int main(int argc, char *argv[]) {
/*
* Script for adding alignments to cactus tree.
*/
int64_t startTime;
stKVDatabaseConf *kvDatabaseConf;
CactusDisk *cactusDisk;
int key, k;
bool (*filterFn)(stPinchSegment *, stPinchSegment *) = NULL;
stSet *outgroupThreads = NULL;
/*
* Arguments/options
*/
char * logLevelString = NULL;
char * alignmentsFile = NULL;
char * constraintsFile = NULL;
char * cactusDiskDatabaseString = NULL;
char * lastzArguments = "";
int64_t minimumSequenceLengthForBlast = 1;
//Parameters for annealing/melting rounds
int64_t *annealingRounds = NULL;
int64_t annealingRoundsLength = 0;
int64_t *meltingRounds = NULL;
int64_t meltingRoundsLength = 0;
//Parameters for melting
float maximumAdjacencyComponentSizeRatio = 10;
int64_t blockTrim = 0;
int64_t alignmentTrimLength = 0;
int64_t *alignmentTrims = NULL;
int64_t chainLengthForBigFlower = 1000000;
int64_t longChain = 2;
int64_t minLengthForChromosome = 1000000;
float proportionOfUnalignedBasesForNewChromosome = 0.8;
bool breakChainsAtReverseTandems = 1;
int64_t maximumMedianSequenceLengthBetweenLinkedEnds = INT64_MAX;
bool realign = 0;
char *realignArguments = "";
bool removeRecoverableChains = false;
bool (*recoverableChainsFilter)(stCactusEdgeEnd *, Flower *) = NULL;
int64_t maxRecoverableChainsIterations = 1;
int64_t maxRecoverableChainLength = INT64_MAX;
//Parameters for removing ancient homologies
bool doPhylogeny = false;
int64_t phylogenyNumTrees = 1;
enum stCaf_RootingMethod phylogenyRootingMethod = BEST_RECON;
enum stCaf_ScoringMethod phylogenyScoringMethod = COMBINED_LIKELIHOOD;
double breakpointScalingFactor = 1.0;
bool phylogenySkipSingleCopyBlocks = 0;
int64_t phylogenyMaxBaseDistance = 1000;
int64_t phylogenyMaxBlockDistance = 100;
bool phylogenyKeepSingleDegreeBlocks = 0;
stList *phylogenyTreeBuildingMethods = stList_construct();
enum stCaf_TreeBuildingMethod defaultMethod = GUIDED_NEIGHBOR_JOINING;
stList_append(phylogenyTreeBuildingMethods, &defaultMethod);
double phylogenyCostPerDupPerBase = 0.2;
double phylogenyCostPerLossPerBase = 0.2;
const char *debugFileName = NULL;
const char *referenceEventHeader = NULL;
double phylogenyDoSplitsWithSupportHigherThanThisAllAtOnce = 1.0;
int64_t numTreeBuildingThreads = 2;
int64_t minimumBlockDegreeToCheckSupport = 10;
double minimumBlockHomologySupport = 0.7;
double nucleotideScalingFactor = 1.0;
HomologyUnitType phylogenyHomologyUnitType = BLOCK;
enum stCaf_DistanceCorrectionMethod phylogenyDistanceCorrectionMethod = JUKES_CANTOR;
bool sortAlignments = false;
///////////////////////////////////////////////////////////////////////////
// (0) Parse the inputs handed by genomeCactus.py / setup stuff.
///////////////////////////////////////////////////////////////////////////
while (1) {
static struct option long_options[] = { { "logLevel", required_argument, 0, 'a' }, { "alignments", required_argument, 0, 'b' }, {
"cactusDisk", required_argument, 0, 'c' }, { "lastzArguments", required_argument, 0, 'd' },
{ "help", no_argument, 0, 'h' }, { "annealingRounds", required_argument, 0, 'i' }, { "trim", required_argument, 0, 'k' }, {
"trimChange", required_argument, 0, 'l', }, { "minimumTreeCoverage", required_argument, 0, 'm' }, { "blockTrim",
required_argument, 0, 'n' }, { "deannealingRounds", required_argument, 0, 'o' }, { "minimumDegree",
required_argument, 0, 'p' }, { "minimumIngroupDegree", required_argument, 0, 'q' }, {
"minimumOutgroupDegree", required_argument, 0, 'r' }, { "alignmentFilter", required_argument, 0, 't' }, {
"minimumSequenceLengthForBlast", required_argument, 0, 'v' }, { "maxAdjacencyComponentSizeRatio",
required_argument, 0, 'w' }, { "constraints", required_argument, 0, 'x' }, { "minLengthForChromosome",
required_argument, 0, 'y' }, { "proportionOfUnalignedBasesForNewChromosome", required_argument, 0, 'z' },
{ "maximumMedianSequenceLengthBetweenLinkedEnds", required_argument, 0, 'A' },
{ "realign", no_argument, 0, 'B' }, { "realignArguments", required_argument, 0, 'C' },
{ "phylogenyNumTrees", required_argument, 0, 'D' },
{ "phylogenyRootingMethod", required_argument, 0, 'E' },
{ "phylogenyScoringMethod", required_argument, 0, 'F' },
{ "phylogenyBreakpointScalingFactor", required_argument, 0, 'G' },
{ "phylogenySkipSingleCopyBlocks", no_argument, 0, 'H' },
{ "phylogenyMaxBaseDistance", required_argument, 0, 'I' },
{ "phylogenyMaxBlockDistance", required_argument, 0, 'J' },
{ "phylogenyDebugFile", required_argument, 0, 'K' },
