File: Splitter.java

package info (click to toggle)
bbmap 39.20%2Bdfsg-3
  • links: PTS, VCS
  • area: main
  • in suites: forky, sid
  • size: 26,024 kB
  • sloc: java: 312,743; sh: 18,099; python: 5,247; ansic: 2,074; perl: 96; makefile: 39; xml: 38
file content (476 lines) | stat: -rwxr-xr-x 15,402 bytes parent folder | download | duplicates (2)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200
201
202
203
204
205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
220
221
222
223
224
225
226
227
228
229
230
231
232
233
234
235
236
237
238
239
240
241
242
243
244
245
246
247
248
249
250
251
252
253
254
255
256
257
258
259
260
261
262
263
264
265
266
267
268
269
270
271
272
273
274
275
276
277
278
279
280
281
282
283
284
285
286
287
288
289
290
291
292
293
294
295
296
297
298
299
300
301
302
303
304
305
306
307
308
309
310
311
312
313
314
315
316
317
318
319
320
321
322
323
324
325
326
327
328
329
330
331
332
333
334
335
336
337
338
339
340
341
342
343
344
345
346
347
348
349
350
351
352
353
354
355
356
357
358
359
360
361
362
363
364
365
366
367
368
369
370
371
372
373
374
375
376
377
378
379
380
381
382
383
384
385
386
387
388
389
390
391
392
393
394
395
396
397
398
399
400
401
402
403
404
405
406
407
408
409
410
411
412
413
414
415
416
417
418
419
420
421
422
423
424
425
426
427
428
429
430
431
432
433
434
435
436
437
438
439
440
441
442
443
444
445
446
447
448
449
450
451
452
453
454
455
456
457
458
459
460
461
462
463
464
465
466
467
468
469
470
471
472
473
474
475
476
package clump;

import java.util.ArrayList;
import java.util.LinkedHashMap;
import java.util.Map.Entry;

import dna.AminoAcid;
import shared.KillSwitch;
import shared.Tools;
import stream.Read;
import structures.IntList;
import structures.LongList;

/**
 * A tool for splitting clumps by allele.
 * @author Brian Bushnell
 * @date September 26, 2016
 *
 */
class Splitter {
	
	static ArrayList<Clump> splitOnPivot(Clump c){
		ArrayList<Clump> list=new ArrayList<Clump>(3);
		list.add(c);
		if(c.size()<minSizeSplit){
//			assert(findBestPivot(c)<0);
			return list;
		}
		return splitOnPivot(list);
	}
	
	static ArrayList<Clump> splitOnPivot(ArrayList<Clump> list){
		ArrayList<Clump> out=new ArrayList<Clump>();
		
		final IntList pivots=new IntList(2);
		for(int i=0; i<list.size(); i++){
			Clump clump=list.get(i);
			list.set(i, null);
			int pivot=findBestPivots(clump, FIND_CORRELATIONS, pivots);
			if(pivot<0){
				assert(pivots.size==0);
				out.add(clump);
			}else{
				assert(pivots.size==1 || pivots.size==2) : pivot+", "+pivots.size+", "+pivots;
				assert(pivots.get(0)==pivot);
				int added=splitAndAdd(clump, pivots.get(0), (pivots.size>1 ? pivots.get(1) : -1), list);
				if(added<2) {//Rare case that caused an assertion once
					assert(added==1);
					out.add(clump);
					i++;
				}
			}
		}
		return out;
	}
	
	static int splitAndAdd(Clump c, final int var1, final int var2, ArrayList<Clump> list) {
		final int maxLeft=c.maxLeft();
		
		final Clump major=Clump.makeClump(c.kmer), minor=Clump.makeClump(c.kmer);
		
		for(Read r : c){
			if(containsVar(var1, r, maxLeft) || (var2>=0 && containsVar(var2, r, maxLeft))){
				minor.add(r);
			}else{
				major.add(r);
			}
		}
		
