tilelib.go

   1 package main
   2
   3 import (
   4         "bufio"
   5         "bytes"
   6         "context"
   7         "encoding/gob"
   8         "fmt"
   9         "io"
  10         "runtime"
  11         "sort"
  12         "strings"
  13         "sync"
  14
  15         log "github.com/sirupsen/logrus"
  16         "golang.org/x/crypto/blake2b"
  17 )
  18
  19 type tileVariantID uint16 // 1-based
  20
  21 type tileLibRef struct {
  22         Tag     tagID
  23         Variant tileVariantID
  24 }
  25
  26 type tileSeq map[string][]tileLibRef
  27
  28 func (tseq tileSeq) Variants() ([]tileVariantID, int, int) {
  29         maxtag := 0
  30         for _, refs := range tseq {
  31                 for _, ref := range refs {
  32                         if maxtag < int(ref.Tag) {
  33                                 maxtag = int(ref.Tag)
  34                         }
  35                 }
  36         }
  37         vars := make([]tileVariantID, maxtag+1)
  38         var kept, dropped int
  39         for _, refs := range tseq {
  40                 for _, ref := range refs {
  41                         if vars[int(ref.Tag)] != 0 {
  42                                 dropped++
  43                         } else {
  44                                 kept++
  45                         }
  46                         vars[int(ref.Tag)] = ref.Variant
  47                 }
  48         }
  49         return vars, kept, dropped
  50 }
  51
  52 type tileLibrary struct {
  53         retainNoCalls       bool
  54         skipOOO             bool
  55         retainTileSequences bool
  56
  57         taglib         *tagLibrary
  58         variant        [][][blake2b.Size256]byte
  59         refseqs        map[string]map[string][]tileLibRef
  60         compactGenomes map[string][]tileVariantID
  61         // count [][]int
  62         seq      map[[blake2b.Size256]byte][]byte
  63         variants int
  64         // if non-nil, write out any tile variants added while tiling
  65         encoder *gob.Encoder
  66
  67         mtx sync.Mutex
  68 }
  69
  70 func (tilelib *tileLibrary) loadTagSet(newtagset [][]byte) error {
  71         // Loading a tagset means either passing it through to the
  72         // output (if it's the first one we've seen), or just ensuring
  73         // it doesn't disagree with what we already have.
  74         if len(newtagset) == 0 {
  75                 return nil
  76         }
  77         tilelib.mtx.Lock()
  78         defer tilelib.mtx.Unlock()
  79         if tilelib.taglib == nil || tilelib.taglib.Len() == 0 {
  80                 tilelib.taglib = &tagLibrary{}
  81                 err := tilelib.taglib.setTags(newtagset)
  82                 if err != nil {
  83                         return err
  84                 }
  85                 if tilelib.encoder != nil {
  86                         err = tilelib.encoder.Encode(LibraryEntry{
  87                                 TagSet: newtagset,
  88                         })
  89                         if err != nil {
  90                                 return err
  91                         }
  92                 }
  93         } else if tilelib.taglib.Len() != len(newtagset) {
  94                 return fmt.Errorf("cannot merge libraries with differing tagsets")
  95         } else {
  96                 current := tilelib.taglib.Tags()
  97                 for i := range newtagset {
  98                         if !bytes.Equal(newtagset[i], current[i]) {
  99                                 return fmt.Errorf("cannot merge libraries with differing tagsets")
 100                         }
 101                 }
 102         }
 103         return nil
 104 }
 105
 106 func (tilelib *tileLibrary) loadTileVariants(tvs []TileVariant, variantmap map[tileLibRef]tileVariantID) error {
 107         for _, tv := range tvs {
 108                 // Assign a new variant ID (unique across all inputs)
 109                 // for each input variant.