{ "phylogenyKeepSingleDegreeBlocks", no_argument, 0, 'L' },
{ "phylogenyTreeBuildingMethod", required_argument, 0, 'M' },
{ "phylogenyCostPerDupPerBase", required_argument, 0, 'N' },
{ "phylogenyCostPerLossPerBase", required_argument, 0, 'O' },
{ "referenceEventHeader", required_argument, 0, 'P' },
{ "phylogenyDoSplitsWithSupportHigherThanThisAllAtOnce", required_argument, 0, 'Q' },
{ "numTreeBuildingThreads", required_argument, 0, 'R' },
{ "phylogeny", no_argument, 0, 'S' },
{ "minimumBlockHomologySupport", required_argument, 0, 'T' },
{ "phylogenyNucleotideScalingFactor", required_argument, 0, 'U' },
{ "minimumBlockDegreeToCheckSupport", required_argument, 0, 'V' },
{ "removeRecoverableChains", required_argument, 0, 'W' },
{ "minimumNumberOfSpecies", required_argument, 0, 'X' },
{ "phylogenyHomologyUnitType", required_argument, 0, 'Y' },
{ "phylogenyDistanceCorrectionMethod", required_argument, 0, 'Z' },
{ "maxRecoverableChainsIterations", required_argument, 0, '1' },
{ "maxRecoverableChainLength", required_argument, 0, '2' },
{ 0, 0, 0, 0 } };
int option_index = 0;
key = getopt_long(argc, argv, "a:b:c:hi:k:m:n:o:p:q:r:stv:w:x:y:z:A:BC:D:E:", long_options, &option_index);
if (key == -1) {
break;
}
switch (key) {
case 'a':
logLevelString = stString_copy(optarg);
st_setLogLevelFromString(logLevelString);
break;
case 'b':
alignmentsFile = stString_copy(optarg);
break;
case 'c':
cactusDiskDatabaseString = stString_copy(optarg);
break;
case 'd':
lastzArguments = stString_copy(optarg);
break;
case 'h':
usage();
return 0;
case 'i':
annealingRounds = getInts(optarg, &annealingRoundsLength);
break;
case 'o':
meltingRounds = getInts(optarg, &meltingRoundsLength);
break;
case 'k':
alignmentTrims = getInts(optarg, &alignmentTrimLength);
break;
case 'm':
k = sscanf(optarg, "%f", &minimumTreeCoverage);
assert(k == 1);
break;
case 'n':
k = sscanf(optarg, "%" PRIi64 "", &blockTrim);
assert(k == 1);
break;
case 'p':
k = sscanf(optarg, "%" PRIi64 "", &minimumDegree);
assert(k == 1);
break;
case 'q':
k = sscanf(optarg, "%" PRIi64 "", &minimumIngroupDegree);
assert(k == 1);
break;
case 'r':
k = sscanf(optarg, "%" PRIi64 "", &minimumOutgroupDegree);
assert(k == 1);
break;
case 't':
if (strcmp(optarg, "singleCopyOutgroup") == 0) {
sortAlignments = true;
filterFn = stCaf_filterByOutgroup;
} else if (strcmp(optarg, "relaxedSingleCopyOutgroup") == 0) {
sortAlignments = true;
filterFn = stCaf_relaxedFilterByOutgroup;
} else if (strcmp(optarg, "singleCopy") == 0) {
sortAlignments = true;
filterFn = stCaf_filterByRepeatSpecies;
} else if (strcmp(optarg, "relaxedSingleCopy") == 0) {
sortAlignments = true;
filterFn = stCaf_relaxedFilterByRepeatSpecies;
} else if (strcmp(optarg, "singleCopyChr") == 0) {
sortAlignments = true;
filterFn = stCaf_singleCopyChr;
} else if (strcmp(optarg, "singleCopyIngroup") == 0) {
sortAlignments = true;
filterFn = stCaf_singleCopyIngroup;
} else if (strcmp(optarg, "relaxedSingleCopyIngroup") == 0) {
sortAlignments = true;
filterFn = stCaf_relaxedSingleCopyIngroup;
} else if (strcmp(optarg, "none") == 0) {
sortAlignments = false;
filterFn = NULL;
} else {
st_errAbort("Could not recognize alignmentFilter option %s", optarg);
}
break;
case 'v':
k = sscanf(optarg, "%" PRIi64 "", &minimumSequenceLengthForBlast);
assert(k == 1);
break;
case 'w':
k = sscanf(optarg, "%f", &maximumAdjacencyComponentSizeRatio);
assert(k == 1);
break;
case 'x':
constraintsFile = stString_copy(optarg);
break;
case 'y':
k = sscanf(optarg, "%" PRIi64 "", &minLengthForChromosome);
assert(k == 1);
break;
case 'z':
k = sscanf(optarg, "%f", &proportionOfUnalignedBasesForNewChromosome);
assert(k == 1);
break;
case 'A':
k = sscanf(optarg, "%" PRIi64 "", &maximumMedianSequenceLengthBetweenLinkedEnds);
assert(k == 1);
break;
case 'B':
realign = 1;
break;
case 'C':
realignArguments = stString_copy(optarg);
break;
case 'D':
k = sscanf(optarg, "%" PRIi64, &phylogenyNumTrees);
assert(k == 1);
break;
case 'E':
if (!strcmp(optarg, "outgroupBranch")) {
phylogenyRootingMethod = OUTGROUP_BRANCH;
} else if (!strcmp(optarg, "longestBranch")) {
phylogenyRootingMethod = LONGEST_BRANCH;
} else if (!strcmp(optarg, "bestRecon")) {
phylogenyRootingMethod = BEST_RECON;
} else {
st_errAbort("Invalid tree rooting method: %s", optarg);
}
break;
case 'F':
if (!strcmp(optarg, "reconCost")) {
phylogenyScoringMethod = RECON_COST;
} else if (!strcmp(optarg, "nucLikelihood")) {
