segmentmodel.py 152 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 .arbdmodel import PointParticle, ParticleType, Group, ArbdModel
from .arbdmodel.coords import rotationAboutAxis, quaternion_from_matrix, quaternion_to_matrix
from .arbdmodel.nonbonded import *
8
from copy import copy, deepcopy
9
from .model.nbPot import nbDnaScheme
10

11
12
import re

cmaffeo2's avatar
cmaffeo2 committed
13
14
from scipy.special import erf
import scipy.optimize as opt
15
from scipy import interpolate
cmaffeo2's avatar
cmaffeo2 committed
16

17
18
from .model.CanonicalNucleotideAtoms import canonicalNtFwd, canonicalNtRev, seqComplement
from .model.CanonicalNucleotideAtoms import enmTemplateHC, enmTemplateSQ, enmCorrectionsHC
cmaffeo2's avatar
cmaffeo2 committed
19

cmaffeo2's avatar
cmaffeo2 committed
20
from .model.spring_from_lp import k_angle as angle_spring_from_lp
21
from .model.spring_from_lp import k_twist as twist_spring_from_lp
cmaffeo2's avatar
cmaffeo2 committed
22

23
24
25
import csv


26
# import pdb
27
"""
cmaffeo2's avatar
cmaffeo2 committed
28
TODO:
cmaffeo2's avatar
cmaffeo2 committed
29
 + fix handling of crossovers for atomic representation
cmaffeo2's avatar
cmaffeo2 committed
30
 + map to atomic representation
31
    + add nicks
cmaffeo2's avatar
cmaffeo2 committed
32
    + transform ssDNA nucleotides 
cmaffeo2's avatar
cmaffeo2 committed
33
    - shrink ssDNA
cmaffeo2's avatar
cmaffeo2 committed
34
    + shrink dsDNA backbone
35
    + make orientation continuous
cmaffeo2's avatar
cmaffeo2 committed
36
    + sequence
37
    + handle circular dna
38
 + ensure crossover bead potentials aren't applied twice 
39
 + remove performance bottlenecks
40
 - test for large systems
cmaffeo2's avatar
cmaffeo2 committed
41
 + assign sequence
42
 + ENM
43
44
 - rework Location class 
 - remove recursive calls
45
 - document
46
 - develop unit test suite
47
48
 - refactor parts of Segment into an abstract_polymer class
 - make each call generate_bead_model, generate_atomic_model, generate_oxdna_model return an object with only have a reference to original object
49
"""
cmaffeo2's avatar
cmaffeo2 committed
50
51
class CircularDnaError(Exception):
    pass
52

cmaffeo2's avatar
cmaffeo2 committed
53
54
55
class ParticleNotConnectedError(Exception):
    pass

56
57
class Location():
    """ Site for connection within an object """
58
    def __init__(self, container, address, type_, on_fwd_strand = True):
59
        ## TODO: remove cyclic references(?)
60
        self.container = container
cmaffeo2's avatar
cmaffeo2 committed
61
        self.address = address  # represents position along contour length in segment
cmaffeo2's avatar
cmaffeo2 committed
62
        # assert( type_ in ("end3","end5") ) # TODO remove or make conditional
63
        self.on_fwd_strand = on_fwd_strand
64
65
        self.type_ = type_
        self.particle = None
66
        self.connection = None
67
        self.is_3prime_side_of_connection = None
68

69
70
        self.prev_in_strand = None
        self.next_in_strand = None
71
72
        
        self.combine = None     # some locations might be combined in bead model 
73
74
75
76
77
78
79

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

80
    def set_connection(self, connection, is_3prime_side_of_connection):
81
        self.connection = connection # TODO weakref? 
82
        self.is_3prime_side_of_connection = is_3prime_side_of_connection
83

84
85
86
87
88
89
90
    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:
91
                pos = self.container.num_nt-1
92
93
94
95
            else:
                raise
        return pos

96
97
98
99
100
    def __repr__(self):
        if self.on_fwd_strand:
            on_fwd = "on_fwd_strand"
        else:
            on_fwd = "on_rev_strand"
101
102
103
104
        try:
            return "<Location {}.{}[{:d},{}]>".format( self.container.name, self.type_, self.get_nt_pos(), on_fwd )
        except:
            return "<Location {}.{}[{:.2f},{:d}]>".format( self.container.name, self.type_, self.address, self.on_fwd_strand)
105
        
