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
@@ -1,337 +1,360 @@
 
 #include "common.h"
 #include "genePred.h"
 #include "gpFx.h"
 
 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++)
     {
     int exonSize = pred->exonEnds[ii] - pred->exonStarts[ii];
     if (pred->cdsStart > pred->exonStarts[ii])
 	break;
 
     ptr += exonSize;
     }
 int exonOffset = pred->cdsStart - pred->exonStarts[ii];
 ptr += exonOffset;
 
 char *newString = cloneString(ptr);
 
 // trim off 3'
 newString[genePredCdsSize(pred)] = 0;
 
 if (*pred->strand == '-')
     {
     reverseComplement(transcriptSequence, strlen(transcriptSequence));
     reverseComplement(newString, strlen(newString));
     }
 
 return newString;
 }
 
 static int firstChange(char *string1, char *string2)
 /* return the position of the first difference between the two sequences */
 {
 int count = 0;
 
 while (*string1++ == *string2++)
     count++;
 
 return count;
 }
 
 struct gpFx *gpFxInCodingExon(struct allele *allele, struct genePred *pred, 
     int exonNum, struct psl *transcriptPsl, struct dnaSeq *transcriptSequence)
 /* generate an effect from a different allele in a coding exon */
 {
 struct gpFx *effectsList = NULL;
 char *newSequence = gpFxModifySequence(allele, pred, exonNum,
 	transcriptPsl, transcriptSequence);
 
 if (sameString(newSequence, transcriptSequence->dna))
     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
     effectsList = slCat(effectsList, gpFxInCodingExon(allele, pred, exonNum,
 	transcriptPsl, transcriptSequence));
     }
 
 if (positiveRangeIntersection(pred->txStart, pred->cdsStart,
 	allele->variant->chromStart, allele->variant->chromEnd))
     {
     // we're in 5' UTR ( or UTR intron )
     }
 
 if (positiveRangeIntersection(pred->txStart, pred->cdsStart,
 	allele->variant->chromStart, allele->variant->chromEnd))
     {
     // we're in 3' UTR
     }
 
 return effectsList;
 }
 
 struct psl *genePredToPsl(struct genePred *pred)
 {
 int qSize = genePredBases(pred);
 #define BOGUS_CHROM_SIZE  0
 struct psl *psl = pslNew(pred->name, qSize, 0, qSize,
                          pred->chrom, BOGUS_CHROM_SIZE, 
 			 pred->txStart, pred->txEnd,
 			 pred->strand, pred->exonCount, 0);
 psl->match = psl->qSize;
 
 int i, qNext = 0;
 for (i = 0; i < pred->exonCount; i++)
     {
     int exonSize =  pred->exonEnds[i] - pred->exonStarts[i];
 
     psl->qStarts[i] = qNext;
     //psl->tStarts[i] = pred->exonStarts[i] + pred->txStart;
     psl->tStarts[i] = pred->exonStarts[i];
     psl->blockSizes[i] = exonSize;
 
 /* notnow
     if (i > 0)
         {
         psl->tNumInsert += 1;
         psl->tBaseInsert += psl->tStarts[i] - pslTEnd(psl, i-1);
         }
 */
 
     psl->blockCount++;
     qNext += psl->blockSizes[i];
     }
 
 return psl;
 }
 
 static struct gpFx *gpFxCheckExons(struct variant *variant, 
     struct genePred *pred, struct dnaSeq *transcriptSequence)
 // check to see if the variant is in an exon
 {
 int ii;
 struct gpFx *effectsList = NULL;
 struct psl *transcriptPsl = genePredToPsl(pred);
 
