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         "runtime"
  16         "sort"
  17         "strings"
  18         "sync"
  19         "time"
  20
  21         "git.arvados.org/arvados.git/sdk/go/arvados"
  22         "github.com/arvados/lightning/hgvs"
  23         log "github.com/sirupsen/logrus"
  24 )
  25
  26 type outputFormat struct {
  27         Print   func(out io.Writer, seqname string, varslice []hgvs.Variant)
  28         PadLeft bool
  29 }
  30
  31 var (
  32         outputFormats = map[string]outputFormat{
  33                 "hgvs-onehot": outputFormatHGVSOneHot,
  34                 "hgvs":        outputFormatHGVS,
  35                 "vcf":         outputFormatVCF,
  36         }
  37         outputFormatHGVS       = outputFormat{Print: printHGVS}
  38         outputFormatHGVSOneHot = outputFormat{Print: printHGVSOneHot}
  39         outputFormatVCF        = outputFormat{Print: printVCF, PadLeft: true}
  40 )
  41
  42 type exporter struct {
  43         outputFormat outputFormat
  44         maxTileSize  int
  45 }
  46
  47 func (cmd *exporter) RunCommand(prog string, args []string, stdin io.Reader, stdout, stderr io.Writer) int {
  48         var err error
  49         defer func() {
  50                 if err != nil {
  51                         fmt.Fprintf(stderr, "%s\n", err)
  52                 }
  53         }()
  54         flags := flag.NewFlagSet("", flag.ContinueOnError)
  55         flags.SetOutput(stderr)
  56         pprof := flags.String("pprof", "", "serve Go profile data at http://`[addr]:port`")
  57         pprofdir := flags.String("pprof-dir", "", "write Go profile data to `directory` periodically")
  58         runlocal := flags.Bool("local", false, "run on local host (default: run in an arvados container)")
  59         projectUUID := flags.String("project", "", "project `UUID` for output data")
  60         priority := flags.Int("priority", 500, "container request priority")
  61         refname := flags.String("ref", "", "reference genome `name`")
  62         inputFilename := flags.String("i", "-", "input `file` (library)")
  63         outputFilename := flags.String("o", "-", "output `file`")
  64         outputFormatStr := flags.String("output-format", "hgvs", "output `format`: hgvs or vcf")
  65         outputBed := flags.String("output-bed", "", "also output bed `file`")
  66         labelsFilename := flags.String("output-labels", "", "also output genome labels csv `file`")
  67         flags.IntVar(&cmd.maxTileSize, "max-tile-size", 50000, "don't try to make annotations for tiles bigger than given `size`")
  68         err = flags.Parse(args)
  69         if err == flag.ErrHelp {
  70                 err = nil
  71                 return 0
  72         } else if err != nil {
  73                 return 2
  74         }
  75
  76         if f, ok := outputFormats[*outputFormatStr]; !ok {
  77                 err = fmt.Errorf("invalid output format %q", *outputFormatStr)
  78                 return 2
  79         } else {
  80                 cmd.outputFormat = f
  81         }
  82
  83         if *pprof != "" {
  84                 go func() {
  85                         log.Println(http.ListenAndServe(*pprof, nil))
  86                 }()
  87         }
  88         if *pprofdir != "" {
  89                 go writeProfilesPeriodically(*pprofdir)
  90         }
  91
  92         if !*runlocal {
  93                 if *outputFilename != "-" {
  94                         err = errors.New("cannot specify output file in container mode: not implemented")
  95                         return 1
  96                 }
  97                 runner := arvadosContainerRunner{
  98                         Name:        "lightning export",
  99                         Client:      arvados.NewClientFromEnv(),
 100                         ProjectUUID: *projectUUID,
 101                         RAM:         700000000000,
 102                         VCPUs:       64,
 103                         Priority:    *priority,
 104                 }
 105                 err = runner.TranslatePaths(inputFilename)
 106                 if err != nil {
 107                         return 1
 108                 }
 109                 if *outputBed != "" {
 110                         if strings.Contains(*outputBed, "/") {
 111                                 err = fmt.Errorf("cannot use -output-bed filename %q containing '/' char", *outputBed)
