4dc2ce3ec067b4ccb7987cbda16289d165954971
angie
  Thu Mar 9 20:04:39 2023 -0800
Translate multiple changes to the same codon correctly, collecting all mutations on the path from root to node.

diff --git src/hg/hgPhyloPlace/phyloPlace.h src/hg/hgPhyloPlace/phyloPlace.h
index 1fc9fc8..da9ea20 100644
--- src/hg/hgPhyloPlace/phyloPlace.h
+++ src/hg/hgPhyloPlace/phyloPlace.h
@@ -1,264 +1,264 @@
 /* Place SARS-CoV-2 sequences in phylogenetic tree using add_missing_samples program. */
 
 #ifndef _PHYLO_PLACE_H_
 #define _PHYLO_PLACE_H_
 
 #include "common.h"
 #include "cart.h"
 #include "dnaseq.h"
 #include "hash.h"
 #include "linefile.h"
 #include "parsimonyProto.h"
 #include "phyloTree.h"
 #include "seqWindow.h"
 #include "trashDir.h"
 
 #define PHYLOPLACE_DATA_DIR "hgPhyloPlaceData"
 
 // Allow users to upload a lot of sequences, but put limits on how much detail we'll show and
 // how many custom tracks we'll create.
 #define MAX_SUBTREE_BUTTONS 5
 #define MAX_SEQ_DETAILS 1000
 #define MAX_SUBTREE_CTS 10
 
 // For usher's -K option (single subtree):
 #define SINGLE_SUBTREE_SIZE "2000"
 #define USHER_NUM_THREADS "16"
 #define USHER_SERVER_CHILD_TIMEOUT "600"
 #define USHER_DEDUP_PREFIX "uploaded_"
 
 #define NEXTSTRAIN_DRAG_DROP_DOC "https://docs.nextstrain.org/projects/auspice/en/latest/advanced-functionality/drag-drop-csv-tsv.html"
 #define OUTBREAK_INFO_URLBASE "https://outbreak.info/situation-reports?pango="
 #define PANGO_DESIGNATION_ISSUE_URLBASE "https://github.com/cov-lineages/pango-designation/issues/"
 
 // usher now preprends "node_" to node numbers when parsing protobuf, although they're still stored
 // numeric in the protobuf.
 #define USHER_NODE_PREFIX "node_"
 
 struct treeChoices
 /* Phylogenetic tree versions for the user to choose from. */
 {
     char **protobufFiles;      // Mutation annotated tree files in protobuf format for UShER
     char **metadataFiles;      // Sample metadata a la GISAID's nextmeta download option
     char **sources;            // GISAID or public
     char **descriptions;       // Menu labels to describe the options to the user
     char **aliasFiles;         // Two-column files associating IDs/aliases with full tree names
     char **sampleNameFiles;    // One-column files with full tree names
     int count;                 // Number of choices (and size of each array)
 };
 
 struct seqInfo
 /* User sequences, alignments and statistics */
 {
     struct seqInfo *next;
     struct dnaSeq *seq;                     // Uploaded sequence
     struct psl *psl;                        // Alignment to reference (if FASTA uploaded)
     struct singleNucChange *sncList;        // SNVs in seq
     struct singleNucChange *maskedSncList;  // SNVs that were masked (not used for placement)
     struct slRef *maskedReasonsList;        // Reason (from Problematic Sites) for masking each SNV
     uint nCountStart;                       // #Ns at beginning of seq
     uint nCountMiddle;                      // #Ns not at beginning or end of seq
     uint nCountEnd;                         // #Ns at end of seq
     uint ambigCount;                        // # ambiguous IUPAC bases
     char *insRanges;                        // ranges and sequences inserted into reference
     char *delRanges;                        // ranges and sequences deleted from reference
     uint insBases;                          // total #bases inserted into reference
     uint delBases;                          // total #bases deleted from reference
 };
 
 struct variantPathNode
 /* A list of these gives a path from phylo tree root to some node (usually user seq leaf). */
     {
     struct variantPathNode *next;
     char *nodeName;                   // Either a numeric internal node ID or the user seq name
     struct singleNucChange *sncList;  // One or more single nucleotide changes associated with node
     };
 
 struct baseVal
 /* List of imputed base positions and values */
     {
     struct baseVal *next;
     int chromStart;         // 0-based position
     char *val;              // nucleotide base(s)
     };
 
