export.go

   1 package lightning
   2
   3 import (
   4         "bufio"
   5         "bytes"
   6         "context"
   7         "errors"
   8         "flag"
   9         "fmt"
  10         "io"
  11         "net/http"
  12         _ "net/http/pprof"
  13         "os"
  14         "path"
  15         "sort"
  16         "strings"
  17         "sync"
  18         "time"
  19
  20         "git.arvados.org/arvados.git/sdk/go/arvados"
  21         "github.com/arvados/lightning/hgvs"
  22         log "github.com/sirupsen/logrus"
  23 )
  24
  25 type outputFormat struct {
  26         Print   func(out io.Writer, seqname string, varslice []hgvs.Variant)
  27         PadLeft bool
  28 }
  29
  30 var (
  31         outputFormats = map[string]outputFormat{
  32                 "hgvs-onehot": outputFormatHGVSOneHot,
  33                 "hgvs":        outputFormatHGVS,
  34                 "vcf":         outputFormatVCF,
  35         }
  36         outputFormatHGVS       = outputFormat{Print: printHGVS}
  37         outputFormatHGVSOneHot = outputFormat{Print: printHGVSOneHot}
  38         outputFormatVCF        = outputFormat{Print: printVCF, PadLeft: true}
  39 )
  40
  41 type exporter struct {
  42         outputFormat outputFormat
  43 }
  44
  45 func (cmd *exporter) RunCommand(prog string, args []string, stdin io.Reader, stdout, stderr io.Writer) int {
  46         var err error
  47         defer func() {
  48                 if err != nil {
  49                         fmt.Fprintf(stderr, "%s\n", err)
  50                 }
  51         }()
  52         flags := flag.NewFlagSet("", flag.ContinueOnError)
  53         flags.SetOutput(stderr)
  54         pprof := flags.String("pprof", "", "serve Go profile data at http://`[addr]:port`")
  55         runlocal := flags.Bool("local", false, "run on local host (default: run in an arvados container)")
  56         projectUUID := flags.String("project", "", "project `UUID` for output data")
  57         priority := flags.Int("priority", 500, "container request priority")
  58         refname := flags.String("ref", "", "reference genome `name`")
  59         inputFilename := flags.String("i", "-", "input `file` (library)")
  60         outputFilename := flags.String("o", "-", "output `file`")
  61         outputFormatStr := flags.String("output-format", "hgvs", "output `format`: hgvs or vcf")
  62         outputBed := flags.String("output-bed", "", "also output bed `file`")
  63         labelsFilename := flags.String("output-labels", "", "also output genome labels csv `file`")
  64         err = flags.Parse(args)
  65         if err == flag.ErrHelp {
  66                 err = nil
  67                 return 0
  68         } else if err != nil {
  69                 return 2
  70         }
  71
  72         if f, ok := outputFormats[*outputFormatStr]; !ok {
  73                 err = fmt.Errorf("invalid output format %q", *outputFormatStr)
  74                 return 2
  75         } else {
  76                 cmd.outputFormat = f
  77         }
  78
  79         if *pprof != "" {
  80                 go func() {
  81                         log.Println(http.ListenAndServe(*pprof, nil))
  82                 }()
  83         }
  84
  85         if !*runlocal {
  86                 if *outputFilename != "-" {
  87                         err = errors.New("cannot specify output file in container mode: not implemented")
  88                         return 1
  89                 }
  90                 runner := arvadosContainerRunner{
  91                         Name:        "lightning export",
  92                         Client:      arvados.NewClientFromEnv(),
  93                         ProjectUUID: *projectUUID,
  94                         RAM:         1600000000000,
  95                         VCPUs:       64,
  96                         Priority:    *priority,
  97                 }
  98                 err = runner.TranslatePaths(inputFilename)
  99                 if err != nil {
 100                         return 1
 101                 }
 102                 if *outputBed != "" {
 103                         if strings.Contains(*outputBed, "/") {
 104                                 err = fmt.Errorf("cannot use -output-bed filename %q containing '/' char", *outputBed)
 105                                 return 1
 106                         }
 107                         *outputBed = "/mnt/output/" + *outputBed
 108                 }
 109                 runner.Args = []string{"export", "-local=true",
 110                         "-ref", *refname,
 111                         "-output-format", *outputFormatStr,
 112                         "-output-bed", *outputBed,
 113                         "-output-labels", "/mnt/output/labels.csv",
 114                         "-i", *inputFilename,
 115                         "-o", "/mnt/output/export.csv",
 116                 }
 117                 var output string
 118                 output, err = runner.Run()
 119                 if err != nil {
 120                         return 1
 121                 }
 122                 fmt.Fprintln(stdout, output+"/export.csv")
 123                 return 0
 124         }
 125
 126         in, err := open(*inputFilename)
 127         if err != nil {
 128                 return 1
 129         }
 130         defer in.Close()
 131         input, ok := in.(io.ReadSeeker)
 132         if !ok {
 133                 err = fmt.Errorf("%s: %T cannot seek", *inputFilename, in)
 134                 return 1
 135         }
 136
 137         // Error out early if seeking doesn't work on the input file.
