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         maxTileSize  int
  44 }
  45
  46 func (cmd *exporter) RunCommand(prog string, args []string, stdin io.Reader, stdout, stderr io.Writer) int {
  47         var err error
  48         defer func() {
  49                 if err != nil {
  50                         fmt.Fprintf(stderr, "%s\n", err)
  51                 }
  52         }()
  53         flags := flag.NewFlagSet("", flag.ContinueOnError)
  54         flags.SetOutput(stderr)
  55         pprof := flags.String("pprof", "", "serve Go profile data at http://`[addr]:port`")
  56         pprofdir := flags.String("pprof-dir", "", "write Go profile data to `directory` periodically")
  57         runlocal := flags.Bool("local", false, "run on local host (default: run in an arvados container)")
  58         projectUUID := flags.String("project", "", "project `UUID` for output data")
  59         priority := flags.Int("priority", 500, "container request priority")
  60         refname := flags.String("ref", "", "reference genome `name`")
  61         inputFilename := flags.String("i", "-", "input `file` (library)")
  62         outputFilename := flags.String("o", "-", "output `file`")
  63         outputFormatStr := flags.String("output-format", "hgvs", "output `format`: hgvs or vcf")
  64         outputBed := flags.String("output-bed", "", "also output bed `file`")
  65         labelsFilename := flags.String("output-labels", "", "also output genome labels csv `file`")
  66         flags.IntVar(&cmd.maxTileSize, "max-tile-size", 50000, "don't try to make annotations for tiles bigger than given `size`")
  67         err = flags.Parse(args)
  68         if err == flag.ErrHelp {
  69                 err = nil
  70                 return 0
  71         } else if err != nil {
  72                 return 2
  73         }
  74
  75         if f, ok := outputFormats[*outputFormatStr]; !ok {
  76                 err = fmt.Errorf("invalid output format %q", *outputFormatStr)
  77                 return 2
  78         } else {
  79                 cmd.outputFormat = f
  80         }
  81
  82         if *pprof != "" {
  83                 go func() {
  84                         log.Println(http.ListenAndServe(*pprof, nil))
  85                 }()
  86         }
  87         if *pprofdir != "" {
  88                 go writeProfilesPeriodically(*pprofdir)
  89         }
  90
  91         if !*runlocal {
  92                 if *outputFilename != "-" {
  93                         err = errors.New("cannot specify output file in container mode: not implemented")
  94                         return 1
  95                 }
  96                 runner := arvadosContainerRunner{
  97                         Name:        "lightning export",
  98                         Client:      arvados.NewClientFromEnv(),
  99                         ProjectUUID: *projectUUID,
 100                         RAM:         1600000000000,
 101                         VCPUs:       64,
 102                         Priority:    *priority,
 103                 }
 104                 err = runner.TranslatePaths(inputFilename)
 105                 if err != nil {
 106                         return 1
 107                 }
 108                 if *outputBed != "" {
 109                         if strings.Contains(*outputBed, "/") {
 110                                 err = fmt.Errorf("cannot use -output-bed filename %q containing '/' char", *outputBed)
 111                                 return 1
 112                         }
 113                         *outputBed = "/mnt/output/" + *outputBed
 114                 }
 115                 runner.Args = []string{"export", "-local=true",
 116                         "-pprof", ":6000",
 117                         "-pprof-dir", "/mnt/output",
 118                         "-ref", *refname,
 119                         "-output-format", *outputFormatStr,
 120                         "-output-bed", *outputBed,
 121                         "-output-labels", "/mnt/output/labels.csv",
 122                         "-max-tile-size", fmt.Sprintf("%d", cmd.maxTileSize),
 123                         "-i", *inputFilename,
 124                         "-o", "/mnt/output/export.csv",
 125                 }
 126                 var output string
 127                 output, err = runner.Run()
 128                 if err != nil {
 129                         return 1
 130                 }
 131                 fmt.Fprintln(stdout, output+"/export.csv")
 132                 return 0
 133         }
 134
 135         in, err := open(*inputFilename)
 136         if err != nil {
 137                 return 1
 138         }
 139         defer in.Close()
 140         input, ok := in.(io.ReadSeeker)
 141         if !ok {
 142                 err = fmt.Errorf("%s: %T cannot seek", *inputFilename, in)
 143                 return 1
 144         }
 145
 146         // Error out early if seeking doesn't work on the input file.
