Seqspec seqspec_parseLine (char *line) {
/**
Parses line into a sequence segment;
@param[in] line - something that can be parsed into a Seqspec object
@return NULL if line could not be parsed, else pointer to a Seqspec object.
This object is read-only to its users
*/
static Seqspec seqspec = NULL;
char *cp;
char *value;
int t;
char c;
int blankSkip;
int strandSeen = 0;
static Stringa s = NULL;
if (seqspec == NULL)
seqspec = seqspec_create ();
stringCreateClear(s,30);
// remove leading blanks and blanks after ':'
blankSkip = 1;
cp = line - 1;
while ((c = *++cp) != '\0') {
if (isspace (c)) {
if (blankSkip)
continue;
}
else if (c == ':')
blankSkip = 1;
else
blankSkip = 0;
stringCatChar (s,c);
}
wordSet (string (s)," \t");
if ((cp = wordGet ()) == NULL)
return NULL;
if (!seqspec_IDset (seqspec,cp))
return NULL;
seqspec->begin = 1;
seqspec->end = SEQSPEC_END;
seqspec->revcompF = 0;
// loop over remaining words of line
while ((cp = wordGet ()) != NULL) {
if (!(value = dbseqDissect (cp)))
continue;
if (strCaseEqual (cp,"begin"))
seqspec->begin = atoi (value);
if (strCaseEqual (cp,"end"))
seqspec->end = atoi (value);
if (strCaseEqual (cp,"strand"))
seqspec->revcompF = (*value == '-');
}
if (seqspec->begin <= 0)
return NULL;
if (seqspec->end != SEQSPEC_END) {
// treat e.g. begin:30 end:20 as revcomp
if (seqspec->end < seqspec->begin) {
if (strandSeen) {
warn ("seqspec: bad segment syntax at %s",seqspec->dbseqname);
return NULL;
}
t = seqspec->end;
seqspec->end = seqspec->begin;
seqspec->begin = t;
seqspec->revcompF = 1;
}
}
return seqspec;
}
int main (int argc, char *argv[])
{
Array intervals;
Interval *currInterval;
SubInterval *currSubInterval;
int h,i,j;
Array seqs;
Seq *currSeq,testSeq;
int index;
Stringa buffer;
Array geneTranscriptEntries;
Texta geneTranscriptIds;
Array alterations;
Alteration *currAlteration,*nextAlteration;
char *proteinSequenceBeforeIndel;
char *proteinSequenceAfterIndel;
int numDisabledTranscripts;
Stringa disabledTranscripts;
int seqLength,refLength,altLength;
char *sequenceBeforeIndel = NULL;
int overlapMode;
int numOverlaps;
int sizeIndel,indelOffset;
int overlap;
Array coordinates;
VcfEntry *currVcfEntry;
VcfGenotype *currVcfGenotype;
int position;
Texta alternateAlleles;
int flag1,flag2;
if (argc != 3) {
usage ("%s <annotation.interval> <annotation.fa>",argv[0]);
}
intervalFind_addIntervalsToSearchSpace (argv[1],0);
geneTranscriptEntries = util_getGeneTranscriptEntries (intervalFind_getAllIntervals ());
seq_init ();
fasta_initFromFile (argv[2]);
seqs = fasta_readAllSequences (0);
fasta_deInit ();
arraySort (seqs,(ARRAYORDERF)util_sortSequencesByName);
buffer = stringCreate (100);
disabledTranscripts = stringCreate (100);
alterations = arrayCreate (100,Alteration);
vcf_init ("-");
stringPrintf (buffer,"##INFO=<ID=VA,Number=.,Type=String,Description=\"Variant Annotation, %s\">",argv[1]);
vcf_addComment (string (buffer));
puts (vcf_writeMetaData ());
puts (vcf_writeColumnHeaders ());
while (currVcfEntry = vcf_nextEntry ()) {
if (vcf_isInvalidEntry (currVcfEntry)) {
continue;
}
flag1 = 0;
flag2 = 0;
position = currVcfEntry->position - 1; // make zero-based
alternateAlleles = vcf_getAlternateAlleles (currVcfEntry);
for (h = 0; h < arrayMax (alternateAlleles); h++) {
refLength = strlen (currVcfEntry->referenceAllele);
altLength = strlen (textItem (alternateAlleles,h));
sizeIndel = abs (refLength - altLength);
indelOffset = MAX (refLength,altLength) - 1;
util_clearAlterations (alterations);
intervals = intervalFind_getOverlappingIntervals (currVcfEntry->chromosome,position,position + indelOffset);
for (i = 0; i < arrayMax (intervals); i++) {
currInterval = arru (intervals,i,Interval*);
overlapMode = OVERLAP_NONE;
numOverlaps = 0;
for (j = 0; j < arrayMax (currInterval->subIntervals); j++) {
currSubInterval = arrp (currInterval->subIntervals,j,SubInterval);
