Fix some tests.
[lightning.git] / tilelib.go
index 12facfdb5f665226f5d1de0952d30ea5c7bb5181..7d4599d4e254bda48a7c0b6436e6ffcaf1d44f30 100644 (file)
@@ -1,4 +1,8 @@
-package main
+// Copyright (C) The Lightning Authors. All rights reserved.
+//
+// SPDX-License-Identifier: AGPL-3.0
+
+package lightning
 
 import (
        "bufio"
@@ -7,12 +11,16 @@ import (
        "encoding/gob"
        "fmt"
        "io"
+       "math/rand"
+       "os"
        "regexp"
        "runtime"
        "sort"
        "strings"
        "sync"
+       "sync/atomic"
 
+       "github.com/klauspost/pgzip"
        log "github.com/sirupsen/logrus"
        "golang.org/x/crypto/blake2b"
 )
@@ -54,18 +62,26 @@ type tileLibrary struct {
        retainNoCalls       bool
        skipOOO             bool
        retainTileSequences bool
+       useDups             bool
 
        taglib         *tagLibrary
        variant        [][][blake2b.Size256]byte
        refseqs        map[string]map[string][]tileLibRef
        compactGenomes map[string][]tileVariantID
-       // count [][]int
-       seq      map[[blake2b.Size256]byte][]byte
-       variants int
+       seq2           map[[2]byte]map[[blake2b.Size256]byte][]byte
+       seq2lock       map[[2]byte]sync.Locker
+       variants       int64
        // if non-nil, write out any tile variants added while tiling
        encoder *gob.Encoder
+       // set Ref flag when writing new variants to encoder
+       encodeRef bool
+
+       onAddTileVariant func(libref tileLibRef, hash [blake2b.Size256]byte, seq []byte) error
+       onAddGenome      func(CompactGenome) error
+       onAddRefseq      func(CompactSequence) error
 
-       mtx sync.Mutex
+       mtx   sync.RWMutex
+       vlock []sync.Locker
 }
 
 func (tilelib *tileLibrary) loadTagSet(newtagset [][]byte) error {
@@ -108,12 +124,12 @@ func (tilelib *tileLibrary) loadTileVariants(tvs []TileVariant, variantmap map[t
        for _, tv := range tvs {
                // Assign a new variant ID (unique across all inputs)
                // for each input variant.
-               variantmap[tileLibRef{Tag: tv.Tag, Variant: tv.Variant}] = tilelib.getRef(tv.Tag, tv.Sequence).Variant
+               variantmap[tileLibRef{Tag: tv.Tag, Variant: tv.Variant}] = tilelib.getRef(tv.Tag, tv.Sequence, tv.Ref).Variant
        }
        return nil
 }
 
-func (tilelib *tileLibrary) loadCompactGenomes(cgs []CompactGenome, variantmap map[tileLibRef]tileVariantID, onLoadGenome func(CompactGenome)) error {
+func (tilelib *tileLibrary) loadCompactGenomes(cgs []CompactGenome, variantmap map[tileLibRef]tileVariantID) error {
        log.Debugf("loadCompactGenomes: %d", len(cgs))
        var wg sync.WaitGroup
        errs := make(chan error, 1)
@@ -139,11 +155,18 @@ func (tilelib *tileLibrary) loadCompactGenomes(cgs []CompactGenome, variantmap m
                                        }
                                        return
                                }
-                               log.Tracef("loadCompactGenomes: cg %s tag %d variant %d => %d", cg.Name, tag, variant, newvariant)
+                               // log.Tracef("loadCompactGenomes: cg %s tag %d variant %d => %d", cg.Name, tag, variant, newvariant)
                                cg.Variants[i] = newvariant
                        }
-                       if onLoadGenome != nil {
-                               onLoadGenome(cg)
+                       if tilelib.onAddGenome != nil {
+                               err := tilelib.onAddGenome(cg)
+                               if err != nil {
+                                       select {
+                                       case errs <- err:
+                                       default:
+                                       }
+                                       return
+                               }
                        }
                        if tilelib.encoder != nil {
                                err := tilelib.encoder.Encode(LibraryEntry{
@@ -170,8 +193,9 @@ func (tilelib *tileLibrary) loadCompactGenomes(cgs []CompactGenome, variantmap m
 }
 