 147         _, err = input.Seek(0, io.SeekEnd)
 148         if err != nil {
 149                 return 1
 150         }
 151         _, err = input.Seek(0, io.SeekStart)
 152         if err != nil {
 153                 return 1
 154         }
 155
 156         var cgs []CompactGenome
 157         tilelib := &tileLibrary{
 158                 retainNoCalls:  true,
 159                 compactGenomes: map[string][]tileVariantID{},
 160         }
 161         err = tilelib.LoadGob(context.Background(), input, strings.HasSuffix(*inputFilename, ".gz"), nil)
 162         if err != nil {
 163                 return 1
 164         }
 165
 166         refseq, ok := tilelib.refseqs[*refname]
 167         if !ok {
 168                 err = fmt.Errorf("reference name %q not found in input; have %v", *refname, func() (names []string) {
 169                         for name := range tilelib.refseqs {
 170                                 names = append(names, name)
 171                         }
 172                         return
 173                 }())
 174                 return 1
 175         }
 176
 177         names := cgnames(tilelib)
 178         for _, name := range names {
 179                 cgs = append(cgs, CompactGenome{Name: name, Variants: tilelib.compactGenomes[name]})
 180         }
 181         if *labelsFilename != "" {
 182                 log.Infof("writing labels to %s", *labelsFilename)
 183                 var f *os.File
 184                 f, err = os.OpenFile(*labelsFilename, os.O_CREATE|os.O_WRONLY, 0777)
 185                 if err != nil {
 186                         return 1
 187                 }
 188                 defer f.Close()
 189                 _, outBasename := path.Split(*outputFilename)
 190                 for i, name := range names {
 191                         _, err = fmt.Fprintf(f, "%d,%q,%q\n", i, trimFilenameForLabel(name), outBasename)
 192                         if err != nil {
 193                                 err = fmt.Errorf("write %s: %w", *labelsFilename, err)
 194                                 return 1
 195                         }
 196                 }
 197                 err = f.Close()
 198                 if err != nil {
 199                         err = fmt.Errorf("close %s: %w", *labelsFilename, err)
 200                         return 1
 201                 }
 202         }
 203
 204         _, err = input.Seek(0, io.SeekStart)
 205         if err != nil {
 206                 return 1
 207         }
 208
 209         var output io.WriteCloser
 210         if *outputFilename == "-" {
 211                 output = nopCloser{stdout}
 212         } else {
 213                 output, err = os.OpenFile(*outputFilename, os.O_CREATE|os.O_WRONLY, 0666)
 214                 if err != nil {
 215                         return 1
 216                 }
 217                 defer output.Close()
 218         }
 219         bufw := bufio.NewWriter(output)
 220
 221         var bedout *os.File
 222         var bedbufw *bufio.Writer
 223         if *outputBed != "" {
 224                 bedout, err = os.OpenFile(*outputBed, os.O_CREATE|os.O_WRONLY, 0666)
 225                 if err != nil {
 226                         return 1
 227                 }
 228                 defer bedout.Close()
 229                 bedbufw = bufio.NewWriter(bedout)
 230         }
 231
 232         err = cmd.export(bufw, bedout, input, strings.HasSuffix(*inputFilename, ".gz"), tilelib, refseq, cgs)
 233         if err != nil {
 234                 return 1
 235         }
 236         err = bufw.Flush()
 237         if err != nil {
 238                 return 1
 239         }
 240         err = output.Close()
 241         if err != nil {
 242                 return 1
 243         }
 244         if bedout != nil {
 245                 err = bedbufw.Flush()
 246                 if err != nil {
 247                         return 1
 248                 }
 249                 err = bedout.Close()
 250                 if err != nil {
 251                         return 1
 252                 }
 253         }
 254         err = in.Close()
 255         if err != nil {
 256                 return 1
 257         }
 258         return 0
 259 }
 260
 261 func (cmd *exporter) export(out, bedout io.Writer, librdr io.Reader, gz bool, tilelib *tileLibrary, refseq map[string][]tileLibRef, cgs []CompactGenome) error {
 262         need := map[tileLibRef]bool{}
 263         var seqnames []string
 264         for seqname, librefs := range refseq {
 265                 seqnames = append(seqnames, seqname)