overlap = rangeIntersection (position,position + indelOffset,currSubInterval->start,currSubInterval->end);
if (currSubInterval->start <= position && (position + indelOffset) < currSubInterval->end) {
overlapMode = OVERLAP_FULLY_CONTAINED;
numOverlaps++;
}
else if (j == 0 && overlap > 0 && position < currSubInterval->start) {
overlapMode = OVERLAP_START;
numOverlaps++;
}
else if (j == (arrayMax (currInterval->subIntervals) - 1) && overlap > 0 && (position + indelOffset) >= currSubInterval->end) {
overlapMode = OVERLAP_END;
numOverlaps++;
}
else if (overlap > 0 && overlap <= indelOffset) {
overlapMode = OVERLAP_SPLICE;
numOverlaps++;
}
}
if (overlapMode == OVERLAP_NONE) {
continue;
}
currAlteration = arrayp (alterations,arrayMax (alterations),Alteration);
if (numOverlaps > 1) {
util_addAlteration (currAlteration,currInterval->name,"multiExonHit",currInterval,position,0);
continue;
}
else if (numOverlaps == 1 && overlapMode == OVERLAP_SPLICE) {
util_addAlteration (currAlteration,currInterval->name,"spliceOverlap",currInterval,position,0);
continue;
}
else if (numOverlaps == 1 && overlapMode == OVERLAP_START) {
util_addAlteration (currAlteration,currInterval->name,"startOverlap",currInterval,position,0);
continue;
}
else if (numOverlaps == 1 && overlapMode == OVERLAP_END) {
util_addAlteration (currAlteration,currInterval->name,"endOverlap",currInterval,position,0);
continue;
}
else if (numOverlaps == 1 && overlapMode == OVERLAP_FULLY_CONTAINED && altLength > refLength) {
if ((sizeIndel % 3) == 0) {
util_addAlteration (currAlteration,currInterval->name,"insertionNFS",currInterval,position,0);
}
else {
util_addAlteration (currAlteration,currInterval->name,"insertionFS",currInterval,position,0);
}
}
else if (numOverlaps == 1 && overlapMode == OVERLAP_FULLY_CONTAINED && altLength < refLength) {
if ((sizeIndel % 3) == 0) {
util_addAlteration (currAlteration,currInterval->name,"deletionNFS",currInterval,position,0);
}
else {
util_addAlteration (currAlteration,currInterval->name,"deletionFS",currInterval,position,0);
}
}
else if (numOverlaps == 1 && overlapMode == OVERLAP_FULLY_CONTAINED && altLength == refLength) {
util_addAlteration (currAlteration,currInterval->name,"substitution",currInterval,position,0);
}
else {
die ("Unexpected type: %d %s %s %s",
currVcfEntry->position,currVcfEntry->chromosome,
currVcfEntry->referenceAllele,currVcfEntry->alternateAllele);
}
if ((sizeIndel % 3) != 0 && altLength != refLength) {
continue;
}
// Only run the remaining block of code if the indel is fully contained (insertion or deletion) AND does not cause a frameshift OR
// if it is a substitution that is fully contained in the coding sequence
stringPrintf (buffer,"%s|%s|%c|",currInterval->name,currInterval->chromosome,currInterval->strand);
for (j = 0; j < arrayMax (currInterval->subIntervals); j++) {
currSubInterval = arrp (currInterval->subIntervals,j,SubInterval);
stringAppendf (buffer,"%d|%d%s",currSubInterval->start,currSubInterval->end,j < arrayMax (currInterval->subIntervals) - 1 ? "|" : "");
}
testSeq.name = hlr_strdup (string (buffer));
if (!arrayFind (seqs,&testSeq,&index,(ARRAYORDERF)util_sortSequencesByName)) {
die ("Expected to find %s in seqs",string (buffer));
}
hlr_free (testSeq.name);
currSeq = arrp (seqs,index,Seq);
strReplace (&sequenceBeforeIndel,currSeq->sequence);
seqLength = strlen (sequenceBeforeIndel);
coordinates = util_getCoordinates (currInterval);
// arraySort (coordinates,(ARRAYORDERF)util_sortCoordinatesByChromosomeAndTranscriptPosition); Array is already sorted by definition
j = 0;
stringClear (buffer);
while (j < seqLength) {
if (util_getGenomicCoordinate (coordinates,j,currVcfEntry->chromosome) == position) {
if (altLength > refLength) {
stringCat (buffer,textItem (alternateAlleles,h));
j++;
continue;
}
else if (altLength < refLength) {
stringCatChar (buffer,sequenceBeforeIndel[j]);
j = j + refLength - altLength + 1;
continue;
}
else {