106
107
108
109
110
111
112
113
114
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_
        
115
116
117
118
119
120
121
    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
122

123
124
    def delete(self):
        self.A.container.connections.remove(self)
125
126
        if self.B.container is not self.A.container:
            self.B.container.connections.remove(self)
127
128
129
        self.A.connection = None
        self.B.connection = None

cmaffeo2's avatar
cmaffeo2 committed
130
131
132
133
    def __repr__(self):
        return "<Connection {}--{}--{}]>".format( self.A, self.type_, self.B )
        

134
        
135
136
137
# class ConnectableElement(Transformable):
class ConnectableElement():
    """ Abstract base class """
cmaffeo2's avatar
cmaffeo2 committed
138
139
140
141
    def __init__(self, connection_locations=None, connections=None):
        if connection_locations is None: connection_locations = []
        if connections is None: connections = []

142
143
        ## TODO decide on names
        self.locations = self.connection_locations = connection_locations
144
145
        self.connections = connections

cmaffeo2's avatar
cmaffeo2 committed
146
    def get_locations(self, type_=None, exclude=()):
147
148
149
150
151
152
153
154
        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] ) )
155
156
157
158
        return locs

    def get_location_at(self, address, on_fwd_strand=True, new_type="crossover"):
        loc = None
159
        if (self.num_nt == 1):
160
161
162
163
164
165
166
            # 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
167
            # assert( loc is not None )
168
169
170
171
172
173
174
175
        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
176

cmaffeo2's avatar
cmaffeo2 committed
177
    def get_connections_and_locations(self, connection_type=None, exclude=()):
178
179
        """ Returns a list with each entry of the form:
            connection, location_in_self, location_in_other """
180
        type_ = connection_type
181
182
        ret = []
        for c in self.connections:
183
            if (type_ is None or c.type_ == type_) and c.type_ not in exclude:
184
                if   c.A.container is self:
185
                    ret.append( [c, c.A, c.B] )
186
                elif c.B.container is self:
187
188
                    ret.append( [c, c.B, c.A] )
                else:
189
190
                    import pdb
                    pdb.set_trace()
191
192
193
                    raise Exception("Object contains connection that fails to refer to object")
        return ret

194
    def _connect(self, other, connection, in_3prime_direction=None):
195
196
        ## TODO fix circular references        
        A,B = [connection.A, connection.B]
197
198
199
200
        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
            
201
        A.connection = B.connection = connection
202
        self.connections.append(connection)
203
204
        if other is not self:
            other.connections.append(connection)
205

206
207
208
209
210
211
        l = A.container.locations
        if A not in l: l.append(A)
        l = B.container.locations
        if B not in l: l.append(B)
        

212
213
    # def _find_connections(self, loc):
    #     return [c for c in self.connections if c.A == loc or c.B == loc]
214
215

class SegmentParticle(PointParticle):
cmaffeo2's avatar
cmaffeo2 committed
216
    def __init__(self, type_, position, name="A", **kwargs):
217
        self.name = name
218
        self.contour_position = None
cmaffeo2's avatar
cmaffeo2 committed
219
        PointParticle.__init__(self, type_, position, name=name, **kwargs)
220
221
        self.intrahelical_neighbors = []
        self.other_neighbors = []
cmaffeo2's avatar
cmaffeo2 committed
222
        self.locations = []
223

224
    def get_intrahelical_above(self, all_types=True):
225
        """ Returns bead directly above self """
226
        # assert( len(self.intrahelical_neighbors) <= 2 )
227
        for b in self.intrahelical_neighbors:
228
            if b.get_contour_position(self.parent, self.contour_position) > self.contour_position:
229
230
                if all_types or isinstance(b,type(self)):
                    return b
231