 266                 for _, libref := range librefs {
 267                         if libref.Variant != 0 {
 268                                 need[libref] = true
 269                         }
 270                 }
 271         }
 272         sort.Strings(seqnames)
 273
 274         for _, cg := range cgs {
 275                 for i, variant := range cg.Variants {
 276                         if variant == 0 {
 277                                 continue
 278                         }
 279                         libref := tileLibRef{Tag: tagID(i / 2), Variant: variant}
 280                         need[libref] = true
 281                 }
 282         }
 283
 284         log.Infof("export: loading %d tile variants", len(need))
 285         tileVariant := map[tileLibRef]TileVariant{}
 286         err := DecodeLibrary(librdr, gz, func(ent *LibraryEntry) error {
 287                 for _, tv := range ent.TileVariants {
 288                         libref := tilelib.getRef(tv.Tag, tv.Sequence)
 289                         if need[libref] {
 290                                 tileVariant[libref] = tv
 291                         }
 292                 }
 293                 return nil
 294         })
 295         if err != nil {
 296                 return err
 297         }
 298
 299         log.Infof("export: loaded %d tile variants", len(tileVariant))
 300         var missing []tileLibRef
 301         for libref := range need {
 302                 if _, ok := tileVariant[libref]; !ok {
 303                         missing = append(missing, libref)
 304                 }
 305         }
 306         if len(missing) > 0 {
 307                 if limit := 100; len(missing) > limit {
 308                         log.Warnf("first %d missing tiles: %v", limit, missing[:limit])
 309                 } else {
 310                         log.Warnf("missing tiles: %v", missing)
 311                 }
 312                 return fmt.Errorf("%d needed tiles are missing from library", len(missing))
 313         }
 314
 315         outw := make([]io.WriteCloser, len(seqnames))
 316         bedw := make([]io.WriteCloser, len(seqnames))
 317
 318         var merges sync.WaitGroup
 319         merge := func(dst io.Writer, src []io.WriteCloser, label string) {
 320                 var mtx sync.Mutex
 321                 for i, seqname := range seqnames {
 322                         pr, pw := io.Pipe()
 323                         src[i] = pw
 324                         merges.Add(1)
 325                         seqname := seqname
 326                         go func() {
 327                                 defer merges.Done()
 328                                 log.Infof("writing %s %s", seqname, label)
 329                                 scanner := bufio.NewScanner(pr)
 330                                 for scanner.Scan() {
 331                                         mtx.Lock()
 332                                         dst.Write(scanner.Bytes())
 333                                         dst.Write([]byte{'\n'})
 334                                         mtx.Unlock()
 335                                 }
 336                                 log.Infof("writing %s %s done", seqname, label)
 337                         }()
 338                 }
 339         }
 340         merge(out, outw, "output")
 341         if bedout != nil {
 342                 merge(bedout, bedw, "bed")
 343         }
 344
 345         throttle := throttle{Max: 8}
 346         log.Infof("assembling %d sequences in %d goroutines", len(seqnames), throttle.Max)
 347         for seqidx, seqname := range seqnames {
 348                 seqidx, seqname := seqidx, seqname
 349                 outw := outw[seqidx]
 350                 bedw := bedw[seqidx]
 351                 throttle.Acquire()
 352                 go func() {
 353                         defer throttle.Release()
 354                         if bedw != nil {
 355                                 defer bedw.Close()
 356                         }
 357                         defer outw.Close()
 358                         outwb := bufio.NewWriter(outw)
 359                         defer outwb.Flush()
 360                         cmd.exportSeq(outwb, bedw, tilelib.taglib.keylen, seqname, refseq[seqname], tileVariant, cgs)
 361                 }()
 362         }
 363
 364         merges.Wait()
 365         return nil
 366 }
 367
 368 // Align genome tiles to reference tiles, write diffs to outw, and (if
 369 // bedw is not nil) write tile coverage to bedw.
