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         "time"
  18
  19         "git.arvados.org/arvados.git/sdk/go/arvados"
  20         "github.com/arvados/lightning/hgvs"
  21         log "github.com/sirupsen/logrus"
  22 )
  23
  24 type outputFormat struct {
  25         Print   func(out io.Writer, seqname string, varslice []hgvs.Variant)
  26         PadLeft bool
  27 }
  28
  29 var (
  30         outputFormats = map[string]outputFormat{
  31                 "hgvs-onehot": outputFormatHGVSOneHot,
  32                 "hgvs":        outputFormatHGVS,
  33                 "vcf":         outputFormatVCF,
  34         }
  35         outputFormatHGVS       = outputFormat{Print: printHGVS}
  36         outputFormatHGVSOneHot = outputFormat{Print: printHGVSOneHot}
  37         outputFormatVCF        = outputFormat{Print: printVCF, PadLeft: true}
  38 )
  39
  40 type exporter struct {
  41         outputFormat outputFormat
  42 }
  43
  44 func (cmd *exporter) RunCommand(prog string, args []string, stdin io.Reader, stdout, stderr io.Writer) int {
  45         var err error
  46         defer func() {
  47                 if err != nil {
  48                         fmt.Fprintf(stderr, "%s\n", err)
  49                 }
  50         }()
  51         flags := flag.NewFlagSet("", flag.ContinueOnError)
  52         flags.SetOutput(stderr)
  53         pprof := flags.String("pprof", "", "serve Go profile data at http://`[addr]:port`")
  54         runlocal := flags.Bool("local", false, "run on local host (default: run in an arvados container)")
  55         projectUUID := flags.String("project", "", "project `UUID` for output data")
  56         priority := flags.Int("priority", 500, "container request priority")
  57         refname := flags.String("ref", "", "reference genome `name`")
  58         inputFilename := flags.String("i", "-", "input `file` (library)")
  59         outputFilename := flags.String("o", "-", "output `file`")
  60         outputFormatStr := flags.String("output-format", "hgvs", "output `format`: hgvs or vcf")
  61         outputBed := flags.String("output-bed", "", "also output bed `file`")
  62         labelsFilename := flags.String("output-labels", "", "also output genome labels csv `file`")
  63         err = flags.Parse(args)
  64         if err == flag.ErrHelp {
  65                 err = nil
  66                 return 0
  67         } else if err != nil {
  68                 return 2
  69         }
  70
  71         if f, ok := outputFormats[*outputFormatStr]; !ok {
  72                 err = fmt.Errorf("invalid output format %q", *outputFormatStr)
  73                 return 2
  74         } else {
  75                 cmd.outputFormat = f
  76         }
  77
  78         if *pprof != "" {
  79                 go func() {
  80                         log.Println(http.ListenAndServe(*pprof, nil))
  81                 }()
  82         }
  83
  84         if !*runlocal {
  85                 if *outputFilename != "-" {
  86                         err = errors.New("cannot specify output file in container mode: not implemented")
  87                         return 1
  88                 }
  89                 runner := arvadosContainerRunner{
  90                         Name:        "lightning export",
  91                         Client:      arvados.NewClientFromEnv(),
  92                         ProjectUUID: *projectUUID,
  93                         RAM:         700000000000,
  94                         VCPUs:       32,
  95                         Priority:    *priority,
  96                 }
  97                 err = runner.TranslatePaths(inputFilename)
  98                 if err != nil {
  99                         return 1
 100                 }
 101                 if *outputBed != "" {
 102                         if strings.Contains(*outputBed, "/") {
 103                                 err = fmt.Errorf("cannot use -output-bed filename %q containing '/' char", *outputBed)
 104                                 return 1
 105                         }
 106                         *outputBed = "/mnt/output/" + *outputBed
 107                 }
 108                 runner.Args = []string{"export", "-local=true",
 109                         "-ref", *refname,
 110                         "-output-format", *outputFormatStr,
 111                         "-output-bed", *outputBed,
 112                         "-output-labels", "/mnt/output/labels.csv",
 113                         "-i", *inputFilename,
 114                         "-o", "/mnt/output/export.csv",
 115                 }
 116                 var output string
 117                 output, err = runner.Run()
 118                 if err != nil {
 119                         return 1
 120                 }
 121                 fmt.Fprintln(stdout, output+"/export.csv")
 122                 return 0
 123         }
 124
 125         in, err := open(*inputFilename)
 126         if err != nil {
 127                 return 1
 128         }
 129         defer in.Close()
 130         input, ok := in.(io.ReadSeeker)
 131         if !ok {
 132                 err = fmt.Errorf("%s: %T cannot seek", *inputFilename, in)
 133                 return 1
 134         }
 135
 136         // Error out early if seeking doesn't work on the input file.