232
    def get_intrahelical_below(self, all_types=True):
233
        """ Returns bead directly below self """
234
        # assert( len(self.intrahelical_neighbors) <= 2 )
235
        for b in self.intrahelical_neighbors:
236
            if b.get_contour_position(self.parent, self.contour_position) < self.contour_position:
237
238
                if all_types or isinstance(b,type(self)):
                    return b
239

cmaffeo2's avatar
cmaffeo2 committed
240
    def _neighbor_should_be_added(self,b):
241
242
243
        if type(self.parent) != type(b.parent):
            return True

cmaffeo2's avatar
cmaffeo2 committed
244
        c1 = self.contour_position
245
        c2 = b.get_contour_position(self.parent,c1)
cmaffeo2's avatar
cmaffeo2 committed
246
247
        if c2 < c1:
            b0 = self.get_intrahelical_below()
248
        else:
cmaffeo2's avatar
cmaffeo2 committed
249
250
251
            b0 = self.get_intrahelical_above()

        if b0 is not None:            
252
            c0 = b0.get_contour_position(self.parent,c1)
cmaffeo2's avatar
cmaffeo2 committed
253
254
255
256
257
258
259
260
261
262
263
264
265
            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:
266
267
            # assert(len(b.intrahelical_neighbors) <= 1)
            # assert(len(self.intrahelical_neighbors) <= 1)
cmaffeo2's avatar
cmaffeo2 committed
268
269
            self.intrahelical_neighbors.append(b)
            b.intrahelical_neighbors.append(self)
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
    def conceptual_get_position(self, context):
        """ 
        context: object

Q: does this function do too much?
Danger of mixing return values

Q: does context describe the system or present an argument?
        """

        ## Validate Inputs
        ...

        ## Algorithm
        """
context specifies:
  - kind of output: real space, nt within segment, fraction of segment
  - absolute or relative
  - constraints: e.g. if passing through
        """
        """
given context, provide the position
        input
"""

    def get_nt_position(self, seg, near_address=None):
cmaffeo2's avatar
cmaffeo2 committed
297
298
299
300
        """ Returns the "address" of the nucleotide relative to seg in
        nucleotides, taking the shortest (intrahelical) contour length route to seg
        """
        if seg == self.parent:
301
            pos = self.contour_position
cmaffeo2's avatar
cmaffeo2 committed
302
        else:
303
304
            pos = self.get_contour_position(seg,near_address)
        return seg.contour_to_nt_pos(pos)
cmaffeo2's avatar
cmaffeo2 committed
305

306
    def get_contour_position(self,seg, address = None):
cmaffeo2's avatar
cmaffeo2 committed
307
308
309
310
        """ TODO: fix paradigm where a bead maps to exactly one location in a polymer
        - One way: modify get_contour_position to take an optional argument that indicates where in the polymer you are looking from
        """

311
312
313
        if seg == self.parent:
            return self.contour_position
        else:
cmaffeo2's avatar
cmaffeo2 committed
314
315
316
317
318
            cutoff = 30*3
            target_seg = seg

            ## depth-first search
            ## TODO cache distances to nearby locations?
cmaffeo2's avatar
cmaffeo2 committed
319
            def descend_search_tree(seg, contour_in_seg, distance=0, visited_segs=None):
cmaffeo2's avatar
cmaffeo2 committed
320
                nonlocal cutoff
cmaffeo2's avatar
cmaffeo2 committed
321
                if visited_segs is None: visited_segs = []
cmaffeo2's avatar
cmaffeo2 committed
322
323
324
325

                if seg == target_seg:
                    # pdb.set_trace()
                    ## Found a segment in our target
326
327
                    sign = 1 if contour_in_seg == 1 else -1
                    if sign == -1: assert( contour_in_seg == 0 )
cmaffeo2's avatar
cmaffeo2 committed
328
329
                    if distance < cutoff: # TODO: check if this does anything
                        cutoff = distance
330
                    return [[distance, contour_in_seg+sign*seg.nt_pos_to_contour(distance)]], [(seg, contour_in_seg, distance)]
cmaffeo2's avatar
cmaffeo2 committed
331
                if distance > cutoff:
332
                    return None,None
cmaffeo2's avatar
cmaffeo2 committed
333
334
                    
                ret_list = []
335
                hist_list = []
cmaffeo2's avatar
cmaffeo2 committed
336
                ## Find intrahelical locations in seg that we might pass through
337
338
339
340
341
                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
342
                    if B.container in visited_segs: continue
343
344
345
                    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
346
347
348
                                                   distance+dx, visited_segs + [seg] )
                    if results is not None:
                        ret_list.extend( results )
349
350
                        hist_list.extend( history )
                return ret_list,hist_list
cmaffeo2's avatar
cmaffeo2 committed
351

