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
|
/*
* Created by Fahimeh Mirhaj on 6/18/19.
*/
#include "SpliceGraph.h"
#define macro_CompareScore(score1,scoreMax,dirInd,dirIndMax) if(score1>scoreMax){dirIndMax=dirInd;scoreMax=score1;}
SpliceGraph::typeAlignScore SpliceGraph::swScoreSpliced
(const char *readSeq, const uint32 readLen, const SuperTranscript &superTr, vector<array<uint32,2>> &cigar)
{//Smith-Waterman alignment with splices
uint32 superTrLen = superTr.length;
typeAlignScore scoreMaxGlobal = 0;
int32 iDonor=0; //current donor in the donor list
int32 iAcceptor=0;//current acceptor in the sjC list (sorted by acceptors
bool sjYes=superTr.sjC.size() > 0; //spliced superTr
typeAlignScore *scoreColumn, *scoreColumnPrev;//pointer to column and prev column
uint32 iTwoColumn = 0;//selects the column from scoreTwoColumn 2-col matrix
scoreColumn = scoreTwoColumns[iTwoColumn];
for(uint32 ii = 0; ii <= readLen; ii++){//fill 0th column
scoreColumn[ii] = 0;
};
uint32 matIndex=0;//current matIndex: starting from 1st column (not 0th)
for(uint32 col=0; col<superTrLen; col++) {//main cycle over columns: note that columns are counted from 0!
scoreColumnPrev = scoreColumn;//prev column pointer
iTwoColumn = iTwoColumn==0 ? 1 : 0; //switch columns
scoreColumn = scoreTwoColumns[iTwoColumn];
//find the splice junction connected donor columns, if any
uint32 sjN=0;
if (sjYes) {//col matches acceptor column
while (iAcceptor < (int32) superTr.sjC.size() && col==superTr.sjC[iAcceptor][1]) {//col matches acceptor column: find all donors
sjDindex[sjN]=superTr.sjC[iAcceptor][2];//index of donor
++sjN;
++iAcceptor;
};
if (iDonor < (int32) superTr.sjDonor.size() && col==superTr.sjDonor[iDonor]) {//donor column, has to be recorded
scoreColumn=scoringMatrix[iDonor];//point to the stored columns
++iDonor; //advance for the next donor column
};
};
scoreColumn[0] = 0; //initialize top row
for(uint row = 1; row <= readLen; row++) {//rows are counte from 1, 0th row is filled with 0
uint8 dirIndMax = 0 ; //direction index
typeAlignScore scoreMax = 0; //max score for this cell
typeAlignScore score1; //calculated score
//down
score1 = scoreColumn[row-1] + gapPenalty;
macro_CompareScore(score1,scoreMax,1,dirIndMax);
//right
score1 = scoreColumnPrev[row] + gapPenalty;
macro_CompareScore(score1,scoreMax,2,dirIndMax);
//diagonal
score1 = scoreColumnPrev[row-1] + (readSeq[row-1] == superTr.seqP[col] ? matchScore : misMatchPenalty);
macro_CompareScore(score1,scoreMax,3,dirIndMax);
for(uint32 ii = 0; ii < sjN; ii++) {
score1 = scoringMatrix[sjDindex[ii]][row] + gapPenalty;
macro_CompareScore(score1,scoreMax,4+ii*2,dirIndMax);
score1 = scoringMatrix[sjDindex[ii]][row - 1] + (readSeq[row - 1] == superTr.seqP[col] ? matchScore : misMatchPenalty);
macro_CompareScore(score1,scoreMax,5+ii*2,dirIndMax);
};
directionMatrix[matIndex]=dirIndMax;
++matIndex;//matIndex stride is (readLen)
scoreColumn[row] = scoreMax;
if(scoreMaxGlobal < scoreMax) {
scoreMaxGlobal = scoreMax;
alignInfo.aEnd[0] = row;
alignInfo.aEnd[1] = col;
};
}; // row for loop
}; // col for loop
alignInfo.aEnd[0]--;//true row
///////////traceback
// int32 row = alignInfo.aEnd[0];//true row
// int32 col = alignInfo.aEnd[1];
// uint32 nMapped=0, nMM=0, nI=0, nD=0, nSJ=0;
// blockSJ.clear();//index of junction blocks, recorded acceptors, then converted to donors
// blockCoord.clear();//bR,bG,bL,type recorded ends, then converted to starts
// vector<uint32> rowCol(readLen), rowSJ(readLen,0); //records col vs row TODO define outside for speed
// --iAcceptor; //= last junction
//
// rowCol.clear();
// rowSJ.clear();
// rowCol.resize(readLen,-1);
// rowSJ.resize(readLen+1,{-1,-1});//one extra element since we are going to check row+1
//
// while(col >= 0 && row >= 0) {
// uint32 dir1= (uint32) directionMatrix[row+col*readLen];
// if (dir1==0) //reached scoringMatrix==0
// break;
// switch (dir1)
// {
// case 1:
// --row;
// ++nI;
// break;
// case 2:
// --col;
// ++nD;
// break;
// case 3:
// ++nMapped;
// nMM+=(uint32)(readSeq[row]!=superTr.seqP[col]);
// rowCol[row]=col;//for each row, point to the column where blocj starts
// --row;
// --col;
// break;
// default: //junction jump
// ++nSJ;
// while (iAcceptor+1!=0 && col <= (int32)superTr.sjC[iAcceptor][1]) {//find (acceptor-1) that matches this column
// --iAcceptor;
// };
// //row: same or -1
// if ((dir1-4)%2 == 1) {//diagonal-like
// ++nMapped;
// nMM+=(uint32)(readSeq[row]!=superTr.seqP[col]);
// rowCol[row]=col;//for each row, point to the column where block starts
// --row;
// } else {
// //++nD; //?
