e46073f856770bdfef4f7637eea8f9f9297aa139 chmalee Tue Nov 19 15:57:08 2019 -0800 Initial commit of new track type vcfPhased trio. A line with ticks, one per haplotype per sample in the VCF, as specified by trackDb variables. diff --git src/hg/hgTracks/vcfTrack.c src/hg/hgTracks/vcfTrack.c index 75140df..a4a9ed8 100644 --- src/hg/hgTracks/vcfTrack.c +++ src/hg/hgTracks/vcfTrack.c @@ -1,1705 +1,2286 @@ /* vcfTrack -- handlers for Variant Call Format data. */ /* Copyright (C) 2014 The Regents of the University of California * See README in this or parent directory for licensing information. */ #include "common.h" #include "bigWarn.h" #include "dystring.h" +#include "rainbow.h" #include "errCatch.h" #include "hacTree.h" #include "hdb.h" #include "hgColors.h" #include "hgTracks.h" #include "pgSnp.h" #include "phyloTree.h" #include "trashDir.h" #include "vcf.h" #include "vcfUi.h" #include "knetUdc.h" #include "udc.h" - +#include "memgfx.h" static boolean getMinQual(struct trackDb *tdb, double *retMinQual) /* Return TRUE and set retMinQual if cart contains minimum QUAL filter */ { if (cartOrTdbBoolean(cart, tdb, VCF_APPLY_MIN_QUAL_VAR, VCF_DEFAULT_APPLY_MIN_QUAL)) { if (retMinQual != NULL) *retMinQual = cartOrTdbDouble(cart, tdb, VCF_MIN_QUAL_VAR, VCF_DEFAULT_MIN_QUAL); return TRUE; } return FALSE; } static boolean minQualFail(struct vcfRecord *record, double minQual) /* Return TRUE if record's QUAL column value is non-numeric or is less than minQual. */ { if (isEmpty(record->qual) || (record->qual[0] != '-' && !isdigit(record->qual[0])) || atof(record->qual) < minQual) return TRUE; return FALSE; } static boolean getFilterValues(struct trackDb *tdb, struct slName **retValues) /* Return TRUE and set retValues if cart contains FILTER column values to exclude */ { if (cartListVarExistsAnyLevel(cart, tdb, FALSE, VCF_EXCLUDE_FILTER_VAR)) { struct slName *selectedValues = cartOptionalSlNameListClosestToHome(cart, tdb, FALSE, VCF_EXCLUDE_FILTER_VAR); if (retValues != NULL) *retValues = selectedValues; return TRUE; } return FALSE; } static boolean filterColumnFail(struct vcfRecord *record, struct slName *filterValues) /* Return TRUE if record's FILTER column value(s) matches one of filterValues (from cart). */ { int i; for (i = 0; i < record->filterCount; i++) if (slNameInList(filterValues, record->filters[i])) return TRUE; return FALSE; } static boolean getMinFreq(struct trackDb *tdb, double *retMinFreq) /* Return TRUE and set retMinFreq if cart contains nonzero minimum minor allele frequency. */ { double minFreq = cartOrTdbDouble(cart, tdb, VCF_MIN_ALLELE_FREQ_VAR, VCF_DEFAULT_MIN_ALLELE_FREQ); if (minFreq > 0) { if (retMinFreq != NULL) *retMinFreq = minFreq; return TRUE; } return FALSE; } static boolean minFreqFail(struct vcfRecord *record, double minFreq) /* Return TRUE if record's INFO include AF (alternate allele frequencies) or AC+AN * (alternate allele counts and total count of observed alleles) and the minor allele * frequency < minFreq -- or rather, major allele frequency > (1 - minFreq) because * variants with > 2 alleles might have some significant minor frequencies along with * tiny minor frequencies). */ { struct vcfFile *vcff = record->file; boolean gotInfo = FALSE; double refFreq = 1.0; double maxAltFreq = 0.0; int i; const struct vcfInfoElement *afEl = vcfRecordFindInfo(record, "AF"); const struct vcfInfoDef *afDef = vcfInfoDefForKey(vcff, "AF"); if (afEl != NULL && afDef != NULL && afDef->type == vcfInfoFloat) { // If INFO includes alt allele freqs, use them directly. gotInfo = TRUE; for (i = 0; i < afEl->count; i++) { if (afEl->missingData[i]) continue; double altFreq = afEl->values[i].datFloat; refFreq -= altFreq; if (altFreq > maxAltFreq) maxAltFreq = altFreq; } } else { // Calculate alternate allele freqs from AC and AN: const struct vcfInfoElement *acEl = vcfRecordFindInfo(record, "AC"); const struct vcfInfoDef *acDef = vcfInfoDefForKey(vcff, "AC"); const struct vcfInfoElement *anEl = vcfRecordFindInfo(record, "AN"); const struct vcfInfoDef *anDef = vcfInfoDefForKey(vcff, "AN"); if (acEl != NULL && acDef != NULL && acDef->type == vcfInfoInteger && anEl != NULL && anDef != NULL && anDef->type == vcfInfoInteger && anEl->count == 1 && anEl->missingData[0] == FALSE) { gotInfo = TRUE; int totalCount = anEl->values[0].datInt; for (i = 0; i < acEl->count; i++) { if (acEl->missingData[i]) continue; int altCount = acEl->values[i].datInt; double altFreq = (double)altCount / totalCount; refFreq -= altFreq; if (altFreq < maxAltFreq) maxAltFreq = altFreq; } } else // Use MAF for alternate allele freqs from MAF: { const struct vcfInfoElement *mafEl = vcfRecordFindInfo(record, "MAF"); const struct vcfInfoDef *mafDef = vcfInfoDefForKey(vcff, "MAF"); if (mafEl != NULL && mafDef != NULL && mafDef->type == vcfInfoString && startsWith("Minor Allele Frequency",mafDef->description)) { // If INFO includes alt allele freqs, use them directly. gotInfo = TRUE; if (mafEl->count >= 1 && !mafEl->missingData[mafEl->count-1]) { char data[64]; safecpy(data,sizeof(data),mafEl->values[mafEl->count-1].datString); maxAltFreq = atof(lastWordInLine(data)); refFreq -= maxAltFreq; } } } } if (gotInfo) { double majorAlFreq = max(refFreq, maxAltFreq); if (majorAlFreq > (1.0 - minFreq)) return TRUE; } return FALSE; } +static void filterRefOnlyAlleles(struct vcfFile *vcff, struct trackDb *tdb) +/* Drop items from VCF that don't differ from the reference for any of the + * samples specified in trackDb */ +{ +struct vcfRecord *rec, *nextRecord, *retList = NULL; +const struct vcfGenotype *gt; + +struct slPair *sample, *sampleOrder = vcfPhasedGetSampleOrder(cart, tdb); +for (rec = vcff->records; rec != NULL; rec = nextRecord) + { + nextRecord = rec->next; + boolean allRef = TRUE; + for (sample = sampleOrder; sample != NULL; sample = sample->next) + { + gt = vcfRecordFindGenotype(rec, sample->name); + if (gt && !(gt->hapIxA == 0 && gt->hapIxB == 0) ) + allRef = FALSE; + } + if (!allRef) + slAddHead(&retList, rec); + } +slReverse(&retList); +vcff->records = retList; +} + static void filterRecords(struct vcfFile *vcff, struct trackDb *tdb) /* If a filter is specified in the cart, remove any records that don't pass filter. */ { double minQual = VCF_DEFAULT_MIN_QUAL; struct slName *filterValues = NULL; double minFreq = VCF_DEFAULT_MIN_ALLELE_FREQ; boolean gotQualFilter = getMinQual(tdb, &minQual); boolean gotFilterFilter = getFilterValues(tdb, &filterValues); boolean gotMinFreqFilter = getMinFreq(tdb, &minFreq); if (! (gotQualFilter || gotFilterFilter || gotMinFreqFilter) ) return; struct vcfRecord *rec, *nextRec, *newList = NULL; for (rec = vcff->records; rec != NULL; rec = nextRec) { nextRec = rec->next; if (! ((gotQualFilter && minQualFail(rec, minQual)) || (gotFilterFilter && filterColumnFail(rec, filterValues)) || (gotMinFreqFilter && minFreqFail(rec, minFreq)) )) slAddHead(&newList, rec); } slReverse(&newList); vcff->records = newList; } struct pgSnpVcfStartEnd /* This extends struct pgSnp by tacking on an original VCF chromStart and End at the end, * for use by indelTweakMapItem below. This can be cast to pgs. */ { struct pgSnp pgs; unsigned int vcfStart; unsigned int vcfEnd; }; static struct pgSnp *vcfFileToPgSnp(struct vcfFile *vcff, struct trackDb *tdb) /* Convert vcff's records to pgSnp; don't free vcff until you're done with pgSnp - * because it contains pointers into vcff's records' chrom. */ + * because it contains pointers into vcff's records' chrom. If the trackDb setting + * sampleName is present, then check whether all the records are phased or not */ { struct pgSnp *pgsList = NULL; struct vcfRecord *rec; int maxLen = 33; int maxAlCount = 5; +struct slPair *sample = NULL, *phasedSamples = NULL; +if (sameString(tdb->type, "vcfPhasedTrio")) + phasedSamples = vcfPhasedGetSampleOrder(cart, tdb); + +vcff->allPhased = TRUE; for (rec = vcff->records; rec != NULL; rec = rec->next) { struct pgSnpVcfStartEnd *psvs = needMem(sizeof(*psvs)); psvs->vcfStart = vcfRecordTrimIndelLeftBase(rec); psvs->vcfEnd = vcfRecordTrimAllelesRight(rec); + for (sample = phasedSamples; sample != NULL; sample = sample->next) + { + const struct vcfGenotype *gt = vcfRecordFindGenotype(rec, sample->name); + if (!gt->isPhased) + vcff->allPhased = FALSE; + } struct pgSnp *pgs = pgSnpFromVcfRecord(rec); memcpy(&(psvs->pgs), pgs, sizeof(*pgs)); pgs = (struct pgSnp *)psvs; // leak mem // Insertion sequences can be quite long; abbreviate here for display. int len = strlen(pgs->name); if (len > maxLen) { int maxAlLen = (maxLen / min(rec->alleleCount, maxAlCount)) - 1; pgs->name[0] = '\0'; int i; for (i = 0; i < rec->alleleCount; i++) { if (i > 0) safencat(pgs->name, len+1, "/", 1); if (i >= maxAlCount) { safecat(pgs->name, len+1, "..."); pgs->alleleCount = maxAlCount; break; } if (strlen(rec->alleles[i]) > maxAlLen-3) strcpy(rec->alleles[i]+maxAlLen-3, "..."); safencat(pgs->name, len+1, rec->alleles[i], maxAlLen); } } slAddHead(&pgsList, pgs); } slReverse(&pgsList); return pgsList; } // Center-weighted alpha clustering of haplotypes -- see Redmine #3711, #2823 note 7 // It might be nice to use an allele-frequency representation here instead of [ACGTN] strings // with "N" for missing info or differences, but keep it simple. struct cwaExtraData /* Helper data for hacTree clustering of haplotypes by center-weighted alpha distance */ { int center; // index from which each point's contribution to distance is to be weighted int len; // total length of haplotype strings double alpha; // weighting factor for distance from center struct lm *localMem; }; // This is the representation of a cluster of up to 65,535 haplotypes of equal length, // where each variant's alleles are specified as 0 (reference) or 1 (alternate) // [or possibly 2 for second alternate, but those are rare so I'll ignore them]. // When an individual is heterozygous and unphased for some variant, we need to // account for missing data. struct hapCluster { struct hapCluster *next; // hacTree wants slList of items unsigned short *refCounts; // per-variant count of reference alleles observed unsigned short *unkCounts; // per-variant count of unknown (or unphased het) alleles unsigned short leafCount; // number of leaves under this node (or 1 if leaf) unsigned short gtHapIx; // if leaf, (genotype index << 1) + hap (0 or 1 for diploid) }; INLINE boolean isRef(const struct hapCluster *c, int varIx) // Return TRUE if the leaves of cluster have at least as many reference alleles // as alternate alleles for variant varIx. { unsigned short altCount = c->leafCount - c->refCounts[varIx] - c->unkCounts[varIx]; return (c->refCounts[varIx] >= altCount); } static double cwaDistance(const struct slList *item1, const struct slList *item2, void *extraData) /* Center-weighted alpha sequence distance function for hacTree clustering of haplotype seqs */ // This is inner-loop so I am not doing defensive checks. Caller must ensure: // 1. kids's sequences' lengths are both equal to helper->len // 2. 