicalNtRev

636
        atoms = nt_dict[ key ].generate() # TODO: clone?
cmaffeo2's avatar
cmaffeo2 committed
637
        atoms.orientation = orientation.dot(atoms.orientation)
638
639
640
641
        if isinstance(self, SingleStrandedSegment):
            if scale is not None and scale != 1:
                for a in atoms:
                    a.position = scale*a.position
642
            atoms.position = pos - atoms.atoms_by_name["C1'"].collapsedPosition()
643
644
645
646
647
648
649
650
651
        else:
            if scale is not None and scale != 1:
                if atoms.sequence in ("A","G"):
                    r0 = atoms.atoms_by_name["N9"].position
                else:
                    r0 = atoms.atoms_by_name["N1"].position
                for a in atoms:
                    if a.name[-1] in ("'","P","T"):
                        a.position = scale*(a.position-r0) + r0
652
                    else:
653
                        a.fixed = 1
654
            atoms.position = pos
cmaffeo2's avatar
cmaffeo2 committed
655
656
657
658
659
660
        
        atoms.contour_position = contour_position
        strand_segment.add(atoms)

        for callback in self._generate_nucleotide_callbacks:
            callback(atoms)
cmaffeo2's avatar
cmaffeo2 committed
661
662

        return atoms
663

664
665
    def add_location(self, nt, type_, on_fwd_strand=True):
        ## Create location if needed, add to segment
666
        c = self.nt_pos_to_contour(nt)
667
668
669
670
671
672
        assert(c >= 0 and c <= 1)
        # TODO? loc = self.Location( address=c, type_=type_, on_fwd_strand=is_fwd )
        loc = Location( self, address=c, type_=type_, on_fwd_strand=on_fwd_strand )
        self.locations.append(loc)

    ## TODO? Replace with abstract strand-based model?
673
674
675
676
677

    def add_nick(self, nt, on_fwd_strand=True):
        self.add_3prime(nt,on_fwd_strand)
        self.add_5prime(nt+1,on_fwd_strand)

678
    def add_5prime(self, nt, on_fwd_strand=True):
679
680
        if isinstance(self,SingleStrandedSegment):
            on_fwd_strand = True
681
        self.add_location(nt,"5prime",on_fwd_strand)
682
683

    def add_3prime(self, nt, on_fwd_strand=True):
684
685
        if isinstance(self,SingleStrandedSegment):
            on_fwd_strand = True
686
        self.add_location(nt,"3prime",on_fwd_strand)
687

688
    def get_3prime_locations(self):
cmaffeo2's avatar
cmaffeo2 committed
689
        return sorted(self.get_locations("3prime"),key=lambda x: x.address)
690
    
cmaffeo2's avatar
cmaffeo2 committed
691
    def get_5prime_locations(self):
692
        ## TODO? ensure that data is consistent before _build_model calls
cmaffeo2's avatar
cmaffeo2 committed
693
        return sorted(self.get_locations("5prime"),key=lambda x: x.address)
cmaffeo2's avatar
cmaffeo2 committed
694

695
    def iterate_connections_and_locations(self, reverse=False):
cmaffeo2's avatar
cmaffeo2 committed
696
697
        ## connections to other segments
        cl = self.get_contour_sorted_connections_and_locations()
698
        if reverse:
cmaffeo2's avatar
cmaffeo2 committed
699
            cl = cl[::-1]
700
701
702
            
        for c in cl:
            yield c
cmaffeo2's avatar
cmaffeo2 committed
703

704
705
706
707
708
709
710
711
712
713
714
715
716
717
718
719
720
721
    ## TODO rename
    def _add_strand_piece(self, strand_piece):
        """ Registers a strand segment within this object """

        ## TODO use weakref
        d = 'fwd' if strand_piece.is_fwd else 'rev'

        ## Validate strand_piece (ensure no clashes)
        for s in self.strand_pieces[d]:
            l,h = sorted((s.start,s.end))
            for value in (strand_piece.start,strand_piece.end):
                assert( value < l or value > h )

        ## Add strand_piece in correct order
        self.strand_pieces[d].append(strand_piece)
        self.strand_pieces[d] = sorted(self.strand_pieces[d],
                                       key = lambda x: x.start)