 struct placementInfo
 /* Info about a sample's mutations and placement in the phylo tree */
     {
     char *sampleId;                       // Sample name from FASTA or VCF header
     struct slName *sampleMuts;            // Differences with the reference genome
                                           // -- NOTE: runUsher used to make this from stderr of
                                           // usher compiled with -DDEBUG=1; now caller must add it.
                                           // (struct seqInfo sncList has the same info)
     struct variantPathNode *variantPath;  // Mutations assigned to nodes along path from root
     struct baseVal *imputedBases;         // Ambiguous bases imputed to ref/alt [ACGT]
     int parsimonyScore;                   // Parsimony cost of placing sample
     int bestNodeCount;                    // Number of equally parsimonious placements
     char *nextClade;                      // Nextstrain clade assigned by UShER
     char *pangoLineage;                   // Pango lineage assigned by UShER
     // Fields above are parsed out of usher result files; below are added on later.
     char *nearestNeighbor;                // Nearest neighbor in phylogenetic tree/NULL if not found
     char *neighborLineage;                // Lineage of nearest neighbor/NULL if not found
     };
 
 struct subtreeInfo
 /* Parsed subtree from usher and derivative products. */
     {
     struct subtreeInfo *next;
     struct tempName *subtreeTn;           // Newick file from usher (may have condensed nodes)
     struct phyloTree *subtree;            // Parsed subtree (#*** with annotated muts?  shoudl we?_
     struct hash *subtreeIdToIx;           // Map of subtree nodes to VCF output sample order
     struct slName *subtreeUserSampleIds;  // List of user-uploaded samples in this subtree
     struct slName *subtreeNameList;       // List of leaf names with nicer names for cond. nodes
     };
 
 struct usherResults
 /* Tree+samples download file, sample placements, and subtrees parsed from usher output. */
     {
     struct tempName *bigTreePlusTn;      // Newick file: original tree plus user's samples
     struct hash *samplePlacements;       // Info about each sample's placement in the tree
     struct subtreeInfo *singleSubtreeInfo;  // Comprehensive subtree with all uploaded samples
     struct subtreeInfo *subtreeInfoList; // For each subtree: tree, file, node info etc.
     };
 
 struct sampleMetadata
 /* Information about a virus sample. */
     {
     char *strain;       // Strain name, usually of the form Country/ArbitraryId/YYYY-MM-DD
     char *epiId;        // GISAID EPI_ISL_[0-9]+ ID
     char *gbAcc;        // GenBank accession
     char *date;         // Sample collection date
     char *author;       // Author(s) to credit
     char *nClade;       // Nextstrain year-letter clade assigned by nextclade
     char *gClade;       // GISAID amino acid change clade
     char *lineage;      // Pango lineage assigned by pangolin
     char *country;      // Country in which sample was collected
     char *division;     // Administrative division in which sample was collected (country or state)
     char *location;     // Location in which sample was collected (city)
     char *countryExp;   // Country in which host was exposed to virus
     char *divExp;       // Administrative division in which host was exposed to virus
     char *origLab;      // Originating lab
     char *subLab;       // Submitting lab
     char *region;       // Continent on which sample was collected
     char *nCladeUsher;  // Nextstrain clade according to annotated tree
     char *lineageUsher; // Pango lineage according to annotated tree
     char *authors;      // Sequence submitters/authors
     char *pubs;         // PubMed ID numbers of publications associated with sequences
     char *nLineage;     // Nextstrain letter-dot-numbers lineage assigned by nextclade
     };
 
 struct geneInfo
 /* Information sufficient to determine whether a genome change causes a coding change. */
     {
     struct geneInfo *next;
     struct psl *psl;        // Alignment of transcript to genome
     struct dnaSeq *txSeq;   // Transcript sequence
     };
 
 struct tempName *vcfFromFasta(struct lineFile *lf, char *db, struct dnaSeq *refGenome,
                               struct slName **maskSites, struct hash *treeNames,
                               struct slName **retSampleIds, struct seqInfo **retSeqInfo,
                               struct slPair **retFailedSeqs, struct slPair **retFailedPsls,
                               int *pStartTime);
 /* Read in FASTA from lf and make sure each item has a reasonable size and not too high
  * percentage of N's.  Align to reference, extract SNVs from alignment, and save as VCF
  * with sample genotype columns. */
 
 struct usherResults *runUsher(char *db, char *usherPath, char *usherAssignmentsPath, char *vcfFile,
                               int subtreeSize, struct slName **pUserSampleIds,
                               struct treeChoices *treeChoices, int *pStartTime);
 /* Open a pipe from Yatish Turakhia's usher program, save resulting big trees and
  * subtrees to trash files, return list of slRef to struct tempName for the trash files
  * and parse other results out of stderr output.  The usher-sampled version of usher might
  * modify userSampleIds, adding a prefix if a sample with the same name is already in the tree. */
 
 struct usherResults *runMatUtilsExtractSubtrees(char *db, char *matUtilsPath, char *protobufPath,
                                                 int subtreeSize, struct slName *sampleIds,
                                                 struct treeChoices *treeChoices, int *pStartTime);
 /* Open a pipe from Yatish Turakhia and Jakob McBroome's matUtils extract to extract subtrees
  * containing sampleIds, save resulting subtrees to trash files, return subtree results.
  * Caller must ensure that sampleIds are names of leaves in the protobuf tree. */
 