 138         _, err = input.Seek(0, io.SeekEnd)
 139         if err != nil {
 140                 return 1
 141         }
 142         _, err = input.Seek(0, io.SeekStart)
 143         if err != nil {
 144                 return 1
 145         }
 146
 147         var cgs []CompactGenome
 148         tilelib := &tileLibrary{
 149                 retainNoCalls:  true,
 150                 compactGenomes: map[string][]tileVariantID{},
 151         }
 152         err = tilelib.LoadGob(context.Background(), input, strings.HasSuffix(*inputFilename, ".gz"), nil)
 153         if err != nil {
 154                 return 1
 155         }
 156
 157         refseq, ok := tilelib.refseqs[*refname]
 158         if !ok {
 159                 err = fmt.Errorf("reference name %q not found in input; have %v", *refname, func() (names []string) {
 160                         for name := range tilelib.refseqs {
 161                                 names = append(names, name)
 162                         }
 163                         return
 164                 }())
 165                 return 1
 166         }
 167
 168         names := cgnames(tilelib)
 169         for _, name := range names {
 170                 cgs = append(cgs, CompactGenome{Name: name, Variants: tilelib.compactGenomes[name]})
 171         }
 172         if *labelsFilename != "" {
 173                 log.Infof("writing labels to %s", *labelsFilename)
 174                 var f *os.File
 175                 f, err = os.OpenFile(*labelsFilename, os.O_CREATE|os.O_WRONLY, 0777)
 176                 if err != nil {
 177                         return 1
 178                 }
 179                 defer f.Close()
 180                 _, outBasename := path.Split(*outputFilename)
 181                 for i, name := range names {
 182                         _, err = fmt.Fprintf(f, "%d,%q,%q\n", i, trimFilenameForLabel(name), outBasename)
 183                         if err != nil {
 184                                 err = fmt.Errorf("write %s: %w", *labelsFilename, err)
 185                                 return 1
 186                         }
 187                 }
 188                 err = f.Close()
 189                 if err != nil {
 190                         err = fmt.Errorf("close %s: %w", *labelsFilename, err)
 191                         return 1
 192                 }
 193         }
 194
 195         _, err = input.Seek(0, io.SeekStart)
 196         if err != nil {
 197                 return 1
 198         }
 199
 200         var output io.WriteCloser
 201         if *outputFilename == "-" {
 202                 output = nopCloser{stdout}
 203         } else {
 204                 output, err = os.OpenFile(*outputFilename, os.O_CREATE|os.O_WRONLY, 0666)
 205                 if err != nil {
 206                         return 1
 207                 }
 208                 defer output.Close()
 209         }
 210         bufw := bufio.NewWriter(output)
 211
 212         var bedout *os.File
 213         var bedbufw *bufio.Writer
 214         if *outputBed != "" {
 215                 bedout, err = os.OpenFile(*outputBed, os.O_CREATE|os.O_WRONLY, 0666)
 216                 if err != nil {
 217                         return 1
 218                 }
 219                 defer bedout.Close()
 220                 bedbufw = bufio.NewWriter(bedout)
 221         }
 222
 223         err = cmd.export(bufw, bedout, input, strings.HasSuffix(*inputFilename, ".gz"), tilelib, refseq, cgs)
 224         if err != nil {
 225                 return 1
 226         }
 227         err = bufw.Flush()
 228         if err != nil {
 229                 return 1
 230         }
 231         err = output.Close()
 232         if err != nil {
 233                 return 1
 234         }
 235         if bedout != nil {
 236                 err = bedbufw.Flush()
 237                 if err != nil {
 238                         return 1
 239                 }
 240                 err = bedout.Close()
 241                 if err != nil {
 242                         return 1
 243                 }
 244         }
 245         err = in.Close()
 246         if err != nil {
 247                 return 1
 248         }
 249         return 0
 250 }
 251
 252 func (cmd *exporter) export(out, bedout io.Writer, librdr io.Reader, gz bool, tilelib *tileLibrary, refseq map[string][]tileLibRef, cgs []CompactGenome) error {
 253         need := map[tileLibRef]bool{}
 254         var seqnames []string
 255         for seqname, librefs := range refseq {
 256                 seqnames = append(seqnames, seqname)
 257                 for _, libref := range librefs {
 258                         if libref.Variant != 0 {
 259                                 need[libref] = true