 137         _, err = input.Seek(0, io.SeekEnd)
 138         if err != nil {
 139                 return 1
 140         }
 141         _, err = input.Seek(0, io.SeekStart)
 142         if err != nil {
 143                 return 1
 144         }
 145
 146         var cgs []CompactGenome
 147         tilelib := &tileLibrary{
 148                 retainNoCalls:  true,
 149                 compactGenomes: map[string][]tileVariantID{},
 150         }
 151         err = tilelib.LoadGob(context.Background(), input, strings.HasSuffix(*inputFilename, ".gz"), nil)
 152         if err != nil {
 153                 return 1
 154         }
 155
 156         refseq, ok := tilelib.refseqs[*refname]
 157         if !ok {
 158                 err = fmt.Errorf("reference name %q not found in input; have %v", *refname, func() (names []string) {
 159                         for name := range tilelib.refseqs {
 160                                 names = append(names, name)
 161                         }
 162                         return
 163                 }())
 164                 return 1
 165         }
 166
 167         names := cgnames(tilelib)
 168         for _, name := range names {
 169                 cgs = append(cgs, CompactGenome{Name: name, Variants: tilelib.compactGenomes[name]})
 170         }
 171         if *labelsFilename != "" {
 172                 log.Infof("writing labels to %s", *labelsFilename)
 173                 var f *os.File
 174                 f, err = os.OpenFile(*labelsFilename, os.O_CREATE|os.O_WRONLY, 0777)
 175                 if err != nil {
 176                         return 1
 177                 }
 178                 defer f.Close()
 179                 _, outBasename := path.Split(*outputFilename)
 180                 for i, name := range names {
 181                         _, err = fmt.Fprintf(f, "%d,%q,%q\n", i, trimFilenameForLabel(name), outBasename)
 182                         if err != nil {
 183                                 err = fmt.Errorf("write %s: %w", *labelsFilename, err)
 184                                 return 1
 185                         }
 186                 }
 187                 err = f.Close()
 188                 if err != nil {
 189                         err = fmt.Errorf("close %s: %w", *labelsFilename, err)
 190                         return 1
 191                 }
 192         }
 193
 194         _, err = input.Seek(0, io.SeekStart)
 195         if err != nil {
 196                 return 1
 197         }
 198
 199         var output io.WriteCloser
 200         if *outputFilename == "-" {
 201                 output = nopCloser{stdout}
 202         } else {
 203                 output, err = os.OpenFile(*outputFilename, os.O_CREATE|os.O_WRONLY, 0666)
 204                 if err != nil {
 205                         return 1
 206                 }
 207                 defer output.Close()
 208         }
 209         bufw := bufio.NewWriter(output)
 210
 211         var bedout *os.File
 212         var bedbufw *bufio.Writer
 213         if *outputBed != "" {
 214                 bedout, err = os.OpenFile(*outputBed, os.O_CREATE|os.O_WRONLY, 0666)
 215                 if err != nil {
 216                         return 1
 217                 }
 218                 defer bedout.Close()
 219                 bedbufw = bufio.NewWriter(bedout)
 220         }
 221
 222         err = cmd.export(bufw, bedout, input, strings.HasSuffix(*inputFilename, ".gz"), tilelib, refseq, cgs)
 223         if err != nil {
 224                 return 1
 225         }
 226         err = bufw.Flush()
 227         if err != nil {
 228                 return 1
 229         }
 230         err = output.Close()
 231         if err != nil {
 232                 return 1
 233         }
 234         if bedout != nil {
 235                 err = bedbufw.Flush()
 236                 if err != nil {
 237                         return 1
 238                 }
 239                 err = bedout.Close()
 240                 if err != nil {
 241                         return 1
 242                 }
 243         }
 244         err = in.Close()
 245         if err != nil {
 246                 return 1
 247         }
 248         return 0
 249 }
 250