phylogenyScoringMethod = NUCLEOTIDE_LIKELIHOOD;
} else if (!strcmp(optarg, "reconLikelihood")) {
phylogenyScoringMethod = RECON_LIKELIHOOD;
} else if (!strcmp(optarg, "combinedLikelihood")) {
phylogenyScoringMethod = COMBINED_LIKELIHOOD;
} else {
st_errAbort("Invalid tree scoring method: %s", optarg);
}
break;
case 'G':
k = sscanf(optarg, "%lf", &breakpointScalingFactor);
assert(k == 1);
break;
case 'H':
phylogenySkipSingleCopyBlocks = true;
break;
case 'I':
k = sscanf(optarg, "%" PRIi64, &phylogenyMaxBaseDistance);
assert(k == 1);
break;
case 'J':
k = sscanf(optarg, "%" PRIi64, &phylogenyMaxBlockDistance);
assert(k == 1);
break;
case 'K':
debugFileName = stString_copy(optarg);
break;
case 'L':
phylogenyKeepSingleDegreeBlocks = true;
break;
case 'M':
// clear the default setting of the list
stList_destruct(phylogenyTreeBuildingMethods);
phylogenyTreeBuildingMethods = stList_construct();
stList *methodStrings = stString_splitByString(optarg, ",");
for (int64_t i = 0; i < stList_length(methodStrings); i++) {
char *methodString = stList_get(methodStrings, i);
enum stCaf_TreeBuildingMethod *method = st_malloc(sizeof(enum stCaf_TreeBuildingMethod));
if (strcmp(methodString, "neighborJoining") == 0) {
*method = NEIGHBOR_JOINING;
} else if (strcmp(methodString, "guidedNeighborJoining") == 0) {
*method = GUIDED_NEIGHBOR_JOINING;
} else if (strcmp(methodString, "splitDecomposition") == 0) {
*method = SPLIT_DECOMPOSITION;
} else if (strcmp(methodString, "strictSplitDecomposition") == 0) {
*method = STRICT_SPLIT_DECOMPOSITION;
} else if (strcmp(methodString, "removeBadChains") == 0) {
*method = REMOVE_BAD_CHAINS;
} else {
st_errAbort("Unknown tree building method: %s", methodString);
}
stList_append(phylogenyTreeBuildingMethods, method);
}
stList_destruct(methodStrings);
break;
case 'N':
k = sscanf(optarg, "%lf", &phylogenyCostPerDupPerBase);
assert(k == 1);
break;
case 'O':
k = sscanf(optarg, "%lf", &phylogenyCostPerLossPerBase);
assert(k == 1);
break;
case 'P':
referenceEventHeader = stString_copy(optarg);
break;
case 'Q':
k = sscanf(optarg, "%lf", &phylogenyDoSplitsWithSupportHigherThanThisAllAtOnce);
assert(k == 1);
break;
case 'R':
k = sscanf(optarg, "%" PRIi64, &numTreeBuildingThreads);
assert(k == 1);
break;
case 'S':
doPhylogeny = true;
break;
case 'T':
k = sscanf(optarg, "%lf", &minimumBlockHomologySupport);
assert(k == 1);
assert(minimumBlockHomologySupport <= 1.0);
assert(minimumBlockHomologySupport >= 0.0);
break;
case 'U':
k = sscanf(optarg, "%lf", &nucleotideScalingFactor);
assert(k == 1);
break;
case 'V':
k = sscanf(optarg, "%" PRIi64, &minimumBlockDegreeToCheckSupport);
assert(k == 1);
break;
case 'W':
if (strcmp(optarg, "1") == 0) {
removeRecoverableChains = true;
recoverableChainsFilter = NULL;
} else if (strcmp(optarg, "unequalNumberOfIngroupCopies") == 0) {
removeRecoverableChains = true;
recoverableChainsFilter = stCaf_chainHasUnequalNumberOfIngroupCopies;
} else if (strcmp(optarg, "unequalNumberOfIngroupCopiesOrNoOutgroup") == 0) {
removeRecoverableChains = true;
recoverableChainsFilter = stCaf_chainHasUnequalNumberOfIngroupCopiesOrNoOutgroup;
} else if (strcmp(optarg, "0") == 0) {
removeRecoverableChains = false;
} else {
st_errAbort("Could not parse removeRecoverableChains argument");
}
break;
case 'X':
k = sscanf(optarg, "%" PRIi64, &minimumNumberOfSpecies);
if (k != 1) {
st_errAbort("Error parsing the minimumNumberOfSpecies argument");
}
break;
case 'Y':
if (strcmp(optarg, "chain") == 0) {
phylogenyHomologyUnitType = CHAIN;
} else if (strcmp(optarg, "block") == 0) {
phylogenyHomologyUnitType = BLOCK;
} else {
st_errAbort("Could not parse the phylogenyHomologyUnitType argument");
}
break;
case 'Z':
if (strcmp(optarg, "jukesCantor") == 0) {
phylogenyDistanceCorrectionMethod = JUKES_CANTOR;
} else if (strcmp(optarg, "none") == 0 ) {
phylogenyDistanceCorrectionMethod = NONE;
} else {
st_errAbort("Could not parse the phylogenyDistanceCorrectionMethod argument");
}
break;
case '1':
k = sscanf(optarg, "%" PRIi64, &maxRecoverableChainsIterations);
if (k != 1) {
st_errAbort("Error parsing the maxRecoverableChainsIterations argument");
}
break;
case '2':
k = sscanf(optarg, "%" PRIi64, &maxRecoverableChainLength);
if (k != 1) {
st_errAbort("Error parsing the maxRecoverableChainLength argument");
}
break;
default:
usage();
return 1;
}
}
///////////////////////////////////////////////////////////////////////////
// (0) Check the inputs.