 func (tilelib *tileLibrary) loadCompactSequences(cseqs []CompactSequence, variantmap map[tileLibRef]tileVariantID) error {
-       log.Debugf("loadCompactSequences: %d", len(cseqs))
+       log.Infof("loadCompactSequences: %d todo", len(cseqs))
        for _, cseq := range cseqs {
+               log.Infof("loadCompactSequences: checking %s", cseq.Name)
                for _, tseq := range cseq.TileSequences {
                        for i, libref := range tseq {
                                if libref.Variant == 0 {
@@ -194,6 +218,13 @@ func (tilelib *tileLibrary) loadCompactSequences(cseqs []CompactSequence, varian
                                return err
                        }
                }
+               if tilelib.onAddRefseq != nil {
+                       err := tilelib.onAddRefseq(cseq)
+                       if err != nil {
+                               return err
+                       }
+               }
+               log.Infof("loadCompactSequences: checking %s done", cseq.Name)
        }
        tilelib.mtx.Lock()
        defer tilelib.mtx.Unlock()
@@ -203,15 +234,252 @@ func (tilelib *tileLibrary) loadCompactSequences(cseqs []CompactSequence, varian
        for _, cseq := range cseqs {
                tilelib.refseqs[cseq.Name] = cseq.TileSequences
        }
+       log.Info("loadCompactSequences: done")
+       return nil
+}
+
+func allFiles(path string, re *regexp.Regexp) ([]string, error) {
+       var files []string
+       f, err := open(path)
+       if err != nil {
+               return nil, err
+       }
+       defer f.Close()
+       fis, err := f.Readdir(-1)
+       if err != nil {
+               return []string{path}, nil
+       }
+       for _, fi := range fis {
+               if fi.Name() == "." || fi.Name() == ".." {
+                       continue
+               } else if child := path + "/" + fi.Name(); fi.IsDir() {
+                       add, err := allFiles(child, re)
+                       if err != nil {
+                               return nil, err
+                       }
+                       files = append(files, add...)
+               } else if re == nil || re.MatchString(child) {
+                       files = append(files, child)
+               }
+       }
+       sort.Strings(files)
+       return files, nil
+}
+
+var matchGobFile = regexp.MustCompile(`\.gob(\.gz)?$`)
+
+func (tilelib *tileLibrary) LoadDir(ctx context.Context, path string) error {
+       log.Infof("LoadDir: walk dir %s", path)
+       files, err := allFiles(path, matchGobFile)
+       if err != nil {
+               return err
+       }
+       ctx, cancel := context.WithCancel(ctx)
+       defer cancel()
+       var mtx sync.Mutex
+       allcgs := make([][]CompactGenome, len(files))
+       allcseqs := make([][]CompactSequence, len(files))
+       allvariantmap := map[tileLibRef]tileVariantID{}
+       errs := make(chan error, len(files))
+       log.Infof("LoadDir: read %d files", len(files))
+       for fileno, path := range files {
+               fileno, path := fileno, path
+               go func() {
+                       f, err := open(path)
+                       if err != nil {
+                               errs <- err
+                               return
+                       }
+                       defer f.Close()
+                       defer log.Infof("LoadDir: finished reading %s", path)
+
+                       var variantmap = map[tileLibRef]tileVariantID{}
+                       var cgs []CompactGenome
+                       var cseqs []CompactSequence
+                       err = DecodeLibrary(f, strings.HasSuffix(path, ".gz"), func(ent *LibraryEntry) error {
+                               if ctx.Err() != nil {
+                                       return ctx.Err()
+                               }
+                               if len(ent.TagSet) > 0 {
+                                       mtx.Lock()
+                                       if tilelib.taglib == nil || tilelib.taglib.Len() != len(ent.TagSet) {
+                                               // load first set of tags, or
+                                               // report mismatch if 2 sets
+                                               // have different #tags.
+                                               if err := tilelib.loadTagSet(ent.TagSet); err != nil {
+                                                       mtx.Unlock()
+                                                       return err
+                                               }
+                                       }
+                                       mtx.Unlock()
+                               }
+                               for _, tv := range ent.TileVariants {
+                                       variantmap[tileLibRef{Tag: tv.Tag, Variant: tv.Variant}] = tilelib.getRef(tv.Tag, tv.Sequence, tv.Ref).Variant
+                               }
+                               cgs = append(cgs, ent.CompactGenomes...)
+                               cseqs = append(cseqs, ent.CompactSequences...)
+                               return nil
+                       })
+                       allcgs[fileno] = cgs
+                       allcseqs[fileno] = cseqs
+                       mtx.Lock()
+                       defer mtx.Unlock()
+                       for k, v := range variantmap {
+                               allvariantmap[k] = v
+                       }
+                       errs <- err
+               }()
+       }
+       for range files {
+               err := <-errs