 251 func (cmd *exporter) export(out, bedout io.Writer, librdr io.Reader, gz bool, tilelib *tileLibrary, refseq map[string][]tileLibRef, cgs []CompactGenome) error {
 252         need := map[tileLibRef]bool{}
 253         var seqnames []string
 254         for seqname, librefs := range refseq {
 255                 seqnames = append(seqnames, seqname)
 256                 for _, libref := range librefs {
 257                         if libref.Variant != 0 {
 258                                 need[libref] = true
 259                         }
 260                 }
 261         }
 262         sort.Strings(seqnames)
 263
 264         for _, cg := range cgs {
 265                 for i, variant := range cg.Variants {
 266                         if variant == 0 {
 267                                 continue
 268                         }
 269                         libref := tileLibRef{Tag: tagID(i / 2), Variant: variant}
 270                         need[libref] = true
 271                 }
 272         }
 273
 274         log.Infof("export: loading %d tile variants", len(need))
 275         tileVariant := map[tileLibRef]TileVariant{}
 276         err := DecodeLibrary(librdr, gz, func(ent *LibraryEntry) error {
 277                 for _, tv := range ent.TileVariants {
 278                         libref := tilelib.getRef(tv.Tag, tv.Sequence)
 279                         if need[libref] {
 280                                 tileVariant[libref] = tv
 281                         }
 282                 }
 283                 return nil
 284         })
 285         if err != nil {
 286                 return err
 287         }
 288
 289         log.Infof("export: loaded %d tile variants", len(tileVariant))
 290         var missing []tileLibRef
 291         for libref := range need {
 292                 if _, ok := tileVariant[libref]; !ok {
 293                         missing = append(missing, libref)
 294                 }
 295         }
 296         if len(missing) > 0 {
 297                 if limit := 100; len(missing) > limit {
 298                         log.Warnf("first %d missing tiles: %v", limit, missing[:limit])
 299                 } else {
 300                         log.Warnf("missing tiles: %v", missing)
 301                 }
 302                 return fmt.Errorf("%d needed tiles are missing from library", len(missing))
 303         }
 304
 305         log.Infof("assembling %d sequences concurrently", len(seqnames))
 306         throttle := throttle{Max: 8}
 307         outbuf := make([]bytes.Buffer, len(seqnames))
 308         bedbuf := make([]bytes.Buffer, len(seqnames))
 309         for seqidx, seqname := range seqnames {
 310                 seqname := seqname
 311                 outbuf := &outbuf[seqidx]
 312                 bedbuf := &bedbuf[seqidx]
 313                 if bedout == nil {
 314                         bedbuf = nil
 315                 }
 316                 throttle.Acquire()
 317                 go func() {
 318                         defer throttle.Release()
 319                         cmd.exportSeq(outbuf, bedbuf, tilelib.taglib.keylen, seqname, refseq[seqname], tileVariant, cgs)
 320                         log.Infof("assembled %q to outbuf %d bedbuf %d", seqname, outbuf.Len(), bedbuf.Len())
 321                 }()
 322         }
 323         throttle.Wait()
 324
 325         throttle.Acquire()
 326         go func() {
 327                 defer throttle.Release()
 328                 for i, seqname := range seqnames {
 329                         log.Infof("writing outbuf %s", seqname)
 330                         io.Copy(out, &outbuf[i])
 331                 }
 332         }()
 333         if bedout != nil {
 334                 throttle.Acquire()
 335                 go func() {
 336                         defer throttle.Release()
 337                         for i, seqname := range seqnames {
 338                                 log.Infof("writing bedbuf %s", seqname)
 339                                 io.Copy(bedout, &bedbuf[i])
 340                         }
 341                 }()
 342         }
 343         throttle.Wait()
 344         return nil
 345 }
 346
 347 // Align genome tiles to reference tiles, write diffs to outw, and (if
 348 // bedw is not nil) write tile coverage to bedw.