 260                         }
 261                 }
 262         }
 263         sort.Strings(seqnames)
 264
 265         for _, cg := range cgs {
 266                 for i, variant := range cg.Variants {
 267                         if variant == 0 {
 268                                 continue
 269                         }
 270                         libref := tileLibRef{Tag: tagID(i / 2), Variant: variant}
 271                         need[libref] = true
 272                 }
 273         }
 274
 275         log.Infof("export: loading %d tile variants", len(need))
 276         tileVariant := map[tileLibRef]TileVariant{}
 277         err := DecodeLibrary(librdr, gz, func(ent *LibraryEntry) error {
 278                 for _, tv := range ent.TileVariants {
 279                         libref := tilelib.getRef(tv.Tag, tv.Sequence)
 280                         if need[libref] {
 281                                 tileVariant[libref] = tv
 282                         }
 283                 }
 284                 return nil
 285         })
 286         if err != nil {
 287                 return err
 288         }
 289
 290         log.Infof("export: loaded %d tile variants", len(tileVariant))
 291         var missing []tileLibRef
 292         for libref := range need {
 293                 if _, ok := tileVariant[libref]; !ok {
 294                         missing = append(missing, libref)
 295                 }
 296         }
 297         if len(missing) > 0 {
 298                 if limit := 100; len(missing) > limit {
 299                         log.Warnf("first %d missing tiles: %v", limit, missing[:limit])
 300                 } else {
 301                         log.Warnf("missing tiles: %v", missing)
 302                 }
 303                 return fmt.Errorf("%d needed tiles are missing from library", len(missing))
 304         }
 305
 306         if true {
 307                 // low memory mode
 308                 for _, seqname := range seqnames {
 309                         log.Infof("assembling %q", seqname)
 310                         cmd.exportSeq(out, bedout, tilelib.taglib.keylen, seqname, refseq[seqname], tileVariant, cgs)
 311                         log.Infof("assembled %q", seqname)
 312                 }
 313                 return nil
 314         }
 315
 316         outbuf := make([]bytes.Buffer, len(seqnames))
 317         bedbuf := make([]bytes.Buffer, len(seqnames))
 318         ready := make([]chan struct{}, len(seqnames))
 319         for i := range ready {
 320                 ready[i] = make(chan struct{})
 321         }
 322
 323         var output sync.WaitGroup
 324         output.Add(1)
 325         go func() {
 326                 defer output.Done()
 327                 for i, seqname := range seqnames {
 328                         <-ready[i]
 329                         log.Infof("writing outbuf %s", seqname)
 330                         io.Copy(out, &outbuf[i])
 331                         log.Infof("writing outbuf %s done", seqname)
 332                 }
 333         }()
 334         output.Add(1)
 335         go func() {
 336                 defer output.Done()
 337                 if bedout != nil {
 338                         for i, seqname := range seqnames {
 339                                 <-ready[i]
 340                                 log.Infof("writing bedbuf %s", seqname)
 341                                 io.Copy(bedout, &bedbuf[i])
 342                                 log.Infof("writing bedbuf %s done", seqname)
 343                         }
 344                 }
 345         }()
 346
 347         throttle := throttle{Max: 8}
 348         log.Infof("assembling %d sequences in %d goroutines", len(seqnames), throttle.Max)
 349         for seqidx, seqname := range seqnames {
 350                 seqidx, seqname := seqidx, seqname
 351                 outbuf := &outbuf[seqidx]
 352                 bedbuf := &bedbuf[seqidx]
 353                 if bedout == nil {
 354                         bedbuf = nil
 355                 }
 356                 throttle.Acquire()
 357                 go func() {
 358                         defer throttle.Release()
 359                         defer close(ready[seqidx])
 360                         cmd.exportSeq(outbuf, bedbuf, tilelib.taglib.keylen, seqname, refseq[seqname], tileVariant, cgs)
 361                         log.Infof("assembled %q to outbuf %d bedbuf %d", seqname, outbuf.Len(), bedbuf.Len())
 362                 }()
 363         }
 364
 365         output.Wait()
 366         return nil
 367 }
 368
 369 // Align genome tiles to reference tiles, write diffs to outw, and (if
 370 // bedw is not nil) write tile coverage to bedw.