0 <= helper->center <= len // 3. 0.0 < helper->alpha <= 1.0 { const struct hapCluster *kid1 = (const struct hapCluster *)item1; const struct hapCluster *kid2 = (const struct hapCluster *)item2; struct cwaExtraData *helper = extraData; double distance = 0; double weight = 1; // start at center: alpha to the 0th power int i; for (i=helper->center; i >= 0; i--) { if (isRef(kid1, i) != isRef(kid2, i)) distance += weight; weight *= helper->alpha; } weight = helper->alpha; // start at center+1: alpha to the 1st power for (i=helper->center+1; i < helper->len; i++) { if (isRef(kid1, i) != isRef(kid2, i)) distance += weight; weight *= helper->alpha; } return distance; } static struct hapCluster *lmHapCluster(struct cwaExtraData *helper) /* Use localMem to allocate a new cluster of the given len. */ { struct hapCluster *c = lmAlloc(helper->localMem, sizeof(struct hapCluster)); c->refCounts = lmAlloc(helper->localMem, helper->len * sizeof(unsigned short)); c->unkCounts = lmAlloc(helper->localMem, helper->len * sizeof(unsigned short)); return c; } static struct slList *cwaMerge(const struct slList *item1, const struct slList *item2, void *extraData) /* Make a consensus haplotype from two input haplotypes, for hacTree clustering by * center-weighted alpha distance. */ // This is inner-loop so I am not doing defensive checks. Caller must ensure that // kids's sequences' lengths are both equal to helper->len. { const struct hapCluster *kid1 = (const struct hapCluster *)item1; const struct hapCluster *kid2 = (const struct hapCluster *)item2; struct cwaExtraData *helper = extraData; struct hapCluster *consensus = lmHapCluster(helper); consensus->leafCount = kid1->leafCount + kid2->leafCount; consensus->gtHapIx = kid1->gtHapIx; int i; for (i=0; i < helper->len; i++) { consensus->refCounts[i] = kid1->refCounts[i] + kid2->refCounts[i]; consensus->unkCounts[i] = kid1->unkCounts[i] + kid2->unkCounts[i]; } return (struct slList *)consensus; } INLINE void hapClusterToString(const struct hapCluster *c, char *s, int len) /* Write a text representation of hapCluster's alleles into s which is at least len+1 long. */ { int i; for (i=0; i < len; i++) s[i] = isRef(c, i) ? '0': '1'; s[i] = 0; } static int cwaCmp(const struct slList *item1, const struct slList *item2, void *extraData) /* Convert hapCluster to allele strings for easy comparison by strcmp. */ { const struct hapCluster *c1 = (const struct hapCluster *)item1; const struct hapCluster *c2 = (const struct hapCluster *)item2; struct cwaExtraData *helper = extraData; char s1[helper->len+1]; char s2[helper->len+1]; hapClusterToString(c1, s1, helper->len); hapClusterToString(c2, s2, helper->len); return strcmp(s1, s2); } void rSetGtHapOrder(struct hacTree *ht, unsigned short *gtHapOrder, unsigned short *retGtHapEnd) /* Traverse hacTree and build an ordered array of genotype + haplotype indices. */ { if (ht->left == NULL && ht->right == NULL) { struct hapCluster *c = (struct hapCluster *)ht->itemOrCluster; gtHapOrder[(*retGtHapEnd)++] = c->gtHapIx; } else if (ht->left == NULL) rSetGtHapOrder(ht->right, gtHapOrder, retGtHapEnd); else if (ht->right == NULL) rSetGtHapOrder(ht->left, gtHapOrder, retGtHapEnd); else { struct hapCluster *cL = (struct hapCluster *)ht->left->itemOrCluster; struct hapCluster *cR = (struct hapCluster *)ht->right->itemOrCluster; if (cL->leafCount >= cR->leafCount) { rSetGtHapOrder(ht->left, gtHapOrder, retGtHapEnd); rSetGtHapOrder(ht->right, gtHapOrder, retGtHapEnd); } else { rSetGtHapOrder(ht->right, gtHapOrder, retGtHapEnd); rSetGtHapOrder(ht->left, gtHapOrder, retGtHapEnd); } } } static unsigned short *clusterHaps(const struct vcfFile *vcff, int centerIx, int startIx, int endIx, unsigned short *retGtHapEnd, struct hacTree **retTree) /* Given a bunch of VCF records with phased genotypes, build up one haplotype string * per chromosome that is the sequence of alleles in all variants (simplified to one base * per variant). Each individual/sample will have two haplotype strings (unless haploid * like Y or male X). Independently cluster the haplotype strings using hacTree with the * center-weighted alpha functions above. Return an array of genotype+haplotype indices * in the order determined by the hacTree, and set retGtHapEnd to its length/end. */ { double alpha = 0.5; struct lm *lm = lmInit(0); struct cwaExtraData helper = { centerIx-startIx, endIx-startIx, alpha, lm }; int ploidy = 2; // Assuming diploid genomes here, no XXY, tetraploid etc. int gtCount = vcff->genotypeCount; // Make an slList of hapClusters, but allocate in a big block so I can use // array indexing. struct hapCluster **hapArray = lmAlloc(lm, sizeof(struct hapCluster *) * gtCount * ploidy); int i; for (i=0; i < ploidy * gtCount; i++) { hapArray[i] = lmHapCluster(&helper); if (i > 0) hapArray[i-1]->next = hapArray[i]; } boolean haveHaploid = FALSE; int varIx; struct vcfRecord *rec; for (varIx = 0, rec = vcff->records; rec != NULL && varIx < endIx; varIx++, rec = rec->next) { if (varIx < startIx) continue; int countIx = varIx - startIx; int gtIx; for (gtIx=0; gtIx < gtCount; gtIx++) { struct vcfGenotype *gt = &(rec->genotypes[gtIx]); struct hapCluster *c1 = hapArray[gtIx]; struct hapCluster *c2 = hapArray[gtCount + gtIx]; // hardwired ploidy=2 c1->gtHapIx = gtIx << 1; c1->leafCount = 1; if (gt->isPhased || gt->isHaploid || (gt->hapIxA == gt->hapIxB)) { // first haplotype's counts: if (gt->hapIxA < 0) c1->unkCounts[countIx] = 1; else if (gt->hapIxA == 0) c1->refCounts[countIx] = 1; if (gt->isHaploid) haveHaploid = TRUE; else { // got second haplotype, fill in its counts: c2->gtHapIx = (gtIx << 1) | 1; c2->leafCount = 1; if (gt->hapIxB < 0) c2->unkCounts[countIx] = 1; else if (gt->hapIxB == 0) c2->refCounts[countIx] = 1; } } else { // Missing data or unphased heterozygote, don't use haplotype info for clustering c2->gtHapIx = (gtIx << 1) | 1; c2->leafCount = 1; c1->unkCounts[countIx] = c2->unkCounts[countIx] = 1; } } if (haveHaploid) { // Some array items will have an empty cluster for missing hap2 -- // trim those from the linked list. struct hapCluster *c = hapArray[0]; while (c != NULL && c->next != NULL) { if (c->next->leafCount == 0) c->next = c->next->next; else c = c->next; } } } struct hacTree *ht = hacTreeFromItems((struct slList *)(hapArray[0]), lm, cwaDistance, cwaMerge, cwaCmp, &helper); unsigned short *gtHapOrder = needMem(vcff->genotypeCount * ploidy * sizeof(unsigned short)); rSetGtHapOrder(ht, gtHapOrder, retGtHapEnd); *retTree = ht; return gtHapOrder; } INLINE Color pgSnpColor(char *allele) /* Color allele by first base according to pgSnp palette. */ { if (allele[0] == 'A') return revCmplDisp ? MG_MAGENTA : MG_RED; else if (allele[0] == 'C') return revCmplDisp ? darkGreenColor : MG_BLUE; else if (allele[0] == 'G') return revCmplDisp ? MG_BLUE : darkGreenColor; else if (allele[0] == 'T') return revCmplDisp ? MG_RED : MG_MAGENTA; else return shadesOfGray[5]; } INLINE void abbrevAndHandleRC(char *abbrevAl, size_t abbrevAlSize, const char *fullAl) /* Limit the size of displayed allele to abbrevAlSize-1 and handle reverse-complemented display. */ { boolean fullLen = strlen(fullAl); boolean truncating = (fullLen > abbrevAlSize-1); if (truncating) { int truncLen = abbrevAlSize - 4; if (revCmplDisp) { safencpy(abbrevAl, abbrevAlSize, (fullAl + fullLen - truncLen), truncLen); reverseComplement(abbrevAl, truncLen); } else safencpy(abbrevAl, abbrevAlSize, fullAl, truncLen); safecat(abbrevAl, abbrevAlSize, "..."); } else { safecpy(abbrevAl, abbrevAlSize, fullAl); if (revCmplDisp) reverseComplement(abbrevAl, fullLen); } } INLINE void gtSummaryString(struct vcfRecord *rec, struct dyString *dy) // Make pgSnp-like mouseover text, but with genotype counts instead of allele counts. { if (isNotEmpty(rec->name) && !sameString(rec->name, ".")) dyStringPrintf(dy, "%s: ", rec->name); if (rec->alleleCount < 2) { dyStringAppendC(dy, '?'); return; } int *gtCounts = NULL, *alCounts = NULL;; int phasedGts = 0, diploidCount = 0; vcfCountGenotypes(rec, >Counts, &alCounts, &phasedGts, &diploidCount); size_t abbrevSize = 16; char displayAls[rec->alleleCount][abbrevSize]; int i; for (i = 0; i < rec->alleleCount; i++) abbrevAndHandleRC(displayAls[i], sizeof displayAls[i], rec->alleles[i]); if (diploidCount == 0) { // No diploid genotypes, just allele counts. for (i = 0; i < rec->alleleCount; i++) { if (i > 0) dyStringAppendC(dy, ' '); dyStringPrintf(dy, "%s:%d", displayAls[i], alCounts[i]); } } else { dyStringPrintf(dy, "%s/%s:%d", displayAls[0], displayAls[0], gtCounts[0]); for (i = 1; i < rec->alleleCount + 1; i++) { int j; for (j = 0; j <= i; j++) { int gtIx = vcfGenotypeIndex(j, i); if (gtCounts[gtIx] > 0) { char *alJ = (j == rec->alleleCount) ? "?" : displayAls[j]; char *alI = (i == rec->alleleCount) ? "?" : displayAls[i]; dyStringPrintf(dy, "; %s/%s:%d", alJ, alI, gtCounts[gtIx]); } } } } } void mapBoxForCenterVariant(struct vcfRecord *rec, struct hvGfx *hvg, struct track *tg, int xOff, int