722
    ## TODO rename
723
    def get_strand_segment(self, nt_pos, is_fwd, move_at_least=0.5):
724
        """ Walks through locations, checking for crossovers """
725
726
727
728
        # if self.name in ("6-1","1-1"):
        #     import pdb
        #     pdb.set_trace()
        move_at_least = 0
729
730

        ## Iterate through locations
cmaffeo2's avatar
cmaffeo2 committed
731
        # locations = sorted(self.locations, key=lambda l:(l.address,not l.on_fwd_strand), reverse=(not is_fwd))
732
733
734
735
736
737
        def loc_rank(l):
            nt = l.get_nt_pos()
            ## optionally add logic about type of connection
            return (nt, not l.on_fwd_strand)
        # locations = sorted(self.locations, key=lambda l:(l.address,not l.on_fwd_strand), reverse=(not is_fwd))
        locations = sorted(self.locations, key=loc_rank, reverse=(not is_fwd))
738
739
        # print(locations)

740
        for l in locations:
cmaffeo2's avatar
cmaffeo2 committed
741
742
743
744
            # TODOTODO probably okay
            if l.address == 0:
                pos = 0.0
            elif l.address == 1:
745
                pos = self.num_nt-1
cmaffeo2's avatar
cmaffeo2 committed
746
747
            else:
                pos = self.contour_to_nt_pos(l.address, round_nt=True)
748
749
750

            ## DEBUG

cmaffeo2's avatar
cmaffeo2 committed
751

752
            ## Skip locations encountered before our strand
753
754
755
756
757
758
759
760
            # tol = 0.1
            # if is_fwd:
            #     if pos-nt_pos <= tol: continue 
            # elif   nt_pos-pos <= tol: continue
            if (pos-nt_pos)*(2*is_fwd-1) < move_at_least: continue
            ## TODO: remove move_at_least
            if np.isclose(pos,nt_pos):
                if l.is_3prime_side_of_connection: continue
761
762

            ## Stop if we found the 3prime end
763
            if l.on_fwd_strand == is_fwd and l.type_ == "3prime" and l.connection is None:
764
                # print("  found end at",l)
765
                return pos, None, None, None, None
766
767
768
769
770
771
772
773

            ## Check location connections
            c = l.connection
            if c is None: continue
            B = c.other(l)            

            ## Found a location on the same strand?
            if l.on_fwd_strand == is_fwd:
774
775
                # print("  passing through",l)
                # print("from {}, connection {} to {}".format(nt_pos,l,B))
776
                Bpos = B.get_nt_pos()
777
                return pos, B.container, Bpos, B.on_fwd_strand, 0.5
778
779
780
                
            ## Stop at other strand crossovers so basepairs line up
            elif c.type_ == "crossover":
781
                if nt_pos == pos: continue
782
                # print("  pausing at",l)
783
                return pos, l.container, pos+(2*is_fwd-1), is_fwd, 0
784
785
786
787
788
789

        raise Exception("Shouldn't be here")
        # print("Shouldn't be here")
        ## Made it to the end of the segment without finding a connection
        return 1*is_fwd, None, None, None

790
791
792
    def get_nearest_bead(self, contour_position):
        if len(self.beads) < 1: return None
        cs = np.array([b.contour_position for b in self.beads]) # TODO: cache
793
        # TODO: include beads in connections?
794
795
796
        i = np.argmin((cs - contour_position)**2)

        return self.beads[i]
797

798
799
800
801
802
803
804
805
806
    def _get_atomic_nucleotide(self, nucleotide_idx, is_fwd=True):
        d = 'fwd' if is_fwd else 'rev'
        for s in self.strand_pieces[d]:
            try:
                return s.get_nucleotide(nucleotide_idx)
            except:
                pass
        raise Exception("Could not find nucleotide in {} at {}.{}".format( self, nucleotide_idx, d ))

807
808
    def get_all_consecutive_beads(self, number):
        assert(number >= 1)
cmaffeo2's avatar
cmaffeo2 committed
809
        ## Assume that consecutive beads in self.beads are bonded
810
        ret = []
cmaffeo2's avatar
cmaffeo2 committed
811
812
        for i in range(len(self.beads)-number+1):
            tmp = [self.beads[i+j] for j in range(0,number)]
813
            ret.append( tmp )
814
        return ret   
815