 110                 variantmap[tileLibRef{Tag: tv.Tag, Variant: tv.Variant}] = tilelib.getRef(tv.Tag, tv.Sequence).Variant
 111         }
 112         return nil
 113 }
 114
 115 func (tilelib *tileLibrary) loadCompactGenomes(cgs []CompactGenome, variantmap map[tileLibRef]tileVariantID, onLoadGenome func(CompactGenome)) error {
 116         log.Debugf("loadCompactGenomes: %d", len(cgs))
 117         var wg sync.WaitGroup
 118         errs := make(chan error, 1)
 119         for _, cg := range cgs {
 120                 wg.Add(1)
 121                 cg := cg
 122                 go func() {
 123                         defer wg.Done()
 124                         for i, variant := range cg.Variants {
 125                                 if len(errs) > 0 {
 126                                         return
 127                                 }
 128                                 if variant == 0 {
 129                                         continue
 130                                 }
 131                                 tag := tagID(i / 2)
 132                                 newvariant, ok := variantmap[tileLibRef{Tag: tag, Variant: variant}]
 133                                 if !ok {
 134                                         err := fmt.Errorf("oops: genome %q has variant %d for tag %d, but that variant was not in its library", cg.Name, variant, tag)
 135                                         select {
 136                                         case errs <- err:
 137                                         default:
 138                                         }
 139                                         return
 140                                 }
 141                                 log.Tracef("loadCompactGenomes: cg %s tag %d variant %d => %d", cg.Name, tag, variant, newvariant)
 142                                 cg.Variants[i] = newvariant
 143                         }
 144                         if onLoadGenome != nil {
 145                                 onLoadGenome(cg)
 146                         }
 147                         if tilelib.encoder != nil {
 148                                 err := tilelib.encoder.Encode(LibraryEntry{
 149                                         CompactGenomes: []CompactGenome{cg},
 150                                 })
 151                                 if err != nil {
 152                                         select {
 153                                         case errs <- err:
 154                                         default:
 155                                         }
 156                                         return
 157                                 }
 158                         }
 159                         if tilelib.compactGenomes != nil {
 160                                 tilelib.mtx.Lock()
 161                                 defer tilelib.mtx.Unlock()
 162                                 tilelib.compactGenomes[cg.Name] = cg.Variants
 163                         }
 164                 }()
 165         }
 166         wg.Wait()
 167         go close(errs)
 168         return <-errs
 169 }
 170
 171 func (tilelib *tileLibrary) loadCompactSequences(cseqs []CompactSequence, variantmap map[tileLibRef]tileVariantID) error {
 172         log.Debugf("loadCompactSequences: %d", len(cseqs))
 173         for _, cseq := range cseqs {
 174                 for _, tseq := range cseq.TileSequences {
 175                         for i, libref := range tseq {
 176                                 if libref.Variant == 0 {
 177                                         // No variant (e.g., import
 178                                         // dropped tiles with
 179                                         // no-calls) = no translation.
 180                                         continue
 181                                 }
 182                                 v, ok := variantmap[libref]
 183                                 if !ok {
 184                                         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)
 185                                 }
 186                                 tseq[i].Variant = v
 187                         }
 188                 }
 189                 if tilelib.encoder != nil {
 190                         if err := tilelib.encoder.Encode(LibraryEntry{
 191                                 CompactSequences: []CompactSequence{cseq},
 192                         }); err != nil {
 193                                 return err
 194                         }
 195                 }
 196         }
 197         tilelib.mtx.Lock()
 198         defer tilelib.mtx.Unlock()
 199         if tilelib.refseqs == nil {
 200                 tilelib.refseqs = map[string]map[string][]tileLibRef{}
 201         }
 202         for _, cseq := range cseqs {
 203                 tilelib.refseqs[cseq.Name] = cseq.TileSequences
 204         }
 205         return nil
 206 }
 207
 208 // Load library data from rdr. Tile variants might be renumbered in
 209 // the process; in that case, genomes variants will be renumbered to
 210 // match.
 211 //
 212 // If onLoadGenome is non-nil, call it on each CompactGenome entry.
 213 func (tilelib *tileLibrary) LoadGob(ctx context.Context, rdr io.Reader, gz bool, onLoadGenome func(CompactGenome)) error {
 214         cgs := []CompactGenome{}
 215         cseqs := []CompactSequence{}
 216         variantmap := map[tileLibRef]tileVariantID{}
 217         err := DecodeLibrary(rdr, gz, func(ent *LibraryEntry) error {
 218                 if ctx.Err() != nil {
 219                         return ctx.Err()
 220                 }
 221                 if err := tilelib.loadTagSet(ent.TagSet); err != nil {
 222                         return err
 223                 }
 224                 if err := tilelib.loadTileVariants(ent.TileVariants, variantmap); err != nil {
 225                         return err
 226                 }
 227                 cgs = append(cgs, ent.CompactGenomes...)
 228                 cseqs = append(cseqs, ent.CompactSequences...)