+               if err != nil {
+                       return err
+               }
+       }
+
+       log.Info("LoadDir: loadCompactGenomes")
+       var flatcgs []CompactGenome
+       for _, cgs := range allcgs {
+               flatcgs = append(flatcgs, cgs...)
+       }
+       err = tilelib.loadCompactGenomes(flatcgs, allvariantmap)
+       if err != nil {
+               return err
+       }
+
+       log.Info("LoadDir: loadCompactSequences")
+       var flatcseqs []CompactSequence
+       for _, cseqs := range allcseqs {
+               flatcseqs = append(flatcseqs, cseqs...)
+       }
+       err = tilelib.loadCompactSequences(flatcseqs, allvariantmap)
+       if err != nil {
+               return err
+       }
+
+       log.Info("LoadDir done")
+       return nil
+}
+
+func (tilelib *tileLibrary) WriteDir(dir string) error {
+       ntilefiles := 128
+       nfiles := ntilefiles + len(tilelib.refseqs)
+       files := make([]*os.File, nfiles)
+       for i := range files {
+               f, err := os.OpenFile(fmt.Sprintf("%s/library.%04d.gob.gz", dir, i), os.O_CREATE|os.O_WRONLY, 0666)
+               if err != nil {
+                       return err
+               }
+               defer f.Close()
+               files[i] = f
+       }
+       bufws := make([]*bufio.Writer, nfiles)
+       for i := range bufws {
+               bufws[i] = bufio.NewWriterSize(files[i], 1<<26)
+       }
+       zws := make([]*pgzip.Writer, nfiles)
+       for i := range zws {
+               zws[i] = pgzip.NewWriter(bufws[i])
+               defer zws[i].Close()
+       }
+       encoders := make([]*gob.Encoder, nfiles)
+       for i := range encoders {
+               encoders[i] = gob.NewEncoder(zws[i])
+       }
+
+       cgnames := make([]string, 0, len(tilelib.compactGenomes))
+       for name := range tilelib.compactGenomes {
+               cgnames = append(cgnames, name)
+       }
+       sort.Strings(cgnames)
+
+       refnames := make([]string, 0, len(tilelib.refseqs))
+       for name := range tilelib.refseqs {
+               refnames = append(refnames, name)
+       }
+       sort.Strings(refnames)
+
+       log.Infof("WriteDir: writing %d files", nfiles)
+       ctx, cancel := context.WithCancel(context.Background())
+       defer cancel()
+       errs := make(chan error, nfiles)
+       for start := range files {
+               start := start
+               go func() {
+                       err := encoders[start].Encode(LibraryEntry{TagSet: tilelib.taglib.Tags()})
+                       if err != nil {
+                               errs <- err
+                               return
+                       }
+                       if refidx := start - ntilefiles; refidx >= 0 {
+                               // write each ref to its own file
+                               // (they seem to load very slowly)
+                               name := refnames[refidx]
+                               errs <- encoders[start].Encode(LibraryEntry{CompactSequences: []CompactSequence{{
+                                       Name:          name,
+                                       TileSequences: tilelib.refseqs[name],
+                               }}})
+                               return
+                       }
+                       for i := start; i < len(cgnames); i += ntilefiles {
+                               err := encoders[start].Encode(LibraryEntry{CompactGenomes: []CompactGenome{{
+                                       Name:     cgnames[i],
+                                       Variants: tilelib.compactGenomes[cgnames[i]],
+                               }}})
+                               if err != nil {
+                                       errs <- err
+                                       return
+                               }
+                       }
+                       tvs := []TileVariant{}
+                       for tag := start; tag < len(tilelib.variant) && ctx.Err() == nil; tag += ntilefiles {
+                               tvs = tvs[:0]
+                               for idx, hash := range tilelib.variant[tag] {
+                                       tvs = append(tvs, TileVariant{
+                                               Tag:      tagID(tag),
+                                               Variant:  tileVariantID(idx + 1),
+                                               Blake2b:  hash,
+                                               Sequence: tilelib.hashSequence(hash),
+                                       })
+                               }
+                               err := encoders[start].Encode(LibraryEntry{TileVariants: tvs})
+                               if err != nil {
+                                       errs <- err
+                                       return
+                               }
+                       }
+                       errs <- nil
+               }()
+       }
+       for range files {
+               err := <-errs
+               if err != nil {
+                       return err
+               }
+       }
+       log.Info("WriteDir: flushing")
+       for i := range zws {
+               err := zws[i].Close()
+               if err != nil {
+                       return err
+               }
+               err = bufws[i].Flush()
+               if err != nil {
+                       return err
+               }
+               err = files[i].Close()
+               if err != nil {
+                       return err
+               }
+       }
+       log.Info("WriteDir: done")
        return nil
 }
 