 112                                 return 1
 113                         }
 114                         *outputBed = "/mnt/output/" + *outputBed
 115                 }
 116                 runner.Args = []string{"export", "-local=true",
 117                         "-pprof", ":6000",
 118                         "-pprof-dir", "/mnt/output",
 119                         "-ref", *refname,
 120                         "-output-format", *outputFormatStr,
 121                         "-output-bed", *outputBed,
 122                         "-output-labels", "/mnt/output/labels.csv",
 123                         "-max-tile-size", fmt.Sprintf("%d", cmd.maxTileSize),
 124                         "-i", *inputFilename,
 125                         "-o", "/mnt/output/export.csv",
 126                 }
 127                 var output string
 128                 output, err = runner.Run()
 129                 if err != nil {
 130                         return 1
 131                 }
 132                 fmt.Fprintln(stdout, output+"/export.csv")
 133                 return 0
 134         }
 135
 136         in, err := open(*inputFilename)
 137         if err != nil {
 138                 return 1
 139         }
 140         defer in.Close()
 141         input, ok := in.(io.ReadSeeker)
 142         if !ok {
 143                 err = fmt.Errorf("%s: %T cannot seek", *inputFilename, in)
 144                 return 1
 145         }
 146
 147         // Error out early if seeking doesn't work on the input file.
 148         _, err = input.Seek(0, io.SeekEnd)
 149         if err != nil {
 150                 return 1
 151         }
 152         _, err = input.Seek(0, io.SeekStart)
 153         if err != nil {
 154                 return 1
 155         }
 156
 157         var cgs []CompactGenome
 158         tilelib := &tileLibrary{
 159                 retainNoCalls:  true,
 160                 compactGenomes: map[string][]tileVariantID{},
 161         }
 162         err = tilelib.LoadGob(context.Background(), input, strings.HasSuffix(*inputFilename, ".gz"), nil)
 163         if err != nil {
 164                 return 1
 165         }
 166
 167         refseq, ok := tilelib.refseqs[*refname]
 168         if !ok {
 169                 err = fmt.Errorf("reference name %q not found in input; have %v", *refname, func() (names []string) {
 170                         for name := range tilelib.refseqs {
 171                                 names = append(names, name)
 172                         }
 173                         return
 174                 }())
 175                 return 1
 176         }
 177
 178         names := cgnames(tilelib)
 179         for _, name := range names {
 180                 cgs = append(cgs, CompactGenome{Name: name, Variants: tilelib.compactGenomes[name]})
 181         }
 182         if *labelsFilename != "" {
 183                 log.Infof("writing labels to %s", *labelsFilename)
 184                 var f *os.File
 185                 f, err = os.OpenFile(*labelsFilename, os.O_CREATE|os.O_WRONLY, 0777)
 186                 if err != nil {
 187                         return 1
 188                 }
 189                 defer f.Close()
 190                 _, outBasename := path.Split(*outputFilename)
 191                 for i, name := range names {
 192                         _, err = fmt.Fprintf(f, "%d,%q,%q\n", i, trimFilenameForLabel(name), outBasename)
 193                         if err != nil {
 194                                 err = fmt.Errorf("write %s: %w", *labelsFilename, err)
 195                                 return 1
 196                         }
 197                 }
 198                 err = f.Close()
 199                 if err != nil {
 200                         err = fmt.Errorf("close %s: %w", *labelsFilename, err)
 201                         return 1
 202                 }
 203         }
 204
 205         _, err = input.Seek(0, io.SeekStart)
 206         if err != nil {
 207                 return 1
 208         }
 209
 210         var output io.WriteCloser
 211         if *outputFilename == "-" {
 212                 output = nopCloser{stdout}
 213         } else {
 214                 output, err = os.OpenFile(*outputFilename, os.O_CREATE|os.O_WRONLY, 0666)
 215                 if err != nil {
 216                         return 1