816
817
818
    def _add_bead(self,b,set_contour=False):
        if set_contour:
            b.contour_position = b.get_contour_position(self)
819
        
820
821
822
        # assert(b.parent is None)
        if b.parent is not None:
            b.parent.children.remove(b)
823
        self.add(b)
824
825
826
827
828
829
        self.beads.append(b) # don't add orientation bead
        if "orientation_bead" in b.__dict__: # TODO: think of a cleaner approach
            o = b.orientation_bead
            o.contour_position = b.contour_position
            if o.parent is not None:
                o.parent.children.remove(o)
830
            self.add(o)
831
832
833
834
835
836
837
838
            self.add_bond(b,o, Segment.orientation_bond, exclude=True)

    def _rebuild_children(self, new_children):
        # print("_rebuild_children on %s" % self.name)
        old_children = self.children
        old_beads = self.beads
        self.children = []
        self.beads = []
839
840

        if True:
841
842
            ## TODO: remove this if duplicates are never found 
            # print("Searching for duplicate particles...")
843
            ## Remove duplicates, preserving order
844
845
846
847
            tmp = []
            for c in new_children:
                if c not in tmp:
                    tmp.append(c)
848
                else:
849
                    print("  DUPLICATE PARTICLE FOUND!")
850
851
            new_children = tmp

852
853
854
855
856
        for b in new_children:
            self.beads.append(b)
            self.children.append(b)
            if "orientation_bead" in b.__dict__: # TODO: think of a cleaner approach
                self.children.append(b.orientation_bead)
857
858
859
860
861
            
        # tmp = [c for c in self.children if c not in old_children]
        # assert(len(tmp) == 0)
        # tmp = [c for c in old_children if c not in self.children]
        # assert(len(tmp) == 0)
862
863
        assert(len(old_children) == len(self.children))
        assert(len(old_beads) == len(self.beads))
864

865

cmaffeo2's avatar
cmaffeo2 committed
866
    def _generate_beads(self, bead_model, max_basepairs_per_bead, max_nucleotides_per_bead):
867

868
        """ Generate beads (positions, types, etc) and bonds, angles, dihedrals, exclusions """
cmaffeo2's avatar
cmaffeo2 committed
869
        ## TODO: decide whether to remove bead_model argument
870
        ##       (currently unused)
cmaffeo2's avatar
cmaffeo2 committed
871

872
        ## First find points between-which beads must be generated
873
874
875
        # conn_locs = self.get_contour_sorted_connections_and_locations()
        # locs = [A for c,A,B in conn_locs]
        # existing_beads = [l.particle for l in locs if l.particle is not None]
cmaffeo2's avatar
cmaffeo2 committed
876
877
        # if self.name == "S001":
        #     pdb.set_trace()
878

cmaffeo2's avatar
cmaffeo2 committed
879
880
        existing_beads0 = {l.particle for l in self.locations if l.particle is not None}
        existing_beads = sorted( list(existing_beads0), key=lambda b: b.get_contour_position(self) )
881

882
883
884
        # if self.num_nt == 1 and all([l.particle is not None for l in self.locations]):
        #     pdb.set_trace()
        #     return
885

886
887
888
889
        for b in existing_beads:
            assert(b.parent is not None)

        ## Add ends if they don't exist yet
890
        ## TODOTODO: test 1 nt segments?
891
        if len(existing_beads) == 0 or existing_beads[0].get_nt_position(self) >= 0.5:
cmaffeo2's avatar
cmaffeo2 committed
892
893
            # if len(existing_beads) > 0:            
            #     assert(existing_beads[0].get_nt_position(self) >= 0.5)
894
            b = self._generate_one_bead( self.nt_pos_to_contour(0), 0)
895
            existing_beads = [b] + existing_beads
cmaffeo2's avatar
cmaffeo2 committed
896

cmaffeo2's avatar
cmaffeo2 committed
897
        if existing_beads[-1].get_nt_position(self)-(self.num_nt-1) < -0.5 or len(existing_beads)==1:
898
            b = self._generate_one_bead( self.nt_pos_to_contour(self.num_nt-1), 0)
899
900
901
902
903
            existing_beads.append(b)
        assert(len(existing_beads) > 1)

