-package main
+package lightning
import (
"bufio"
"bytes"
+ "context"
+ "encoding/gob"
+ "fmt"
"io"
+ "regexp"
+ "runtime"
+ "sort"
"strings"
"sync"
+ "sync/atomic"
log "github.com/sirupsen/logrus"
"golang.org/x/crypto/blake2b"
type tileVariantID uint16 // 1-based
type tileLibRef struct {
- tag tagID
- variant tileVariantID
+ Tag tagID
+ Variant tileVariantID
}
type tileSeq map[string][]tileLibRef
maxtag := 0
for _, refs := range tseq {
for _, ref := range refs {
- if maxtag < int(ref.tag) {
- maxtag = int(ref.tag)
+ if maxtag < int(ref.Tag) {
+ maxtag = int(ref.Tag)
}
}
}
var kept, dropped int
for _, refs := range tseq {
for _, ref := range refs {
- if vars[int(ref.tag)] != 0 {
+ if vars[int(ref.Tag)] != 0 {
dropped++
} else {
kept++
}
- vars[int(ref.tag)] = ref.variant
+ vars[int(ref.Tag)] = ref.Variant
}
}
return vars, kept, dropped
}
type tileLibrary struct {
- skipOOO bool
- taglib *tagLibrary
- variant [][][blake2b.Size256]byte
+ retainNoCalls bool
+ skipOOO bool
+ retainTileSequences bool
+
+ taglib *tagLibrary
+ variant [][][blake2b.Size256]byte
+ refseqs map[string]map[string][]tileLibRef
+ compactGenomes map[string][]tileVariantID
// count [][]int
- // seq map[[blake2b.Size]byte][]byte
- variants int
+ seq map[[blake2b.Size256]byte][]byte
+ variants int64
+ // if non-nil, write out any tile variants added while tiling
+ encoder *gob.Encoder
+
+ mtx sync.RWMutex
+ vlock []sync.Locker
+}
- mtx sync.Mutex
+func (tilelib *tileLibrary) loadTagSet(newtagset [][]byte) error {
+ // Loading a tagset means either passing it through to the
+ // output (if it's the first one we've seen), or just ensuring
+ // it doesn't disagree with what we already have.
+ if len(newtagset) == 0 {
+ return nil
+ }
+ tilelib.mtx.Lock()
+ defer tilelib.mtx.Unlock()
+ if tilelib.taglib == nil || tilelib.taglib.Len() == 0 {
+ tilelib.taglib = &tagLibrary{}
+ err := tilelib.taglib.setTags(newtagset)
+ if err != nil {
+ return err
+ }
+ if tilelib.encoder != nil {
+ err = tilelib.encoder.Encode(LibraryEntry{
+ TagSet: newtagset,
+ })
+ if err != nil {
+ return err
+ }
+ }
+ } else if tilelib.taglib.Len() != len(newtagset) {
+ return fmt.Errorf("cannot merge libraries with differing tagsets")
+ } else {
+ current := tilelib.taglib.Tags()
+ for i := range newtagset {
+ if !bytes.Equal(newtagset[i], current[i]) {
+ return fmt.Errorf("cannot merge libraries with differing tagsets")
+ }
+ }
+ }
+ return nil
}
-func (tilelib *tileLibrary) TileFasta(filelabel string, rdr io.Reader) (tileSeq, error) {
+func (tilelib *tileLibrary) loadTileVariants(tvs []TileVariant, variantmap map[tileLibRef]tileVariantID) error {
+ 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
+ }
+ return nil
+}
+
+func (tilelib *tileLibrary) loadCompactGenomes(cgs []CompactGenome, variantmap map[tileLibRef]tileVariantID, onLoadGenome func(CompactGenome)) error {
+ log.Debugf("loadCompactGenomes: %d", len(cgs))
+ var wg sync.WaitGroup
+ errs := make(chan error, 1)
+ for _, cg := range cgs {
+ wg.Add(1)
+ cg := cg
+ go func() {
+ defer wg.Done()
+ for i, variant := range cg.Variants {
+ if len(errs) > 0 {
+ return
+ }
+ if variant == 0 {
+ continue
+ }
+ tag := tagID(i / 2)
+ newvariant, ok := variantmap[tileLibRef{Tag: tag, Variant: variant}]
+ if !ok {
+ err := fmt.Errorf("oops: genome %q has variant %d for tag %d, but that variant was not in its library", cg.Name, variant, tag)
+ select {
+ case errs <- err:
+ default:
+ }
+ return
+ }