 217                 }
 218                 defer output.Close()
 219         }
 220         bufw := bufio.NewWriter(output)
 221
 222         var bedout *os.File
 223         var bedbufw *bufio.Writer
 224         if *outputBed != "" {
 225                 bedout, err = os.OpenFile(*outputBed, os.O_CREATE|os.O_WRONLY, 0666)
 226                 if err != nil {
 227                         return 1
 228                 }
 229                 defer bedout.Close()
 230                 bedbufw = bufio.NewWriter(bedout)
 231         }
 232
 233         err = cmd.export(bufw, bedout, input, strings.HasSuffix(*inputFilename, ".gz"), tilelib, refseq, cgs)
 234         if err != nil {
 235                 return 1
 236         }
 237         err = bufw.Flush()
 238         if err != nil {
 239                 return 1
 240         }
 241         err = output.Close()
 242         if err != nil {
 243                 return 1
 244         }
 245         if bedout != nil {
 246                 err = bedbufw.Flush()
 247                 if err != nil {
 248                         return 1
 249                 }
 250                 err = bedout.Close()
 251                 if err != nil {
 252                         return 1
 253                 }
 254         }
 255         err = in.Close()
 256         if err != nil {
 257                 return 1
 258         }
 259         return 0
 260 }
 261
 262 func (cmd *exporter) export(out, bedout io.Writer, librdr io.Reader, gz bool, tilelib *tileLibrary, refseq map[string][]tileLibRef, cgs []CompactGenome) error {
 263         need := map[tileLibRef]bool{}
 264         var seqnames []string
 265         for seqname, librefs := range refseq {
 266                 seqnames = append(seqnames, seqname)
 267                 for _, libref := range librefs {
 268                         if libref.Variant != 0 {
 269                                 need[libref] = true
 270                         }
 271                 }
 272         }
 273         sort.Strings(seqnames)
 274
 275         for _, cg := range cgs {
 276                 for i, variant := range cg.Variants {
 277                         if variant == 0 {
 278                                 continue
 279                         }
 280                         libref := tileLibRef{Tag: tagID(i / 2), Variant: variant}
 281                         need[libref] = true
 282                 }
 283         }
 284
 285         log.Infof("export: loading %d tile variants", len(need))
 286         tileVariant := map[tileLibRef]TileVariant{}
 287         err := DecodeLibrary(librdr, gz, func(ent *LibraryEntry) error {
 288                 for _, tv := range ent.TileVariants {
 289                         libref := tilelib.getRef(tv.Tag, tv.Sequence)
 290                         if need[libref] {
 291                                 tileVariant[libref] = tv
 292                         }
 293                 }
 294                 return nil
 295         })
 296         if err != nil {
 297                 return err
 298         }
 299
 300         log.Infof("export: loaded %d tile variants", len(tileVariant))
 301         var missing []tileLibRef
 302         for libref := range need {
 303                 if _, ok := tileVariant[libref]; !ok {
 304                         missing = append(missing, libref)
 305                 }
 306         }
 307         if len(missing) > 0 {
 308                 if limit := 100; len(missing) > limit {
 309                         log.Warnf("first %d missing tiles: %v", limit, missing[:limit])
 310                 } else {
 311                         log.Warnf("missing tiles: %v", missing)
 312                 }
 313                 return fmt.Errorf("%d needed tiles are missing from library", len(missing))
 314         }
 315
 316         outw := make([]io.WriteCloser, len(seqnames))
 317         bedw := make([]io.WriteCloser, len(seqnames))
 318
 319         var merges sync.WaitGroup
 320         merge := func(dst io.Writer, src []io.WriteCloser, label string) {
 321                 var mtx sync.Mutex
 322                 for i, seqname := range seqnames {
 323                         pr, pw := io.Pipe()
 324                         src[i] = pw
 325                         merges.Add(1)
 326                         seqname := seqname
 327                         go func() {