        ## Walk through existing_beads, add beads between
        tmp_children = []       # build list of children in nice order
904
        last = None
cmaffeo2's avatar
cmaffeo2 committed
905

906
907
        for I in range(len(existing_beads)-1):
            eb1,eb2 = [existing_beads[i] for i in (I,I+1)]
908
            assert( eb1 is not eb2 )
909

cmaffeo2's avatar
cmaffeo2 committed
910
911
912
913
            # if np.isclose(eb1.position[2], eb2.position[2]):
            #     import pdb
            #     pdb.set_trace()

914
            # print(" %s working on %d to %d" % (self.name, eb1.position[2], eb2.position[2]))
915
916
            e_ds = eb2.get_contour_position(self) - eb1.get_contour_position(self)
            num_beads = self._get_num_beads( e_ds, max_basepairs_per_bead, max_nucleotides_per_bead )
cmaffeo2's avatar
cmaffeo2 committed
917
918
919
920
921
922

            ## Ensure there is a ssDNA bead between dsDNA beads
            if num_beads == 0 and isinstance(self,SingleStrandedSegment) and isinstance(eb1.parent,DoubleStrandedSegment) and isinstance(eb2.parent,DoubleStrandedSegment):
                num_beads = 1
            ## TODO similarly ensure there is a dsDNA bead between ssDNA beads

923
            ds = e_ds / (num_beads+1)
924
925
926
            nts = ds*self.num_nt
            eb1.num_nt += 0.5*nts
            eb2.num_nt += 0.5*nts
927
928
929
930
931
932
933

            ## Add beads
            if eb1.parent == self:
                tmp_children.append(eb1)

            s0 = eb1.get_contour_position(self)
            if last is not None:
cmaffeo2's avatar
cmaffeo2 committed
934
                last.make_intrahelical_neighbor(eb1)
935
936
937
            last = eb1
            for j in range(num_beads):
                s = ds*(j+1) + s0
938
                # if self.name in ("51-2","51-3"):
cmaffeo2's avatar
cmaffeo2 committed
939
                # if self.name in ("31-2",):
940
                #     print(" adding bead at {}".format(s))
941
942
                b = self._generate_one_bead(s,nts)

cmaffeo2's avatar
cmaffeo2 committed
943
                last.make_intrahelical_neighbor(b)
944
945
946
                last = b
                tmp_children.append(b)

cmaffeo2's avatar
cmaffeo2 committed
947
        last.make_intrahelical_neighbor(eb2)
948
949
950

        if eb2.parent == self:
            tmp_children.append(eb2)
cmaffeo2's avatar
cmaffeo2 committed
951
        # if self.name in ("31-2",):
952
        #     pdb.set_trace()
953
        self._rebuild_children(tmp_children)
954

cmaffeo2's avatar
cmaffeo2 committed
955
956
957
        for callback in self._generate_bead_callbacks:
            callback(self)

958
959
960
961
962
963
964
965
966
    def _regenerate_beads(self, max_nts_per_bead=4, ):
        ...
    

class DoubleStrandedSegment(Segment):

    """ Class that describes a segment of ssDNA. When built from
    cadnano models, should not span helices """

967
    def __init__(self, name, num_bp, start_position = np.array((0,0,0)),
968
969
                 end_position = None, 
                 segment_model = None,
cmaffeo2's avatar
cmaffeo2 committed
970
971
                 local_twist = False,
                 num_turns = None,
cmaffeo2's avatar
cmaffeo2 committed
972
                 start_orientation = None,
cmaffeo2's avatar
cmaffeo2 committed
973
974
                 twist_persistence_length = 90,
                 **kwargs):
cmaffeo2's avatar
cmaffeo2 committed
975
976
977
        
        self.helical_rise = 10.44
        self.distance_per_nt = 3.4
978
        Segment.__init__(self, name, num_bp,
979
980
                         start_position,
                         end_position, 
cmaffeo2's avatar
cmaffeo2 committed
981
982
                         segment_model,
                         **kwargs)
983
        self.num_bp = self.num_nt