// };
// rowSJ[row][1]=col;//acceptor
// //column: jump to donor
// col=superTr.sjDonor[ superTr.sjC[iAcceptor+1+(dir1-4)/2][2] ];
// rowSJ[row][0]=col;//donor
// };
// };
//
// row=max(0,row);
// while (rowCol[row]<0)
// row++; //find first col>=0 - this is the alignment start.
// alignInfo.aStart[0]=row;
// alignInfo.aStart[1]=rowCol[row];
cigar.clear();
cigar.reserve(readLen);
int32 row = alignInfo.aEnd[0];//true row
int32 col = alignInfo.aEnd[1];
alignInfo.nMap=0;
alignInfo.nMM=0;
alignInfo.nI=0;
alignInfo.nD=0;
alignInfo.nSJ=0;
iAcceptor=superTr.sjC.size()-1; //= last junction
if (row!=(int32)readLen-1) //soft-clip
cigar.push_back({BAM_CIGAR_S, readLen-1-row});
uint32 cigarOp=0, cigarLen=0, cigarOpPrev=(uint32)-1;
uint32 sjGap=0;
while(col >= 0 && row >= 0) {
uint32 dir1= (uint32) directionMatrix[row+col*readLen];
if (dir1==0) //reached scoringMatrix==0
break;
switch (dir1)
{
case 1:
--row;
alignInfo.nI++;
cigarOp=BAM_CIGAR_I;
break;
case 2:
--col;
alignInfo.nD++;
cigarOp=BAM_CIGAR_D;
break;
case 3:
alignInfo.nMap++;
alignInfo.nMM += (uint32)(readSeq[row]!=superTr.seqP[col]);
cigarOp=BAM_CIGAR_M;
--row;
--col;
break;
default: //junction jump
alignInfo.nSJ++;
while (iAcceptor+1!=0 && col <= (int32)superTr.sjC[iAcceptor][1]) {//find (acceptor-1) that matches this column
--iAcceptor;
};
//row: same or -1
if ((dir1-4)%2 == 1) {//diagonal-like
alignInfo.nMap++;
alignInfo.nMM+=(uint32)(readSeq[row]!=superTr.seqP[col]);
--row;
cigarOp=BAM_CIGAR_M;
} else {
alignInfo.nD++;
cigarOp=BAM_CIGAR_D;
};
//column: jump to donor
sjGap=col;
col=superTr.sjDonor[ superTr.sjC[iAcceptor+1+(dir1-4)/2][2] ];
sjGap=sjGap-col-1;
};
if (cigarOp!=cigarOpPrev) {//changed direction - record new cigar op
if (cigarLen>0)
cigar.push_back({cigarOpPrev, cigarLen});
cigarLen=0;
cigarOpPrev=cigarOp;
};
++cigarLen;
if (sjGap>0) {
cigar.push_back({cigarOp, cigarLen});//record previous opeartion
cigar.push_back({BAM_CIGAR_N, sjGap});//record N
cigarLen=0; //keep cigarLen=0: after SJ, the blocks start anew
cigarOpPrev=(uint32)-1;
sjGap=0;
};
};
if (cigarLen>0)
cigar.push_back({cigarOp, cigarLen});
// row=max(0,row);
// col=max(0,col);
++row;
++col;
alignInfo.aStart[0]=row;
alignInfo.aStart[1]=col;
if (row>0)
cigar.push_back({BAM_CIGAR_S, (uint32)row});
std::reverse(cigar.begin(), cigar.end());
return scoreMaxGlobal;
};
|