 328                                 defer merges.Done()
 329                                 log.Infof("writing %s %s", seqname, label)
 330                                 scanner := bufio.NewScanner(pr)
 331                                 for scanner.Scan() {
 332                                         mtx.Lock()
 333                                         dst.Write(scanner.Bytes())
 334                                         dst.Write([]byte{'\n'})
 335                                         mtx.Unlock()
 336                                 }
 337                                 log.Infof("writing %s %s done", seqname, label)
 338                         }()
 339                 }
 340         }
 341         merge(out, outw, "output")
 342         if bedout != nil {
 343                 merge(bedout, bedw, "bed")
 344         }
 345
 346         throttle := throttle{Max: runtime.NumCPU()}
 347         log.Infof("assembling %d sequences in %d goroutines", len(seqnames), throttle.Max)
 348         for seqidx, seqname := range seqnames {
 349                 seqidx, seqname := seqidx, seqname
 350                 outw := outw[seqidx]
 351                 bedw := bedw[seqidx]
 352                 throttle.Acquire()
 353                 go func() {
 354                         defer throttle.Release()
 355                         if bedw != nil {
 356                                 defer bedw.Close()
 357                         }
 358                         defer outw.Close()
 359                         outwb := bufio.NewWriter(outw)
 360                         defer outwb.Flush()
 361                         cmd.exportSeq(outwb, bedw, tilelib.taglib.keylen, seqname, refseq[seqname], tileVariant, cgs)
 362                 }()
 363         }
 364
 365         merges.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                                 if len(genometile.Sequence) > cmd.maxTileSize {
 398                                         continue
 399                                 }
 400                                 refSequence := reftile.Sequence
 401                                 // If needed, extend the reference
 402                                 // sequence up to the tag at the end
 403                                 // of the genometile sequence.
 404                                 refstepend := refstep + 1
 405                                 for refstepend < len(reftiles) && len(refSequence) >= taglen && !bytes.EqualFold(refSequence[len(refSequence)-taglen:], genometile.Sequence[len(genometile.Sequence)-taglen:]) && len(refSequence) <= cmd.maxTileSize {
 406                                         if &refSequence[0] == &reftile.Sequence[0] {
 407                                                 refSequence = append([]byte(nil), refSequence...)
 408                                         }
 409                                         refSequence = append(refSequence, tileVariant[reftiles[refstepend]].Sequence...)
 410                                         refstepend++
 411                                 }
 412                                 // (TODO: handle no-calls)
 413                                 vars, _ := hgvs.Diff(strings.ToUpper(string(refSequence)), strings.ToUpper(string(genometile.Sequence)), time.Second)
 414                                 for _, v := range vars {
 415                                         if cmd.outputFormat.PadLeft {
 416                                                 v = v.PadLeft()
 417                                         }
 418                                         v.Position += refpos
 419                                         varslice := variantAt[v.Position]
 420                                         if varslice == nil {
 421                                                 varslice = make([]hgvs.Variant, len(cgs)*2)
 422                                                 variantAt[v.Position] = varslice
 423                                         }
 424                                         varslice[cgidx*2+phase] = v
 425                                 }
 426                         }
 427                 }
 428                 refpos += len(reftile.Sequence) - taglen
 429
 430                 // Flush entries from variantAt that are behind
 431                 // refpos. Flush all entries if this is the last
 432                 // reftile of the path/chromosome.