352
            results,history = descend_search_tree(self.parent, self.contour_position)
cmaffeo2's avatar
cmaffeo2 committed
353
354
            if results is None or len(results) == 0:
                raise Exception("Could not find location in segment") # TODO better error
355
356
357
358
            if address is not None:
                return sorted(results,key=lambda x:(x[0],(x[1]-address)**2))[0][1]
            else:
                return sorted(results,key=lambda x:x[0])[0][1]
cmaffeo2's avatar
cmaffeo2 committed
359
360
361
            # nt_pos = self.get_nt_position(seg)
            # return seg.nt_pos_to_contour(nt_pos)

362
363
364
365
366
367
368
369
370
371
372
373
374
375
376
377
378
379
380
381
382
383
384
385
    def combine(self, other):
        assert(other in self.intrahelical_neighbors)
        assert(self in other.intrahelical_neighbors)

        self.intrahelical_neighbors.remove(other)
        other.intrahelical_neighbors.remove(self)
        for b in other.intrahelical_neighbors:
            b.intrahelical_neighbors.remove(other)
            b.intrahelical_neighbors.append(self)
            self.intrahelical_neighbors.append(b)
        for l in other.locations:
            self.locations.append(l)
            l.particle = self
        
        ## Remove bead
        other.parent.children.remove(other)
        if other in other.parent.beads:
            other.parent.beads.remove(other)
        if 'orientation_bead' in other.__dict__:
            other.parent.children.remove(other.orientation_bead)

        for b in list(other.parent.bonds):
            if other in b[:2]: other.parent.bonds.remove(b)

cmaffeo2's avatar
cmaffeo2 committed
386
387
388
389
390
391
392
393
394
395
396
397
    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
398
399
400
    def __repr__(self):
        return "<SegmentParticle {} on {}[{:.2f}]>".format( self.name, self.parent, self.contour_position)

401
402

## TODO break this class into smaller, better encapsulated pieces
403
404
405
406
407
408
409
410
411
412
413
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
414
415
416
417
418
    orientation_particle = ParticleType("O",
                                        diffusivity = 100,
                                        mass = 300,
                                        radius = 1,
                                    )
419

cmaffeo2's avatar
cmaffeo2 committed
420
    # orientation_bond = HarmonicBond(10,2)
421
    orientation_bond = HarmonicBond(30,1.5, rRange = (0,500) )
422
423
424
425
426
427
428

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

429
    def __init__(self, name, num_nt, 
cmaffeo2's avatar
cmaffeo2 committed
430
                 start_position = None,
431
                 end_position = None, 
cmaffeo2's avatar
cmaffeo2 committed
432
433
                 segment_model = None,
                 **kwargs):
434

cmaffeo2's avatar
cmaffeo2 committed
435
436
        if start_position is None: start_position = np.array((0,0,0))

cmaffeo2's avatar
cmaffeo2 committed
437
        Group.__init__(self, name, children=[], **kwargs)
438
        ConnectableElement.__init__(self, connection_locations=[], connections=[])
439

cmaffeo2's avatar
cmaffeo2 committed
440
441
442
        if 'segname' not in kwargs:
            self.segname = name
        # self.resname = name
cmaffeo2's avatar
cmaffeo2 committed
443
444
445
446
447
        self.start_orientation = None
        self.twist_per_nt = 0

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

448
449
450
        self._bead_model_generation = 0    # TODO: remove?
        self.segment_model = segment_model # TODO: remove?