yOff, int width) /* Special mouseover for center variant */ { struct dyString *dy = dyStringNew(0); unsigned int chromStartMap = vcfRecordTrimIndelLeftBase(rec); unsigned int chromEndMap = vcfRecordTrimAllelesRight(rec); gtSummaryString(rec, dy); dyStringAppend(dy, " Haplotypes sorted on "); char *centerChrom = cartOptionalStringClosestToHome(cart, tg->tdb, FALSE, "centerVariantChrom"); if (centerChrom == NULL || !sameString(chromName, centerChrom)) dyStringAppend(dy, "middle variant by default. "); else dyStringAppend(dy, "this variant. "); dyStringAppend(dy, "To anchor sorting to a different variant, click on that variant and " "then click on the 'Use this variant' button below the variant name."); const double scale = scaleForPixels(width); int x1 = round((double)(rec->chromStart-winStart)*scale) + xOff; int x2 = round((double)(rec->chromEnd-winStart)*scale) + xOff; int w = x2-x1; if (w <= 1) { x1--; w = 3; } mapBoxHgcOrHgGene(hvg, chromStartMap, chromEndMap, x1, yOff, w, tg->height, tg->track, rec->name, dy->string, NULL, TRUE, NULL); } // These are initialized when we start drawing, then constant. static Color purple = 0; static Color undefYellow = 0; enum hapColorMode { altOnlyMode, refAltMode, baseMode }; static Color colorByAltOnly(int refs, int alts, int unks) /* Coloring alternate alleles only: shade by proportion of alt alleles to refs, unknowns */ { if (unks > (refs + alts)) return undefYellow; int grayIx = hGrayInRange(alts, 0, alts+refs+unks, maxShade+1) - 1; // undo force to 1 return shadesOfGray[grayIx]; } static Color colorByRefAlt(int refs, int alts, int unks) /* Color blue for reference allele, red for alternate allele, gray for unknown, purple * for reasonably mixed. */ { const int fudgeFactor = 4; // Threshold factor for calling one color or the other when mixed if (unks > (refs + alts)) return undefYellow; if (alts > fudgeFactor * refs) return MG_RED; if (refs > fudgeFactor * alts) return MG_BLUE; return purple; } static Color colorByBase(int refs, int alts, int unks, char *refAl, char *altAl) /* Color gray for unknown or mixed, otherwise pgSnpColor of predominant allele. */ { const int fudgeFactor = 4; // Threshold for calling for one color or the other when mixed if (unks > (refs + alts)) return undefYellow; if (alts > fudgeFactor * refs) return pgSnpColor(altAl); if (refs > fudgeFactor * alts) return pgSnpColor(refAl); return shadesOfGray[5]; } // tg->height needs an extra pixel at the bottom; it's eaten by the clipping rectangle: #define CLIP_PAD 1 static void drawOneRec(struct vcfRecord *rec, unsigned short *gtHapOrder, unsigned short gtHapCount, struct track *tg, struct hvGfx *hvg, int xOff, int yOff, int width, boolean isClustered, boolean isCenter, enum hapColorMode colorMode) /* Draw a stack of genotype bars for this record */ { unsigned int chromStartMap = vcfRecordTrimIndelLeftBase(rec); unsigned int chromEndMap = vcfRecordTrimAllelesRight(rec); const double scale = scaleForPixels(width); int x1 = round((double)(rec->chromStart-winStart)*scale) + xOff; int x2 = round((double)(rec->chromEnd-winStart)*scale) + xOff; int w = x2-x1; if (w <= 1) { x1--; w = 3; } // When coloring mode is altOnly, we draw one extra pixel row at the top & one at bottom // to show the locations of variants, since the reference alleles are invisible: int extraPixel = 0; int hapHeight = tg->height - CLIP_PAD; if (colorMode == altOnlyMode) { hvGfxLine(hvg, x1, yOff, x2, yOff, (isClustered ? purple : shadesOfGray[5])); extraPixel = 1; hapHeight -= extraPixel*2; } double hapsPerPix = (double)gtHapCount / hapHeight; int pixIx; for (pixIx = 0; pixIx < hapHeight; pixIx++) { int gtHapOrderIxStart = (int)(hapsPerPix * pixIx); int gtHapOrderIxEnd = round(hapsPerPix * (pixIx + 1)); if (gtHapOrderIxEnd == gtHapOrderIxStart) gtHapOrderIxEnd++; int unks = 0, refs = 0, alts = 0; int gtHapOrderIx; for (gtHapOrderIx = gtHapOrderIxStart; gtHapOrderIx < gtHapOrderIxEnd; gtHapOrderIx++) { int gtHapIx = gtHapOrder[gtHapOrderIx]; int hapIx = gtHapIx & 1; int gtIx = gtHapIx >>1; struct vcfGenotype *gt = &(rec->genotypes[gtIx]); if (gt->isPhased || gt->isHaploid || (gt->hapIxA == gt->hapIxB)) { int alIx = hapIx ? gt->hapIxB : gt->hapIxA; if (alIx < 0) unks++; else if (alIx > 0) alts++; else refs++; } else unks++; } int y = yOff + extraPixel + pixIx; Color col; if (colorMode == baseMode) col = colorByBase(refs, alts, unks, rec->alleles[0], rec->alleles[1]); else if (colorMode == refAltMode) col = colorByRefAlt(refs, alts, unks); else col = colorByAltOnly(refs, alts, unks); if (col != MG_WHITE) hvGfxLine(hvg, x1, y, x2, y, col); } int yBot = yOff + tg->height - CLIP_PAD - 1; if (isCenter) { if (colorMode == altOnlyMode) { // Colorful outline to distinguish this variant: hvGfxLine(hvg, x1-1, yOff, x1-1, yBot, purple); hvGfxLine(hvg, x2+1, yOff, x2+1, yBot, purple); hvGfxLine(hvg, x1-1, yOff, x2+1, yOff, purple); hvGfxLine(hvg, x1-1, yBot, x2+1, yBot, purple); } else { // Thick black lines to distinguish this variant: hvGfxBox(hvg, x1-3, yOff, 3, tg->height, MG_BLACK); hvGfxBox(hvg, x2, yOff, 3, tg->height, MG_BLACK); hvGfxLine(hvg, x1-2, yOff, x2+2, yOff, MG_BLACK); hvGfxLine(hvg, x1-2, yBot, x2+2, yBot, MG_BLACK); } // Mouseover was handled already by mapBoxForCenterVariant } else { struct dyString *dy = dyStringNew(0); gtSummaryString(rec, dy); mapBoxHgcOrHgGene(hvg, chromStartMap, chromEndMap, x1, yOff, w, tg->height, tg->track, rec->name, dy->string, NULL, TRUE, NULL); } if (colorMode == altOnlyMode) hvGfxLine(hvg, x1, yBot, x2, yBot, (isClustered ? purple : shadesOfGray[5])); } static int getCenterVariantIx(struct track *tg, int seqStart, int seqEnd, struct vcfRecord *records) // If the user hasn't specified a local variant/position to use as center, // just use the median variant in window. { int defaultIx = (slCount(records)-1) / 2; char *centerChrom = cartOptionalStringClosestToHome(cart, tg->tdb, FALSE, "centerVariantChrom"); if (centerChrom != NULL && sameString(chromName, centerChrom)) { int centerPos = cartUsualIntClosestToHome(cart, tg->tdb, FALSE, "centerVariantPos", -1); int winSize = seqEnd - seqStart; if (centerPos > (seqStart - winSize) && centerPos < (seqEnd + winSize)) { int i; struct vcfRecord *rec; for (rec = records, i = 0; rec != NULL; rec = rec->next, i++) if (rec->chromStart >= centerPos) return i; return i-1; } } return defaultIx; } /* Data used when drawing mouseover titles for clusters: */ struct titleHelper { char *track; // For imageV2's map item code int startIx; // Index of first record (variant) used in clustering int centerIx; // Index of center record (variant) used in clustering int endIx; // Half-open index of last record (variant) used in clustering int nRecords; // Total number of records in position range char **refs; // Array of reference alleles for records used in clustering char **alts; // Array of alternate alleles for records used in clustering // (refs[0] and alts[0] are from record at startIx) }; void addClusterMapItem(struct hacTree *ht, int x1, int y1, int x2, int y2, struct titleHelper *helper) /* If using imageV2, add mouseover text (no link) with info about this cluster. */ { if (theImgBox && curImgTrack) { struct dyString *dy = dyStringNew(0); struct hapCluster *c = (struct hapCluster *)ht->itemOrCluster; dyStringPrintf(dy, "N=%d ", c->leafCount); while (dyStringLen(dy) < 7) dyStringAppendC(dy, ' '); if (helper->startIx > 0) dyStringAppend(dy, "..."); int i, nHapsForClustering = helper->endIx - helper->startIx; for (i=0; i < nHapsForClustering; i++) { boolean isCenter = (helper->startIx+i == helper->centerIx); char *allele = isRef(c, i) ? helper->refs[i] : helper->alts[i]; if (isCenter) dyStringAppendC(dy, '['); int altCount = c->leafCount - c->refCounts[i] - c->unkCounts[i]; if (c->refCounts[i] > 0 && altCount > 0) dyStringAppendC(dy, '*'); else if (strlen(allele) == 1) dyStringAppendC(dy, allele[0]); else dyStringPrintf(dy, "(%s)", allele); if (isCenter) dyStringAppendC(dy, ']'); } if (helper->endIx < helper->nRecords) dyStringAppend(dy, "..."); imgTrackAddMapItem(curImgTrack, TITLE_BUT_NO_LINK, dy->string, x1, y1, x2, y2, helper->track); } } /* Pixel y offset return type for recursive tree-drawing: */ enum yRetType { yrtMidPoint, yrtStart, yrtEnd, }; /* Callback for calculating y (in pixels) for a cluster node: */ typedef int yFromNodeFunc(const struct slList *itemOrCluster, void *extraData, enum yRetType yType); static int rDrawTreeInLabelArea(struct hacTree *ht, struct hvGfx *hvg, enum yRetType yType, int x, yFromNodeFunc *yFromNode, void *yh, struct titleHelper *th, boolean drawRectangle) /* Recursively draw the haplotype clustering tree in the left label area. * Returns pixel height for use at non-leaf levels of tree. */ { const int branchW = 4; int labelEnd = leftLabelX + leftLabelWidth; if (yType == yrtStart || yType == yrtEnd) { // We're just getting vertical span of a leaf cluster, not drawing any lines. int yLeft, yRight; if (ht->left) yLeft = rDrawTreeInLabelArea(ht->left, hvg, yType, x, yFromNode, yh, th, drawRectangle); else yLeft = yFromNode(ht->itemOrCluster, yh, yType); if (ht->right) yRight = rDrawTreeInLabelArea(ht->right, hvg, yType, x, yFromNode, yh, th, drawRectangle); else yRight = yFromNode(ht->itemOrCluster, yh, yType); if (yType == yrtStart) return min(yLeft, yRight); else return max(yLeft, yRight); } // Otherwise yType is yrtMidPoint. If we have 2 children, we'll be drawing some lines: if (ht->left != NULL && ht->right != NULL) { int midY; if (ht->childDistance == 0 || x+(2*branchW) > labelEnd) { // Treat this as a leaf cluster. // Recursing twice is wasteful. Could be avoided if this, and yFromNode, // returned both yStart and yEnd. However, the time to draw a tree of // 2188 hap's (1kG phase1 interim) is in the noise, so I consider it // not worth the effort of refactoring to save a sub-millisecond here. int yStartLeft = rDrawTreeInLabelArea(ht->left, hvg, yrtStart, x+branchW, yFromNode, yh, th, drawRectangle); int