+ 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.encoder != nil {
+ err := tilelib.encoder.Encode(LibraryEntry{
+ CompactGenomes: []CompactGenome{cg},
+ })
+ if err != nil {
+ select {
+ case errs <- err:
+ default:
+ }
+ return
+ }
+ }
+ if tilelib.compactGenomes != nil {
+ tilelib.mtx.Lock()
+ defer tilelib.mtx.Unlock()
+ tilelib.compactGenomes[cg.Name] = cg.Variants
+ }
+ }()
+ }
+ wg.Wait()
+ go close(errs)
+ return <-errs
+}
+
+func (tilelib *tileLibrary) loadCompactSequences(cseqs []CompactSequence, variantmap map[tileLibRef]tileVariantID) error {
+ log.Debugf("loadCompactSequences: %d", len(cseqs))
+ for _, cseq := range cseqs {
+ for _, tseq := range cseq.TileSequences {
+ for i, libref := range tseq {
+ if libref.Variant == 0 {
+ // No variant (e.g., import
+ // dropped tiles with
+ // no-calls) = no translation.
+ continue
+ }
+ v, ok := variantmap[libref]
+ if !ok {
+ return fmt.Errorf("oops: CompactSequence %q has variant %d for tag %d, but that variant was not in its library", cseq.Name, libref.Variant, libref.Tag)
+ }
+ tseq[i].Variant = v
+ }
+ }
+ if tilelib.encoder != nil {
+ if err := tilelib.encoder.Encode(LibraryEntry{
+ CompactSequences: []CompactSequence{cseq},
+ }); err != nil {
+ return err
+ }
+ }
+ }
+ tilelib.mtx.Lock()
+ defer tilelib.mtx.Unlock()
+ if tilelib.refseqs == nil {
+ tilelib.refseqs = map[string]map[string][]tileLibRef{}
+ }
+ for _, cseq := range cseqs {
+ tilelib.refseqs[cseq.Name] = cseq.TileSequences
+ }
+ 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 {
+ cgs := []CompactGenome{}
+ cseqs := []CompactSequence{}
+ variantmap := map[tileLibRef]tileVariantID{}
+ err := DecodeLibrary(rdr, gz, func(ent *LibraryEntry) error {
+ if ctx.Err() != nil {
+ return ctx.Err()
+ }
+ if err := tilelib.loadTagSet(ent.TagSet); err != nil {
+ return err
+ }
+ if err := tilelib.loadTileVariants(ent.TileVariants, variantmap); err != nil {
+ return err
+ }
+ cgs = append(cgs, ent.CompactGenomes...)
+ cseqs = append(cseqs, ent.CompactSequences...)
+ return nil
+ })
+ if err != nil {
+ return err
+ }
+ if ctx.Err() != nil {
+ return ctx.Err()
+ }
+ err = tilelib.loadCompactGenomes(cgs, variantmap, onLoadGenome)
+ if err != nil {
+ return err
+ }
+ err = tilelib.loadCompactSequences(cseqs, variantmap)
+ if err != nil {
+ return err
+ }
+ return nil
+}
+
+type importStats struct {
+ InputFile string
+ InputLabel string
+ InputLength int
+ InputCoverage int
+ PathLength int
+ DroppedOutOfOrderTiles int
+}
+
+func (tilelib *tileLibrary) TileFasta(filelabel string, rdr io.Reader, matchChromosome *regexp.Regexp) (tileSeq, []importStats, error) {
ret := tileSeq{}
type jobT struct {
label string
fasta []byte
}
- todo := make(chan jobT)
+ todo := make(chan jobT, 1)
scanner := bufio.NewScanner(rdr)
go func() {
defer close(todo)
var seqlabel string
for scanner.Scan() {
buf := scanner.Bytes()
- if len(buf) == 0 || buf[0] == '>' {
- todo <- jobT{seqlabel, fasta}
- seqlabel, fasta = string(buf[1:]), nil
+ if len(buf) > 0 && buf[0] == '>' {
+ todo <- jobT{seqlabel, append([]byte(nil), fasta...)}
+ seqlabel, fasta = strings.SplitN(string(buf[1:]), " ", 2)[0], fasta[:0]
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
+ taglen := tilelib.taglib.TagLen()
+ var stats []importStats
for job := range todo {
if len(job.fasta) == 0 {
continue
- } else if strings.Contains(job.label, "_") {
+ } else if !matchChromosome.MatchString(job.label) {
skippedSequences++
continue
}
found = found[:0]