451
452
453
454
        self.strand_pieces = dict()
        for d in ('fwd','rev'):
            self.strand_pieces[d] = []

455
        self.num_nt = int(num_nt)
456
        if end_position is None:
457
            end_position = np.array((0,0,self.distance_per_nt*num_nt)) + start_position
458
459
460
        self.start_position = start_position
        self.end_position = end_position

cmaffeo2's avatar
cmaffeo2 committed
461
462
463
464
        ## Used to assign cadnano names to beads
        self._generate_bead_callbacks = []
        self._generate_nucleotide_callbacks = []

465
        ## Set up interpolation for positions
466
467
468
469
        self._set_splines_from_ends()

        self.sequence = None

470
    def __repr__(self):
471
        return "<{} {}[{:d}]>".format( str(type(self)).split('.')[-1], self.name, self.num_nt )
472

cmaffeo2's avatar
cmaffeo2 committed
473
    def set_splines(self, contours, coords):
474
        tck, u = interpolate.splprep( coords.T, u=contours, s=0, k=1)
475
        self.position_spline_params = (tck,u)
476

477
478
    def set_orientation_splines(self, contours, quaternions):
        tck, u = interpolate.splprep( quaternions.T, u=contours, s=0, k=1)
479
480
481
482
483
484
        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)

485
486
487
488
    def get_bounding_box( self, num_points=3 ):
        positions = np.zeros( (num_points, 3) )
        i = 0
        for c in np.linspace(0,1,num_points):
489
            positions[i] = self.contour_to_position(c)
490
491
492
493
494
            i += 1
        min_ = np.array([np.min(positions[:,i]) for i in range(3)])
        max_ = np.array([np.max(positions[:,i]) for i in range(3)])
        return min_,max_

495
496
497
    def _get_location_positions(self):
        return [self.contour_to_nt_pos(l.address) for l in self.locations]

cmaffeo2's avatar
cmaffeo2 committed
498
    def insert_dna(self, at_nt: int, num_nt: int, seq=tuple()):
499
500
501
502
503
504
505
506
507
508
509
510
        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
511
512
        ## TODO: handle sequence

513
514
515
516
517
518
        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
519
        """ Removes nucleotides between first_nt and last_nt, inclusive """
520
521
522
523
524
525
526
527
528
529
530
531
532
533
534
535
536
537
538
539
540
541
        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
542
543
544
545
546
547
548
549
        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 )
550

cmaffeo2's avatar
cmaffeo2 committed
551
        self.num_nt = num_nt
552
553
554
555

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

556
557
558
559
560
561
562
563
564
565
566
567
    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

568
    def translate(self, translation_vector, position_filter=None, contour_filter=None):
569
570
571
572
573
        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)
cmaffeo2's avatar
cmaffeo2 committed
574
        if len(ids) == 0: return
575
576
577

        ## Translate
        r[ids,:] = r[ids,:] + dr[np.newaxis,:]
578
        self.set_splines(u,r)
579
580
581
582
583
584

    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)
cmaffeo2's avatar
cmaffeo2 committed
585
        if len(ids) == 0: return
586
587
588

        if about is None:
            ## TODO: do this more efficiently
589
            r[ids,:] = np.array([rotation_matrix.dot(r[i,:]) for i in ids])
590
591
592
        else:
            dr = np.array(about)
            ## TODO: do this more efficiently
593
            r[ids,:] = np.array([rotation_matrix.dot(r[i,:]-dr) + dr for i in ids])
594

595
        self.set_splines(u,r)
596
597
598
599

        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
600
            orientations = np.array([self.contour_to_orientation(v) for v in u])
601
602
            for i in ids:
                orientations[i,:] = rotation_matrix.dot(orientations[i])
603
            quats = np.array([quaternion_from_matrix(o) for o in orientations])
604
            self.set_orientation_splines(u, quats)
605

606
    def _set_splines_from_ends(self, resolution=4):
607
        self.quaternion_spline_params = None
608
609
610
611
612
613
        r0 = np.array(self.start_position)[np.newaxis,:]
        r1 = np.array(self.end_position)[np.newaxis,:]
        u = np.linspace(0,1, max(3,self.num_nt//int(resolution)))
        s = u[:,np.newaxis]
        coords = (1-s)*r0 + s*r1
        self.set_splines(u, coords)
614

615
616
617
    def clear_all(self):
        Group.clear_all(self)  # TODO: use super?
        self.beads = []
618
619
620
621
622
        # for c,loc,other in self.get_connections_and_locations():
        #     loc.particle = None
        #     other.particle = None
        for l in self.locations:
            l.particle = None
623