 371 func (cmd *exporter) exportSeq(outw, bedw io.Writer, taglen int, seqname string, reftiles []tileLibRef, tileVariant map[tileLibRef]TileVariant, cgs []CompactGenome) {
 372         refpos := 0
 373         variantAt := map[int][]hgvs.Variant{} // variantAt[chromOffset][genomeIndex*2+phase]
 374         for refstep, libref := range reftiles {
 375                 reftile := tileVariant[libref]
 376                 tagcoverage := 0 // number of times the start tag was found in genomes -- max is len(cgs)*2
 377                 for cgidx, cg := range cgs {
 378                         for phase := 0; phase < 2; phase++ {
 379                                 if len(cg.Variants) <= int(libref.Tag)*2+phase {
 380                                         continue
 381                                 }
 382                                 variant := cg.Variants[int(libref.Tag)*2+phase]
 383                                 if variant == 0 {
 384                                         continue
 385                                 }
 386                                 tagcoverage++
 387                                 if variant == libref.Variant {
 388                                         continue
 389                                 }
 390                                 genometile := tileVariant[tileLibRef{Tag: libref.Tag, Variant: variant}]
 391                                 if len(genometile.Sequence) == 0 {
 392                                         // Hash is known but sequence
 393                                         // is not, e.g., retainNoCalls
 394                                         // was false during import
 395                                         continue
 396                                 }
 397                                 refSequence := reftile.Sequence
 398                                 // If needed, extend the reference
 399                                 // sequence up to the tag at the end
 400                                 // of the genometile sequence.
 401                                 refstepend := refstep + 1
 402                                 for refstepend < len(reftiles) && len(refSequence) >= taglen && !bytes.EqualFold(refSequence[len(refSequence)-taglen:], genometile.Sequence[len(genometile.Sequence)-taglen:]) {
 403                                         if &refSequence[0] == &reftile.Sequence[0] {
 404                                                 refSequence = append([]byte(nil), refSequence...)
 405                                         }
 406                                         refSequence = append(refSequence, tileVariant[reftiles[refstepend]].Sequence...)
 407                                         refstepend++
 408                                 }
 409                                 // (TODO: handle no-calls)
 410                                 vars, _ := hgvs.Diff(strings.ToUpper(string(refSequence)), strings.ToUpper(string(genometile.Sequence)), time.Second)
 411                                 for _, v := range vars {
 412                                         if cmd.outputFormat.PadLeft {
 413                                                 v = v.PadLeft()
 414                                         }
 415                                         v.Position += refpos
 416                                         varslice := variantAt[v.Position]
 417                                         if varslice == nil {
 418                                                 varslice = make([]hgvs.Variant, len(cgs)*2)
 419                                                 variantAt[v.Position] = varslice
 420                                         }
 421                                         varslice[cgidx*2+phase] = v
 422                                 }
 423                         }
 424                 }
 425                 refpos += len(reftile.Sequence) - taglen
 426
 427                 // Flush entries from variantAt that are behind
 428                 // refpos. Flush all entries if this is the last
 429                 // reftile of the path/chromosome.