 349 func (cmd *exporter) exportSeq(outw, bedw io.Writer, taglen int, seqname string, reftiles []tileLibRef, tileVariant map[tileLibRef]TileVariant, cgs []CompactGenome) {
 350         refpos := 0
 351         variantAt := map[int][]hgvs.Variant{} // variantAt[chromOffset][genomeIndex*2+phase]
 352         for refstep, libref := range reftiles {
 353                 reftile := tileVariant[libref]
 354                 tagcoverage := 0 // number of times the start tag was found in genomes -- max is len(cgs)*2
 355                 for cgidx, cg := range cgs {
 356                         for phase := 0; phase < 2; phase++ {
 357                                 if len(cg.Variants) <= int(libref.Tag)*2+phase {
 358                                         continue
 359                                 }
 360                                 variant := cg.Variants[int(libref.Tag)*2+phase]
 361                                 if variant == 0 {
 362                                         continue
 363                                 }
 364                                 tagcoverage++
 365                                 if variant == libref.Variant {
 366                                         continue
 367                                 }
 368                                 genometile := tileVariant[tileLibRef{Tag: libref.Tag, Variant: variant}]
 369                                 if len(genometile.Sequence) == 0 {
 370                                         // Hash is known but sequence
 371                                         // is not, e.g., retainNoCalls
 372                                         // was false during import
 373                                         continue
 374                                 }
 375                                 refSequence := reftile.Sequence
 376                                 // If needed, extend the reference
 377                                 // sequence up to the tag at the end
 378                                 // of the genometile sequence.
 379                                 refstepend := refstep + 1
 380                                 for refstepend < len(reftiles) && len(refSequence) >= taglen && !bytes.EqualFold(refSequence[len(refSequence)-taglen:], genometile.Sequence[len(genometile.Sequence)-taglen:]) {
 381                                         if &refSequence[0] == &reftile.Sequence[0] {
 382                                                 refSequence = append([]byte(nil), refSequence...)
 383                                         }
 384                                         refSequence = append(refSequence, tileVariant[reftiles[refstepend]].Sequence...)
 385                                         refstepend++
 386                                 }
 387                                 // (TODO: handle no-calls)
 388                                 vars, _ := hgvs.Diff(strings.ToUpper(string(refSequence)), strings.ToUpper(string(genometile.Sequence)), time.Second)
 389                                 for _, v := range vars {
 390                                         if cmd.outputFormat.PadLeft {
 391                                                 v = v.PadLeft()
 392                                         }
 393                                         v.Position += refpos
 394                                         varslice := variantAt[v.Position]
 395                                         if varslice == nil {
 396                                                 varslice = make([]hgvs.Variant, len(cgs)*2)
 397                                                 variantAt[v.Position] = varslice
 398                                         }
 399                                         varslice[cgidx*2+phase] = v
 400                                 }
 401                         }
 402                 }
 403                 refpos += len(reftile.Sequence) - taglen
 404
 405                 // Flush entries from variantAt that are behind
 406                 // refpos. Flush all entries if this is the last
 407                 // reftile of the path/chromosome.