 // should copy transcriptSequence if we have more than one variant!!
 for(; variant ; variant = variant->next)
     {
     struct allele *allele = variant->alleles;
     for(; allele ; allele = allele->next)
 	{
 	for(ii=0; ii < pred->exonCount; ii++)
 	    {
 	    // check if in an exon
 	    int size;
 	    if ((size = positiveRangeIntersection(pred->exonStarts[ii], 
 		pred->exonEnds[ii], 
 		variant->chromStart, variant->chromEnd)) > 0)
 		{
 
 		if (size != variant->chromEnd - variant->chromStart)
 		    errAbort("variant crosses exon boundary");
 
 		effectsList = slCat(effectsList, gpFxInExon(allele, pred, ii,
 		    transcriptPsl, transcriptSequence));
 		}
 	    }
 	}
     }
 
 return effectsList;
 }
 
 static struct gpFx *gpFxCheckIntrons(struct variant *variant, 
     struct genePred *pred)
 // check to see if a single variant is in an exon or an intron
 {
 int ii;
 struct gpFx *effectsList = NULL;
 
 for(ii=0; ii < pred->exonCount - 1; ii++)
     {
     // check if in intron
     if (positiveRangeIntersection(pred->exonEnds[ii], 
 	    pred->exonStarts[ii+1],
 	    variant->chromStart, variant->chromEnd))
 	{
 	struct gpFx *effects;
 	AllocVar(effects);
 	effects->so.soNumber = intron_variant;
 	effects->so.sub.intron.transcript = cloneString(pred->name);
 	effects->so.sub.intron.intronNumber = ii;
 	slAddHead(&effectsList, effects);
 	}
     }
 
 return effectsList;
 }
 
 
 static struct gpFx *gpFxCheckBackground(struct variant *variant, 
     struct genePred *pred)
 // check to see if the variant is up or downstream or in intron of the gene 
 {
 struct gpFx *effectsList = NULL, *effects;
 
 for(; variant ; variant = variant->next)
     {
     // is this variant in an intron
     effectsList = slCat(effectsList, gpFxCheckIntrons(variant, pred));
 
     if (positiveRangeIntersection(pred->txStart - GPRANGE, pred->txStart,
 	    variant->chromStart, variant->chromEnd))
 	{
 	AllocVar(effects);
 	if (*pred->strand == '+')
 	    ;//effects->gpFxType = gpFxUpstream;
 	else
 	    ;//ffects->gpFxType = gpFxDownstream;
 	effectsList = slCat(effectsList, effects);
 	}
 
     if (positiveRangeIntersection(pred->txEnd, pred->txEnd + GPRANGE,
 	    variant->chromStart, variant->chromEnd))
 	{
 	AllocVar(effects);
 	if (*pred->strand == '+')
 	    ;//ffects->gpFxType = gpFxDownstream;
 	else
 	    ;//ffects->gpFxType = gpFxUpstream;
 	effectsList = slCat(effectsList, effects);
 	}
     }
 
 return effectsList;
 }
 
 static void checkVariantList(struct variant *variant)
 // check to see that we either have one variant (possibly with multiple
 // alleles) or that if we have a list of variants, they only have
 // one allele a piece.
 {
 if (variant->next == NULL)	 // just one variant
     return;
 
 for(; variant; variant = variant->next)
     if (variant->numAlleles != 1)
 	errAbort("gpFxPredEffect needs either 1 variant, or only 1 allele in all variants");
 }
 
 struct gpFx *gpFxPredEffect(struct variant *variant, struct genePred *pred,
     struct dnaSeq *transcriptSequence)
 // return the predicted effect(s) of a variation list on a genePred
 {
 struct gpFx *effectsList = NULL;
 
 // make sure we can deal with the variants that are coming in
 checkVariantList(variant);
 
 // check to see if SNP is up or downstream in intron 
 effectsList = slCat(effectsList, gpFxCheckBackground(variant, pred));
 
 // check to see if SNP is in the transcript
 effectsList = slCat(effectsList, gpFxCheckExons(variant, pred, 
     transcriptSequence));
 
 if (effectsList != NULL)
     return effectsList;
 
 // default is no effect
 struct gpFx *noEffect;
 
 AllocVar(noEffect);
 noEffect->next = NULL;
 ;//oEffect->gpFxType = gpFxNone;
 
 return noEffect;
 }