//		assert(major.size()>0) : c.size()+", "+major.size()+", "+minor.size()+
//			", "+(var1>>2)+", "+(var1&alleleMask)+", "+(var2>>2)+", "+(var2&alleleMask)+
//			", "+list.size()+", "+c.get(0);
//		assert(minor.size()>0) : c.size()+", "+major.size()+", "+minor.size()+
//			", "+(var1>>2)+", "+(var1&alleleMask)+", "+(var2>>2)+", "+(var2&alleleMask)+
//			", "+list.size()+", "+c.get(0);
//		assert(major.size()+minor.size()==c.size()) : c.size()+", "+major.size()+", "+minor.size()+
//			", "+(var1>>2)+", "+(var1&alleleMask)+", "+(var2>>2)+", "+(var2&alleleMask)+
//			", "+list.size()+", "+c.get(0);
		
//		Exception in thread "Thread-110" java.lang.AssertionError: 21, 0, 21, 163, 1, 104, 2, 71,      
//		TTTTGGCAGCCCCCCCCCCCCCCCCCCCCCCCCCCCGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGCGCCACGCCGCCCCCCCCCCCC <-90
//		CCCCCCCCCCGGGGGGGGGGGGCAGGGGGGGGGGGGGGGGGGGGGGGCGCCCCCCCCCC
//		        at clump.Splitter.splitAndAdd(Splitter.java:72)
//		        at clump.Splitter.splitOnPivot(Splitter.java:46)
//		        at clump.Splitter.splitOnPivot(Splitter.java:29)
//		        at clump.Clump.splitAndErrorCorrect(Clump.java:612)
//		        at clump.ClumpList$ProcessThread.run(ClumpList.java:342)
		
		
		int added=(major.size()>0 ? 1 : 0)+(minor.size()>0 ? 1 : 0);
		if(major.size()>0) {list.add(major);}
		if(minor.size()>0) {list.add(minor);}
		assert(added>0) : c.size()+", "+major.size()+", "+minor.size();
		return added;
	}
	
	//Returns the c
	static int countVariants(Clump c, LongList varCounts){
		varCounts.clear();
		final int[][] bcounts=c.baseCounts();
		final int[][] qcounts=c.qualityCounts();
		final int len=bcounts[0].length;
		for(int i=0; i<len; i++){
			final int major=c.getConsensusAtPosition(qcounts, i);
			for(int x=0; x<4; x++){
				final int bcount=bcounts[x][i];
				if(bcount>1 && x!=major){
					final long var=(((long)bcount)<<32)|((i<<shift)|x);
					varCounts.add(var);
				}
			}
		}
		if(varCounts.size()<1){return 0;}
		varCounts.sort();
		varCounts.reverse();
		return (int)(varCounts.get(0)>>>32);
	}
	
	static LinkedHashMap<Integer, ArrayList<Read>> findReadVariants(Clump c, boolean makeMap){
		if(c.size()<5){return null;} //Not really needed with tiny clumps
//		assert(c.size()>3); //TODO
		LinkedHashMap<Integer, ArrayList<Read>> map=null;
		map=(makeMap ? new LinkedHashMap<Integer, ArrayList<Read>>() : null);
//		if(makeMap){
//			map=localMap.get();
//			if(map==null){
//				map=new LinkedHashMap<Integer, ArrayList<Read>>();
//				localMap.set(map);
//			}
//			map.clear();
//		}
		
		final int[][] bcounts=c.baseCounts();
		final Read ref=c.consensusRead();
		final byte[] rbases=ref.bases;
		for(Read r : c){
			final byte[] bases=r.bases;
			final ReadKey key=(ReadKey) r.obj;
			IntList list=key.vars;
			if(list!=null){list.clear();}
			
			
			final int cStart=0, rStart=c.maxLeft()-key.position;
			
			for(int i=cStart, j=rStart; i<bases.length; i++, j++){
				final byte cb=bases[i], rb=rbases[j];
				if(cb!=rb){
					byte x=AminoAcid.baseToNumber[cb];
					if(x>=0){
						int count=bcounts[x][j];
						if(count>1){
							int var=(j<<2)|x;
							if(list==null){list=key.vars=new IntList(4);}
							list.add(var);
							
							if(map!=null){
								Integer mapkey=var;//mapKeys[var];
								ArrayList<Read> alr=map.get(mapkey);
								if(alr==null){
									alr=new ArrayList<Read>(4);
									map.put(mapkey, alr);
								}
								alr.add(r);
							}
							