624
    def contour_to_nt_pos(self, contour_pos, round_nt=False):
625
        nt = contour_pos*(self.num_nt) - 0.5
626
        if round_nt:
cmaffeo2's avatar
cmaffeo2 committed
627
            assert( np.isclose(np.around(nt),nt) )
628
629
630
            nt = np.around(nt)
        return nt

631
    def nt_pos_to_contour(self,nt_pos):
632
        return (nt_pos+0.5)/(self.num_nt)
633

634
    def contour_to_position(self,s):
635
        p = interpolate.splev( s, self.position_spline_params[0] )
636
637
638
639
        if len(p) > 1: p = np.array(p).T
        return p

    def contour_to_tangent(self,s):
640
        t = interpolate.splev( s, self.position_spline_params[0], der=1 )
641
642
        t = (t / np.linalg.norm(t,axis=0))
        return t.T
643
644
645
        

    def contour_to_orientation(self,s):
646
        assert( isinstance(s,float) or isinstance(s,int) or len(s) == 1 )   # TODO make vectorized version
647

648
649
650
651
652
        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)
653
            zAxis = np.array((0,0,1))
654
655

            if rotAxisL > 0.001:
656
657
658
                theta = np.arcsin(rotAxisL) * 180/np.pi
                if axis.dot(zAxis) < 0: theta = 180-theta
                orientation0 = rotationAboutAxis( rotAxis/rotAxisL, theta, normalizeAxis=False ).T
659
            else:
660
661
                orientation0 = np.eye(3) if axis.dot(zAxis) > 0 else \
                               rotationAboutAxis( np.array((1,0,0)), 180, normalizeAxis=False )
662
663
664
            if self.start_orientation is not None:
                orientation0 = orientation0.dot(self.start_orientation)

665
666
667
            orientation = rotationAboutAxis( axis, self.twist_per_nt*self.contour_to_nt_pos(s), normalizeAxis=False )
            orientation = orientation.dot(orientation0)
        else:
668
            q = interpolate.splev( s, self.quaternion_spline_params[0] )
669
670
            if len(q) > 1: q = np.array(q).T # TODO: is this needed?
            orientation = quaternion_to_matrix(q)
671

672
        return orientation
673

cmaffeo2's avatar
cmaffeo2 committed
674
    def get_contour_sorted_connections_and_locations(self,type_):
cmaffeo2's avatar
cmaffeo2 committed
675
        sort_fn = lambda c: c[1].address
cmaffeo2's avatar
cmaffeo2 committed
676
        cl = self.get_connections_and_locations(type_)
cmaffeo2's avatar
cmaffeo2 committed
677
        return sorted(cl, key=sort_fn)
678
679
680
    
    def randomize_unset_sequence(self):
        bases = list(seqComplement.keys())
681
        # bases = ['T']        ## FOR DEBUG
682
        if self.sequence is None:
683
            self.sequence = [random.choice(bases) for i in range(self.num_nt)]
684
        else:
685
            assert(len(self.sequence) == self.num_nt) # TODO move
686
687
688
            for i in range(len(self.sequence)):
                if self.sequence[i] is None:
                    self.sequence[i] = random.choice(bases)
689

cmaffeo2's avatar
cmaffeo2 committed
690
691
692
    def _get_num_beads(self, max_basepairs_per_bead, max_nucleotides_per_bead ):
        raise NotImplementedError

693
    def _generate_one_bead(self, contour_position, nts):
694
695
        raise NotImplementedError

cmaffeo2's avatar
cmaffeo2 committed
696
    def _generate_atomic_nucleotide(self, contour_position, is_fwd, seq, scale, strand_segment):
cmaffeo2's avatar
cmaffeo2 committed
697
698
699
700
701
        """ 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)
702
        orientation = self.contour_to_orientation(contour_position)
cmaffeo2's avatar
cmaffeo2 committed
703

704
705
706
707
708
709
710
711
712
713
714
715
716
717
718
719
720
721
        """ 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
722
        key = seq
723
724
        nt_dict = canonicalNtFwd if is_fwd else canonicalNtRev