tilelib.taglib.FindAll(job.fasta, func(tagid tagID, pos, taglen int) {
- found = append(found, foundtag{pos: pos, tagid: tagid, taglen: taglen})
+ found = append(found, foundtag{pos: pos, tagid: tagid})
})
totalFoundTags += len(found)
+ if len(found) == 0 {
+ log.Warnf("%s %s no tags found", filelabel, job.label)
+ }
skipped := 0
- path = path[:0]
- last := foundtag{tagid: -1}
if tilelib.skipOOO {
+ log.Infof("%s %s keeping longest increasing subsequence", filelabel, job.label)
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)
found = found[:len(keep)]
}
+
+ log.Infof("%s %s getting %d librefs", filelabel, job.label, len(found))
+ throttle := &throttle{Max: runtime.NumCPU()}
+ path = path[:len(found)]
+ var lowquality int64
for i, f := range found {
- log.Tracef("%s %s found[%d] == %#v", filelabel, job.label, i, f)
- if last.taglen > 0 {
- path = append(path, tilelib.getRef(last.tagid, job.fasta[last.pos:f.pos+f.taglen]))
- }
- last = f
- }
- if last.taglen > 0 {
- path = append(path, tilelib.getRef(last.tagid, job.fasta[last.pos:]))
+ i, f := i, f
+ throttle.Acquire()
+ go func() {
+ defer throttle.Release()
+ var startpos, endpos int
+ if i == 0 {
+ startpos = 0
+ } else {
+ startpos = f.pos
+ }
+ if i == len(found)-1 {
+ endpos = len(job.fasta)
+ } else {
+ endpos = found[i+1].pos + taglen
+ }
+ path[i] = tilelib.getRef(f.tagid, job.fasta[startpos:endpos])
+ if countBases(job.fasta[startpos:endpos]) != endpos-startpos {
+ atomic.AddInt64(&lowquality, 1)
+ }
+ }()
}
+ throttle.Wait()
+
+ log.Infof("%s %s copying path", filelabel, job.label)
pathcopy := make([]tileLibRef, len(path))
copy(pathcopy, path)
ret[job.label] = pathcopy
- log.Debugf("%s %s tiled with path len %d, skipped %d", filelabel, job.label, len(path), skipped)
+
+ basesIn := countBases(job.fasta)
+ log.Infof("%s %s fasta in %d coverage in %d path len %d low-quality %d skipped-out-of-order %d", filelabel, job.label, len(job.fasta), basesIn, len(path), lowquality, skipped)
+ stats = append(stats, importStats{
+ InputFile: filelabel,
+ InputLabel: job.label,
+ InputLength: len(job.fasta),
+ InputCoverage: basesIn,
+ PathLength: len(path),
+ DroppedOutOfOrderTiles: skipped,
+ })
+
totalPathLen += len(path)
}
- log.Printf("%s tiled with total path len %d in %d sequences (skipped %d sequences with '_' in name, skipped %d out-of-order tags)", filelabel, totalPathLen, len(ret), skippedSequences, totalFoundTags-totalPathLen)
- return ret, scanner.Err()
+ 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()
}
-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 {
- for _, b := range seq {
- if b != 'a' && b != 'c' && b != 'g' && b != 't' {
- // return "tile not found" if seq has any
- // no-calls
- return tileLibRef{tag: tag}
+ dropSeq := false
+ if !tilelib.retainNoCalls {
+ for _, b := range seq {
+ if b != 'a' && b != 'c' && b != 'g' && b != 't' {
+ dropSeq = true
+ break
+ }
}
}
- tilelib.mtx.Lock()
- defer tilelib.mtx.Unlock()
- // if tilelib.seq == nil {
- // tilelib.seq = map[[blake2b.Size]byte][]byte{}
- // }
- if tilelib.variant == nil {
- tilelib.variant = make([][][blake2b.Size256]byte, tilelib.taglib.Len())
- }
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()
+ }
+
+ vlock.Lock()
for i, varhash := range tilelib.variant[tag] {
if varhash == seqhash {
- return tileLibRef{tag: tag, variant: tileVariantID(i + 1)}
+ 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)
- // tilelib.seq[seqhash] = append([]byte(nil), seq...)