 430                 var flushpos []int
 431                 lastrefstep := refstep == len(reftiles)-1
 432                 for pos := range variantAt {
 433                         if lastrefstep || pos <= refpos {
 434                                 flushpos = append(flushpos, pos)
 435                         }
 436                 }
 437                 sort.Slice(flushpos, func(i, j int) bool { return flushpos[i] < flushpos[j] })
 438                 for _, pos := range flushpos {
 439                         varslice := variantAt[pos]
 440                         delete(variantAt, pos)
 441                         for i := range varslice {
 442                                 if varslice[i].Position == 0 {
 443                                         varslice[i].Position = pos
 444                                 }
 445                         }
 446                         cmd.outputFormat.Print(outw, seqname, varslice)
 447                 }
 448                 if bedw != nil && len(reftile.Sequence) > 0 {
 449                         tilestart := refpos - len(reftile.Sequence) + taglen
 450                         tileend := refpos
 451                         if !lastrefstep {
 452                                 tileend += taglen
 453                         }
 454                         thickstart := tilestart + taglen
 455                         if refstep == 0 {
 456                                 thickstart = 0
 457                         }
 458                         thickend := refpos
 459
 460                         // coverage score, 0 to 1000
 461                         score := 1000
 462                         if len(cgs) > 0 {
 463                                 score = 1000 * tagcoverage / len(cgs) / 2
 464                         }
 465
 466                         fmt.Fprintf(bedw, "%s %d %d %d %d . %d %d\n",
 467                                 seqname, tilestart, tileend,
 468                                 libref.Tag,
 469                                 score,
 470                                 thickstart, thickend)
 471                 }
 472         }
 473 }
 474
 475 func printVCF(out io.Writer, seqname string, varslice []hgvs.Variant) {
 476         refs := map[string]map[string]int{}
 477         for _, v := range varslice {
 478                 if v.Ref == "" && v.New == "" {
 479                         continue
 480                 }
 481                 alts := refs[v.Ref]
 482                 if alts == nil {
 483                         alts = map[string]int{}
 484                         refs[v.Ref] = alts
 485                 }
 486                 alts[v.New] = 0
 487         }
 488         for ref, alts := range refs {
 489                 var altslice []string
 490                 for alt := range alts {
 491                         altslice = append(altslice, alt)
 492                 }
 493                 sort.Strings(altslice)
 494                 for i, a := range altslice {
 495                         alts[a] = i + 1
 496                 }
 497                 fmt.Fprintf(out, "%s\t%d\t%s\t%s", seqname, varslice[0].Position, ref, strings.Join(altslice, ","))
 498                 for i := 0; i < len(varslice); i += 2 {
 499                         v1, v2 := varslice[i], varslice[i+1]
 500                         a1, a2 := alts[v1.New], alts[v2.New]
 501                         if v1.Ref != ref {
 502                                 a1 = 0
 503                         }
 504                         if v2.Ref != ref {
 505                                 a2 = 0
 506                         }
 507                         fmt.Fprintf(out, "\t%d/%d", a1, a2)
 508                 }
 509                 out.Write([]byte{'\n'})
 510         }
 511 }
 512
 513 func printHGVS(out io.Writer, seqname string, varslice []hgvs.Variant) {
 514         for i := 0; i < len(varslice)/2; i++ {
 515                 if i > 0 {
 516                         out.Write([]byte{'\t'})
 517                 }
 518                 var1, var2 := varslice[i*2], varslice[i*2+1]
 519                 if var1 == var2 {
 520                         if var1.Ref == var1.New {
 521                                 out.Write([]byte{'.'})
 522                         } else {
 523                                 fmt.Fprintf(out, "%s:g.%s", seqname, var1.String())
 524                         }
 525                 } else {
 526                         fmt.Fprintf(out, "%s:g.[%s];[%s]", seqname, var1.String(), var2.String())
 527                 }
 528         }
 529         out.Write([]byte{'\n'})
 530 }
 531
 532 func printHGVSOneHot(out io.Writer, seqname string, varslice []hgvs.Variant) {
 533         vars := map[hgvs.Variant]bool{}
 534         for _, v := range varslice {
 535                 if v.Ref != v.New {
 536                         vars[v] = true
 537                 }
 538         }
 539
 540         // sort variants to ensure output is deterministic
 541         sorted := make([]hgvs.Variant, 0, len(vars))
 542         for v := range vars {
 543                 sorted = append(sorted, v)
 544         }
 545         sort.Slice(sorted, func(a, b int) bool { return hgvs.Less(sorted[a], sorted[b]) })
 546
 547         for _, v := range sorted {
 548                 fmt.Fprintf(out, "%s.%s", seqname, v.String())
 549                 for i := 0; i < len(varslice); i += 2 {
 550                         if varslice[i] == v || varslice[i+1] == v {
 551                                 out.Write([]byte("\t1"))
 552                         } else {
 553                                 out.Write([]byte("\t0"))
 554                         }
 555                 }
 556                 out.Write([]byte{'\n'})
 557         }
 558 }