 408                 var flushpos []int
 409                 lastrefstep := refstep == len(reftiles)-1
 410                 for pos := range variantAt {
 411                         if lastrefstep || pos <= refpos {
 412                                 flushpos = append(flushpos, pos)
 413                         }
 414                 }
 415                 sort.Slice(flushpos, func(i, j int) bool { return flushpos[i] < flushpos[j] })
 416                 for _, pos := range flushpos {
 417                         varslice := variantAt[pos]
 418                         delete(variantAt, pos)
 419                         for i := range varslice {
 420                                 if varslice[i].Position == 0 {
 421                                         varslice[i].Position = pos
 422                                 }
 423                         }
 424                         cmd.outputFormat.Print(outw, seqname, varslice)
 425                 }
 426                 if bedw != nil && len(reftile.Sequence) > 0 {
 427                         tilestart := refpos - len(reftile.Sequence) + taglen
 428                         tileend := refpos
 429                         if !lastrefstep {
 430                                 tileend += taglen
 431                         }
 432                         thickstart := tilestart + taglen
 433                         if refstep == 0 {
 434                                 thickstart = 0
 435                         }
 436                         thickend := refpos
 437
 438                         // coverage score, 0 to 1000
 439                         score := 1000
 440                         if len(cgs) > 0 {
 441                                 score = 1000 * tagcoverage / len(cgs) / 2
 442                         }
 443
 444                         fmt.Fprintf(bedw, "%s %d %d %d %d . %d %d\n",
 445                                 seqname, tilestart, tileend,
 446                                 libref.Tag,
 447                                 score,
 448                                 thickstart, thickend)
 449                 }
 450         }
 451 }
 452
 453 func printVCF(out io.Writer, seqname string, varslice []hgvs.Variant) {
 454         refs := map[string]map[string]int{}
 455         for _, v := range varslice {
 456                 if v.Ref == "" && v.New == "" {
 457                         continue
 458                 }
 459                 alts := refs[v.Ref]
 460                 if alts == nil {
 461                         alts = map[string]int{}
 462                         refs[v.Ref] = alts
 463                 }
 464                 alts[v.New] = 0
 465         }
 466         for ref, alts := range refs {
 467                 var altslice []string
 468                 for alt := range alts {
 469                         altslice = append(altslice, alt)
 470                 }
 471                 sort.Strings(altslice)
 472                 for i, a := range altslice {
 473                         alts[a] = i + 1
 474                 }
 475                 fmt.Fprintf(out, "%s\t%d\t%s\t%s", seqname, varslice[0].Position, ref, strings.Join(altslice, ","))
 476                 for i := 0; i < len(varslice); i += 2 {
 477                         v1, v2 := varslice[i], varslice[i+1]
 478                         a1, a2 := alts[v1.New], alts[v2.New]
 479                         if v1.Ref != ref {
 480                                 a1 = 0
 481                         }
 482                         if v2.Ref != ref {
 483                                 a2 = 0
 484                         }
 485                         fmt.Fprintf(out, "\t%d/%d", a1, a2)
 486                 }
 487                 out.Write([]byte{'\n'})
 488         }
 489 }
 490
 491 func printHGVS(out io.Writer, seqname string, varslice []hgvs.Variant) {
 492         for i := 0; i < len(varslice)/2; i++ {
 493                 if i > 0 {
 494                         out.Write([]byte{'\t'})
 495                 }
 496                 var1, var2 := varslice[i*2], varslice[i*2+1]
 497                 if var1 == var2 {
 498                         if var1.Ref == var1.New {
 499                                 out.Write([]byte{'.'})
 500                         } else {
 501                                 fmt.Fprintf(out, "%s:g.%s", seqname, var1.String())
 502                         }
 503                 } else {
 504                         fmt.Fprintf(out, "%s:g.[%s];[%s]", seqname, var1.String(), var2.String())
 505                 }
 506         }
 507         out.Write([]byte{'\n'})
 508 }
 509
 510 func printHGVSOneHot(out io.Writer, seqname string, varslice []hgvs.Variant) {
 511         vars := map[hgvs.Variant]bool{}
 512         for _, v := range varslice {
 513                 if v.Ref != v.New {
 514                         vars[v] = true
 515                 }
 516         }
 517
 518         // sort variants to ensure output is deterministic
 519         sorted := make([]hgvs.Variant, 0, len(vars))
 520         for v := range vars {
 521                 sorted = append(sorted, v)
 522         }
 523         sort.Slice(sorted, func(a, b int) bool { return hgvs.Less(sorted[a], sorted[b]) })
 524
 525         for _, v := range sorted {
 526                 fmt.Fprintf(out, "%s.%s", seqname, v.String())
 527                 for i := 0; i < len(varslice); i += 2 {
 528                         if varslice[i] == v || varslice[i+1] == v {
 529                                 out.Write([]byte("\t1"))
 530                         } else {
 531                                 out.Write([]byte("\t0"))
 532                         }
 533                 }
 534                 out.Write([]byte{'\n'})
 535         }
 536 }