 // Load library data from rdr. Tile variants might be renumbered in
 // the process; in that case, genomes variants will be renumbered to
 // match.
-//
-// If onLoadGenome is non-nil, call it on each CompactGenome entry.
-func (tilelib *tileLibrary) LoadGob(ctx context.Context, rdr io.Reader, gz bool, onLoadGenome func(CompactGenome)) error {
+func (tilelib *tileLibrary) LoadGob(ctx context.Context, rdr io.Reader, gz bool) error {
        cgs := []CompactGenome{}
        cseqs := []CompactSequence{}
        variantmap := map[tileLibRef]tileVariantID{}
@@ -235,7 +503,7 @@ func (tilelib *tileLibrary) LoadGob(ctx context.Context, rdr io.Reader, gz bool,
        if ctx.Err() != nil {
                return ctx.Err()
        }
-       err = tilelib.loadCompactGenomes(cgs, variantmap, onLoadGenome)
+       err = tilelib.loadCompactGenomes(cgs, variantmap)
        if err != nil {
                return err
        }
@@ -246,147 +514,196 @@ func (tilelib *tileLibrary) LoadGob(ctx context.Context, rdr io.Reader, gz bool,
        return nil
 }
 
+func (tilelib *tileLibrary) dump(out io.Writer) {
+       printTV := func(tag int, variant tileVariantID) {
+               if variant < 1 {
+                       fmt.Fprintf(out, " -")
+               } else if tag >= len(tilelib.variant) {
+                       fmt.Fprintf(out, " (!tag=%d)", tag)
+               } else if int(variant) > len(tilelib.variant[tag]) {
+                       fmt.Fprintf(out, " (tag=%d,!variant=%d)", tag, variant)
+               } else {
+                       fmt.Fprintf(out, " %x", tilelib.variant[tag][variant-1][:8])
+               }
+       }
+       for refname, refseqs := range tilelib.refseqs {
+               for seqname, seq := range refseqs {
+                       fmt.Fprintf(out, "ref %s %s", refname, seqname)
+                       for _, libref := range seq {
+                               printTV(int(libref.Tag), libref.Variant)
+                       }
+                       fmt.Fprintf(out, "\n")
+               }
+       }
+       for name, cg := range tilelib.compactGenomes {
+               fmt.Fprintf(out, "cg %s", name)
+               for tag, variant := range cg {
+                       printTV(tag/2, variant)
+               }
+               fmt.Fprintf(out, "\n")
+       }
+}
+
 type importStats struct {
-       InputFile              string
-       InputLabel             string
-       InputLength            int
-       InputCoverage          int
-       TileCoverage           int
-       PathLength             int
-       DroppedOutOfOrderTiles int
+       InputFile             string
+       InputLabel            string
+       InputLength           int
+       InputCoverage         int
+       PathLength            int
+       DroppedRepeatedTags   int
+       DroppedOutOfOrderTags int
 }
 