 229                 return nil
 230         })
 231         if err != nil {
 232                 return err
 233         }
 234         if ctx.Err() != nil {
 235                 return ctx.Err()
 236         }
 237         err = tilelib.loadCompactGenomes(cgs, variantmap, onLoadGenome)
 238         if err != nil {
 239                 return err
 240         }
 241         err = tilelib.loadCompactSequences(cseqs, variantmap)
 242         if err != nil {
 243                 return err
 244         }
 245         return nil
 246 }
 247
 248 type importStats struct {
 249         InputFile              string
 250         InputLabel             string
 251         InputLength            int
 252         InputCoverage          int
 253         TileCoverage           int
 254         PathLength             int
 255         DroppedOutOfOrderTiles int
 256 }
 257
 258 func (tilelib *tileLibrary) TileFasta(filelabel string, rdr io.Reader) (tileSeq, []importStats, error) {
 259         ret := tileSeq{}
 260         type jobT struct {
 261                 label string
 262                 fasta []byte
 263         }
 264         todo := make(chan jobT)
 265         scanner := bufio.NewScanner(rdr)
 266         go func() {
 267                 defer close(todo)
 268                 var fasta []byte
 269                 var seqlabel string
 270                 for scanner.Scan() {
 271                         buf := scanner.Bytes()
 272                         if len(buf) > 0 && buf[0] == '>' {
 273                                 todo <- jobT{seqlabel, fasta}
 274                                 seqlabel, fasta = strings.SplitN(string(buf[1:]), " ", 2)[0], nil
 275                                 log.Debugf("%s %s reading fasta", filelabel, seqlabel)
 276                         } else {
 277                                 fasta = append(fasta, bytes.ToLower(buf)...)
 278                         }
 279                 }
 280                 todo <- jobT{seqlabel, fasta}
 281         }()
 282         type foundtag struct {
 283                 pos    int
 284                 tagid  tagID
 285                 taglen int
 286         }
 287         found := make([]foundtag, 2000000)
 288         path := make([]tileLibRef, 2000000)
 289         totalFoundTags := 0
 290         totalPathLen := 0
 291         skippedSequences := 0
 292         stats := make([]importStats, 0, len(todo))
 293         for job := range todo {
 294                 if len(job.fasta) == 0 {
 295                         continue
 296                 } else if strings.Contains(job.label, "_") {
 297                         skippedSequences++
 298                         continue
 299                 }
 300                 log.Debugf("%s %s tiling", filelabel, job.label)
 301
 302                 found = found[:0]
 303                 tilelib.taglib.FindAll(job.fasta, func(tagid tagID, pos, taglen int) {
 304                         found = append(found, foundtag{pos: pos, tagid: tagid, taglen: taglen})
 305                 })
 306                 totalFoundTags += len(found)
 307
 308                 basesOut := 0
 309                 skipped := 0
 310                 path = path[:0]
 311                 last := foundtag{tagid: -1}
 312                 if tilelib.skipOOO {
 313                         keep := longestIncreasingSubsequence(len(found), func(i int) int { return int(found[i].tagid) })
 314                         for i, x := range keep {
 315                                 found[i] = found[x]
 316                         }
 317                         skipped = len(found) - len(keep)
 318                         found = found[:len(keep)]
 319                 }
 320                 for i, f := range found {
 321                         log.Tracef("%s %s found[%d] == %#v", filelabel, job.label, i, f)
 322                         if last.tagid < 0 {
 323                                 // first tag in sequence
 324                                 last = foundtag{tagid: f.tagid}
 325                                 continue
 326                         }
 327                         libref := tilelib.getRef(last.tagid, job.fasta[last.pos:f.pos+f.taglen])
 328                         path = append(path, libref)
 329                         if libref.Variant > 0 {
 330                                 // Count output coverage from
 331                                 // the end of the previous tag
 332                                 // (if any) to the end of the
 333                                 // current tag, IOW don't
 334                                 // double-count coverage for
 335                                 // the previous tag.
 336                                 basesOut += countBases(job.fasta[last.pos+last.taglen : f.pos+f.taglen])
 337                         } else {
 338                                 // If we dropped this tile
 339                                 // (because !retainNoCalls),
 340                                 // set taglen=0 so the
 341                                 // overlapping tag is counted
 342                                 // toward coverage on the
 343                                 // following tile.
