1212de18f5cfcd2473cc9f761ff7b089b3e88493 braney Fri Apr 20 16:47:23 2012 -0700 more work to advance #6152. Now with documentation of synonymous changes, the actual changes in (non)synonumous changes, and a fix to gnawing problem of the exonstarts in the genePred disappearing diff --git src/hg/lib/gpFx.c src/hg/lib/gpFx.c index 268481a..1341d24 100644 --- src/hg/lib/gpFx.c +++ src/hg/lib/gpFx.c @@ -6,36 +6,42 @@ char *gpFxModifySequence(struct allele *allele, struct genePred *pred, int exonNum, struct psl *transcriptPsl, struct dnaSeq *transcriptSequence) /* modify a transcript to what it'd be if the alternate allele were present */ { //if ((pred->optFields & genePredExonFramesFld) == 0) // genePredAddExonFrames(pred); // change transcript at variant point int exonOffset = allele->variant->chromStart - transcriptPsl->tStarts[exonNum]; int transcriptOffset = transcriptPsl->qStarts[exonNum] + exonOffset; if (allele->length != allele->variant->chromEnd - allele->variant->chromStart) errAbort("only support alleles the same length as the reference"); char *retSequence = cloneString(transcriptSequence->dna); +char *newAllele = cloneString(allele->sequence); if (*pred->strand == '-') + { transcriptOffset = transcriptSequence->size - (transcriptOffset + 1); + reverseComplement(newAllele, strlen(newAllele)); + } // make the change in the sequence -memcpy(&retSequence[transcriptOffset], allele->sequence, - allele->length); +memcpy(&retSequence[transcriptOffset], newAllele, allele->length); + +// clean up +freeMem(newAllele); return retSequence; } char *getCodingSequence(struct genePred *pred, char *transcriptSequence) /* extract the CDS from a transcript */ { int ii; if (*pred->strand == '-') reverseComplement(transcriptSequence, strlen(transcriptSequence)); // trim off the 5' char *ptr = transcriptSequence; for(ii=0; ii < pred->exonCount; ii++) @@ -86,57 +92,74 @@ return effectsList; // no change in transcript // check to see if coding sequence is changed // calculate original coding AA's char *oldCodingSequence = getCodingSequence(pred, transcriptSequence->dna); struct dnaSeq *oldCodingDna = newDnaSeq(oldCodingSequence, strlen(oldCodingSequence), pred->name); aaSeq *oldaa = translateSeq(oldCodingDna, 0, FALSE); // calculate variant coding AA's char *newCodingSequence = getCodingSequence(pred, newSequence); struct dnaSeq *newCodingDna = newDnaSeq(newCodingSequence, strlen(newCodingSequence), pred->name); aaSeq *newaa = translateSeq(newCodingDna, 0, FALSE); -//transcript ID, exon number(s), cDNA position, CDS position, peptide position, alternate amino acids, alternate codons" 9 +struct gpFx *effects; +AllocVar(effects); +slAddHead(&effectsList, effects); +effects->so.sub.codingChange.transcript = cloneString(pred->name); +effects->so.sub.codingChange.cDnaPosition = firstChange( newSequence, + transcriptSequence->dna); +effects->so.sub.codingChange.cdsPosition = firstChange( newCodingSequence, + oldCodingSequence); +if (*pred->strand == '-') + effects->so.sub.codingChange.exonNumber = pred->exonCount - exonNum; +else + effects->so.sub.codingChange.exonNumber = exonNum; + +int codonPos = (effects->so.sub.codingChange.cdsPosition / 3) * 3; + +char buffer[100]; +safef(buffer, sizeof buffer, "%c%c%c > %c%c%c", + toupper(oldCodingSequence[codonPos + 0]), + toupper(oldCodingSequence[codonPos + 1]), + toupper(oldCodingSequence[codonPos + 2]), + toupper(newCodingSequence[codonPos + 0]), + toupper(newCodingSequence[codonPos + 1]), + toupper(newCodingSequence[codonPos + 2])); + +effects->so.sub.codingChange.codonChanges = cloneString(buffer); if (sameString(newaa->dna, oldaa->dna)) { // synonymous change + effects->so.soNumber = synonymous_variant; + effects->so.sub.codingChange.pepPosition = 0; + effects->so.sub.codingChange.aaChanges = ""; } else { // non-synonymous change - struct gpFx *effects; - AllocVar(effects); effects->so.soNumber = non_synonymous_variant; - effects->so.sub.codingChange.transcript = cloneString(pred->name); - if (*pred->strand == '-') - effects->so.sub.codingChange.exonNumber = exonNum; - effects->so.sub.codingChange.exonNumber = pred->exonCount - exonNum; - effects->so.sub.codingChange.cDnaPosition = firstChange( newSequence, - transcriptSequence->dna); - effects->so.sub.codingChange.cdsPosition = firstChange( newCodingSequence, - oldCodingSequence); + effects->so.sub.codingChange.pepPosition = firstChange( newaa->dna, oldaa->dna); - /* - char *aaChanges; - char *codonChanges; - */ - slAddHead(&effectsList, effects); + safef(buffer, sizeof buffer, "%c > %c", + toupper(oldaa->dna[effects->so.sub.codingChange.pepPosition]), + toupper(newaa->dna[effects->so.sub.codingChange.pepPosition])); + effects->so.sub.codingChange.aaChanges = cloneString(buffer); } return effectsList; } struct gpFx *gpFxInExon(struct allele *allele, struct genePred *pred, int exonNum, struct psl *transcriptPsl, struct dnaSeq *transcriptSequence) { struct gpFx *effectsList = NULL; if (positiveRangeIntersection(pred->cdsStart, pred->cdsEnd, allele->variant->chromStart, allele->variant->chromEnd)) { // we're in CDS