						}
					}
				}
			}
		}
		return map==null || map.isEmpty() ? null : map;
	}
	
	static int findBestPivot_Correlated(Clump c, IntList pivots){
		assert(pivots.size==0);
		LinkedHashMap<Integer, ArrayList<Read>> map=findReadVariants(c, true);
		if(map==null){return -1;}
		
		IntList collection=new IntList(32);
		int[] rvector=KillSwitch.allocInt1D(5);
		
		int bestVar=-1;
		int bestVarCount=-1;
		int bestVar2=-1;
		int bestVar2Count=-1;
		int bestDifferent=-1;
		float bestCorrelation=-1;
		float bestScore=-1;
		
		final float minCorrelation=0.75f;
		final int minVar2Count=2;
		
		int max=0;
		for(Entry<Integer, ArrayList<Read>> entry : map.entrySet()){
			max=Tools.max(max, entry.getValue().size());
		}
		if(max<2){return -1;}
		final int thresh=Tools.max(2, max/2);
		final int thresh2=max/4;
		int numOverThresh=0;
		ArrayList<Integer> remove=new ArrayList<Integer>();
		for(Entry<Integer, ArrayList<Read>> entry : map.entrySet()){
			int x=entry.getValue().size();
			if(x>=thresh){numOverThresh++;}
			else if(x<thresh2){remove.add(entry.getKey());}
		}
		for(Integer key : remove){map.remove(key);}
		if(numOverThresh>MAX_CORRELATIONS){return -1;}
		
		for(Entry<Integer, ArrayList<Read>> entry : map.entrySet()){
			final ArrayList<Read> rlist=entry.getValue();
			final Integer key=entry.getKey();
			final int var=key;
			if(rlist.size()>=thresh){
				
				final int var2=examineVar(var, rlist, collection, rvector, map);

				if(var2>=0){

					final int varCount=rvector[1];
					final int var2Count=rvector[3];
					final int different=rvector[4];

					final int var2reads;
					final int var2ReadsWithoutVar;
					{
						ArrayList<Read> temp=map.get(var2);
						var2reads=(temp==null ? 0 : temp.size());

//						if(var2reads==var2Count){
//							var2ReadsWithoutVar=0;
//						}else{
//							var2ReadsWithoutVar=countDifferentAlleles(var, temp);
//						}

						var2ReadsWithoutVar=var2reads-varCount;

					}

//					final float correlation=(var2Count-0.05f)/(float)varCount;
//					final float correlation=(varCount-different)/(float)varCount;
					final float correlation=(Tools.max(varCount, var2reads)-different)/(float)Tools.max(varCount, var2reads);
					final int distance=Tools.absdif(var>>2, var2>>2);

//					final float score=correlation*((var2Count-1)-0.5f*var2ReadsWithoutVar-different+1.0f*(varCount));

					final float score=correlation*(var2reads/*var2Count*/+varCount-different+0.5f*var2ReadsWithoutVar)*(distance+250);

//					final float score=correlation*((var2Count-1)-1.0f*var2ReadsWithoutVar+1.0f*(varCount));
					if(correlation>=minCorrelation && var2Count>=minVar2Count){
						if(score>bestScore || (score==bestScore && varCount>bestVarCount)){
							bestVar=var;
							bestVarCount=varCount;
							bestVar2=var2;
							bestVar2Count=var2Count;
							bestCorrelation=correlation;
							bestScore=score;
							bestDifferent=different;
						}
					}
				}
			}
		}
		
		if(bestVar2Count>=minVar2Count && bestCorrelation>=minCorrelation){
			pivots.add(bestVar);
			pivots.add(bestVar2);
			return bestVar;
		}
		return -1;
	}
	
