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/filepath"
  15         "runtime"
  16         "sort"
  17         "strconv"
  18         "strings"
  19         "sync"
  20         "time"
  21
  22         "git.arvados.org/arvados.git/sdk/go/arvados"
  23         "github.com/arvados/lightning/hgvs"
  24         "github.com/klauspost/pgzip"
  25         "github.com/kshedden/gonpy"
  26         "github.com/sirupsen/logrus"
  27         log "github.com/sirupsen/logrus"
  28 )
  29
  30 type tvVariant struct {
  31         hgvs.Variant
  32         librefs map[tileLibRef]bool
  33 }
  34
  35 type outputFormat interface {
  36         Filename() string
  37         PadLeft() bool
  38         Head(out io.Writer, cgs []CompactGenome) error
  39         Print(out io.Writer, seqname string, varslice []tvVariant) error
  40         Finish(outdir string, out io.Writer, seqname string) error
  41         MaxGoroutines() int
  42 }
  43
  44 var outputFormats = map[string]func() outputFormat{
  45         "hgvs-numpy": func() outputFormat {
  46                 return &formatHGVSNumpy{alleles: map[string][][]bool{}}
  47         },
  48         "hgvs-onehot": func() outputFormat { return formatHGVSOneHot{} },
  49         "hgvs":        func() outputFormat { return formatHGVS{} },
  50         "pvcf":        func() outputFormat { return formatPVCF{} },
  51         "vcf":         func() outputFormat { return formatVCF{} },
  52 }
  53
  54 type exporter struct {
  55         outputFormat   outputFormat
  56         outputPerChrom bool
  57         compress       bool
  58         maxTileSize    int
  59 }
  60
  61 func (cmd *exporter) RunCommand(prog string, args []string, stdin io.Reader, stdout, stderr io.Writer) int {
  62         var err error
  63         defer func() {
  64                 if err != nil {
  65                         fmt.Fprintf(stderr, "%s\n", err)
  66                 }
  67         }()
  68         flags := flag.NewFlagSet("", flag.ContinueOnError)
  69         flags.SetOutput(stderr)
  70         pprof := flags.String("pprof", "", "serve Go profile data at http://`[addr]:port`")
  71         pprofdir := flags.String("pprof-dir", "", "write Go profile data to `directory` periodically")
  72         runlocal := flags.Bool("local", false, "run on local host (default: run in an arvados container)")
  73         projectUUID := flags.String("project", "", "project `UUID` for output data")
  74         priority := flags.Int("priority", 500, "container request priority")
  75         refname := flags.String("ref", "", "reference genome `name`")
  76         inputDir := flags.String("input-dir", ".", "input `directory`")
  77         outputDir := flags.String("output-dir", ".", "output `directory`")
  78         outputFormatStr := flags.String("output-format", "hgvs", "output `format`: hgvs, pvcf, or vcf")
  79         outputBed := flags.String("output-bed", "", "also output bed `file`")
  80         flags.BoolVar(&cmd.outputPerChrom, "output-per-chromosome", true, "output one file per chromosome")
  81         flags.BoolVar(&cmd.compress, "z", false, "write gzip-compressed output files")
  82         labelsFilename := flags.String("output-labels", "", "also output genome labels csv `file`")
  83         flags.IntVar(&cmd.maxTileSize, "max-tile-size", 50000, "don't try to make annotations for tiles bigger than given `size`")
  84         err = flags.Parse(args)
  85         if err == flag.ErrHelp {
  86                 err = nil
  87                 return 0
  88         } else if err != nil {
  89                 return 2
  90         }
  91         if flag.NArg() > 0 {
  92                 err = fmt.Errorf("extra unparsed command line arguments: %q", flag.Args())
  93                 return 2
  94         }
  95
  96         if f, ok := outputFormats[*outputFormatStr]; !ok {
  97                 err = fmt.Errorf("invalid output format %q", *outputFormatStr)
  98                 return 2
  99         } else {
 100                 cmd.outputFormat = f()
 101         }
 102
 103         if *pprof != "" {
 104                 go func() {
 105                         log.Println(http.ListenAndServe(*pprof, nil))
 106                 }()
 107         }
 108         if *pprofdir != "" {
 109                 go writeProfilesPeriodically(*pprofdir)
 110         }
 111
 112         if !*runlocal {
 113                 if *outputDir != "." {
 114                         err = errors.New("cannot specify output directory in container mode: not implemented")
 115                         return 1
 116                 }
 117                 runner := arvadosContainerRunner{
 118                         Name:        "lightning export",
 119                         Client:      arvados.NewClientFromEnv(),
 120                         ProjectUUID: *projectUUID,
 121                         RAM:         750000000000,
 122                         VCPUs:       96,
 123                         Priority:    *priority,
 124                         APIAccess:   true,
 125                 }
 126                 err = runner.TranslatePaths(inputDir)
 127                 if err != nil {
 128                         return 1
 129                 }
 130                 if *outputBed != "" {
 131                         if strings.Contains(*outputBed, "/") {