725
        atoms = nt_dict[ key ].generate() # TODO: clone?
cmaffeo2's avatar
cmaffeo2 committed
726
        atoms.orientation = orientation.dot(atoms.orientation)
727
728
729
730
        if isinstance(self, SingleStrandedSegment):
            if scale is not None and scale != 1:
                for a in atoms:
                    a.position = scale*a.position
731
            atoms.position = pos - atoms.atoms_by_name["C1'"].collapsedPosition()
732
733
734
735
736
737
738
739
740
        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
741
                    else:
742
                        a.fixed = 1
743
            atoms.position = pos
cmaffeo2's avatar
cmaffeo2 committed
744
745
746
747
748
749
        
        atoms.contour_position = contour_position
        strand_segment.add(atoms)

        for callback in self._generate_nucleotide_callbacks:
            callback(atoms)
cmaffeo2's avatar
cmaffeo2 committed
750
751

        return atoms
752

753
754
755
756
757
758
759
760
761
762
763
764
765
766
767
768
769
770
771
772
773
774
    def _generate_oxdna_nucleotide(self, contour_position, is_fwd, seq):
        bp_center = self.contour_to_position(contour_position)
        orientation = self.contour_to_orientation(contour_position)

        DefaultOrientation = rotationAboutAxis([0,0,1], 90)
        if is_fwd: 
            DefaultOrientation = rotationAboutAxis([1,0,0], 180).dot(DefaultOrientation)

        o = orientation.dot(DefaultOrientation)

        if isinstance(self, SingleStrandedSegment):
            pos = bp_center
        else:
            pos = bp_center - 5*o.dot(np.array((1,0,0)))

        nt = PointParticle("oxdna_nt", position= pos,
                             orientation = o)

        nt.contour_position = contour_position
        return nt


775
776
    def add_location(self, nt, type_, on_fwd_strand=True):
        ## Create location if needed, add to segment
777
        c = self.nt_pos_to_contour(nt)
778
779
780
781
782
783
        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?
784
785

    def add_nick(self, nt, on_fwd_strand=True):
786
787
788
789
790
791
792
        if on_fwd_strand:
            self.add_3prime(nt,on_fwd_strand)
            self.add_5prime(nt+1,on_fwd_strand)
        else:
            self.add_5prime(nt,on_fwd_strand)
            self.add_3prime(nt+1,on_fwd_strand)

793

794
    def add_5prime(self, nt, on_fwd_strand=True):
795
796
        if isinstance(self,SingleStrandedSegment):
            on_fwd_strand = True
797
        self.add_location(nt,"5prime",on_fwd_strand)
798
799

    def add_3prime(self, nt, on_fwd_strand=True):
800
801
        if isinstance(self,SingleStrandedSegment):
            on_fwd_strand = True
802
        self.add_location(nt,"3prime",on_fwd_strand)
803

804
805
806
807
808
809
810
811
812
813
814
815
816
817
818
819
820
821
822
823
824
825
826
827
    ## Real work
    def _connect_ends(self, end1, end2, type_, force_connection=False):
        debug = False
        ## TODO remove self?
        ## validate the input
        for end in (end1, end2):
            assert( isinstance(end, Location) )
            assert( end.type_ in ("end3","end5") )
        assert( end1.type_ != end2.type_ )

        ## Remove other connections involving these points
        if end1.connection is not None:
            if debug: print("WARNING: reconnecting {}".format(end1))
            end1.connection.delete()
        if end2.connection is not None:
            if debug: print("WARNING: reconnecting {}".format(end2))
            end2.connection.delete()

        ## Create and add connection
        if end2.type_ == "end5":
            end1.container._connect( end2.container, Connection( end1, end2, type_=type_ ), in_3prime_direction=True )
        else:
            end2.container._connect( end1.container, Connection( end2, end1, type_=type_ ), in_3prime_direction=True )

828
    def get_3prime_locations(self):
cmaffeo2's avatar
cmaffeo2 committed
829
        return sorted(self.get_locations("3prime"),key=lambda x: x.address)
830
    
cmaffeo2's avatar
cmaffeo2 committed
831
    def get_5prime_locations(self):
832
        ## TODO? ensure that data is consistent before _build_model calls
cmaffeo2's avatar
cmaffeo2 committed
833
        return sorted(self.get_locations("5prime"),key=lambda x: x.address)
cmaffeo2's avatar
cmaffeo2 committed
834