 370 func (cmd *exporter) exportSeq(outw, bedw io.Writer, taglen int, seqname string, reftiles []tileLibRef, tileVariant map[tileLibRef]TileVariant, cgs []CompactGenome) {
 371         refpos := 0
 372         variantAt := map[int][]hgvs.Variant{} // variantAt[chromOffset][genomeIndex*2+phase]
 373         for refstep, libref := range reftiles {
 374                 reftile := tileVariant[libref]
 375                 tagcoverage := 0 // number of times the start tag was found in genomes -- max is len(cgs)*2
 376                 for cgidx, cg := range cgs {
 377                         for phase := 0; phase < 2; phase++ {
 378                                 if len(cg.Variants) <= int(libref.Tag)*2+phase {
 379                                         continue
 380                                 }
 381                                 variant := cg.Variants[int(libref.Tag)*2+phase]
 382                                 if variant == 0 {
 383                                         continue
 384                                 }
 385                                 tagcoverage++
 386                                 if variant == libref.Variant {
 387                                         continue
 388                                 }
 389                                 genometile := tileVariant[tileLibRef{Tag: libref.Tag, Variant: variant}]
 390                                 if len(genometile.Sequence) == 0 {
 391                                         // Hash is known but sequence
 392                                         // is not, e.g., retainNoCalls
 393                                         // was false during import
 394                                         continue
 395                                 }
 396                                 if len(genometile.Sequence) > cmd.maxTileSize {
 397                                         continue
 398                                 }
 399                                 refSequence := reftile.Sequence
 400                                 // If needed, extend the reference
 401                                 // sequence up to the tag at the end
 402                                 // of the genometile sequence.
 403                                 refstepend := refstep + 1
 404                                 for refstepend < len(reftiles) && len(refSequence) >= taglen && !bytes.EqualFold(refSequence[len(refSequence)-taglen:], genometile.Sequence[len(genometile.Sequence)-taglen:]) && len(refSequence) <= cmd.maxTileSize {
 405                                         if &refSequence[0] == &reftile.Sequence[0] {
 406                                                 refSequence = append([]byte(nil), refSequence...)
 407                                         }
 408                                         refSequence = append(refSequence, tileVariant[reftiles[refstepend]].Sequence...)
 409                                         refstepend++
 410                                 }
 411                                 // (TODO: handle no-calls)
 412                                 vars, _ := hgvs.Diff(strings.ToUpper(string(refSequence)), strings.ToUpper(string(genometile.Sequence)), time.Second)
 413                                 for _, v := range vars {
 414                                         if cmd.outputFormat.PadLeft {
 415                                                 v = v.PadLeft()
 416                                         }
 417                                         v.Position += refpos
 418                                         varslice := variantAt[v.Position]
 419                                         if varslice == nil {
 420                                                 varslice = make([]hgvs.Variant, len(cgs)*2)
 421                                                 variantAt[v.Position] = varslice
 422                                         }
 423                                         varslice[cgidx*2+phase] = v
 424                                 }
 425                         }
 426                 }
 427                 refpos += len(reftile.Sequence) - taglen
 428
 429                 // Flush entries from variantAt that are behind
 430                 // refpos. Flush all entries if this is the last
 431                 // reftile of the path/chromosome.