///////////////////////////////////////////////////////////////////////////
assert(cactusDiskDatabaseString != NULL);
assert(minimumTreeCoverage >= 0.0);
assert(minimumTreeCoverage <= 1.0);
assert(blockTrim >= 0);
assert(annealingRoundsLength >= 0);
for (int64_t i = 0; i < annealingRoundsLength; i++) {
assert(annealingRounds[i] >= 0);
}
assert(meltingRoundsLength >= 0);
for (int64_t i = 1; i < meltingRoundsLength; i++) {
assert(meltingRounds[i - 1] < meltingRounds[i]);
assert(meltingRounds[i - 1] >= 1);
}
assert(alignmentTrimLength >= 0);
for (int64_t i = 0; i < alignmentTrimLength; i++) {
assert(alignmentTrims[i] >= 0);
}
assert(minimumOutgroupDegree >= 0);
assert(minimumIngroupDegree >= 0);
//////////////////////////////////////////////
//Set up logging
//////////////////////////////////////////////
st_setLogLevelFromString(logLevelString);
//////////////////////////////////////////////
//Log (some of) the inputs
//////////////////////////////////////////////
st_logInfo("Flower disk name : %s\n", cactusDiskDatabaseString);
//////////////////////////////////////////////
//Load the database
//////////////////////////////////////////////
kvDatabaseConf = stKVDatabaseConf_constructFromString(cactusDiskDatabaseString);
cactusDisk = cactusDisk_construct(kvDatabaseConf, 0);
st_logInfo("Set up the flower disk\n");
///////////////////////////////////////////////////////////////////////////
// Sort the constraints
///////////////////////////////////////////////////////////////////////////
stPinchIterator *pinchIteratorForConstraints = NULL;
if (constraintsFile != NULL) {
pinchIteratorForConstraints = stPinchIterator_constructFromFile(constraintsFile);
st_logInfo("Created an iterator for the alignment constaints from file: %s\n", constraintsFile);
}
///////////////////////////////////////////////////////////////////////////
// Do the alignment
///////////////////////////////////////////////////////////////////////////
startTime = time(NULL);
stList *flowers = flowerWriter_parseFlowersFromStdin(cactusDisk);
if (alignmentsFile == NULL) {
cactusDisk_preCacheStrings(cactusDisk, flowers);
}
char *tempFile1 = NULL;
for (int64_t i = 0; i < stList_length(flowers); i++) {
flower = stList_get(flowers, i);
if (!flower_builtBlocks(flower)) { // Do nothing if the flower already has defined blocks
st_logDebug("Processing flower: %lli\n", flower_getName(flower));
stCaf_setFlowerForAlignmentFiltering(flower);
//Set up the graph and add the initial alignments
stPinchThreadSet *threadSet = stCaf_setup(flower);
//Build the set of outgroup threads
outgroupThreads = stCaf_getOutgroupThreads(flower, threadSet);
//Setup the alignments
stPinchIterator *pinchIterator;
stList *alignmentsList = NULL;
if (alignmentsFile != NULL) {
assert(i == 0);
assert(stList_length(flowers) == 1);
if (sortAlignments) {
tempFile1 = getTempFile();
stCaf_sortCigarsFileByScoreInDescendingOrder(alignmentsFile, tempFile1);
pinchIterator = stPinchIterator_constructFromFile(tempFile1);
} else {
pinchIterator = stPinchIterator_constructFromFile(alignmentsFile);
}
} else {
if (tempFile1 == NULL) {
tempFile1 = getTempFile();
}
alignmentsList = stCaf_selfAlignFlower(flower, minimumSequenceLengthForBlast, lastzArguments, realign, realignArguments, tempFile1);
if (sortAlignments) {
stCaf_sortCigarsByScoreInDescendingOrder(alignmentsList);
}
st_logDebug("Ran lastz and have %" PRIi64 " alignments\n", stList_length(alignmentsList));
pinchIterator = stPinchIterator_constructFromList(alignmentsList);
}
for (int64_t annealingRound = 0; annealingRound < annealingRoundsLength; annealingRound++) {
int64_t minimumChainLength = annealingRounds[annealingRound];
int64_t alignmentTrim = annealingRound < alignmentTrimLength ? alignmentTrims[annealingRound] : 0;
st_logDebug("Starting annealing round with a minimum chain length of %" PRIi64 " and an alignment trim of %" PRIi64 "\n", minimumChainLength, alignmentTrim);
stPinchIterator_setTrim(pinchIterator, alignmentTrim);
//Add back in the constraints
if (pinchIteratorForConstraints != NULL) {
stCaf_anneal(threadSet, pinchIteratorForConstraints, filterFn);
}
//Do the annealing
if (annealingRound == 0) {
stCaf_anneal(threadSet, pinchIterator, filterFn);
} else {
stCaf_annealBetweenAdjacencyComponents(threadSet, pinchIterator, filterFn);
}
// Dump the block degree and length distribution to a file
if (debugFileName != NULL) {
dumpBlockInfo(threadSet, stString_print("%s-blockStats-preMelting", debugFileName));
}
printf("Sequence graph statistics after annealing:\n");
printThreadSetStatistics(threadSet, flower, stdout);
// Check for poorly-supported blocks--those that have
// been transitively aligned together but with very
// few homologies supporting the transitive
// alignment. These "megablocks" can snarl up the
// graph so that a lot of extra gets thrown away in
// the first melting step.