835
    def iterate_connections_and_locations(self, reverse=False):
cmaffeo2's avatar
cmaffeo2 committed
836
837
        ## connections to other segments
        cl = self.get_contour_sorted_connections_and_locations()
838
        if reverse:
cmaffeo2's avatar
cmaffeo2 committed
839
            cl = cl[::-1]
840
841
842
            
        for c in cl:
            yield c
cmaffeo2's avatar
cmaffeo2 committed
843

844
845
846
847
848
849
850
851
852
853
854
    ## 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):
855
856
                if value >= l and value <= h:
                    raise Exception("Strand piece already exists! DNA may be circular.")
857
858
859
860
861
862

        ## 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)

863
    ## TODO rename
864
    def get_strand_segment(self, nt_pos, is_fwd, move_at_least=0.5):
865
        """ Walks through locations, checking for crossovers """
866
867
868
869
        # if self.name in ("6-1","1-1"):
        #     import pdb
        #     pdb.set_trace()
        move_at_least = 0
870
871

        ## Iterate through locations
cmaffeo2's avatar
cmaffeo2 committed
872
        # locations = sorted(self.locations, key=lambda l:(l.address,not l.on_fwd_strand), reverse=(not is_fwd))
873
874
875
876
877
878
        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))
879
880
        # print(locations)

881
        for l in locations:
cmaffeo2's avatar
cmaffeo2 committed
882
883
884
885
            # TODOTODO probably okay
            if l.address == 0:
                pos = 0.0
            elif l.address == 1:
886
                pos = self.num_nt-1
cmaffeo2's avatar
cmaffeo2 committed
887
888
            else:
                pos = self.contour_to_nt_pos(l.address, round_nt=True)
889
890
891

            ## DEBUG

cmaffeo2's avatar
cmaffeo2 committed
892

893
            ## Skip locations encountered before our strand
894
895
896
897
898
899
900
901
            # 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
902
903

            ## Stop if we found the 3prime end
904
            if l.on_fwd_strand == is_fwd and l.type_ == "3prime" and l.connection is None:
905
                # print("  found end at",l)
906
                return pos, None, None, None, None
907
908
909
910
911
912
913
914

            ## 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:
915
916
                # print("  passing through",l)
                # print("from {}, connection {} to {}".format(nt_pos,l,B))
917
                Bpos = B.get_nt_pos()
918
                return pos, B.container, Bpos, B.on_fwd_strand, 0.5
919
920
921
                
            ## Stop at other strand crossovers so basepairs line up
            elif c.type_ == "crossover":
922
                if nt_pos == pos: continue
923
                # print("  pausing at",l)
924
                return pos, l.container, pos+(2*is_fwd-1), is_fwd, 0
925
926
927
928
929
930

        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

931
932
933
    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
934
        # TODO: include beads in connections?
935
936
937
        i = np.argmin((cs - contour_position)**2)

        return self.beads[i]
938

939
940
941
942
943
944
945
946
947
    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 ))

948
949
    def get_all_consecutive_beads(self, number):
        assert(number >= 1)
cmaffeo2's avatar
cmaffeo2 committed
950
        ## Assume that consecutive beads in self.beads are bonded
951
        ret = []
cmaffeo2's avatar
cmaffeo2 committed
952
953
        for i in range(len(self.beads)-number+1):
            tmp = [self.beads[i+j] for j in range(0,number)]
954
            ret.append( tmp )
955
        return ret   
956

957
    def _add_bead(self,b):
958
        
959
960
961
        # assert(b.parent is None)
        if b.parent is not None:
            b.parent.children.remove(b)
962
        self.add(b)
963
964
965
966
967
968
        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)
969
            self.add(o)
970
971
972
973
974
975
976
977
            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 = []
978
979

        if True:
980
981
            ## TODO: remove this if duplicates are never found 
            # print("Searching for duplicate particles...")
982
            ## Remove duplicates, preserving order
983
984
985
986
            tmp = []
            for c in new_children:
                if c not in tmp:
                    tmp.append(c)
987
                else:
988
                    print("  DUPLICATE PARTICLE FOUND!")
989
990
            new_children = tmp

991
992
993
994
995
        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)
996
997
998
999
1000
            
        # 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)
1001
1002
        assert(len(old_children) == len(self.children))
        assert(len(old_beads) == len(self.beads))
1003