 boolean serverIsConfigured(char *db);
 /* Return TRUE if all necessary configuration settings are in place to run usher-sampled-server. */
 
 boolean serverIsRunning(char *db, FILE *errFile);
 /* Return TRUE if we can find a PID for server and that PID looks alive according to /proc. */
 
 boolean startServer(char *db, struct treeChoices *treeChoices, FILE *errFile);
 /* Start up an usher-sampled-server process to run in the background. */
 
 void serverReloadProtobufs(char *db, struct treeChoices *treeChoices);
 /* Send a reload command and list of protobufs for db to usher server. */
 
 void serverStop(char *db);
 /* Send stop command to usher server. */
 
 void serverSetThreadCount(char *db, int val);
 /* Send thread command and value to usher server. */
 
 void serverSetTimeout(char *db, int val);
 /* Send timeout command and value (in seconds) to usher server. */
 
-struct slPair *getAaMutations(struct singleNucChange *sncList, struct geneInfo *geneInfoList,
-                              struct seqWindow *gSeqWin);
+struct slPair *getAaMutations(struct singleNucChange *sncList, struct singleNucChange *ancestorMuts,
+                              struct geneInfo *geneInfoList, struct seqWindow *gSeqWin);
 /* Given lists of SNVs and genes, return a list of pairs of { gene name, AA change list }. */
 
 struct geneInfo *getGeneInfoList(char *bigGenePredFile, struct dnaSeq *refGenome);
 /* If config.ra has a source of gene annotations, then return the gene list. */
 
 void treeToAuspiceJson(struct subtreeInfo *sti, char *db, struct geneInfo *geneInfoList,
                        struct seqWindow *gSeqWin, struct hash *sampleMetadata,
                        struct hash *sampleUrls, struct hash *samplePlacements,
                        char *jsonFile, char *source);
 /* Write JSON for tree in Nextstrain's Augur/Auspice V2 JSON format
  * (https://github.com/nextstrain/augur/blob/master/augur/data/schema-export-v2.json). */
 
 struct tempName *writeCustomTracks(char *db, struct tempName *vcfTn, struct usherResults *ur,
                                    struct slName *sampleIds, char *source, int fontHeight,
                                    struct phyloTree **retSampleTree, int *pStartTime);
 /* Write one custom track per subtree, and one custom track with just the user's uploaded samples. */
 
 
 struct sampleMetadata *metadataForSample(struct hash *sampleMetadata, char *sampleId);
 /* Look up sampleId in sampleMetadata, by accession if sampleId seems to include an accession. */
 
 struct phyloTree *phyloPruneToIds(struct phyloTree *node, struct slName *sampleIds);
 /* Prune all descendants of node that have no leaf descendants in sampleIds. */
 
 struct slName *phyloPlaceDbList(struct cart *cart);
 /* Each subdirectory of PHYLOPLACE_DATA_DIR that contains a config.ra file is a supported db
  * or track hub name (without the hub_number_ prefix).  Return a list of them, or NULL if none
  * are found. */
 
 char *phyloPlaceDbSetting(char *db, char *settingName);
 /* Return a setting from hgPhyloPlaceData/<db>/config.ra or NULL if not found. */
 
 char *phyloPlaceDbSettingPath(char *db, char *settingName);
 /* Return path to a file named by a setting from hgPhyloPlaceData/<db>/config.ra,
  * or NULL if not found.  (Append hgPhyloPlaceData/<db>/ to the beginning of relative path) */
 
 struct treeChoices *loadTreeChoices(char *db);
 /* If <db>/config.ra specifies a treeChoices file, load it up, else return NULL. */
 
 boolean isInternalNodeName(char *nodeName, int minNewNode);
 /* Return TRUE if nodeName looks like an internal node ID from the protobuf tree, i.e. is numeric
  * or <USHER_NODE_PREFIX>_<number> and, if minNewNode > 0, number is less than minNewNode. */
 
 void reportTiming(int *pStartTime, char *message);
 /* Print out a report to stderr of how much time something took. */
 
 boolean hgPhyloPlaceEnabled();
 /* Return TRUE if hgPhyloPlace is enabled in hg.conf and db wuhCor1 exists. */
 
 char *phyloPlaceSamples(struct lineFile *lf, char *db, char *defaultProtobuf,
                         boolean doMeasureTiming, int subtreeSize, int fontHeight,
                         boolean *retSuccess);
 /* Given a lineFile that contains either FASTA, VCF, or a list of sequence names/ids:
  * If FASTA/VCF, then prepare VCF for usher; if that goes well then run usher, report results,
  * make custom track files and return the top-level custom track file.
  * If list of seq names/ids, then attempt to find their full names in the protobuf, run matUtils
  * to make subtrees, show subtree results, and return NULL.  Set retSuccess to TRUE if we were
  * able to get at least some results for the user's input. */
 
 #endif //_PHYLO_PLACE_H_