stPinchThreadSetBlockIt blockIt = stPinchThreadSet_getBlockIt(threadSet);
stPinchBlock *block;
while ((block = stPinchThreadSetBlockIt_getNext(&blockIt)) != NULL) {
if (stPinchBlock_getDegree(block) > minimumBlockDegreeToCheckSupport) {
uint64_t supportingHomologies = stPinchBlock_getNumSupportingHomologies(block);
uint64_t possibleSupportingHomologies = numPossibleSupportingHomologies(block, flower);
double support = ((double) supportingHomologies) / possibleSupportingHomologies;
if (support < minimumBlockHomologySupport) {
fprintf(stdout, "Destroyed a megablock with degree %" PRIi64
" and %" PRIi64 " supporting homologies out of a maximum "
"of %" PRIi64 " (%lf%%).\n", stPinchBlock_getDegree(block),
supportingHomologies, possibleSupportingHomologies, support);
stPinchBlock_destruct(block);
}
}
}
//Do the melting rounds
for (int64_t meltingRound = 0; meltingRound < meltingRoundsLength; meltingRound++) {
int64_t minimumChainLengthForMeltingRound = meltingRounds[meltingRound];
st_logDebug("Starting melting round with a minimum chain length of %" PRIi64 " \n", minimumChainLengthForMeltingRound);
if (minimumChainLengthForMeltingRound >= minimumChainLength) {
break;
}
stCaf_melt(flower, threadSet, NULL, 0, minimumChainLengthForMeltingRound, 0, INT64_MAX);
} st_logDebug("Last melting round of cycle with a minimum chain length of %" PRIi64 " \n", minimumChainLength);
stCaf_melt(flower, threadSet, NULL, 0, minimumChainLength, breakChainsAtReverseTandems, maximumMedianSequenceLengthBetweenLinkedEnds);
//This does the filtering of blocks that do not have the required species/tree-coverage/degree.
stCaf_melt(flower, threadSet, blockFilterFn, blockTrim, 0, 0, INT64_MAX);
}
if (removeRecoverableChains) {
stCaf_meltRecoverableChains(flower, threadSet, breakChainsAtReverseTandems, maximumMedianSequenceLengthBetweenLinkedEnds, recoverableChainsFilter, maxRecoverableChainsIterations, maxRecoverableChainLength);
}
if (debugFileName != NULL) {
dumpBlockInfo(threadSet, stString_print("%s-blockStats-postMelting", debugFileName));
}
printf("Sequence graph statistics after melting:\n");
printThreadSetStatistics(threadSet, flower, stdout);
// Build a tree for each block, then use each tree to
// partition the homologies between the ingroups sequences
// into those that occur before the speciation with the
// outgroup and those which occur late.
if (stSet_size(outgroupThreads) > 0 && doPhylogeny) {
st_logDebug("Starting to build trees and partition ingroup homologies\n");
stHash *threadStrings = stCaf_getThreadStrings(flower, threadSet);
st_logDebug("Got sets of thread strings and set of threads that are outgroups\n");
stCaf_PhylogenyParameters params;
params.distanceCorrectionMethod = phylogenyDistanceCorrectionMethod;
params.treeBuildingMethods = phylogenyTreeBuildingMethods;
params.rootingMethod = phylogenyRootingMethod;
params.scoringMethod = phylogenyScoringMethod;
params.breakpointScalingFactor = breakpointScalingFactor;
params.nucleotideScalingFactor = nucleotideScalingFactor;
params.skipSingleCopyBlocks = phylogenySkipSingleCopyBlocks;
params.keepSingleDegreeBlocks = phylogenyKeepSingleDegreeBlocks;
params.costPerDupPerBase = phylogenyCostPerDupPerBase;
params.costPerLossPerBase = phylogenyCostPerLossPerBase;
params.maxBaseDistance = phylogenyMaxBaseDistance;
params.maxBlockDistance = phylogenyMaxBlockDistance;
params.numTrees = phylogenyNumTrees;
params.ignoreUnalignedBases = 1;
params.onlyIncludeCompleteFeatureBlocks = 0;
params.doSplitsWithSupportHigherThanThisAllAtOnce = phylogenyDoSplitsWithSupportHigherThanThisAllAtOnce;
params.numTreeBuildingThreads = numTreeBuildingThreads;
assert(params.numTreeBuildingThreads >= 1);
stCaf_buildTreesToRemoveAncientHomologies(
threadSet, phylogenyHomologyUnitType, threadStrings, outgroupThreads, flower, ¶ms,
debugFileName == NULL ? NULL : stString_print("%s-phylogeny", debugFileName), referenceEventHeader);
stHash_destruct(threadStrings);
st_logDebug("Finished building trees\n");
if (removeRecoverableChains) {
// We melt recoverable chains after splitting, as
// well as before, to alleviate coverage loss
// caused by bad splits.
stCaf_meltRecoverableChains(flower, threadSet, breakChainsAtReverseTandems, maximumMedianSequenceLengthBetweenLinkedEnds, recoverableChainsFilter, maxRecoverableChainsIterations, maxRecoverableChainLength);
}
// Enforce the block constraints on minimum degree,
// etc. after splitting.