yEndLeft = rDrawTreeInLabelArea(ht->left, hvg, yrtEnd, x+branchW, yFromNode, yh, th, drawRectangle); int yStartRight = rDrawTreeInLabelArea(ht->right, hvg, yrtStart, x+branchW, yFromNode, yh, th, drawRectangle); int yEndRight = rDrawTreeInLabelArea(ht->right, hvg, yrtEnd, x+branchW, yFromNode, yh, th, drawRectangle); int yStart = min(yStartLeft, yStartRight); int yEnd = max(yEndLeft, yEndRight); midY = (yStart + yEnd) / 2; Color col = (ht->childDistance == 0) ? purple : MG_BLACK; if (drawRectangle || ht->childDistance != 0) { hvGfxLine(hvg, x+branchW, yStart, x+branchW, yEnd-1, col); hvGfxLine(hvg, x+branchW, yStart, labelEnd, yStart, col); hvGfxLine(hvg, x+branchW, yEnd-1, labelEnd, yEnd-1, col); } else { hvGfxLine(hvg, x, midY, x+1, midY, col); hvGfxLine(hvg, x+1, midY, labelEnd-1, yStart, col); hvGfxLine(hvg, x+1, midY, labelEnd-1, yEnd-1, col); } addClusterMapItem(ht, x, yStart, labelEnd, yEnd-1, th); } else { int leftMid = rDrawTreeInLabelArea(ht->left, hvg, yrtMidPoint, x+branchW, yFromNode, yh, th, drawRectangle); int rightMid = rDrawTreeInLabelArea(ht->right, hvg, yrtMidPoint, x+branchW, yFromNode, yh, th, drawRectangle); midY = (leftMid + rightMid) / 2; hvGfxLine(hvg, x+branchW, leftMid, x+branchW, rightMid, MG_BLACK); addClusterMapItem(ht, x, min(leftMid, rightMid), x+branchW-1, max(leftMid, rightMid), th); } if (drawRectangle || ht->childDistance != 0) hvGfxLine(hvg, x, midY, x+branchW, midY, MG_BLACK); return midY; } else if (ht->left != NULL) return rDrawTreeInLabelArea(ht->left, hvg, yType, x, yFromNode, yh, th, drawRectangle); else if (ht->right != NULL) return rDrawTreeInLabelArea(ht->right, hvg, yType, x, yFromNode, yh, th, drawRectangle); // Leaf node -- return pixel height. Draw a line if yType is midpoint. int y = yFromNode(ht->itemOrCluster, yh, yType); if (yType == yrtMidPoint && x < labelEnd) { hvGfxLine(hvg, x, y, labelEnd, y, purple); addClusterMapItem(ht, x, y, labelEnd, y+1, th); } return y; } struct yFromNodeHelper /* Pre-computed mapping from cluster nodes' gtHapIx to pixel heights. */ { unsigned short gtHapCount; unsigned short *gtHapIxToPxStart; unsigned short *gtHapIxToPxEnd; }; void initYFromNodeHelper(struct yFromNodeHelper *helper, int yOff, int height, unsigned short gtHapCount, unsigned short *gtHapOrder, int genotypeCount) /* Build a mapping of genotype and haplotype to pixel y coords. */ { helper->gtHapCount = gtHapCount; helper->gtHapIxToPxStart = needMem(genotypeCount * 2 * sizeof(unsigned short)); helper->gtHapIxToPxEnd = needMem(genotypeCount * 2 * sizeof(unsigned short)); double pxPerHap = (double)height / gtHapCount; int i; for (i = 0; i < gtHapCount; i++) { int yStart = round(i * pxPerHap); int yEnd = round((i+1) * pxPerHap); if (yEnd == yStart) yEnd++; int gtHapIx = gtHapOrder[i]; helper->gtHapIxToPxStart[gtHapIx] = yOff + yStart; helper->gtHapIxToPxEnd[gtHapIx] = yOff + yEnd; } } static int yFromHapNode(const struct slList *itemOrCluster, void *extraData, enum yRetType yType) /* Extract the gtHapIx from hapCluster (hacTree node item), find out its relative order * and translate that to a pixel height. */ { unsigned short gtHapIx = ((const struct hapCluster *)itemOrCluster)->gtHapIx; struct yFromNodeHelper *helper = extraData; int y; if (yType == yrtStart) y = helper->gtHapIxToPxStart[gtHapIx]; else if (yType == yrtEnd) y = helper->gtHapIxToPxEnd[gtHapIx]; else y = (helper->gtHapIxToPxStart[gtHapIx] + helper->gtHapIxToPxEnd[gtHapIx]) / 2; return y; } void initTitleHelper(struct titleHelper *th, char *track, int startIx, int centerIx, int endIx, int nRecords, struct vcfFile *vcff) /* Set up info including arrays of ref & alt alleles for cluster mouseover. */ { th->track = track; th->startIx = startIx; th->centerIx = centerIx; th->endIx = endIx; th->nRecords = nRecords; int len = endIx - startIx; AllocArray(th->refs, len); AllocArray(th->alts, len); struct vcfRecord *rec; int i; for (rec = vcff->records, i = 0; rec != NULL && i < endIx; rec = rec->next, i++) { if (i < startIx) continue; char refAl[16]; abbrevAndHandleRC(refAl, sizeof(refAl), rec->alleles[0]); th->refs[i-startIx] = vcfFilePooledStr(vcff, refAl); char altAl1[16]; abbrevAndHandleRC(altAl1, sizeof(altAl1), rec->alleles[1]); tolowers(altAl1); th->alts[i-startIx] = vcfFilePooledStr(vcff, altAl1); } } static void drawTreeInLabelArea(struct hacTree *ht, struct hvGfx *hvg, int yOff, int clipHeight, struct yFromNodeHelper *yHelper, struct titleHelper *titleHelper, boolean drawRectangle) /* Draw the haplotype clustering in the left label area (as much as fits there). */ { // Figure out which hvg to use, save current clipping, and clip to left label coords: struct hvGfx *hvgLL = (hvgSide != NULL) ? hvgSide : hvg; int clipXBak, clipYBak, clipWidthBak, clipHeightBak; hvGfxGetClip(hvgLL, &clipXBak, &clipYBak, &clipWidthBak, &clipHeightBak); hvGfxUnclip(hvgLL); hvGfxSetClip(hvgLL, leftLabelX, yOff, leftLabelWidth, clipHeight); // Draw the tree: int x = leftLabelX; (void)rDrawTreeInLabelArea(ht, hvgLL, yrtMidPoint, x, yFromHapNode, yHelper, titleHelper, drawRectangle); // Restore the prior clipping: hvGfxUnclip(hvgLL); hvGfxSetClip(hvgLL, clipXBak, clipYBak, clipWidthBak, clipHeightBak); } static void ignoreEm(char *format, va_list args) /* Ignore warnings from genotype parsing -- when there's one, there * are usually hundreds more just like it. */ { } static enum hapColorMode getColorMode(struct trackDb *tdb) /* Get the hap-cluster coloring mode from cart & tdb. */ { enum hapColorMode colorMode = altOnlyMode; char *colorBy = cartOrTdbString(cart, tdb, VCF_HAP_COLORBY_VAR, VCF_DEFAULT_HAP_COLORBY); if (sameString(colorBy, VCF_HAP_COLORBY_ALTONLY)) colorMode = altOnlyMode; else if (sameString(colorBy, VCF_HAP_COLORBY_REFALT)) colorMode = refAltMode; else if (sameString(colorBy, VCF_HAP_COLORBY_BASE)) colorMode = baseMode; return colorMode; } static boolean vcfHapClusterDrawInit(struct track *tg, struct vcfFile *vcff, struct hvGfx *hvg, enum hapColorMode *retHapColorMode) /* Parse vcff's genotypes and get ready to draw haplotypes. Return FALSE if nothing to draw. */ { if (vcff->records == NULL) return FALSE; undefYellow = hvGfxFindRgb(hvg, &undefinedYellowColor); if (retHapColorMode) *retHapColorMode = getColorMode(tg->tdb); pushWarnHandler(ignoreEm); struct vcfRecord *rec; for (rec = vcff->records; rec != NULL; rec = rec->next) vcfParseGenotypes(rec); popWarnHandler(); return TRUE; } static void vcfHapClusterDraw(struct track *tg, int seqStart, int seqEnd, struct hvGfx *hvg, int xOff, int yOff, int width, MgFont *font, Color color, enum trackVisibility vis) /* Split samples' chromosomes (haplotypes), cluster them by center-weighted * alpha similarity, and draw in the order determined by clustering. */ { struct vcfFile *vcff = tg->extraUiData; enum hapColorMode colorMode; if (!vcfHapClusterDrawInit(tg, vcff, hvg, &colorMode)) return; purple = hvGfxFindColorIx(hvg, 0x99, 0x00, 0xcc); unsigned short gtHapCount = 0; int nRecords = slCount(vcff->records); int centerIx = getCenterVariantIx(tg, seqStart, seqEnd, vcff->records); // Limit the number of variants that we compare, to keep from timing out: // (really what we should limit is the number of distinct haplo's passed to hacTree!) // In the meantime, this should at least be a cart var... int maxVariantsPerSide = 50; int startIx = max(0, centerIx - maxVariantsPerSide); int endIx = min(nRecords, centerIx+1 + maxVariantsPerSide); struct hacTree *ht = NULL; unsigned short *gtHapOrder = clusterHaps(vcff, centerIx, startIx, endIx, >HapCount, &ht); struct vcfRecord *centerRec = NULL; struct vcfRecord *rec; int ix; // Unlike drawing order (last drawn is on top), the first mapBox gets priority, // so map center variant before drawing & mapping other variants! for (rec = vcff->records, ix=0; rec != NULL; rec = rec->next, ix++) { if (ix == centerIx) { centerRec = rec; mapBoxForCenterVariant(rec, hvg, tg, xOff, yOff, width); break; } } for (rec = vcff->records, ix=0; rec != NULL; rec = rec->next, ix++) { boolean isClustered = (ix >= startIx && ix < endIx); if (ix != centerIx) drawOneRec(rec, gtHapOrder, gtHapCount, tg, hvg, xOff, yOff, width, isClustered, FALSE, colorMode); } // Draw the center rec on top, outlined with black lines, to make sure it is very visible: drawOneRec(centerRec, gtHapOrder, gtHapCount, tg, hvg, xOff, yOff, width, TRUE, TRUE, colorMode); // Draw as much of the tree as can fit in the left label area: int extraPixel = (colorMode == altOnlyMode) ? 1 : 0; int hapHeight = tg->height- CLIP_PAD - 2*extraPixel; struct yFromNodeHelper yHelper = {0, NULL, NULL}; initYFromNodeHelper(&yHelper, yOff+extraPixel, hapHeight, gtHapCount, gtHapOrder, vcff->genotypeCount); struct titleHelper titleHelper = { NULL, 0, 0, 0, 0, NULL, NULL }; initTitleHelper(&titleHelper, tg->track, startIx, centerIx, endIx, nRecords, vcff); char *treeAngle = cartOrTdbString(cart, tg->tdb, VCF_HAP_TREEANGLE_VAR, VCF_DEFAULT_HAP_TREEANGLE); boolean drawRectangle = sameString(treeAngle, VCF_HAP_TREEANGLE_RECTANGLE); drawTreeInLabelArea(ht, hvg, yOff+extraPixel, hapHeight+CLIP_PAD, &yHelper, &titleHelper, drawRectangle); } static void drawSampleLabels(struct vcfFile *vcff, struct hvGfx *hvg, boolean isAllDiploid, int yStart, int height, unsigned short *gtHapOrder, int gtHapCount, MgFont *font, Color color, char *track) /* Draw sample names as left labels. */ { // Figure out which hvg to use, save current clipping, and clip to left label coords: struct hvGfx *hvgLL = (hvgSide != NULL) ? hvgSide : hvg; int clipXBak, clipYBak, clipWidthBak, clipHeightBak; hvGfxGetClip(hvgLL, &clipXBak, &clipYBak, &clipWidthBak, &clipHeightBak); hvGfxUnclip(hvgLL); hvGfxSetClip(hvgLL, leftLabelX, yStart, leftLabelWidth, height); if (isAllDiploid) { double pxPerGt = (double)height / vcff->genotypeCount; if (pxPerGt < tl.fontHeight + 1) warn("track %s: drawSampleLabels called with insufficient height", track); int gtIx; for (gtIx = 0; gtIx < vcff->genotypeCount; gtIx++) { int y = gtIx * pxPerGt; hvGfxTextRight(hvgLL, leftLabelX, y+yStart, leftLabelWidth-1, (int)pxPerGt, color, font, vcff->genotypeIds[gtIx]); } } else { double pxPerHt = (double)height / gtHapCount; if (pxPerHt < tl.fontHeight + 1) warn("track %s: drawSampleLabels called with insufficient height", track); int orderIx; for (orderIx = 0; orderIx < gtHapCount; orderIx++) { int gtHapIx = gtHapOrder[orderIx]; int gtIx = (gtHapIx >> 1); int y = gtIx * pxPerHt; hvGfxTextRight(hvgLL, leftLabelX, y+yStart, leftLabelWidth-1, (int)pxPerHt, color, font, vcff->genotypeIds[gtIx]); } } // Restore the prior clipping: hvGfxUnclip(hvgLL); hvGfxSetClip(hvgLL, clipXBak, clipYBak, clipWidthBak, clipHeightBak); } static void drawSampleTitles(struct vcfFile *vcff, int yStart, int height, unsigned short *gtHapOrder, int gtHapCount, char *track) /* Draw mouseover labels / titles with the samples that are drawn at each pixel y offset */ { double hapPerPx = (double)gtHapCount / height; int labelEnd = leftLabelX + leftLabelWidth; struct dyString *dy = dyStringNew(0); int y; for (y = 0; y < height; y++) { dyStringClear(dy); int gtHapStart = y * hapPerPx; int gtHapEnd = (y + 1) * hapPerPx; if (gtHapEnd == gtHapStart) gtHapEnd++; char *lastSample = NULL; int gtHapIx; for (gtHapIx = gtHapStart; gtHapIx < gtHapEnd; gtHapIx++) { int gtIx = (gtHapOrder[gtHapIx] >> 1); char *sample = vcff->genotypeIds[gtIx]; if (!lastSample || differentString(sample, lastSample)) { if (isNotEmpty(dy->string)) dyStringAppend(dy, ", "); dyStringAppend(dy, sample); lastSample = sample; } } imgTrackAddMapItem(curImgTrack, TITLE_BUT_NO_LINK, dy->string, leftLabelX, y+yStart, labelEnd, y+yStart+1, track); } } static unsigned short *gtHapOrderFromGtOrder(struct vcfFile *vcff, boolean *retIsAllDiploid, int *retGtHapCount) { int ploidy = 2; // Assuming diploid genomes here, no XXY, tetraploid etc. int gtCount = vcff->genotypeCount; boolean isAllDiploid = TRUE; unsigned short *gtHapOrder = needMem(gtCount * ploidy * sizeof(unsigned short)); int orderIx = 0; int gtIx; // Determine the number of chromosome rows; for chrX, can be mix of diploid and haploid. for (gtIx=0; gtIx < gtCount; gtIx++) { int gtHapIx = (gtIx << 1); gtHapOrder[orderIx] = gtHapIx; orderIx++; struct vcfRecord *rec; for (rec = vcff->records; rec != NULL; rec = rec->next) { struct vcfGenotype *gt = &(rec->genotypes[gtIx]); if (!gt->isHaploid) { gtHapOrder[orderIx] = gtHapIx+1; orderIx++; break; } else isAllDiploid = FALSE; } } if (retIsAllDiploid) *retIsAllDiploid = isAllDiploid; if (retGtHapCount) *retGtHapCount = orderIx; return gtHapOrder; } static void vcfGtHapFileOrderDraw(struct track *tg, int seqStart, int seqEnd, struct hvGfx *hvg, int xOff, int yOff, int width, MgFont *font, Color color, enum trackVisibility vis) /* Draw rows in the same fashion as vcfHapClusterDraw, but instead of clustering, use the * order in which samples appear in the VCF file. */ { struct vcfFile *vcff = tg->extraUiData; enum hapColorMode colorMode; if (!vcfHapClusterDrawInit(tg, vcff, hvg, &colorMode)) return; boolean isAllDiploid; int gtHapCount; unsigned short *gtHapOrder = gtHapOrderFromGtOrder(vcff, &isAllDiploid, >HapCount); struct vcfRecord *rec; for (rec = vcff->records; rec != NULL; rec = rec->next) drawOneRec(rec, gtHapOrder, gtHapCount, tg, hvg, xOff, yOff, width, FALSE, FALSE, colorMode); // If height is sufficient, draw sample names as left labels; otherwise make mouseover titles // with sample names for each pixel y offset. int extraPixel = (colorMode == altOnlyMode) ? 1 : 0; int hapHeight = tg->height - CLIP_PAD - 2*extraPixel; int minHeightForLabels; if (isAllDiploid) minHeightForLabels = vcff->genotypeCount * (tl.fontHeight + 1); else minHeightForLabels = gtHapCount * (tl.fontHeight + 1); if (hapHeight >= minHeightForLabels) drawSampleLabels(vcff, hvg, isAllDiploid, yOff+extraPixel, hapHeight, gtHapOrder, gtHapCount, font, color, tg->track); else drawSampleTitles(vcff, yOff+extraPixel, hapHeight, gtHapOrder, gtHapCount, tg->track); } static struct phyloTree *getTreeFromFile(struct trackDb *tdb) /* Get the filename that follows trackDb setting 'hapClusterMethod treeFile ' and read it in * as a phyloTree. */ { char *hapMethod = cloneString(trackDbSetting(tdb, VCF_HAP_METHOD_VAR)); if (! startsWithWord(VCF_HAP_METHOD_TREE_FILE, nextWord(&hapMethod))) errAbort("getTreeFromFile: expected trackDb setting " VCF_HAP_METHOD_VAR "to start with '" VCF_HAP_METHOD_TREE_FILE "' followed by a file name, but got '%s'", hapMethod); char *fileName = hReplaceGbdb(nextWord(&hapMethod)); return phyloOpenTree(fileName); } struct hash *makeSampleToIx(struct vcfFile *vcff) /* Alloc & return a hash of sample names to genotype indices in vcff. */ { struct hash *sampleToIx = hashNew(0); int gtIx; for (gtIx = 0; gtIx < vcff->genotypeCount; gtIx++) hashAddInt(sampleToIx, vcff->genotypeIds[gtIx], gtIx); return sampleToIx; } static int gtIxFromSample(struct hash *sampleToIx, char *sample, char *vcfFileName) /* Look up sample's genotype index in sampleToIx, die complaining about vcfFileName if not found. */ { int gtIx = hashIntValDefault(sampleToIx, sample, -1); if (gtIx < 0) errAbort("gtIxFromSample: sample '%s' not found in VCF file %s", sample, vcfFileName); return gtIx; } static void rSetGtHapOrderFromTree(struct phyloTree *node, struct vcfFile *vcff, struct hash *sampleToIx, unsigned short *gtHapOrder, int *pGtHapCount, unsigned short *leafOrderToHapOrderStart, unsigned short *leafOrderToHapOrderEnd, int *pLeafCount) /* Set gtHapOrder to sample gt & hap indices in the order we encounter the samples in tree. */ { if (node->numEdges > 0) { int ix; for (ix = 0; ix < node->numEdges; ix++) rSetGtHapOrderFromTree(node->edges[ix], vcff, sampleToIx, gtHapOrder, pGtHapCount, leafOrderToHapOrderStart, leafOrderToHapOrderEnd, pLeafCount); } else { int gtIx = gtIxFromSample(sampleToIx, node->ident->name, vcff->fileOrUrl); int gtHapIx = (gtIx << 1); gtHapOrder[*pGtHapCount] = gtHapIx; leafOrderToHapOrderStart[*pLeafCount] = leafOrderToHapOrderEnd[*pLeafCount] = *pGtHapCount; *pGtHapCount += 1; struct vcfRecord *rec; for (rec = vcff->records; rec != NULL; rec = rec->next) { struct vcfGenotype *gt = &(rec->genotypes[gtIx]); if (!gt->isHaploid) { gtHapOrder[*pGtHapCount] = gtHapIx+1; leafOrderToHapOrderEnd[*pLeafCount] = *pGtHapCount; *pGtHapCount += 1; break; } } *pLeafCount += 1; } } static unsigned short *gtHapOrderFromTree(struct vcfFile *vcff, struct phyloTree *tree, unsigned short **retLeafOrderToHapOrderStart, unsigned short **retLeafOrderToHapOrderEnd, int *retGtHapCount) /* Alloc & return gtHapOrder, set to samples in the order we encounter them in tree. * Also build up maps of leaf order to low and high gtHapIx, for drawing the tree later. */ { struct hash *sampleToIx = makeSampleToIx(vcff); int ploidy = 2; // Assuming diploid genomes here, no XXY, tetraploid etc. int gtCount = vcff->genotypeCount; unsigned short *gtHapOrder = needMem(gtCount * ploidy * sizeof(unsigned short)); *retLeafOrderToHapOrderStart = needMem(gtCount * sizeof(unsigned short)); *retLeafOrderToHapOrderEnd = needMem(gtCount * sizeof(unsigned short)); *retGtHapCount = 0; int leafCount = 0; rSetGtHapOrderFromTree(tree, vcff, sampleToIx, gtHapOrder, retGtHapCount, *retLeafOrderToHapOrderStart, *retLeafOrderToHapOrderEnd, &leafCount); if (leafCount != vcff->genotypeCount) errAbort("gtHapOrderFromTree: tree has %d leaves, but VCF file %s has %d genotype columns", leafCount, vcff->fileOrUrl, vcff->genotypeCount); return gtHapOrder; } // Relative coordinates for tree layout, to be transformed into pixel coords later. struct nodeCoords { double rank; // Centerpoint of children's rank in terms of hap order (0 = top haplotype) int depth; // Maximum child depth + 1 }; static int phyloTreeAddNodeCoords(struct phyloTree *node, unsigned short *leafOrderToHapOrderStart, unsigned short *leafOrderToHapOrderEnd, int leafIx) /* Recursively annotate node and descendants with nodeCoords to prepare for drawing the tree. */ { struct nodeCoords *coords; AllocVar(coords); node->priv = coords; if (node->numEdges > 0) { double minRank = -1, maxRank = 0; int maxDepth = 0; int ix; for (ix = 0; ix < node->numEdges; ix++) { struct phyloTree *child = node->edges[ix]; leafIx = phyloTreeAddNodeCoords(child, leafOrderToHapOrderStart, leafOrderToHapOrderEnd, leafIx); struct nodeCoords *childCoords = child->priv; if (minRank < 0 || childCoords->rank < minRank) minRank = childCoords->rank; if (childCoords->rank > maxRank) maxRank = childCoords->rank; if (childCoords->depth > maxDepth) maxDepth = childCoords->depth; } coords->rank = (minRank + maxRank) / 2.0; coords->depth = maxDepth + 1; } else { // Leaf (sample) double rankStart = leafOrderToHapOrderStart[leafIx]; double rankEnd = leafOrderToHapOrderStart[leafIx]; coords->rank = (rankStart + rankEnd) / 2.0; leafIx++; coords->depth = 0; } return leafIx; } static void rDrawPhyloTreeInLabelArea(struct phyloTree *node, struct hvGfx *hvg, int x, int yOff, double pxPerHap, MgFont *font, boolean drawRectangle) /* Recursively draw the tree in the left label area. */ { const int branchW = 4; int labelEnd = leftLabelX + leftLabelWidth; // Misuse the branch length value as RGB color (if it's the typical small number, will still // draw as approximately black): unsigned int rgb = node->ident->length; Color color = MAKECOLOR_32( ((rgb>>16)&0xff), ((rgb>>8)&0xff), (rgb&0xff) ); if (node->numEdges > 0) { // Draw each child and a horizontal line to child int minY = -1, maxY = 0; int ix; for (ix = 0; ix < node->numEdges; ix++) { struct phyloTree *child = node->edges[ix]; rDrawPhyloTreeInLabelArea(child, hvg, x+branchW, yOff, pxPerHap, font, drawRectangle); struct nodeCoords *childCoords = child->priv; int childY = yOff + ((0.5 + childCoords->rank) * pxPerHap); hvGfxLine(hvg, x, childY, x+branchW, childY, color); if (minY < 0 || childY < minY) minY = childY; if (childY > maxY) maxY = childY; } // Draw a vertical line to connect the children