 132                                 err = fmt.Errorf("cannot use -output-bed filename %q containing '/' char", *outputBed)
 133                                 return 1
 134                         }
 135                         *outputBed = "/mnt/output/" + *outputBed
 136                 }
 137                 runner.Args = []string{"export", "-local=true",
 138                         "-pprof", ":6000",
 139                         "-pprof-dir", "/mnt/output",
 140                         "-ref", *refname,
 141                         "-output-format", *outputFormatStr,
 142                         "-output-bed", *outputBed,
 143                         "-output-labels", "/mnt/output/labels.csv",
 144                         "-output-per-chromosome=" + fmt.Sprintf("%v", cmd.outputPerChrom),
 145                         "-max-tile-size", fmt.Sprintf("%d", cmd.maxTileSize),
 146                         "-input-dir", *inputDir,
 147                         "-output-dir", "/mnt/output",
 148                         "-z=" + fmt.Sprintf("%v", cmd.compress),
 149                 }
 150                 var output string
 151                 output, err = runner.Run()
 152                 if err != nil {
 153                         return 1
 154                 }
 155                 fmt.Fprintln(stdout, output)
 156                 return 0
 157         }
 158
 159         var cgs []CompactGenome
 160         tilelib := &tileLibrary{
 161                 retainNoCalls:       true,
 162                 retainTileSequences: true,
 163                 compactGenomes:      map[string][]tileVariantID{},
 164         }
 165         err = tilelib.LoadDir(context.Background(), *inputDir, nil)
 166         if err != nil {
 167                 return 1
 168         }
 169
 170         refseq, ok := tilelib.refseqs[*refname]
 171         if !ok {
 172                 err = fmt.Errorf("reference name %q not found in input; have %v", *refname, func() (names []string) {
 173                         for name := range tilelib.refseqs {
 174                                 names = append(names, name)
 175                         }
 176                         return
 177                 }())
 178                 return 1
 179         }
 180
 181         names := cgnames(tilelib)
 182         for _, name := range names {
 183                 cgs = append(cgs, CompactGenome{Name: name, Variants: tilelib.compactGenomes[name]})
 184         }
 185         if *labelsFilename != "" {
 186                 log.Infof("writing labels to %s", *labelsFilename)
 187                 var f *os.File
 188                 f, err = os.OpenFile(*labelsFilename, os.O_CREATE|os.O_WRONLY, 0777)
 189                 if err != nil {
 190                         return 1
 191                 }
 192                 defer f.Close()
 193                 for i, name := range names {
 194                         _, err = fmt.Fprintf(f, "%d,%q,%q\n", i, trimFilenameForLabel(name), cmd.outputFormat.Filename())
 195                         if err != nil {
 196                                 err = fmt.Errorf("write %s: %w", *labelsFilename, err)
 197                                 return 1
 198                         }
 199                 }
 200                 err = f.Close()
 201                 if err != nil {
 202                         err = fmt.Errorf("close %s: %w", *labelsFilename, err)
 203                         return 1
 204                 }
 205         }
 206
 207         var bedout io.Writer
 208         var bedfile *os.File
 209         var bedbufw *bufio.Writer
 210         if *outputBed != "" {
 211                 bedfile, err = os.OpenFile(*outputBed, os.O_CREATE|os.O_WRONLY, 0666)
 212                 if err != nil {
 213                         return 1
 214                 }
 215                 defer bedfile.Close()
 216                 bedbufw = bufio.NewWriterSize(bedfile, 16*1024*1024)
 217                 bedout = bedbufw
 218         }
 219
 220         err = cmd.export(*outputDir, bedout, tilelib, refseq, cgs)
 221         if err != nil {
 222                 return 1
 223         }
 224         if bedout != nil {
 225                 err = bedbufw.Flush()
 226                 if err != nil {
 227                         return 1
 228                 }
 229                 err = bedfile.Close()
 230                 if err != nil {
 231                         return 1
 232                 }
 233         }
 234         return 0
 235 }
 236
 237 func (cmd *exporter) export(outdir string, bedout io.Writer, tilelib *tileLibrary, refseq map[string][]tileLibRef, cgs []CompactGenome) error {
 238         var seqnames []string
 239         var missing []tileLibRef
 240         for seqname, librefs := range refseq {
 241                 seqnames = append(seqnames, seqname)
 242                 for _, libref := range librefs {
 243                         if libref.Variant != 0 && tilelib.TileVariantSequence(libref) == nil {
 244                                 missing = append(missing, libref)
 245                         }
 246                 }
 247         }
 248         sort.Strings(seqnames)
 249
 250         if len(missing) > 0 {
 251                 if limit := 100; len(missing) > limit {
 252                         log.Warnf("first %d missing tiles: %v", limit, missing[:limit])
 253                 } else {