stCaf_melt(flower, threadSet, blockFilterFn, 0, 0, 0, INT64_MAX);
}
//Sort out case when we allow blocks of degree 1
if (minimumDegree < 2) {
st_logDebug("Creating degree 1 blocks\n");
stCaf_makeDegreeOneBlocks(threadSet);
stCaf_melt(flower, threadSet, blockFilterFn, blockTrim, 0, 0, INT64_MAX);
} else if (maximumAdjacencyComponentSizeRatio < INT64_MAX) { //Deal with giant components
st_logDebug("Breaking up components greedily\n");
stCaf_breakupComponentsGreedily(threadSet, maximumAdjacencyComponentSizeRatio);
}
//Finish up
stCaf_finish(flower, threadSet, chainLengthForBigFlower, longChain, minLengthForChromosome,
proportionOfUnalignedBasesForNewChromosome); //Flower is then destroyed at this point.
st_logInfo("Ran the cactus core script\n");
//Cleanup
stPinchThreadSet_destruct(threadSet);
stPinchIterator_destruct(pinchIterator);
stSet_destruct(outgroupThreads);
if (alignmentsList != NULL) {
stList_destruct(alignmentsList);
}
st_logInfo("Cleaned up from main loop\n");
} else {
st_logInfo("We've already built blocks / alignments for this flower\n");
}
}
stList_destruct(flowers);
if (tempFile1 != NULL) {
st_system("rm %s", tempFile1);
}
if (constraintsFile != NULL) {
stPinchIterator_destruct(pinchIteratorForConstraints);
}
///////////////////////////////////////////////////////////////////////////
// Write the flower to disk.
///////////////////////////////////////////////////////////////////////////
st_logDebug("Writing the flowers to disk\n");
cactusDisk_write(cactusDisk);
st_logInfo("Updated the flower on disk and %" PRIi64 " seconds have elapsed\n", time(NULL) - startTime);
///////////////////////////////////////////////////////////////////////////
// Clean up.
///////////////////////////////////////////////////////////////////////////
cactusDisk_destruct(cactusDisk);
}
int main(int argc, char *argv[]) {
char * logLevelString = NULL;
char * cactusDiskDatabaseString = NULL;
int64_t i, j;
int64_t spanningTrees = 10;
int64_t maximumLength = 1500;
bool useProgressiveMerging = 0;
float matchGamma = 0.5;
bool useBanding = 0;
int64_t k;
stList *listOfEndAlignmentFiles = NULL;
char *endAlignmentsToPrecomputeOutputFile = NULL;
bool calculateWhichEndsToComputeSeparately = 0;
int64_t largeEndSize = 1000000;
int64_t chainLengthForBigFlower = 1000000;
int64_t longChain = 2;
char *ingroupCoverageFilePath = NULL;
int64_t minimumSizeToRescue = 1;
double minimumCoverageToRescue = 0.0;
PairwiseAlignmentParameters *pairwiseAlignmentBandingParameters = pairwiseAlignmentBandingParameters_construct();
/*
* Setup the input parameters for cactus core.
*/
bool pruneOutStubAlignments = 0;
/*
* Parse the options.
*/
while (1) {
static struct option long_options[] = { { "logLevel", required_argument, 0, 'a' }, { "cactusDisk", required_argument, 0, 'b' }, {
"help", no_argument, 0, 'h' }, { "spanningTrees", required_argument, 0, 'i' },
{ "maximumLength", required_argument, 0, 'j' }, { "useBanding", no_argument, 0, 'k' },
{ "gapGamma", required_argument, 0, 'l' }, { "matchGamma", required_argument, 0, 'L' },
{ "splitMatrixBiggerThanThis", required_argument, 0, 'o' }, { "anchorMatrixBiggerThanThis",
required_argument, 0, 'p' }, { "repeatMaskMatrixBiggerThanThis", required_argument, 0, 'q' }, {
"diagonalExpansion", required_argument, 0, 'r' }, { "constraintDiagonalTrim", required_argument, 0, 't' }, {
"minimumDegree", required_argument, 0, 'u' }, { "alignAmbiguityCharacters", no_argument, 0, 'w' }, {
"pruneOutStubAlignments", no_argument, 0, 'y' }, {
"minimumIngroupDegree", required_argument, 0, 'A' }, { "minimumOutgroupDegree", required_argument, 0, 'B' },
{ "precomputedAlignments", required_argument, 0, 'D' }, {
"endAlignmentsToPrecomputeOutputFile", required_argument, 0, 'E' }, { "useProgressiveMerging",
no_argument, 0, 'F' }, { "calculateWhichEndsToComputeSeparately", no_argument, 0, 'G' }, { "largeEndSize",
required_argument, 0, 'I' },
{"ingroupCoverageFile", required_argument, 0, 'J'},
{"minimumSizeToRescue", required_argument, 0, 'K'},
{"minimumCoverageToRescue", required_argument, 0, 'M'},
{ "minimumNumberOfSpecies", required_argument, 0, 'N' },
{ 0, 0, 0, 0 } };
int option_index = 0;
int key = getopt_long(argc, argv, "a:b:hi:j:kl:o:p:q:r:t:u:wy:A:B:D:E:FGI:J:K:L:M:N:", long_options, &option_index);
if (key == -1) {
break;
}