- return tileLibRef{tag: tag, variant: tileVariantID(len(tilelib.variant[tag]))}
+ variant := tileVariantID(len(tilelib.variant[tag]))
+ vlock.Unlock()
+
+ if tilelib.retainTileSequences && !dropSeq {
+ tilelib.mtx.Lock()
+ if tilelib.seq == nil {
+ tilelib.seq = map[[blake2b.Size256]byte][]byte{}
+ }
+ tilelib.seq[seqhash] = append([]byte(nil), seq...)
+ tilelib.mtx.Unlock()
+ }
+
+ 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,
+ Variant: variant,
+ Blake2b: seqhash,
+ Sequence: saveSeq,
+ }},
+ })
+ }
+ return tileLibRef{Tag: tag, Variant: variant}
+}
+
+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]]
+}
+
+// Tidy deletes unreferenced tile variants and renumbers variants so
+// more common variants have smaller IDs.
+func (tilelib *tileLibrary) Tidy() {
+ log.Print("Tidy: compute inref")
+ inref := map[tileLibRef]bool{}
+ for _, refseq := range tilelib.refseqs {
+ for _, librefs := range refseq {
+ for _, libref := range librefs {
+ inref[libref] = true
+ }
+ }
+ }
+ log.Print("Tidy: compute remap")
+ remap := make([][]tileVariantID, len(tilelib.variant))
+ throttle := throttle{Max: runtime.NumCPU() + 1}
+ for tag, oldvariants := range tilelib.variant {
+ tag, oldvariants := tagID(tag), oldvariants
+ if tag%1000000 == 0 {
+ log.Printf("Tidy: tag %d", tag)
+ }
+ throttle.Acquire()
+ go func() {
+ defer throttle.Release()
+ uses := make([]int, len(oldvariants))
+ for _, cg := range tilelib.compactGenomes {
+ for phase := 0; phase < 2; phase++ {
+ cgi := int(tag)*2 + phase
+ if cgi < len(cg) && cg[cgi] > 0 {
+ uses[cg[cgi]-1]++
+ }
+ }
+ }
+
+ // Compute desired order of variants:
+ // neworder[x] == index in oldvariants that
+ // should move to position x.
+ neworder := make([]int, len(oldvariants))
+ for i := range neworder {
+ neworder[i] = i
+ }
+ sort.Slice(neworder, func(i, j int) bool {
+ if cmp := uses[neworder[i]] - uses[neworder[j]]; cmp != 0 {
+ return cmp > 0
+ } else {
+ return bytes.Compare(oldvariants[neworder[i]][:], oldvariants[neworder[j]][:]) < 0
+ }
+ })
+
+ // 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)
+ newvariants := make([][blake2b.Size256]byte, 0, len(neworder))
+ for _, oldi := range neworder {
+ if uses[oldi] > 0 || inref[tileLibRef{Tag: tag, Variant: tileVariantID(oldi + 1)}] {
+ newvariants = append(newvariants, oldvariants[oldi])
+ remaptag[oldi+1] = tileVariantID(len(newvariants))
+ }
+ }
+ tilelib.variant[tag] = newvariants
+ remap[tag] = remaptag
+ }()
+ }
+ throttle.Wait()
+
+ // Apply remap to genomes and reference sequences, so they
+ // refer to the same tile variants using the changed IDs.
+ log.Print("Tidy: apply remap")
+ for _, cg := range tilelib.compactGenomes {
+ 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]
+ }
+ }
+ }
+ log.Print("Tidy: done")
+}
+
+func countBases(seq []byte) int {
+ n := 0
+ for _, c := range seq {
+ if isbase[c] {
+ n++
+ }
+ }
+ return n
}