 254                         log.Warnf("missing tiles: %v", missing)
 255                 }
 256                 return fmt.Errorf("%d needed tiles are missing from library", len(missing))
 257         }
 258
 259         outw := make([]io.WriteCloser, len(seqnames))
 260         bedw := make([]io.WriteCloser, len(seqnames))
 261
 262         var merges sync.WaitGroup
 263         merge := func(dst io.Writer, src []io.WriteCloser, label string) {
 264                 var mtx sync.Mutex
 265                 for i, seqname := range seqnames {
 266                         pr, pw := io.Pipe()
 267                         src[i] = pw
 268                         merges.Add(1)
 269                         seqname := seqname
 270                         go func() {
 271                                 defer merges.Done()
 272                                 log.Infof("writing %s %s", seqname, label)
 273                                 scanner := bufio.NewScanner(pr)
 274                                 for scanner.Scan() {
 275                                         mtx.Lock()
 276                                         dst.Write(scanner.Bytes())
 277                                         dst.Write([]byte{'\n'})
 278                                         mtx.Unlock()
 279                                 }
 280                                 log.Infof("writing %s %s done", seqname, label)
 281                         }()
 282                 }
 283         }
 284         if cmd.outputPerChrom {
 285                 for i, seqname := range seqnames {
 286                         fnm := filepath.Join(outdir, strings.Replace(cmd.outputFormat.Filename(), ".", "."+seqname+".", 1))
 287                         if cmd.compress {
 288                                 fnm += ".gz"
 289                         }
 290                         f, err := os.OpenFile(fnm, os.O_CREATE|os.O_WRONLY|os.O_TRUNC, 0666)
 291                         if err != nil {
 292                                 return err
 293                         }
 294                         defer f.Close()
 295                         log.Infof("writing %q", f.Name())
 296                         outw[i] = f
 297                         if cmd.compress {
 298                                 z := pgzip.NewWriter(f)
 299                                 defer z.Close()
 300                                 outw[i] = z
 301                         }
 302                         err = cmd.outputFormat.Head(outw[i], cgs)
 303                         if err != nil {
 304                                 return err
 305                         }
 306                 }
 307         } else {
 308                 fnm := filepath.Join(outdir, cmd.outputFormat.Filename())
 309                 if cmd.compress {
 310                         fnm += ".gz"
 311                 }
 312                 f, err := os.OpenFile(fnm, os.O_CREATE|os.O_WRONLY|os.O_TRUNC, 0666)
 313                 if err != nil {
 314                         return err
 315                 }
 316                 defer f.Close()
 317                 log.Infof("writing %q", fnm)
 318                 var out io.Writer = f
 319                 if cmd.compress {
 320                         z := pgzip.NewWriter(out)
 321                         defer z.Close()
 322                         out = z
 323                 }
 324                 cmd.outputFormat.Head(out, cgs)
 325                 merge(out, outw, "output")
 326         }
 327         if bedout != nil {
 328                 merge(bedout, bedw, "bed")
 329         }
 330
 331         throttle := throttle{Max: runtime.NumCPU()}
 332         if max := cmd.outputFormat.MaxGoroutines(); max > 0 {
 333                 throttle.Max = max
 334         }
 335         log.Infof("assembling %d sequences in %d goroutines", len(seqnames), throttle.Max)
 336         for seqidx, seqname := range seqnames {
 337                 seqidx, seqname := seqidx, seqname
 338                 outw := outw[seqidx]
 339                 bedw := bedw[seqidx]
 340                 throttle.Acquire()
 341                 go func() {
 342                         defer throttle.Release()
 343                         if bedw != nil {
 344                                 defer bedw.Close()
 345                         }
 346                         outwb := bufio.NewWriterSize(outw, 8*1024*1024)
 347                         eachVariant(bedw, tilelib.taglib.keylen, seqname, refseq[seqname], tilelib, cgs, cmd.outputFormat.PadLeft(), cmd.maxTileSize, func(varslice []tvVariant) {
 348                                 err := cmd.outputFormat.Print(outwb, seqname, varslice)
 349                                 throttle.Report(err)
 350                         })
 351                         err := cmd.outputFormat.Finish(outdir, outwb, seqname)
 352                         throttle.Report(err)
 353                         err = outwb.Flush()
 354                         throttle.Report(err)
 355                         err = outw.Close()
 356                         throttle.Report(err)
 357                 }()
 358         }
 359
 360         merges.Wait()
 361         throttle.Wait()
 362         return throttle.Err()
 363 }
 364
 365 // Align genome tiles to reference tiles, call callback func on each
 366 // variant, and (if bedw is not nil) write tile coverage to bedw.