-func (tilelib *tileLibrary) TileFasta(filelabel string, rdr io.Reader, matchChromosome *regexp.Regexp) (tileSeq, []importStats, error) {
+func (tilelib *tileLibrary) TileFasta(filelabel string, rdr io.Reader, matchChromosome *regexp.Regexp, isRef bool) (tileSeq, []importStats, error) {
        ret := tileSeq{}
-       type jobT struct {
-               label string
-               fasta []byte
-       }
-       todo := make(chan jobT)
-       scanner := bufio.NewScanner(rdr)
-       go func() {
-               defer close(todo)
-               var fasta []byte
-               var seqlabel string
-               for scanner.Scan() {
-                       buf := scanner.Bytes()
-                       if len(buf) > 0 && buf[0] == '>' {
-                               todo <- jobT{seqlabel, fasta}
-                               seqlabel, fasta = strings.SplitN(string(buf[1:]), " ", 2)[0], nil
-                               log.Debugf("%s %s reading fasta", filelabel, seqlabel)
-                       } else {
-                               fasta = append(fasta, bytes.ToLower(buf)...)
-                       }
-               }
-               todo <- jobT{seqlabel, fasta}
-       }()
        type foundtag struct {
-               pos    int
-               tagid  tagID
-               taglen int
+               pos   int
+               tagid tagID
        }
        found := make([]foundtag, 2000000)
        path := make([]tileLibRef, 2000000)
        totalFoundTags := 0
        totalPathLen := 0
        skippedSequences := 0
-       stats := make([]importStats, 0, len(todo))
-       for job := range todo {
-               if len(job.fasta) == 0 {
-                       continue
-               } else if !matchChromosome.MatchString(job.label) {
+       taglen := tilelib.taglib.TagLen()
+       var stats []importStats
+
+       in := bufio.NewReader(rdr)
+readall:
+       for {
+               var seqlabel string
+               // Advance to next '>', then
+               // read seqlabel up to \r?\n
+       readseqlabel:
+               for seqlabelStarted := false; ; {
+                       rune, _, err := in.ReadRune()
+                       if err == io.EOF {
+                               break readall
+                       } else if err != nil {
+                               return nil, nil, err
+                       }
+                       switch {
+                       case rune == '\r':
+                       case seqlabelStarted && rune == '\n':
+                               break readseqlabel
+                       case seqlabelStarted:
+                               seqlabel += string(rune)
+                       case rune == '>':
+                               seqlabelStarted = true
+                       default:
+                       }
+               }
+               log.Debugf("%s %s reading fasta", filelabel, seqlabel)
+               if !matchChromosome.MatchString(seqlabel) {
                        skippedSequences++
                        continue
                }
-               log.Debugf("%s %s tiling", filelabel, job.label)
+               log.Debugf("%s %s tiling", filelabel, seqlabel)
 
+               fasta := bytes.NewBuffer(nil)
                found = found[:0]
-               tilelib.taglib.FindAll(job.fasta, func(tagid tagID, pos, taglen int) {
-                       found = append(found, foundtag{pos: pos, tagid: tagid, taglen: taglen})
+               err := tilelib.taglib.FindAll(in, fasta, func(tagid tagID, pos, taglen int) {
+                       found = append(found, foundtag{pos: pos, tagid: tagid})
                })
+               if err != nil {
+                       return nil, nil, err
+               }
                totalFoundTags += len(found)
+               if len(found) == 0 {
+                       log.Warnf("%s %s no tags found", filelabel, seqlabel)
+               }
 
-               basesOut := 0
-               skipped := 0
-               path = path[:0]
-               last := foundtag{tagid: -1}
+               droppedDup := 0
+               if !tilelib.useDups {
+                       // Remove any tags that appeared more than once
+                       dup := map[tagID]bool{}
+                       for _, ft := range found {
+                               _, dup[ft.tagid] = dup[ft.tagid]
+                       }
+                       dst := 0
+                       for _, ft := range found {
+                               if !dup[ft.tagid] {
+                                       found[dst] = ft
+                                       dst++
+                               }
+                       }
+                       droppedDup = len(found) - dst
+                       log.Infof("%s %s dropping %d non-unique tags", filelabel, seqlabel, droppedDup)
+                       found = found[:dst]
+               }
+
+               droppedOOO := 0
                if tilelib.skipOOO {
                        keep := longestIncreasingSubsequence(len(found), func(i int) int { return int(found[i].tagid) })
                        for i, x := range keep {
                                found[i] = found[x]
                        }
-                       skipped = len(found) - len(keep)
+                       droppedOOO = len(found) - len(keep)
+                       log.Infof("%s %s dropping %d out-of-order tags", filelabel, seqlabel, droppedOOO)
                        found = found[:len(keep)]
                }
-               for i, f := range found {
-                       log.Tracef("%s %s found[%d] == %#v", filelabel, job.label, i, f)
-                       if last.tagid < 0 {
-                               // first tag in sequence
-                               last = foundtag{tagid: f.tagid}
-                               continue
-                       }
-                       libref := tilelib.getRef(last.tagid, job.fasta[last.pos:f.pos+f.taglen])
-                       path = append(path, libref)
-                       if libref.Variant > 0 {
-                               // Count output coverage from
-                               // the end of the previous tag
-                               // (if any) to the end of the
-                               // current tag, IOW don't
-                               // double-count coverage for
-                               // the previous tag.
-                               basesOut += countBases(job.fasta[last.pos+last.taglen : f.pos+f.taglen])
+
+               log.Infof("%s %s getting %d librefs", filelabel, seqlabel, len(found))
+               path = path[:len(found)]
+               var lowquality int64
+               // Visit each element of found, but start at a random
+               // index, to reduce the likelihood of lock contention
+               // when importing many samples concurrently.
+               startpoint := rand.Int() % len(found)
+               for offset := range found {
+                       i := startpoint + offset
+                       if i >= len(found) {
+                               i -= len(found)
+                       }
+                       f := found[i]
+                       var startpos, endpos int
+                       if i == 0 {
+                               startpos = 0
                        } else {
-                               // If we dropped this tile
-                               // (because !retainNoCalls),
-                               // set taglen=0 so the
-                               // overlapping tag is counted
-                               // toward coverage on the
-                               // following tile.
-                               f.taglen = 0
-                       }
-                       last = f
-               }
-               if last.tagid < 0 {
-                       log.Warnf("%s %s no tags found", filelabel, job.label)
-               } else {
-                       libref := tilelib.getRef(last.tagid, job.fasta[last.pos:])
-                       path = append(path, libref)
-                       if libref.Variant > 0 {
-                               basesOut += countBases(job.fasta[last.pos+last.taglen:])
+                               startpos = f.pos
+                       }
+                       if i == len(found)-1 {
+                               endpos = fasta.Len()
+                       } else {
+                               endpos = found[i+1].pos + taglen
+                       }
+                       path[i] = tilelib.getRef(f.tagid, fasta.Bytes()[startpos:endpos], isRef)
+                       if countBases(fasta.Bytes()[startpos:endpos]) != endpos-startpos {
+                               lowquality++
                        }
                }
 