hvGfxLine(hvg, x, minY, x, maxY, color); } else { // Leaf node -- draw a horizontal line, and label if there is space to right of tree struct nodeCoords *coords = node->priv; int y = yOff + ((0.5 + coords->rank) * pxPerHap); hvGfxLine(hvg, x, y, x+branchW, y, color); int textX = x + branchW + 3; if (pxPerHap >= tl.fontHeight+1 && textX < labelEnd) hvGfxText(hvg, textX, y, MG_BLACK, font, node->ident->name); } } static void drawPhyloTreeInLabelArea(struct phyloTree *tree, struct hvGfx *hvg, int yOff, int clipHeight, int gtHapCount, MgFont *font, boolean drawRectangle, unsigned short *leafOrderToHapOrderStart, unsigned short *leafOrderToHapOrderEnd) { struct hvGfx *hvgLL = (hvgSide != NULL) ? hvgSide : hvg; int clipXBak, clipYBak, clipWidthBak, clipHeightBak; hvGfxGetClip(hvgLL, &clipXBak, &clipYBak, &clipWidthBak, &clipHeightBak); hvGfxUnclip(hvgLL); hvGfxSetClip(hvgLL, leftLabelX, yOff, leftLabelWidth, clipHeight); // Figure out rank (vertical position) and depth (horizontal position) of every node in tree: phyloTreeAddNodeCoords(tree, leafOrderToHapOrderStart, leafOrderToHapOrderEnd, 0); // Draw the tree: int x = leftLabelX; double pxPerHap = (double)clipHeight / gtHapCount; rDrawPhyloTreeInLabelArea(tree, hvgLL, x, yOff, pxPerHap, font, drawRectangle); // Restore the prior clipping: hvGfxUnclip(hvgLL); hvGfxSetClip(hvgLL, clipXBak, clipYBak, clipWidthBak, clipHeightBak); } static void vcfGtHapTreeFileDraw(struct track *tg, int seqStart, int seqEnd, struct hvGfx *hvg, int xOff, int yOff, int width, MgFont *font, Color color, enum trackVisibility vis) /* Draw rows in the same fashion as vcfHapClusterDraw, but instead of clustering, use the * order in which samples appear in the VCF file. */ { struct vcfFile *vcff = tg->extraUiData; enum hapColorMode colorMode; if (!vcfHapClusterDrawInit(tg, vcff, hvg, &colorMode)) return; struct phyloTree *tree = getTreeFromFile(tg->tdb); int gtHapCount; unsigned short *leafOrderToHapOrderStart, *leafOrderToHapOrderEnd; unsigned short *gtHapOrder = gtHapOrderFromTree(vcff, tree, &leafOrderToHapOrderStart, &leafOrderToHapOrderEnd, >HapCount); struct vcfRecord *rec; for (rec = vcff->records; rec != NULL; rec = rec->next) drawOneRec(rec, gtHapOrder, gtHapCount, tg, hvg, xOff, yOff, width, FALSE, FALSE, colorMode); int extraPixel = (colorMode == altOnlyMode) ? 1 : 0; int hapHeight = tg->height - CLIP_PAD - 2*extraPixel; char *treeAngle = cartOrTdbString(cart, tg->tdb, VCF_HAP_TREEANGLE_VAR, VCF_DEFAULT_HAP_TREEANGLE); boolean drawRectangle = sameString(treeAngle, VCF_HAP_TREEANGLE_RECTANGLE); drawPhyloTreeInLabelArea(tree, hvg, yOff+extraPixel, hapHeight, gtHapCount, font, drawRectangle, leafOrderToHapOrderStart, leafOrderToHapOrderEnd); drawSampleTitles(vcff, yOff+extraPixel, hapHeight, gtHapOrder, gtHapCount, tg->track); } static int vcfHapClusterTotalHeight(struct track *tg, enum trackVisibility vis) /* Return height of haplotype graph (2 * #samples * lineHeight); * 2 because we're assuming diploid genomes here, no XXY, tetraploid etc. */ { const struct vcfFile *vcff = tg->extraUiData; if (vcff->records == NULL) return 0; int ploidy = sameString(chromName, "chrY") ? 1 : 2; int simpleHeight = ploidy * vcff->genotypeCount * tg->lineHeight; int defaultHeight = min(simpleHeight, VCF_DEFAULT_HAP_HEIGHT); char *tdbHeight = trackDbSettingOrDefault(tg->tdb, VCF_HAP_HEIGHT_VAR, NULL); if (isNotEmpty(tdbHeight)) defaultHeight = atoi(tdbHeight); int cartHeight = cartOrTdbInt(cart, tg->tdb, VCF_HAP_HEIGHT_VAR, defaultHeight); if (tg->visibility == tvSquish) cartHeight /= 2; int extraPixel = (getColorMode(tg->tdb) == altOnlyMode) ? 1 : 0; int totalHeight = cartHeight + CLIP_PAD + 2*extraPixel; tg->height = min(totalHeight, maximumTrackHeight(tg)); return tg->height; } static char *vcfHapClusterTrackName(struct track *tg, void *item) /* If someone asks for itemName/mapItemName, just send name of track like wiggle. */ { return tg->track; } static void vcfHapClusterOverloadMethods(struct track *tg, struct vcfFile *vcff) /* If we confirm at load time that we can draw a haplotype graph, use * this to overwrite the methods for the rest of execution: */ { tg->heightPer = (tg->visibility == tvSquish) ? (tl.fontHeight/4) : (tl.fontHeight / 2); tg->lineHeight = tg->heightPer + 1; char *hapMethod = cartOrTdbString(cart, tg->tdb, VCF_HAP_METHOD_VAR, VCF_DEFAULT_HAP_METHOD); if (sameString(hapMethod, VCF_HAP_METHOD_FILE_ORDER)) tg->drawItems = vcfGtHapFileOrderDraw; else if (startsWithWord(VCF_HAP_METHOD_TREE_FILE, hapMethod)) tg->drawItems = vcfGtHapTreeFileDraw; else tg->drawItems = vcfHapClusterDraw; tg->totalHeight = vcfHapClusterTotalHeight; tg->itemHeight = tgFixedItemHeight; tg->itemName = vcfHapClusterTrackName; tg->mapItemName = vcfHapClusterTrackName; tg->itemStart = tgItemNoStart; tg->itemEnd = tgItemNoEnd; tg->mapsSelf = TRUE; tg->extraUiData = vcff; } static void indelTweakMapItem(struct track *tg, struct hvGfx *hvg, void *item, char *itemName, char *mapItemName, int start, int end, int x, int y, int width, int height) /* Pass the original vcf chromStart to pgSnpMapItem, so if we have trimmed an identical * first base from item's alleles and start, we will still pass the correct start to hgc. */ { struct pgSnpVcfStartEnd *psvs = item; pgSnpMapItem(tg, hvg, item, itemName, mapItemName, psvs->vcfStart, psvs->vcfEnd, x, y, width, height); } +static void vcfPhasedLoadItems(struct track *tg) +/* Load up one individuals phased genotypes in window */ +{ +char *fileOrUrl = NULL; +char *tbiFileOrUrl = trackDbSetting(tg->tdb, "bigDataIndex"); // unrelated to mysql + +/* Figure out url or file name. */ +if (tg->parallelLoading) + { + /* do not use mysql during parallel-fetch load */ + fileOrUrl = trackDbSetting(tg->tdb, "bigDataUrl"); + } +else + { + struct sqlConnection *conn = hAllocConnTrack(database, tg->tdb); + fileOrUrl = bbiNameFromSettingOrTableChrom(tg->tdb, conn, tg->table, chromName); + hFreeConn(&conn); + } + +if (isEmpty(fileOrUrl)) + return; +int vcfMaxErr = -1; +struct vcfFile *vcff = NULL; + +/* protect against temporary network error */ +struct errCatch *errCatch = errCatchNew(); +if (errCatchStart(errCatch)) + { + vcff = vcfTabixFileAndIndexMayOpen(fileOrUrl, tbiFileOrUrl, chromName, winStart, winEnd, vcfMaxErr, -1); + if (vcff != NULL) + { + filterRecords(vcff, tg->tdb); + filterRefOnlyAlleles(vcff, tg->tdb); // remove items that don't differ from reference + + // TODO: in multi-region mode, different windows end up with different sets of variants where + // all are phased or not, which throws off track heights in each window. Similar to hapCluster + // mode, just switch to pgSnp view when in multi-region for now. + if (slCount(windows) > 1 || tg->visibility == tvDense) + pgSnpMethods(tg); + tg->items = vcfFileToPgSnp(vcff, tg->tdb); + // pgSnp bases coloring/display decision on count of items: + tg->extraUiData = vcff; + tg->customInt = slCount(tg->items); + // Don't vcfFileFree here -- we are using its string pointers! + } + else + { + if (tbiFileOrUrl) + errAbort("Unable to open VCF file/URL '%s' with tabix index '%s'", fileOrUrl, tbiFileOrUrl); + else + errAbort("Unable to open VCF file/URL '%s'", fileOrUrl); + } + } +errCatchEnd(errCatch); +if (errCatch->gotError || vcff == NULL) + { + if (isNotEmpty(errCatch->message->string)) + tg->networkErrMsg = cloneString(errCatch->message->string); + tg->drawItems = bigDrawWarning; + tg->totalHeight = bigWarnTotalHeight; + } +errCatchFree(&errCatch); +} + +static void vcfPhasedAddMapBox(struct hvGfx *hvg, struct vcfRecord *rec, struct pgSnpVcfStartEnd *psvs, char *text, int x, int y, int width, int height, struct track *track) +// Add mapbox for a tick in the vcfPhased track +{ +mapBoxHgcOrHgGene(hvg, psvs->vcfStart, psvs->vcfEnd, x, y, width, height, track->track, rec->name, text, NULL, TRUE, NULL); +} + +struct hapDistanceMatrixCell +{ +/* The pair of alleles and how distant they are */ + struct hapDistanceMatrixCell *next; + char *sampleId; // name of this sample + char *otherId; // name of other sample + short alleleIx; // index into vcfRecord->genotypes + short otherAlleleIx; // index into vcfRecord->genotypes for other sample + double dist; // distance between this sample/allele and another sample/allele +}; + +struct hapDistanceMatrix +{ +/* A row of hapDistanceMatrixCells, which store the distance computed by cwaDistance() + * between two different alleles */ + struct hapDistanceMatrix *next; // next row in matrix + char *sampleId; // name of this sample + short alleleIx; // allele id of this sample, 0 or 1 + struct hapDistanceMatrixCell *row; // a row of cwaDistance scores +}; + +static int hapDistanceMatrixCellCmp(const void *item1, const void *item2) +{ +const struct hapDistanceMatrixCell *cell1 = *(struct hapDistanceMatrixCell **)item1; +const struct hapDistanceMatrixCell *cell2 = *(struct hapDistanceMatrixCell **)item2; +return cell1->dist > cell2->dist; +} + +static struct hapDistanceMatrixCell *findClosestChildAlleleToParent(char *parent, char *child, + struct hapDistanceMatrix *matrix) +/* Get all cells belonging to a certain parent onto a list and sort by distance */ +{ +struct hapDistanceMatrix *vec = NULL; +struct hapDistanceMatrixCell *cellList = NULL, *cell = NULL; +for (vec = matrix; vec != NULL; vec = vec->next) + { + for (cell = vec->row; cell != NULL; cell = cell->next) + { + if (sameString(cell->sampleId, parent)) + { + struct hapDistanceMatrixCell *tmp = needMem(sizeof(struct hapDistanceMatrixCell)); + tmp->next = NULL; + tmp->sampleId = cloneString(cell->sampleId); + tmp->alleleIx = cell->alleleIx; + tmp->otherId = cloneString(vec->sampleId); + tmp->otherAlleleIx = vec->alleleIx; + tmp->dist = cell->dist; + slAddHead(&cellList, tmp); + } + } + } +slSort(&cellList, hapDistanceMatrixCellCmp); +return cellList; +} + +static unsigned short toggleShort(unsigned short s) +/* Add or subtract one */ +{ +return s & 1 ? s - 1 : s + 1; +} + +static void fillOutHapOrder(unsigned short *hapOrder, unsigned