 344                                 f.taglen = 0
 345                         }
 346                         last = f
 347                 }
 348                 if last.tagid < 0 {
 349                         log.Warnf("%s %s no tags found", filelabel, job.label)
 350                 } else {
 351                         libref := tilelib.getRef(last.tagid, job.fasta[last.pos:])
 352                         path = append(path, libref)
 353                         if libref.Variant > 0 {
 354                                 basesOut += countBases(job.fasta[last.pos+last.taglen:])
 355                         }
 356                 }
 357
 358                 pathcopy := make([]tileLibRef, len(path))
 359                 copy(pathcopy, path)
 360                 ret[job.label] = pathcopy
 361
 362                 basesIn := countBases(job.fasta)
 363                 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)
 364                 stats = append(stats, importStats{
 365                         InputFile:              filelabel,
 366                         InputLabel:             job.label,
 367                         InputLength:            len(job.fasta),
 368                         InputCoverage:          basesIn,
 369                         TileCoverage:           basesOut,
 370                         PathLength:             len(path),
 371                         DroppedOutOfOrderTiles: skipped,
 372                 })
 373
 374                 totalPathLen += len(path)
 375         }
 376         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)
 377         return ret, stats, scanner.Err()
 378 }
 379
 380 func (tilelib *tileLibrary) Len() int {
 381         tilelib.mtx.Lock()
 382         defer tilelib.mtx.Unlock()
 383         return tilelib.variants
 384 }
 385
 386 // Return a tileLibRef for a tile with the given tag and sequence,
 387 // adding the sequence to the library if needed.
 388 func (tilelib *tileLibrary) getRef(tag tagID, seq []byte) tileLibRef {
 389         dropSeq := false
 390         if !tilelib.retainNoCalls {
 391                 for _, b := range seq {
 392                         if b != 'a' && b != 'c' && b != 'g' && b != 't' {
 393                                 dropSeq = true
 394                                 break
 395                         }
 396                 }
 397         }
 398         tilelib.mtx.Lock()
 399         if tilelib.variant == nil && tilelib.taglib != nil {
 400                 tilelib.variant = make([][][blake2b.Size256]byte, tilelib.taglib.Len())
 401         }
 402         if int(tag) >= len(tilelib.variant) {
 403                 // If we haven't seen the tag library yet (as in a
 404                 // merge), tilelib.taglib.Len() is zero. We can still
 405                 // behave correctly, we just need to expand the
 406                 // tilelib.variant slice as needed.
 407                 if int(tag) >= cap(tilelib.variant) {
 408                         // Allocate 2x capacity.
 409                         newslice := make([][][blake2b.Size256]byte, int(tag)+1, (int(tag)+1)*2)
 410                         copy(newslice, tilelib.variant)
 411                         tilelib.variant = newslice[:int(tag)+1]
 412                 } else {
 413                         // Use previously allocated capacity, avoiding
 414                         // copy.
 415                         tilelib.variant = tilelib.variant[:int(tag)+1]
 416                 }
 417         }
 418         seqhash := blake2b.Sum256(seq)
 419         for i, varhash := range tilelib.variant[tag] {
 420                 if varhash == seqhash {
 421                         tilelib.mtx.Unlock()
 422                         return tileLibRef{Tag: tag, Variant: tileVariantID(i + 1)}
 423                 }
 424         }
 425         tilelib.variants++
 426         tilelib.variant[tag] = append(tilelib.variant[tag], seqhash)
 427         if tilelib.retainTileSequences && !dropSeq {
 428                 if tilelib.seq == nil {
 429                         tilelib.seq = map[[blake2b.Size256]byte][]byte{}
 430                 }
 431                 tilelib.seq[seqhash] = append([]byte(nil), seq...)