+               log.Infof("%s %s copying path", filelabel, seqlabel)
+
                pathcopy := make([]tileLibRef, len(path))
                copy(pathcopy, path)
-               ret[job.label] = pathcopy
+               ret[seqlabel] = pathcopy
 
-               basesIn := countBases(job.fasta)
-               log.Infof("%s %s fasta in %d coverage in %d coverage out %d path len %d skipped %d", filelabel, job.label, len(job.fasta), basesIn, basesOut, len(path), skipped)
+               basesIn := countBases(fasta.Bytes())
+               log.Infof("%s %s fasta in %d coverage in %d path len %d low-quality %d", filelabel, seqlabel, fasta.Len(), basesIn, len(path), lowquality)
                stats = append(stats, importStats{
-                       InputFile:              filelabel,
-                       InputLabel:             job.label,
-                       InputLength:            len(job.fasta),
-                       InputCoverage:          basesIn,
-                       TileCoverage:           basesOut,
-                       PathLength:             len(path),
-                       DroppedOutOfOrderTiles: skipped,
+                       InputFile:             filelabel,
+                       InputLabel:            seqlabel,
+                       InputLength:           fasta.Len(),
+                       InputCoverage:         basesIn,
+                       PathLength:            len(path),
+                       DroppedOutOfOrderTags: droppedOOO,
+                       DroppedRepeatedTags:   droppedDup,
                })
 
                totalPathLen += len(path)
        }
        log.Printf("%s tiled with total path len %d in %d sequences (skipped %d sequences that did not match chromosome regexp, skipped %d out-of-order tags)", filelabel, totalPathLen, len(ret), skippedSequences, totalFoundTags-totalPathLen)
-       return ret, stats, scanner.Err()
+       return ret, stats, nil
 }
 
-func (tilelib *tileLibrary) Len() int {
-       tilelib.mtx.Lock()
-       defer tilelib.mtx.Unlock()
-       return tilelib.variants
+func (tilelib *tileLibrary) Len() int64 {
+       return atomic.LoadInt64(&tilelib.variants)
 }
 