switch (key) {
case 'a':
logLevelString = stString_copy(optarg);
st_setLogLevelFromString(logLevelString);
break;
case 'b':
cactusDiskDatabaseString = stString_copy(optarg);
break;
case 'h':
usage();
return 0;
case 'i':
i = sscanf(optarg, "%" PRIi64 "", &spanningTrees);
(void) i;
assert(i == 1);
assert(spanningTrees >= 0);
break;
case 'j':
i = sscanf(optarg, "%" PRIi64 "", &maximumLength);
assert(i == 1);
assert(maximumLength >= 0);
break;
case 'k':
useBanding = !useBanding;
break;
case 'l':
i = sscanf(optarg, "%f", &pairwiseAlignmentBandingParameters->gapGamma);
assert(i == 1);
assert(pairwiseAlignmentBandingParameters->gapGamma >= 0.0);
break;
case 'L':
i = sscanf(optarg, "%f", &matchGamma);
assert(i == 1);
assert(matchGamma >= 0.0);
break;
case 'o':
i = sscanf(optarg, "%" PRIi64 "", &k);
assert(i == 1);
assert(k >= 0);
pairwiseAlignmentBandingParameters->splitMatrixBiggerThanThis = (int64_t) k * k;
break;
case 'p':
i = sscanf(optarg, "%" PRIi64 "", &k);
assert(i == 1);
assert(k >= 0);
pairwiseAlignmentBandingParameters->anchorMatrixBiggerThanThis = (int64_t) k * k;
break;
case 'q':
i = sscanf(optarg, "%" PRIi64 "", &k);
assert(i == 1);
assert(k >= 0);
pairwiseAlignmentBandingParameters->repeatMaskMatrixBiggerThanThis = (int64_t) k * k;
break;
case 'r':
i = sscanf(optarg, "%" PRIi64 "", &pairwiseAlignmentBandingParameters->diagonalExpansion);
assert(i == 1);
assert(pairwiseAlignmentBandingParameters->diagonalExpansion >= 0);
assert(pairwiseAlignmentBandingParameters->diagonalExpansion % 2 == 0);
break;
case 't':
i = sscanf(optarg, "%" PRIi64 "", &pairwiseAlignmentBandingParameters->constraintDiagonalTrim);
assert(i == 1);
assert(pairwiseAlignmentBandingParameters->constraintDiagonalTrim >= 0);
break;
case 'u':
i = sscanf(optarg, "%" PRIi64 "", &minimumDegree);
assert(i == 1);
break;
case 'w':
pairwiseAlignmentBandingParameters->alignAmbiguityCharacters = 1;
break;
case 'y':
pruneOutStubAlignments = 1;
break;
case 'A':
i = sscanf(optarg, "%" PRIi64 "", &minimumIngroupDegree);
assert(i == 1);
break;
case 'B':
i = sscanf(optarg, "%" PRIi64 "", &minimumOutgroupDegree);
assert(i == 1);
break;
case 'D':
listOfEndAlignmentFiles = stString_split(optarg);
break;
case 'E':
endAlignmentsToPrecomputeOutputFile = stString_copy(optarg);
break;
case 'F':
useProgressiveMerging = 1;
break;
case 'G':
calculateWhichEndsToComputeSeparately = 1;
break;
case 'I':
i = sscanf(optarg, "%" PRIi64 "", &largeEndSize);
assert(i == 1);
break;
case 'J':
ingroupCoverageFilePath = stString_copy(optarg);
break;
case 'K':
i = sscanf(optarg, "%" PRIi64, &minimumSizeToRescue);
assert(i == 1);
break;
case 'M':
i = sscanf(optarg, "%lf", &minimumCoverageToRescue);
assert(i == 1);
break;
case 'N':
i = sscanf(optarg, "%" PRIi64, &minimumNumberOfSpecies);
if (i != 1) {
st_errAbort("Error parsing minimumNumberOfSpecies parameter");
}
break;
default:
usage();
return 1;
}
}
st_setLogLevelFromString(logLevelString);
/*
* Load the flowerdisk
*/
stKVDatabaseConf *kvDatabaseConf = stKVDatabaseConf_constructFromString(cactusDiskDatabaseString);
CactusDisk *cactusDisk = cactusDisk_construct(kvDatabaseConf, 0); //We precache the sequences
st_logInfo("Set up the flower disk\n");
/*
* Load the hmm
*/
StateMachine *sM = stateMachine5_construct(fiveState);
/*
* For each flower.
*/
if (calculateWhichEndsToComputeSeparately) {
stList *flowers = flowerWriter_parseFlowersFromStdin(cactusDisk);
if (stList_length(flowers) != 1) {
st_errAbort("We are breaking up a flower's end alignments for precomputation but we have %" PRIi64 " flowers.\n", stList_length(flowers));
}
stSortedSet *endsToAlignSeparately = getEndsToAlignSeparately(stList_get(flowers, 0), maximumLength, largeEndSize);
assert(stSortedSet_size(endsToAlignSeparately) != 1);
stSortedSetIterator *it = stSortedSet_getIterator(endsToAlignSeparately);
End *end;
while ((end = stSortedSet_getNext(it)) != NULL) {
fprintf(stdout, "%s\t%" PRIi64 "\t%" PRIi64 "\n", cactusMisc_nameToStringStatic(end_getName(end)), end_getInstanceNumber(end), getTotalAdjacencyLength(end));
}
return 0; //avoid cleanup costs
stSortedSet_destructIterator(it);
stSortedSet_destruct(endsToAlignSeparately);
} else if (endAlignmentsToPrecomputeOutputFile != NULL) {
/*
* In this case we will align a set of end and save the alignments in a file.