stringCat (buffer,textItem (alternateAlleles,h));
j = j + altLength;
continue;
}
}
stringCatChar (buffer,sequenceBeforeIndel[j]);
j++;
}
util_destroyCoordinates (coordinates);
proteinSequenceBeforeIndel = hlr_strdup (util_translate (currInterval,sequenceBeforeIndel));
proteinSequenceAfterIndel = hlr_strdup (util_translate (currInterval,string (buffer)));
addSubstitution (currAlteration,proteinSequenceBeforeIndel,proteinSequenceAfterIndel,indelOffset);
hlr_free (proteinSequenceBeforeIndel);
hlr_free (proteinSequenceAfterIndel);
}
if (arrayMax (alterations) == 0) {
continue;
}
arraySort (alterations,(ARRAYORDERF)util_sortAlterationsByGeneIdAndType);
stringClear (buffer);
i = 0;
while (i < arrayMax (alterations)) {
currAlteration = arrp (alterations,i,Alteration);
stringAppendf (buffer,"%s%d:%s:%s:%c:%s",stringLen (buffer) == 0 ? "" : ",",h + 1,currAlteration->geneName,currAlteration->geneId,currAlteration->strand,currAlteration->type);
stringClear (disabledTranscripts);
if (currAlteration->substitution[0] != '\0') {
stringAppendf (disabledTranscripts,"%s:%s:%d_%d_%s",currAlteration->transcriptName,currAlteration->transcriptId,currAlteration->transcriptLength,currAlteration->relativePosition,currAlteration->substitution);
}
else if (strEqual (currAlteration->type,"multiExonHit") || strEqual (currAlteration->type,"spliceOverlap") ||
strEqual (currAlteration->type,"startOverlap") || strEqual (currAlteration->type,"endOverlap")) {
stringAppendf (disabledTranscripts,"%s:%s:%d",currAlteration->transcriptName,currAlteration->transcriptId,currAlteration->transcriptLength);
}
else {
stringAppendf (disabledTranscripts,"%s:%s:%d_%d",currAlteration->transcriptName,currAlteration->transcriptId,currAlteration->transcriptLength,currAlteration->relativePosition);
}
numDisabledTranscripts = 1;
j = i + 1;
while (j < arrayMax (alterations)) {
nextAlteration = arrp (alterations,j,Alteration);
if (strEqual (currAlteration->geneId,nextAlteration->geneId) &&
strEqual (currAlteration->type,nextAlteration->type)) {
if (nextAlteration->substitution[0] != '\0') {
stringAppendf (disabledTranscripts,":%s:%s:%d_%d_%s",nextAlteration->transcriptName,nextAlteration->transcriptId,nextAlteration->transcriptLength,nextAlteration->relativePosition,nextAlteration->substitution);
}
else if (strEqual (nextAlteration->type,"multiExonHit") || strEqual (nextAlteration->type,"spliceOverlap") ||
strEqual (nextAlteration->type,"startOverlap") || strEqual (nextAlteration->type,"endOverlap")) {
stringAppendf (disabledTranscripts,":%s:%s:%d",nextAlteration->transcriptName,nextAlteration->transcriptId,nextAlteration->transcriptLength);
}
else {
stringAppendf (disabledTranscripts,":%s:%s:%d_%d",nextAlteration->transcriptName,nextAlteration->transcriptId,nextAlteration->transcriptLength,nextAlteration->relativePosition);
}
numDisabledTranscripts++;
}
else {
break;
}
j++;
}
i = j;
geneTranscriptIds = util_getTranscriptIdsForGeneId (geneTranscriptEntries,currAlteration->geneId);
stringAppendf (buffer,":%d/%d:%s",numDisabledTranscripts,arrayMax (geneTranscriptIds),string (disabledTranscripts));
}
if (flag1 == 0) {
printf ("%s\t%d\t%s\t%s\t%s\t%s\t%s\t%s;VA=",
currVcfEntry->chromosome,currVcfEntry->position,currVcfEntry->id,
currVcfEntry->referenceAllele,currVcfEntry->alternateAllele,
currVcfEntry->quality,currVcfEntry->filter,currVcfEntry->info);
flag1 = 1;
}
printf ("%s%s",flag2 == 1 ? "," : "",string (buffer));
flag2 = 1;
}
if (flag1 == 1) {
for (i = 0; i < arrayMax (currVcfEntry->genotypes); i++) {
currVcfGenotype = arrp (currVcfEntry->genotypes,i,VcfGenotype);
if (i == 0) {
printf ("\t%s\t",currVcfEntry->genotypeFormat);
}
printf ("%s%s%s%s",currVcfGenotype->genotype,
currVcfGenotype->details[0] != '\0' ? ":" : "",
currVcfGenotype->details[0] != '\0' ? currVcfGenotype->details : "",
i < arrayMax (currVcfEntry->genotypes) - 1 ? "\t" : "");
}
puts ("");
}
}
vcf_deInit ();
return 0;
}