 // Return a tileLibRef for a tile with the given tag and sequence,
 // adding the sequence to the library if needed.
-func (tilelib *tileLibrary) getRef(tag tagID, seq []byte) tileLibRef {
+func (tilelib *tileLibrary) getRef(tag tagID, seq []byte, usedByRef bool) tileLibRef {
        dropSeq := false
        if !tilelib.retainNoCalls {
                for _, b := range seq {
@@ -396,67 +713,141 @@ func (tilelib *tileLibrary) getRef(tag tagID, seq []byte) tileLibRef {
                        }
                }
        }
-       tilelib.mtx.Lock()
-       if tilelib.variant == nil && tilelib.taglib != nil {
-               tilelib.variant = make([][][blake2b.Size256]byte, tilelib.taglib.Len())
-       }
-       if int(tag) >= len(tilelib.variant) {
-               // If we haven't seen the tag library yet (as in a
-               // merge), tilelib.taglib.Len() is zero. We can still
-               // behave correctly, we just need to expand the
-               // tilelib.variant slice as needed.
-               if int(tag) >= cap(tilelib.variant) {
-                       // Allocate 2x capacity.
-                       newslice := make([][][blake2b.Size256]byte, int(tag)+1, (int(tag)+1)*2)
-                       copy(newslice, tilelib.variant)
-                       tilelib.variant = newslice[:int(tag)+1]
-               } else {
-                       // Use previously allocated capacity, avoiding
-                       // copy.
-                       tilelib.variant = tilelib.variant[:int(tag)+1]
+       seqhash := blake2b.Sum256(seq)
+       var vlock sync.Locker
+
+       tilelib.mtx.RLock()
+       if len(tilelib.vlock) > int(tag) {
+               vlock = tilelib.vlock[tag]
+       }
+       tilelib.mtx.RUnlock()
+
+       if vlock != nil {
+               vlock.Lock()
+               for i, varhash := range tilelib.variant[tag] {
+                       if varhash == seqhash {
+                               vlock.Unlock()
+                               return tileLibRef{Tag: tag, Variant: tileVariantID(i + 1)}
+                       }
                }
+               vlock.Unlock()
+       } else {
+               tilelib.mtx.Lock()
+               if tilelib.variant == nil && tilelib.taglib != nil {
+                       tilelib.variant = make([][][blake2b.Size256]byte, tilelib.taglib.Len())
+                       tilelib.vlock = make([]sync.Locker, tilelib.taglib.Len())
+                       for i := range tilelib.vlock {
+                               tilelib.vlock[i] = new(sync.Mutex)
+                       }
+               }
+               if int(tag) >= len(tilelib.variant) {
+                       oldlen := len(tilelib.vlock)
+                       for i := 0; i < oldlen; i++ {
+                               tilelib.vlock[i].Lock()
+                       }
+                       // If we haven't seen the tag library yet (as
+                       // in a merge), tilelib.taglib.Len() is
+                       // zero. We can still behave correctly, we
+                       // just need to expand the tilelib.variant and
+                       // tilelib.vlock slices as needed.
+                       if int(tag) >= cap(tilelib.variant) {
+                               // Allocate 2x capacity.
+                               newslice := make([][][blake2b.Size256]byte, int(tag)+1, (int(tag)+1)*2)
+                               copy(newslice, tilelib.variant)
+                               tilelib.variant = newslice[:int(tag)+1]
+                               newvlock := make([]sync.Locker, int(tag)+1, (int(tag)+1)*2)
+                               copy(newvlock, tilelib.vlock)
+                               tilelib.vlock = newvlock[:int(tag)+1]
+                       } else {
+                               // Use previously allocated capacity,
+                               // avoiding copy.
+                               tilelib.variant = tilelib.variant[:int(tag)+1]
+                               tilelib.vlock = tilelib.vlock[:int(tag)+1]
+                       }
+                       for i := oldlen; i < len(tilelib.vlock); i++ {
+                               tilelib.vlock[i] = new(sync.Mutex)
+                       }
+                       for i := 0; i < oldlen; i++ {
+                               tilelib.vlock[i].Unlock()
+                       }
+               }
+               vlock = tilelib.vlock[tag]
+               tilelib.mtx.Unlock()
        }
-       seqhash := blake2b.Sum256(seq)
+
+       vlock.Lock()
        for i, varhash := range tilelib.variant[tag] {
                if varhash == seqhash {
-                       tilelib.mtx.Unlock()
+                       vlock.Unlock()
                        return tileLibRef{Tag: tag, Variant: tileVariantID(i + 1)}
                }
        }
-       tilelib.variants++
+       atomic.AddInt64(&tilelib.variants, 1)
        tilelib.variant[tag] = append(tilelib.variant[tag], seqhash)
+       variant := tileVariantID(len(tilelib.variant[tag]))
+       vlock.Unlock()
+
        if tilelib.retainTileSequences && !dropSeq {
-               if tilelib.seq == nil {
-                       tilelib.seq = map[[blake2b.Size256]byte][]byte{}
+               seqCopy := append([]byte(nil), seq...)
+               if tilelib.seq2 == nil {
+                       tilelib.mtx.Lock()
+                       if tilelib.seq2 == nil {
+                               tilelib.seq2lock = map[[2]byte]sync.Locker{}
+                               m := map[[2]byte]map[[blake2b.Size256]byte][]byte{}
+                               var k [2]byte
+                               for i := 0; i < 256; i++ {
+                                       k[0] = byte(i)
+                                       for j := 0; j < 256; j++ {
+                                               k[1] = byte(j)
+                                               m[k] = map[[blake2b.Size256]byte][]byte{}
+                                               tilelib.seq2lock[k] = &sync.Mutex{}
+                                       }
+                               }
+                               tilelib.seq2 = m
+                       }
+                       tilelib.mtx.Unlock()
                }
-               tilelib.seq[seqhash] = append([]byte(nil), seq...)
+               var k [2]byte
+               copy(k[:], seqhash[:])
+               locker := tilelib.seq2lock[k]
+               locker.Lock()
+               tilelib.seq2[k][seqhash] = seqCopy
+               locker.Unlock()
        }
-       variant := tileVariantID(len(tilelib.variant[tag]))
-       tilelib.mtx.Unlock()
 