short hapCount, struct hapDistanceMatrixCell *c1, struct hapDistanceMatrixCell *c2) +/* Assign indices to hapOrder in the order we should draw the alleles. Allows for the second parent + * cell to be NULL */ +{ +if (c1 == NULL) + errAbort("Error: fillOutHapOrder passed NULL parent"); +int numSamplesToDraw = hapCount / 2; +int i; +for (i = 0; i < numSamplesToDraw; i++) + { + short hapIx = 2*i; + if (i == 0) // top set of lines + { + hapOrder[hapIx] = toggleShort(c1->alleleIx); + hapOrder[hapIx+1] = c1->alleleIx; + } + else if (i + 1 == numSamplesToDraw) // last set of lines + { + if (c2) + { + hapOrder[hapIx] = c2->alleleIx; + hapOrder[hapIx+1] = toggleShort(c2->alleleIx); + } + else + { + hapOrder[hapIx] = c1->otherAlleleIx; + hapOrder[hapIx+1] = toggleShort(c1->otherAlleleIx); + } + } + else // orient based on above and below + { + hapOrder[hapIx] = c1->otherAlleleIx; + hapOrder[hapIx+1] = c2->otherAlleleIx; + } + } +} + +static void setHapOrderFromMatrix(unsigned short *hapOrder, unsigned short hapCount, + struct hapDistanceMatrix *matrix, struct hapCluster **hapArray, + struct vcfFile *vcff, char *childName, char **sampleDrawOrder) +/* Given a matrix where each row is an allele of the child, and each column + * is the distance from the child allele to a parent allele, fill out the order + * in which the haplotypes will be drawn. The order are the indexes into rec->genotypes. */ +{ +char *parentNames[(hapCount/2) - 1]; +struct hapDistanceMatrixCell *c1 = NULL; +struct hapDistanceMatrixCell *c2 = NULL; +int i, ix = 0; +if (hapCount > 2) // is there a trio or at least part of one? + { + for (i = 0; i < hapCount/2 ; i++) + if (!sameString(sampleDrawOrder[i], childName)) + parentNames[ix++] = sampleDrawOrder[i]; + + // For a parent/child combo, find the most likely set of transmitted + // alleles. Depending on the number of variants in the window and the + // haplotypes in question, both parents can tie as the person who + // contributed a given allele + c1 = findClosestChildAlleleToParent(parentNames[0], childName, matrix); + c2 = findClosestChildAlleleToParent(parentNames[1], childName, matrix); // NULL if only one parent + if (c1 && c2) + { + if (c1->otherAlleleIx == c2->otherAlleleIx) + { + // first choose the lowest score, if a tie then just advance c1 + if (c1->dist >= c2->dist) + { + while (c1->dist >= c2->dist && c1->otherAlleleIx == c2->otherAlleleIx) + c1 = c1->next; + } + else + { + while (c1->dist < c2->dist && c1->otherAlleleIx == c2->otherAlleleIx) + c2 = c2->next; + } + } + } + fillOutHapOrder(hapOrder, hapCount, c1, c2); + } +else + { + hapOrder[0] = matrix->alleleIx; + hapOrder[1] = matrix->next->alleleIx; + } +} + +static void assignHapArrayIx(short *ret, struct hapCluster **hapArray, struct vcfFile *vcff, char *sample, boolean doChild) +{ +int i; +struct vcfRecord *rec = vcff->records; +int ix = 0; // index into ret +for (i = 0; i < slCount(hapArray); i++) + { + struct hapCluster *hc = hapArray[i]; + struct vcfGenotype *gt = &(rec->genotypes[hc->gtHapIx >> 1]); + if (!doChild && !sameString(gt->id, sample)) + ret[ix++] = i; + else if (doChild && sameString(gt->id, sample)) + ret[ix++] = i; + } +} + +static struct hapDistanceMatrix *fillOutDistanceMatrix(struct hapCluster **hapArray, struct vcfFile *vcff, char *sample, struct cwaExtraData *helper, int gtCount) +{ +short parGtCount = (gtCount - 1) * 2; +int i,j; +struct vcfRecord *rec = vcff->records; +struct hapDistanceMatrix *matrix = NULL; +short childHapArrayIndices[2]; +short parentHapArrayIndices[parGtCount]; +assignHapArrayIx(childHapArrayIndices, hapArray, vcff, sample, TRUE); +assignHapArrayIx(parentHapArrayIndices, hapArray, vcff, sample, FALSE); +for (i = 0; i < 2; i++) + { + struct hapDistanceMatrix *row = needMem(sizeof(struct hapDistanceMatrix)); + struct hapCluster *hcChild = hapArray[childHapArrayIndices[i]]; + struct vcfGenotype *gt = &(rec->genotypes[hcChild->gtHapIx >> 1]); + row->row = NULL; + row->sampleId = cloneString(gt->id); + row->alleleIx = hcChild->gtHapIx; + for (j = 0; j < parGtCount; j++) + { + struct hapDistanceMatrixCell *cell = needMem(sizeof(struct hapDistanceMatrixCell)); + struct hapCluster *hcParent = hapArray[parentHapArrayIndices[j]]; + struct vcfGenotype *parGt = &(rec->genotypes[hcParent->gtHapIx >> 1]); + cell->sampleId = cloneString(parGt->id); + cell->alleleIx = hcParent->gtHapIx; + cell->dist = cwaDistance((struct slList *)hcChild, (struct slList *)hcParent, helper); + slAddHead(&(row->row), cell); + } + slAddHead(&matrix, row); + } +return matrix; +} + +unsigned short *computeHapDist(struct vcfFile *vcff, int centerIx, int startIx, int endIx, char *sample, int gtCount, char **sampleDrawOrder) +// similar to clusterHaps(), but instead of making a hacTree at the end, call cwaDistance +// on each of the pairs in hapArray to make a distance matrix, then compute a hapOrder from that +{ +double alpha = 0.5; +struct lm *lm = lmInit(0); +struct cwaExtraData helper = { centerIx-startIx, endIx-startIx, alpha, lm }; +struct hapCluster **hapArray = lmAlloc(lm, sizeof(struct hapCluster *) * gtCount * 2); +int i; +for (i=0; i < 2 * gtCount; i++) + { + hapArray[i] = lmHapCluster(&helper); + if (i > 0) + hapArray[i-1]->next = hapArray[i]; + } +struct vcfRecord *rec; +int varIx; +boolean haveHaploid; +for (varIx = 0, rec = vcff->records; rec != NULL && varIx < endIx; varIx++, rec = rec->next) + { + if (varIx < startIx) + continue; + int countIx = varIx - startIx; + int gtIx; + for (gtIx=0; gtIx < gtCount; gtIx++) + { + // VCF may contain genotypes other than the few we are interested, so sampleDrawOrder[gtIx] + // may not be the right index in rec->genotypes we want, look it up here + const struct vcfGenotype *gt = vcfRecordFindGenotype(rec, sampleDrawOrder[gtIx]); + int ix = stringArrayIx(sampleDrawOrder[gtIx], vcff->genotypeIds, vcff->genotypeCount); + struct hapCluster *c1 = hapArray[gtIx]; + struct hapCluster *c2 = hapArray[gtCount + gtIx]; // hardwired ploidy=2 + c1->gtHapIx = ix << 1; + c1->leafCount = 1; + if (gt->isPhased || gt->isHaploid || (gt->hapIxA == gt->hapIxB)) + { + // first haplotype's counts: + if (gt->hapIxA < 0) + c1->unkCounts[countIx] = 1; + else if (gt->hapIxA == 0) + c1->refCounts[countIx] = 1; + if (gt->isHaploid) + haveHaploid = TRUE; + else + { + // got second haplotype, fill in its counts: + c2->gtHapIx = (ix << 1) | 1; + c2->leafCount = 1; + if (gt->hapIxB < 0) + c2->unkCounts[countIx] = 1; + else if (gt->hapIxB == 0) + c2->refCounts[countIx] = 1; + } + } + else + { + // Missing data or unphased heterozygote, don't use haplotype info for clustering + c2->gtHapIx = (ix << 1) | 1; + c2->leafCount = 1; + c1->unkCounts[countIx] = c2->unkCounts[countIx] = 1; + } + } + if (haveHaploid) + { + // Some array items will have an empty cluster for missing hap2 -- + // trim those from the linked list. + struct hapCluster *c = hapArray[0]; + while (c != NULL && c->next != NULL) + { + if (c->next->leafCount == 0) + c->next = c->next->next; + else + c = c->next; + } + } + } + +// now fill out a distance matrix based on the cwaDistance between all the pairs in hapArray +struct hapDistanceMatrix *hapDistMatrix = fillOutDistanceMatrix(hapArray, vcff, sample, &helper, gtCount); +unsigned short hapCount = 2 * gtCount; +unsigned short *hapOrder = needMem(sizeof(unsigned short) * hapCount); +setHapOrderFromMatrix(hapOrder, hapCount, hapDistMatrix, hapArray, vcff, sample, sampleDrawOrder); +return hapOrder; +} + +#define VCFPHASED_UNPHASED_COLOR MG_RED + + +void vcfPhasedDrawOneRecord(struct track *track, struct hvGfx *hvg, struct vcfRecord *rec, void *item, + unsigned short *gtHapOrder, int gtHapCount, int xOff, int yOffsets[], + char *sampleOrder[], double scale) +// Draw a record's haplotypes on the appropriate lines +{ +int i; +int x1 = round((double)(rec->chromStart-winStart)*scale) + xOff; +int x2 = round((double)(rec->chromEnd-winStart)*scale) + xOff; +struct pgSnpVcfStartEnd *psvs = (struct pgSnpVcfStartEnd *)item; +int w = x2-x1; +if (w < 1) + w = 1; +int tickHeight = track->itemHeight(track, track->items); +for (i = 0; i < gtHapCount ; i++) + { + struct vcfGenotype *gt = &(rec->genotypes[gtHapOrder[i] >> 1]); + int nameIx = stringArrayIx(gt->id, sampleOrder, track->customInt); + struct dyString *mouseover = dyStringNew(0); + if (gt->isPhased || (gt->hapIxA == 1 && gt->hapIxB == 1)) // if phased or homozygous alt + { + int alIx = gtHapOrder[i] & 1 ? gt->hapIxB : gt->hapIxA; + int tickColor = MG_BLACK; + dyStringPrintf(mouseover, "%s ", gt->id); + if (alIx != 0) // non-reference allele + { + if (i > 1 && i < 4) // we're drawing child ticks + { + dyStringPrintf(mouseover, "allele: %s", rec->alleles[alIx]); + } + else + { + dyStringPrintf(mouseover, "%s allele: %s", i == 0 || i == 5 ? "untransmitted" : "transmitted", rec->alleles[alIx]); + } + int y = yOffsets[i] - (tickHeight/2); + hvGfxBox(hvg, x1, y, w, tickHeight, tickColor); + vcfPhasedAddMapBox(hvg, rec, psvs, mouseover->string, x1, y, w, tickHeight, track); + } + } + else if (gt->hapIxA != 0 || gt->hapIxB != 0)// draw the tick between the two haplotype lines + { + int yMid = ((yOffsets[2*nameIx] + yOffsets[(2*nameIx)+1]) / 2); // midpoint of two haplotype lines + hvGfxBox(hvg, x1, yMid - (tickHeight / 2), w, tickHeight, VCFPHASED_UNPHASED_COLOR); + dyStringPrintf(mouseover, "%s Unphased genotype: %s/%s", gt->id, rec->alleles[0], rec->alleles[1]); + vcfPhasedAddMapBox(hvg, rec, psvs, mouseover->string, x1, yMid, w, tickHeight, track); + } + } +} + +static void vcfPhasedAddLabel(struct track *track, struct hvGfx *hvg, char *label, int trackY, int labelY, MgFont *font, Color color) +// Add a VCF Sample name to the left label of the haplotype representation +{ +int clipXBak, clipYBak, clipWidthBak, clipHeightBak; +struct hvGfx *hvgLL = (hvgSide != NULL) ? hvgSide : hvg; +hvGfxGetClip(hvgLL, &clipXBak, &clipYBak, &clipWidthBak, &clipHeightBak); +hvGfxUnclip(hvgLL); +hvGfxSetClip(hvgLL, leftLabelX, trackY, leftLabelWidth, track->height); + +hvGfxTextRight(hvgLL, leftLabelX, labelY, leftLabelWidth, track->lineHeight, color, + font, label); + +// Restore the prior clipping: +hvGfxUnclip(hvgLL); +hvGfxSetClip(hvgLL, clipXBak, clipYBak, clipWidthBak, clipHeightBak); +} + +static void vcfPhasedSetupHaplotypesLines(struct track *track, struct hvGfx *hvg, int xOff, + int yOff, int width, int *retYOffsets, struct slPair *sampleNames, + MgFont *font) +/* Setup the background for drawing the ticks, the two haplotype lines for each sample, and the + * transparent gray box to help distinguish between consecutive samples */ +{ +int sampleHeight = round(track->height / track->customInt); +double yHap1 = track->lineHeight; // relative offset of first haplotype line +double yHap2 = sampleHeight - track->lineHeight; // relative offset of second line +struct slPair *name; +int i, y1, y2; +struct rgbColor yellow = lightRainbowAtPos(0.2); +int transYellow = MAKECOLOR_32_A(yellow.r, yellow.g, yellow.b, 100); + +char defaultLabelVar[1024], aliasLabelVar[1024]; +safef(defaultLabelVar, sizeof(defaultLabelVar), "%s.