*/
stList *names = flowerWriter_parseNames(stdin);
Flower *flower = cactusDisk_getFlower(cactusDisk, *((Name *)stList_get(names, 0)));
FILE *fileHandle = fopen(endAlignmentsToPrecomputeOutputFile, "w");
for(int64_t i=1; i<stList_length(names); i++) {
End *end = flower_getEnd(flower, *((Name *)stList_get(names, i)));
if (end == NULL) {
st_errAbort("The end %" PRIi64 " was not found in the flower\n", *((Name *)stList_get(names, i)));
}
stSortedSet *endAlignment = makeEndAlignment(sM, end, spanningTrees, maximumLength, useProgressiveMerging,
matchGamma, pairwiseAlignmentBandingParameters);
writeEndAlignmentToDisk(end, endAlignment, fileHandle);
stSortedSet_destruct(endAlignment);
}
fclose(fileHandle);
return 0; //avoid cleanup costs
stList_destruct(names);
st_logInfo("Finished precomputing end alignments\n");
} else {
/*
* Compute complete flower alignments, possibly loading some precomputed alignments.
*/
bedRegion *bedRegions = NULL;
size_t numBeds = 0;
if (ingroupCoverageFilePath != NULL) {
// Pre-load the mmap for the coverage file.
FILE *coverageFile = fopen(ingroupCoverageFilePath, "rb");
if (coverageFile == NULL) {
st_errnoAbort("Opening coverage file %s failed",
ingroupCoverageFilePath);
}
fseek(coverageFile, 0, SEEK_END);
int64_t coverageFileLen = ftell(coverageFile);
assert(coverageFileLen >= 0);
assert(coverageFileLen % sizeof(bedRegion) == 0);
if (coverageFileLen == 0) {
// mmap doesn't like length-0 mappings, for obvious
// reasons. Pretend that the coverage file doesn't
// exist in this case, since it contains no data.
ingroupCoverageFilePath = NULL;
} else {
// Establish a memory mapping for the file.
bedRegions = mmap(NULL, coverageFileLen, PROT_READ, MAP_SHARED,
fileno(coverageFile), 0);
if (bedRegions == MAP_FAILED) {
st_errnoAbort("Failure mapping coverage file");
}
numBeds = coverageFileLen / sizeof(bedRegion);
}
fclose(coverageFile);
}
stList *flowers = flowerWriter_parseFlowersFromStdin(cactusDisk);
if (listOfEndAlignmentFiles != NULL && stList_length(flowers) != 1) {
st_errAbort("We have precomputed alignments but %" PRIi64 " flowers to align.\n", stList_length(flowers));
}
cactusDisk_preCacheStrings(cactusDisk, flowers);
for (j = 0; j < stList_length(flowers); j++) {
flower = stList_get(flowers, j);
st_logInfo("Processing a flower\n");
stSortedSet *alignedPairs = makeFlowerAlignment3(sM, flower, listOfEndAlignmentFiles, spanningTrees, maximumLength,
useProgressiveMerging, matchGamma, pairwiseAlignmentBandingParameters, pruneOutStubAlignments);
st_logInfo("Created the alignment: %" PRIi64 " pairs\n", stSortedSet_size(alignedPairs));
stPinchIterator *pinchIterator = stPinchIterator_constructFromAlignedPairs(alignedPairs, getNextAlignedPairAlignment);
/*
* Run the cactus caf functions to build cactus.
*/
stPinchThreadSet *threadSet = stCaf_setup(flower);
stCaf_anneal(threadSet, pinchIterator, NULL);
if (minimumDegree < 2) {
stCaf_makeDegreeOneBlocks(threadSet);
}
if (minimumIngroupDegree > 0 || minimumOutgroupDegree > 0 || minimumDegree > 1) {
stCaf_melt(flower, threadSet, blockFilterFn, 0, 0, 0, INT64_MAX);
}
if (ingroupCoverageFilePath != NULL) {
// Rescue any sequence that is covered by outgroups
// but currently unaligned into single-degree blocks.
stPinchThreadSetIt pinchIt = stPinchThreadSet_getIt(threadSet);
stPinchThread *thread;
while ((thread = stPinchThreadSetIt_getNext(&pinchIt)) != NULL) {
Cap *cap = flower_getCap(flower,
stPinchThread_getName(thread));
assert(cap != NULL);
Sequence *sequence = cap_getSequence(cap);
assert(sequence != NULL);
rescueCoveredRegions(thread, bedRegions, numBeds,
sequence_getName(sequence),
minimumSizeToRescue,
minimumCoverageToRescue);
}
stCaf_joinTrivialBoundaries(threadSet);
}
stCaf_finish(flower, threadSet, chainLengthForBigFlower, longChain, INT64_MAX, INT64_MAX); //Flower now destroyed.
stPinchThreadSet_destruct(threadSet);
st_logInfo("Ran the cactus core script.\n");
/*
* Cleanup
*/
//Clean up the sorted set after cleaning up the iterator
stPinchIterator_destruct(pinchIterator);
stSortedSet_destruct(alignedPairs);
st_logInfo("Finished filling in the alignments for the flower\n");
}
stList_destruct(flowers);
//st_errAbort("Done\n");
/*
* Write and close the cactusdisk.
*/
cactusDisk_write(cactusDisk);
return 0; //Exit without clean up is quicker, enable cleanup when doing memory leak detection.
if (bedRegions != NULL) {
// Clean up our mapping.
munmap(bedRegions, numBeds * sizeof(bedRegion));
}
}
///////////////////////////////////////////////////////////////////////////
// Cleanup
///////////////////////////////////////////////////////////////////////////
stateMachine_destruct(sM);
cactusDisk_destruct(cactusDisk);
stKVDatabaseConf_destruct(kvDatabaseConf);
//destructCactusCoreInputParameters(cCIP);
free(cactusDiskDatabaseString);
if (listOfEndAlignmentFiles != NULL) {
stList_destruct(listOfEndAlignmentFiles);
}
if (logLevelString != NULL) {
free(logLevelString);
}
st_logInfo("Finished with the flower disk for this flower.\n");
//while(1);
return 0;
}