 433                 var flushpos []int
 434                 lastrefstep := refstep == len(reftiles)-1
 435                 for pos := range variantAt {
 436                         if lastrefstep || pos <= refpos {
 437                                 flushpos = append(flushpos, pos)
 438                         }
 439                 }
 440                 sort.Slice(flushpos, func(i, j int) bool { return flushpos[i] < flushpos[j] })
 441                 for _, pos := range flushpos {
 442                         varslice := variantAt[pos]
 443                         delete(variantAt, pos)
 444                         for i := range varslice {
 445                                 if varslice[i].Position == 0 {
 446                                         varslice[i].Position = pos
 447                                 }
 448                         }
 449                         cmd.outputFormat.Print(outw, seqname, varslice)
 450                 }
 451                 if bedw != nil && len(reftile.Sequence) > 0 {
 452                         tilestart := refpos - len(reftile.Sequence) + taglen
 453                         tileend := refpos
 454                         if !lastrefstep {
 455                                 tileend += taglen
 456                         }
 457                         thickstart := tilestart + taglen
 458                         if refstep == 0 {
 459                                 thickstart = 0
 460                         }
 461                         thickend := refpos
 462
 463                         // coverage score, 0 to 1000
 464                         score := 1000
 465                         if len(cgs) > 0 {
 466                                 score = 1000 * tagcoverage / len(cgs) / 2
 467                         }
 468
 469                         fmt.Fprintf(bedw, "%s %d %d %d %d . %d %d\n",
 470                                 seqname, tilestart, tileend,
 471                                 libref.Tag,
 472                                 score,
 473                                 thickstart, thickend)
 474                 }
 475         }
 476 }
 477
 478 func printVCF(out io.Writer, seqname string, varslice []hgvs.Variant) {
 479         refs := map[string]map[string]int{}
 480         for _, v := range varslice {
 481                 if v.Ref == "" && v.New == "" {
 482                         continue
 483                 }
 484                 alts := refs[v.Ref]
 485                 if alts == nil {
 486                         alts = map[string]int{}
 487                         refs[v.Ref] = alts
 488                 }
 489                 alts[v.New] = 0
 490         }
 491         for ref, alts := range refs {
 492                 var altslice []string
 493                 for alt := range alts {
 494                         altslice = append(altslice, alt)
 495                 }
 496                 sort.Strings(altslice)
 497                 for i, a := range altslice {
 498                         alts[a] = i + 1
 499                 }
 500                 fmt.Fprintf(out, "%s\t%d\t%s\t%s", seqname, varslice[0].Position, ref, strings.Join(altslice, ","))
 501                 for i := 0; i < len(varslice); i += 2 {
 502                         v1, v2 := varslice[i], varslice[i+1]
 503                         a1, a2 := alts[v1.New], alts[v2.New]
 504                         if v1.Ref != ref {
 505                                 a1 = 0
 506                         }
 507                         if v2.Ref != ref {
 508                                 a2 = 0
 509                         }
 510                         fmt.Fprintf(out, "\t%d/%d", a1, a2)
 511                 }
 512                 out.Write([]byte{'\n'})
 513         }
 514 }
 515
 516 func printHGVS(out io.Writer, seqname string, varslice []hgvs.Variant) {
 517         for i := 0; i < len(varslice)/2; i++ {
 518                 if i > 0 {
 519                         out.Write([]byte{'\t'})
 520                 }
 521                 var1, var2 := varslice[i*2], varslice[i*2+1]
 522                 if var1 == var2 {
 523                         if var1.Ref == var1.New {
 524                                 out.Write([]byte{'.'})
 525                         } else {
 526                                 fmt.Fprintf(out, "%s:g.%s", seqname, var1.String())
 527                         }
 528                 } else {
 529                         fmt.Fprintf(out, "%s:g.[%s];[%s]", seqname, var1.String(), var2.String())
 530                 }
 531         }
 532         out.Write([]byte{'\n'})
 533 }
 534
 535 func printHGVSOneHot(out io.Writer, seqname string, varslice []hgvs.Variant) {
 536         vars := map[hgvs.Variant]bool{}
 537         for _, v := range varslice {
 538                 if v.Ref != v.New {
 539                         vars[v] = true
 540                 }
 541         }
 542
 543         // sort variants to ensure output is deterministic
 544         sorted := make([]hgvs.Variant, 0, len(vars))
 545         for v := range vars {
 546                 sorted = append(sorted, v)
 547         }
 548         sort.Slice(sorted, func(a, b int) bool { return hgvs.Less(sorted[a], sorted[b]) })
 549
 550         for _, v := range sorted {
 551                 fmt.Fprintf(out, "%s.%s", seqname, v.String())
 552                 for i := 0; i < len(varslice); i += 2 {
 553                         if varslice[i] == v || varslice[i+1] == v {
 554                                 out.Write([]byte("\t1"))
 555                         } else {
 556                                 out.Write([]byte("\t0"))
 557                         }
 558                 }
 559                 out.Write([]byte{'\n'})
 560         }
 561 }