 432                 var flushpos []int
 433                 lastrefstep := refstep == len(reftiles)-1
 434                 for pos := range variantAt {
 435                         if lastrefstep || pos <= refpos {
 436                                 flushpos = append(flushpos, pos)
 437                         }
 438                 }
 439                 sort.Slice(flushpos, func(i, j int) bool { return flushpos[i] < flushpos[j] })
 440                 for _, pos := range flushpos {
 441                         varslice := variantAt[pos]
 442                         delete(variantAt, pos)
 443                         for i := range varslice {
 444                                 if varslice[i].Position == 0 {
 445                                         varslice[i].Position = pos
 446                                 }
 447                         }
 448                         cmd.outputFormat.Print(outw, seqname, varslice)
 449                 }
 450                 if bedw != nil && len(reftile.Sequence) > 0 {
 451                         tilestart := refpos - len(reftile.Sequence) + taglen
 452                         tileend := refpos
 453                         if !lastrefstep {
 454                                 tileend += taglen
 455                         }
 456                         thickstart := tilestart + taglen
 457                         if refstep == 0 {
 458                                 thickstart = 0
 459                         }
 460                         thickend := refpos
 461
 462                         // coverage score, 0 to 1000
 463                         score := 1000
 464                         if len(cgs) > 0 {
 465                                 score = 1000 * tagcoverage / len(cgs) / 2
 466                         }
 467
 468                         fmt.Fprintf(bedw, "%s %d %d %d %d . %d %d\n",
 469                                 seqname, tilestart, tileend,
 470                                 libref.Tag,
 471                                 score,
 472                                 thickstart, thickend)
 473                 }
 474         }
 475 }
 476
 477 func printVCF(out io.Writer, seqname string, varslice []hgvs.Variant) {
 478         refs := map[string]map[string]int{}
 479         for _, v := range varslice {
 480                 if v.Ref == "" && v.New == "" {
 481                         continue
 482                 }
 483                 alts := refs[v.Ref]
 484                 if alts == nil {
 485                         alts = map[string]int{}
 486                         refs[v.Ref] = alts
 487                 }
 488                 alts[v.New] = 0
 489         }
 490         for ref, alts := range refs {
 491                 var altslice []string
 492                 for alt := range alts {
 493                         altslice = append(altslice, alt)
 494                 }
 495                 sort.Strings(altslice)
 496                 for i, a := range altslice {
 497                         alts[a] = i + 1
 498                 }
 499                 fmt.Fprintf(out, "%s\t%d\t%s\t%s", seqname, varslice[0].Position, ref, strings.Join(altslice, ","))
 500                 for i := 0; i < len(varslice); i += 2 {
 501                         v1, v2 := varslice[i], varslice[i+1]
 502                         a1, a2 := alts[v1.New], alts[v2.New]
 503                         if v1.Ref != ref {
 504                                 a1 = 0
 505                         }
 506                         if v2.Ref != ref {
 507                                 a2 = 0
 508                         }
 509                         fmt.Fprintf(out, "\t%d/%d", a1, a2)
 510                 }
 511                 out.Write([]byte{'\n'})
 512         }
 513 }
 514
 515 func printHGVS(out io.Writer, seqname string, varslice []hgvs.Variant) {
 516         for i := 0; i < len(varslice)/2; i++ {
 517                 if i > 0 {
 518                         out.Write([]byte{'\t'})
 519                 }
 520                 var1, var2 := varslice[i*2], varslice[i*2+1]
 521                 if var1 == var2 {
 522                         if var1.Ref == var1.New {
 523                                 out.Write([]byte{'.'})
 524                         } else {
 525                                 fmt.Fprintf(out, "%s:g.%s", seqname, var1.String())
 526                         }
 527                 } else {
 528                         fmt.Fprintf(out, "%s:g.[%s];[%s]", seqname, var1.String(), var2.String())
 529                 }
 530         }
 531         out.Write([]byte{'\n'})
 532 }
 533
 534 func printHGVSOneHot(out io.Writer, seqname string, varslice []hgvs.Variant) {
 535         vars := map[hgvs.Variant]bool{}
 536         for _, v := range varslice {
 537                 if v.Ref != v.New {
 538                         vars[v] = true
 539                 }
 540         }
 541
 542         // sort variants to ensure output is deterministic
 543         sorted := make([]hgvs.Variant, 0, len(vars))
 544         for v := range vars {
 545                 sorted = append(sorted, v)
 546         }
 547         sort.Slice(sorted, func(a, b int) bool { return hgvs.Less(sorted[a], sorted[b]) })
 548
 549         for _, v := range sorted {
 550                 fmt.Fprintf(out, "%s.%s", seqname, v.String())
 551                 for i := 0; i < len(varslice); i += 2 {
 552                         if varslice[i] == v || varslice[i+1] == v {
 553                                 out.Write([]byte("\t1"))
 554                         } else {
 555                                 out.Write([]byte("\t0"))
 556                         }
 557                 }
 558                 out.Write([]byte{'\n'})
 559         }
 560 }