 432         }
 433         variant := tileVariantID(len(tilelib.variant[tag]))
 434         tilelib.mtx.Unlock()
 435
 436         if tilelib.encoder != nil {
 437                 saveSeq := seq
 438                 if dropSeq {
 439                         // Save the hash, but not the sequence
 440                         saveSeq = nil
 441                 }
 442                 tilelib.encoder.Encode(LibraryEntry{
 443                         TileVariants: []TileVariant{{
 444                                 Tag:      tag,
 445                                 Variant:  variant,
 446                                 Blake2b:  seqhash,
 447                                 Sequence: saveSeq,
 448                         }},
 449                 })
 450         }
 451         return tileLibRef{Tag: tag, Variant: variant}
 452 }
 453
 454 func (tilelib *tileLibrary) TileVariantSequence(libref tileLibRef) []byte {
 455         if libref.Variant == 0 || len(tilelib.variant) <= int(libref.Tag) || len(tilelib.variant[libref.Tag]) < int(libref.Variant) {
 456                 return nil
 457         }
 458         return tilelib.seq[tilelib.variant[libref.Tag][libref.Variant-1]]
 459 }
 460
 461 // Tidy deletes unreferenced tile variants and renumbers variants so
 462 // more common variants have smaller IDs.
 463 func (tilelib *tileLibrary) Tidy() {
 464         log.Print("Tidy: compute inref")
 465         inref := map[tileLibRef]bool{}
 466         for _, refseq := range tilelib.refseqs {
 467                 for _, librefs := range refseq {
 468                         for _, libref := range librefs {
 469                                 inref[libref] = true
 470                         }
 471                 }
 472         }
 473         log.Print("Tidy: compute remap")
 474         remap := make([][]tileVariantID, len(tilelib.variant))
 475         throttle := throttle{Max: runtime.NumCPU() + 1}
 476         for tag, oldvariants := range tilelib.variant {
 477                 tag, oldvariants := tagID(tag), oldvariants
 478                 if tag%10000 == 0 {
 479                         log.Printf("Tidy: tag %d", tag)
 480                 }
 481                 throttle.Acquire()
 482                 go func() {
 483                         defer throttle.Release()
 484                         uses := make([]int, len(oldvariants))
 485                         for _, cg := range tilelib.compactGenomes {
 486                                 for phase := 0; phase < 2; phase++ {
 487                                         cgi := int(tag)*2 + phase
 488                                         if cgi < len(cg) && cg[cgi] > 0 {
 489                                                 uses[cg[cgi]-1]++
 490                                         }
 491                                 }
 492                         }
 493
 494                         // Compute desired order of variants:
 495                         // neworder[x] == index in oldvariants that
 496                         // should move to position x.
 497                         neworder := make([]int, len(oldvariants))
 498                         for i := range neworder {
 499                                 neworder[i] = i
 500                         }
 501                         sort.Slice(neworder, func(i, j int) bool {
 502                                 if cmp := uses[neworder[i]] - uses[neworder[j]]; cmp != 0 {
 503                                         return cmp > 0
 504                                 } else {
 505                                         return bytes.Compare(oldvariants[neworder[i]][:], oldvariants[neworder[j]][:]) < 0
 506                                 }
 507                         })
 508
 509                         // Replace tilelib.variants[tag] with a new
 510                         // re-ordered slice of hashes, and make a
 511                         // mapping from old to new variant IDs.
 512                         remaptag := make([]tileVariantID, len(oldvariants)+1)
 513                         newvariants := make([][blake2b.Size256]byte, 0, len(neworder))
 514                         for _, oldi := range neworder {
 515                                 if uses[oldi] > 0 || inref[tileLibRef{Tag: tag, Variant: tileVariantID(oldi + 1)}] {
 516                                         newvariants = append(newvariants, oldvariants[oldi])
 517                                         remaptag[oldi+1] = tileVariantID(len(newvariants))
 518                                 }
 519                         }
 520                         tilelib.variant[tag] = newvariants
 521                         remap[tag] = remaptag
 522                 }()
 523         }
 524         throttle.Wait()
 525
 526         // Apply remap to genomes and reference sequences, so they
 527         // refer to the same tile variants using the changed IDs.
 528         log.Print("Tidy: apply remap")
 529         for _, cg := range tilelib.compactGenomes {
 530                 for idx, variant := range cg {
 531                         cg[idx] = remap[tagID(idx/2)][variant]
 532                 }
 533         }
 534         for _, refcs := range tilelib.refseqs {
 535                 for _, refseq := range refcs {
 536                         for i, tv := range refseq {
 537                                 refseq[i].Variant = remap[tv.Tag][tv.Variant]
 538                         }
 539                 }
 540         }
 541         log.Print("Tidy: done")
 542 }
 543
 544 func countBases(seq []byte) int {
 545         n := 0
 546         for _, c := range seq {
 547                 if isbase[c] {
 548                         n++
 549                 }
 550         }
 551         return n
 552 }