	static boolean containsVar(final int var, final Read r, final int maxLeft){
		final int varPos=var>>2;
		final int varAllele=var&alleleMask;
		final ReadKey rk=(ReadKey) r.obj;
		final int rloc=toReadLocation(varPos, maxLeft, rk.position);
		if(rloc<0 || rloc>=r.length()){
			return false;
		}
		final int readAllele=AminoAcid.baseToNumber[r.bases[rloc]];
		return readAllele==varAllele;
	}
	
	static boolean hasDifferentAllele(final int var, final Read r/*, final Clump c*/){
		final int varPos=var>>2;
		final int varAllele=var&alleleMask;
		final ReadKey rk=(ReadKey) r.obj;
		final IntList vars=rk.vars;
		final Clump c=rk.clump;
		assert(c==rk.clump);
		final int maxLeft=c.maxLeft();
		final int rloc=toReadLocation(varPos, maxLeft, rk.position);
		if(rloc<0 || rloc>=r.length()){
			assert(!vars.contains(var));
			return false;
		}
		final int readAllele=AminoAcid.baseToNumber[r.bases[rloc]];
		assert((readAllele==varAllele)==vars.contains(var));
		
		return readAllele!=varAllele;
	}
	
	static int countDifferentAlleles(final int var, ArrayList<Read> list){
		if(list==null){return 0;}
		int sum=0;
		for(Read r : list){
			if(hasDifferentAllele(var, r)){sum++;}
		}
		return sum;
	}
	
	static int examineVar(final int var, final ArrayList<Read> list, final IntList collection, final int[] rvector, LinkedHashMap<Integer, ArrayList<Read>> map){
		collection.clear();
		
		for(Read r : list){
			final ReadKey rk=(ReadKey) r.obj;
			final IntList vars=rk.vars;
			
			for(int i=0; i<vars.size; i++){
				final int v2=vars.get(i);
				if(v2!=var){
					collection.add(v2);
				}
			}
		}
		collection.sort();
		
		final int varCount=list.size();
		
		int lastVar2=-1, bestVar2=-1;
		int sharedCount=0, bestSharedCount=0, bestDifferent=999;
		for(int i=0; i<collection.size; i++){//TODO: Note that not all reads actually cover a given var
			int currentVar2=collection.get(i);
			if(currentVar2==lastVar2){sharedCount++;}
			else{
				if(sharedCount>bestSharedCount){
					final int different1=(sharedCount==varCount ? 0 : countDifferentAlleles(lastVar2, list));
					if(different1*8<varCount){
						ArrayList<Read> list2=map.get(lastVar2);
						final int varCount2=(list2==null ? 0 : list2.size());
						final int different2=(sharedCount==varCount2 ? 0 : countDifferentAlleles(var, list2));
						if(different2*8<varCount2){
							bestVar2=lastVar2;
							bestSharedCount=sharedCount;
							bestDifferent=Tools.max(different1, different2);
						}
					}
				}
				sharedCount=1;
			}
			lastVar2=currentVar2;
		}
		if(sharedCount>bestSharedCount){
			final int different1=(sharedCount==varCount ? 0 : countDifferentAlleles(lastVar2, list));
			if(different1*8<varCount){
				ArrayList<Read> list2=map.get(lastVar2);
				final int varCount2=(list2==null ? 0 : list2.size());
				final int different2=(sharedCount==varCount2 ? 0 : countDifferentAlleles(var, list2));
				if(different2*8<varCount2){
					bestVar2=lastVar2;
					bestSharedCount=sharedCount;
					bestDifferent=Tools.max(different1, different2);
				}
			}
		}
		rvector[0]=var;
		rvector[1]=list.size();
		rvector[2]=bestVar2;
		rvector[3]=sharedCount;
		rvector[4]=bestDifferent;
		
		return bestVar2;
	}
	
	static final int toReadLocation(final int clumpLocation, final int maxLeft, final int readPos){
		final int readLocation=clumpLocation+readPos-maxLeft;
		return readLocation;
	}
	