%s", track->track, VCF_PHASED_DEFAULT_LABEL_VAR); +safef(aliasLabelVar, sizeof(aliasLabelVar), "%s.%s", track->track, VCF_PHASED_ALIAS_LABEL_VAR); +boolean useDefaultLabel = cartUsualBoolean(cart, defaultLabelVar, TRUE); +boolean useAliasLabel = cartUsualBoolean(cart, aliasLabelVar, FALSE); + +for (name = sampleNames, i = 0; name != NULL; name = name->next, i++) + { + y1 = yOff + yHap1 + (i * sampleHeight); + y2 = yOff + yHap2 + (i * sampleHeight); + retYOffsets[2*i] = y1; + retYOffsets[(2*i) + 1] = y2; + // make the background of every other lane light yellow, but only when NOT doing PDF/EPS output + if ((hvg->pixelBased && i & 1)) + { + hvGfxBox(hvg, xOff, y1-(track->lineHeight), width, (y2 + track->lineHeight) - (y1-track->lineHeight), transYellow); + } + hvGfxLine(hvg, xOff, y1, xOff+width, y1, MG_BLACK); + hvGfxLine(hvg, xOff, y2, xOff+width, y2, MG_BLACK); + struct dyString *label = dyStringNew(0); + dyStringPrintf(label, "%s%s%s", + useDefaultLabel ? name->name : "", + useDefaultLabel && useAliasLabel ? "/" : "", + useAliasLabel ? (char *)name->val : ""); + vcfPhasedAddLabel(track, hvg, label->string, yOff, round(((y1 + y2) / 2) - (track->lineHeight / 2)), font, MG_BLACK); + } +} + +static void vcfPhasedDrawItems(struct track *track, int seqStart, int seqEnd, + struct hvGfx *hvg, int xOff, int yOff, int width, + MgFont *font, Color color, enum trackVisibility vis) +/* Split samples' chromosomes (haplotypes), cluster them by parents, and + * draw them all along a line representing each chromosome*/ +{ +struct vcfFile *vcff = track->extraUiData; +if (vcff->records == NULL) + return; + +const double scale = scaleForPixels(width); +struct slPair *pair, *sampleNames = vcfPhasedGetSampleOrder(cart, track->tdb); +int gtCount = slCount(sampleNames); +int yOffsets[gtCount * 2]; // y offsets of each haplotype line +char *sampleOrder[gtCount]; // order of sampleName lines +int i; +for (pair = sampleNames, i = 0; pair != NULL && i < gtCount; pair = pair->next, i++) + sampleOrder[i] = pair->name; +// child sample is required to be in the middle/bottom of the trio +char *childSample = gtCount > 2 ? sampleOrder[1] : sampleOrder[0]; + +// set up the "haplotype" lines and the transparent yellow box to delineate samples +vcfPhasedSetupHaplotypesLines(track, hvg, xOff, yOff, width, yOffsets, sampleNames, font); + +// sort the variants by haplotype then draw ticks +int nRecords = slCount(vcff->records); +int centerIx = getCenterVariantIx(track, seqStart, seqEnd, vcff->records); +int startIx = 0; +int endIx = nRecords; +unsigned short *hapOrder = computeHapDist(vcff, centerIx, startIx, endIx, childSample, gtCount, sampleOrder); +struct vcfRecord *rec = NULL; +struct slList *item = NULL; +for (rec = vcff->records, item = track->items; rec != NULL && item != NULL; rec = rec->next, item = item->next) + { + vcfPhasedDrawOneRecord(track, hvg, rec, item, hapOrder, gtCount * 2, xOff, yOffsets, sampleOrder, scale); + } +} + +static int vcfPhasedItemHeight(struct track *tg, void *item) +{ +return tg->heightPer; +} + +int vcfPhasedTrackHeight(struct track *tg, enum trackVisibility vis) +{ +const struct vcfFile *vcff = tg->extraUiData; +// when doing composite track height, vcfPhasedLoadItems won't have been called yet! +if (!vcff || vcff->records == NULL) + return 0; +int totalSamples = slCount(vcfPhasedGetSampleOrder(cart, tg->tdb)); +tg->lineHeight = tl.fontHeight + 1; +tg->heightPer = tl.fontHeight; +// if all variants in view are phased, then 3 lines per sample, +// else 4 lines. The extra 2 is for clear separation +int heightPerSample; +if (vcff->allPhased) + heightPerSample = (3 * tg->lineHeight) + 2; +else + heightPerSample = (4 * tg->lineHeight) + 2; +tg->height = totalSamples * heightPerSample; +tg->itemHeight = vcfPhasedItemHeight; +// custom int is reserved for doing pgSnp coloring but as far as I can tell is +// never actually used? +tg->customInt = totalSamples; +return tg->height; +} + +void vcfPhasedMethods(struct track *track) +/* Load items from a VCF of one individuals phased genotypes */ +{ +knetUdcInstall(); +pgSnpMethods(track); +track->drawItems = vcfPhasedDrawItems; +// Disinherit next/prev flag and methods since we don't support next/prev: +track->nextExonButtonable = FALSE; +track->nextPrevExon = NULL; +track->nextPrevItem = NULL; +track->loadItems = vcfPhasedLoadItems; +track->totalHeight = vcfPhasedTrackHeight; +track->itemName = vcfHapClusterTrackName; +track->mapsSelf = TRUE; +} static void vcfTabixLoadItems(struct track *tg) /* Load items in window from VCF file using its tabix index file. */ { char *fileOrUrl = NULL; char *tbiFileOrUrl = trackDbSetting(tg->tdb, "bigDataIndex"); // unrelated to mysql /* Figure out url or file name. */ if (tg->parallelLoading) { /* do not use mysql during parallel-fetch load */ fileOrUrl = trackDbSetting(tg->tdb, "bigDataUrl"); } else { struct sqlConnection *conn = hAllocConnTrack(database, tg->tdb); fileOrUrl = bbiNameFromSettingOrTableChrom(tg->tdb, conn, tg->table, chromName); hFreeConn(&conn); } if (isEmpty(fileOrUrl)) return; fileOrUrl = hReplaceGbdb(fileOrUrl); int vcfMaxErr = -1; struct vcfFile *vcff = NULL; boolean hapClustEnabled = cartOrTdbBoolean(cart, tg->tdb, VCF_HAP_ENABLED_VAR, TRUE); if (slCount(windows)>1) hapClustEnabled = FALSE; // haplotype sorting display not currently available with multiple windows. /* protect against temporary network error */ struct errCatch *errCatch = errCatchNew(); if (errCatchStart(errCatch)) { vcff = vcfTabixFileAndIndexMayOpen(fileOrUrl, tbiFileOrUrl, chromName, winStart, winEnd, vcfMaxErr, -1); if (vcff != NULL) { filterRecords(vcff, tg->tdb); int vis = tdbVisLimitedByAncestors(cart,tg->tdb,TRUE,TRUE); if (hapClustEnabled && vcff->genotypeCount > 1 && (vis == tvPack || vis == tvSquish)) vcfHapClusterOverloadMethods(tg, vcff); else { tg->items = vcfFileToPgSnp(vcff, tg->tdb); // pgSnp bases coloring/display decision on count of items: tg->customInt = slCount(tg->items); } // Don't vcfFileFree here -- we are using its string pointers! } else { if (tbiFileOrUrl) errAbort("Unable to open VCF file/URL '%s' with tabix index '%s'", fileOrUrl, tbiFileOrUrl); else errAbort("Unable to open VCF file/URL '%s'", fileOrUrl); } } errCatchEnd(errCatch); if (errCatch->gotError || vcff == NULL) { if (isNotEmpty(errCatch->message->string)) tg->networkErrMsg = cloneString(errCatch->message->string); tg->drawItems = bigDrawWarning; tg->totalHeight = bigWarnTotalHeight; } errCatchFree(&errCatch); } void vcfTabixMethods(struct track *track) /* Methods for VCF + tabix files. */ { knetUdcInstall(); pgSnpMethods(track); track->mapItem = indelTweakMapItem; // Disinherit next/prev flag and methods since we don't support next/prev: track->nextExonButtonable = FALSE; track->nextPrevExon = NULL; track->nextPrevItem = NULL; track->loadItems = vcfTabixLoadItems; track->canPack = TRUE; } static void vcfLoadItems(struct track *tg) /* Load items in window from VCF file. */ { int vcfMaxErr = -1; struct vcfFile *vcff = NULL; boolean hapClustEnabled = cartOrTdbBoolean(cart, tg->tdb, VCF_HAP_ENABLED_VAR, TRUE); if (slCount(windows)>1) hapClustEnabled = FALSE; // haplotype sorting display not currently available with multiple windows. char *table = tg->table; struct customTrack *ct = tg->customPt; struct sqlConnection *conn; if (ct == NULL) conn = hAllocConnTrack(database, tg->tdb); else { conn = hAllocConn(CUSTOM_TRASH); table = ct->dbTableName; } char *vcfFile = bbiNameFromSettingOrTable(tg->tdb, conn, table); hFreeConn(&conn); /* protect against parse error */ struct errCatch *errCatch = errCatchNew(); if (errCatchStart(errCatch)) { vcff = vcfFileMayOpen(vcfFile, chromName, winStart, winEnd, vcfMaxErr, -1, TRUE); if (vcff != NULL) { filterRecords(vcff, tg->tdb); int vis = tdbVisLimitedByAncestors(cart,tg->tdb,TRUE,TRUE); if (hapClustEnabled && vcff->genotypeCount > 1 && vcff->genotypeCount < 3000 && (vis == tvPack || vis == tvSquish)) vcfHapClusterOverloadMethods(tg, vcff); else { tg->items = vcfFileToPgSnp(vcff, tg->tdb); // pgSnp bases coloring/display decision on count of items: tg->customInt = slCount(tg->items); } // Don't vcfFileFree here -- we are using its string pointers! } else errAbort("Unable to open VCF file '%s'", vcfFile); } errCatchEnd(errCatch); if (errCatch->gotError || vcff == NULL) { if (isNotEmpty(errCatch->message->string)) tg->networkErrMsg = cloneString(errCatch->message->string); tg->drawItems = bigDrawWarning; tg->totalHeight = bigWarnTotalHeight; } errCatchFree(&errCatch); } void vcfMethods(struct track *track) /* Methods for Variant Call Format. */ { pgSnpMethods(track); track->mapItem = indelTweakMapItem; // Disinherit next/prev flag and methods since we don't support next/prev: track->nextExonButtonable = FALSE; track->nextPrevExon = NULL; track->nextPrevItem = NULL; track->loadItems = vcfLoadItems; track->canPack = TRUE; }