+       saveSeq := seq
+       if dropSeq {
+               // Save the hash, but not the sequence
+               saveSeq = nil
+       }
        if tilelib.encoder != nil {
-               saveSeq := seq
-               if dropSeq {
-                       // Save the hash, but not the sequence
-                       saveSeq = nil
-               }
                tilelib.encoder.Encode(LibraryEntry{
                        TileVariants: []TileVariant{{
                                Tag:      tag,
+                               Ref:      usedByRef,
                                Variant:  variant,
                                Blake2b:  seqhash,
                                Sequence: saveSeq,
                        }},
                })
        }
+       if tilelib.onAddTileVariant != nil {
+               tilelib.onAddTileVariant(tileLibRef{tag, variant}, seqhash, saveSeq)
+       }
        return tileLibRef{Tag: tag, Variant: variant}
 }
 
+func (tilelib *tileLibrary) hashSequence(hash [blake2b.Size256]byte) []byte {
+       var partition [2]byte
+       copy(partition[:], hash[:])
+       return tilelib.seq2[partition][hash]
+}
+
 func (tilelib *tileLibrary) TileVariantSequence(libref tileLibRef) []byte {
        if libref.Variant == 0 || len(tilelib.variant) <= int(libref.Tag) || len(tilelib.variant[libref.Tag]) < int(libref.Variant) {
                return nil
        }
-       return tilelib.seq[tilelib.variant[libref.Tag][libref.Variant-1]]
+       return tilelib.hashSequence(tilelib.variant[libref.Tag][libref.Variant-1])
 }
 
 // Tidy deletes unreferenced tile variants and renumbers variants so
@@ -476,7 +867,7 @@ func (tilelib *tileLibrary) Tidy() {
        throttle := throttle{Max: runtime.NumCPU() + 1}
        for tag, oldvariants := range tilelib.variant {
                tag, oldvariants := tagID(tag), oldvariants
-               if tag%10000 == 0 {
+               if tag%1000000 == 0 {
                        log.Printf("Tidy: tag %d", tag)
                }
                throttle.Acquire()
@@ -507,7 +898,7 @@ func (tilelib *tileLibrary) Tidy() {
                                }
                        })
 
-                       // Replace tilelib.variants[tag] with a new
+                       // Replace tilelib.variant[tag] with a new
                        // re-ordered slice of hashes, and make a
                        // mapping from old to new variant IDs.
                        remaptag := make([]tileVariantID, len(oldvariants)+1)
@@ -527,18 +918,30 @@ func (tilelib *tileLibrary) Tidy() {
        // Apply remap to genomes and reference sequences, so they
        // refer to the same tile variants using the changed IDs.
        log.Print("Tidy: apply remap")
+       var wg sync.WaitGroup
        for _, cg := range tilelib.compactGenomes {
-               for idx, variant := range cg {
-                       cg[idx] = remap[tagID(idx/2)][variant]
-               }
+               cg := cg
+               wg.Add(1)
+               go func() {
+                       defer wg.Done()
+                       for idx, variant := range cg {
+                               cg[idx] = remap[tagID(idx/2)][variant]
+                       }
+               }()
        }
        for _, refcs := range tilelib.refseqs {
                for _, refseq := range refcs {
-                       for i, tv := range refseq {
-                               refseq[i].Variant = remap[tv.Tag][tv.Variant]
-                       }
+                       refseq := refseq
+                       wg.Add(1)
+                       go func() {
+                               defer wg.Done()
+                               for i, tv := range refseq {
+                                       refseq[i].Variant = remap[tv.Tag][tv.Variant]
+                               }
+                       }()
                }
        }
+       wg.Wait()
        log.Print("Tidy: done")
 }