	static final int toClumpLocation(final int readLocation, final int maxLeft, final int readPos){
		final int clumpLocation=readLocation-readPos+maxLeft;
		assert(readLocation==toReadLocation(clumpLocation, maxLeft, readPos));
		return clumpLocation;
	}
	
	static int findBestPivots(Clump c, boolean findCorrelations, IntList pivots){
		pivots.clear();
		final int size=c.size();
		if(size<minSizeSplit){return -1;}
		
		if(findCorrelations){
			int x=findBestPivot_Correlated(c, pivots);
			if(x>-1){return x;}
		}
		
		final int[][] bcounts=c.baseCounts();
		final int[][] qcounts=c.qualityCounts();
		final float[][] qAvgs=c.qualityAverages();
		final int width=c.width();
		
		int bestPosition=-1;
		int bestVar=-1;
		long bestBsecond=0;
		long bestQsecond=0;

//		final float bmult=8f, bmult2=15f, qmult=(c.useQuality() ? 1.5f : 100f);
		final boolean useQuality=c.useQuality();
		final float bmult=20f, bmult2=20f;
		final float qmult=20f, qamult=1.5f;
		
		final int minPivotDepth=Tools.max(4, (int)(minSizeFractionSplit*size));
//		final int minMinorAllele=Tools.max((conservative ? 1 : 2), (int)(0.25f+size/bmult2));
		final int minMinorAllele=Tools.max(2, (int)(size/bmult2));
		final int minMinorAlleleQ=minMinorAllele*10;
		
//		assert(false) : size+", "+minSizeSplit+", "+minPivotDepth+", "+minMinorAllele;
		
		for(int i=0; i<width; i++){
			final long sum=c.getSumAtPosition(bcounts, i);
			if(sum>=minPivotDepth){
				final int pmajor=c.getConsensusAtPosition(bcounts, i);
				final int pminor=c.getSecondHighest(bcounts, i);
				if(pmajor>=0){
					final long bmajor=bcounts[pmajor][i];
					final long bsecond=bcounts[pminor][i];

					final long qmajor=qcounts[pmajor][i];
					final long qsecond=qcounts[pminor][i];

					final float qamajor=qAvgs[pmajor][i];
					final float qasecond=qAvgs[pminor][i];

					if(bsecond*bmult>=bmajor && bsecond>=minMinorAllele){
						if(!useQuality || (qsecond*qmult>=qmajor && qasecond*qamult>=qamajor && qsecond>=minMinorAlleleQ)){//candidate
							if(bsecond>bestBsecond || (bsecond==bestBsecond && qsecond>bestQsecond)){//Perhaps Qsecond should be more important...?

//								assert(false) : size+", "+minSizeSplit+", "+minPivotDepth+", "+minMinorAllele+", "+bmajor+", "+bsecond+", "+qmajor+", "+qsecond+", "+minMinorAlleleQ;
								
								bestBsecond=bsecond;
								bestQsecond=qsecond;
								bestPosition=i;
								bestVar=(bestPosition<<2)|pminor;
							}
						}
					}
				}
			}
		}
		
//		if(bestVar<0 && findCorrelations){
//			bestVar=findBestPivot_Correlated(c);
//		}
		
		if(bestVar>=0){pivots.add(bestVar);}
		return bestVar;
	}

	static int minSizeSplit=4; //5 is actually better than 4 in allele separation tests...?
	static float minSizeFractionSplit=0.17f; //0.2 is substantially worse, 0.14 is a tiny bit better than 0.17
	static boolean conservative=false;
	
	private static final int alleleMask=0x3;
	private static final int posMask=~alleleMask;
	private static final int shift=2;
	
	static boolean FIND_CORRELATIONS=true;
	static int MAX_CORRELATIONS=12;
	
//	private static final ThreadLocal<LinkedHashMap<Integer, ArrayList<Read>>> localMap=new ThreadLocal<LinkedHashMap<Integer, ArrayList<Read>>>();
//	private static final Integer[] mapKeys=new Integer[2000];
//	static{
//		for(int i=0; i<mapKeys.length; i++){mapKeys[i]=i;}
//	}
	
}