 367 func eachVariant(bedw io.Writer, taglen int, seqname string, reftiles []tileLibRef, tilelib *tileLibrary, cgs []CompactGenome, padLeft bool, maxTileSize int, callback func(varslice []tvVariant)) {
 368         t0 := time.Now()
 369         progressbar := time.NewTicker(time.Minute)
 370         defer progressbar.Stop()
 371         var outmtx sync.Mutex
 372         defer outmtx.Lock()
 373         refpos := 0
 374         variantAt := map[int][]tvVariant{} // variantAt[chromOffset][genomeIndex*2+phase]
 375         for refstep, libref := range reftiles {
 376                 select {
 377                 case <-progressbar.C:
 378                         var eta interface{}
 379                         if refstep > 0 {
 380                                 fin := t0.Add(time.Duration(float64(time.Now().Sub(t0)) * float64(len(reftiles)) / float64(refstep)))
 381                                 eta = fmt.Sprintf("%v (%v)", fin.Format(time.RFC3339), fin.Sub(time.Now()))
 382                         } else {
 383                                 eta = "N/A"
 384                         }
 385                         log.Printf("exportSeq: %s: refstep %d of %d, %.0f/s, ETA %v", seqname, refstep, len(reftiles), float64(refstep)/time.Now().Sub(t0).Seconds(), eta)
 386                 default:
 387                 }
 388                 diffs := map[tileLibRef][]hgvs.Variant{}
 389                 refseq := tilelib.TileVariantSequence(libref)
 390                 tagcoverage := 0 // number of times the start tag was found in genomes -- max is len(cgs)*2
 391                 for cgidx, cg := range cgs {
 392                         for phase := 0; phase < 2; phase++ {
 393                                 if len(cg.Variants) <= int(libref.Tag)*2+phase {
 394                                         continue
 395                                 }
 396                                 variant := cg.Variants[int(libref.Tag)*2+phase]
 397                                 if variant == 0 {
 398                                         continue
 399                                 }
 400                                 tagcoverage++
 401                                 if variant == libref.Variant {
 402                                         continue
 403                                 }
 404                                 glibref := tileLibRef{Tag: libref.Tag, Variant: variant}
 405                                 vars, ok := diffs[glibref]
 406                                 if !ok {
 407                                         genomeseq := tilelib.TileVariantSequence(glibref)
 408                                         if len(genomeseq) == 0 {
 409                                                 // Hash is known but sequence
 410                                                 // is not, e.g., retainNoCalls
 411                                                 // was false during import
 412                                                 continue
 413                                         }
 414                                         if len(genomeseq) > maxTileSize {
 415                                                 continue
 416                                         }
 417                                         refSequence := refseq
 418                                         // If needed, extend the
 419                                         // reference sequence up to
 420                                         // the tag at the end of the
 421                                         // genomeseq sequence.
 422                                         refstepend := refstep + 1
 423                                         for refstepend < len(reftiles) && len(refSequence) >= taglen && !bytes.EqualFold(refSequence[len(refSequence)-taglen:], genomeseq[len(genomeseq)-taglen:]) && len(refSequence) <= maxTileSize {
 424                                                 if &refSequence[0] == &refseq[0] {
 425                                                         refSequence = append([]byte(nil), refSequence...)
 426                                                 }
 427                                                 refSequence = append(refSequence, tilelib.TileVariantSequence(reftiles[refstepend])...)
 428                                                 refstepend++
 429                                         }
 430                                         // (TODO: handle no-calls)
 431                                         if len(refSequence) <= maxTileSize {
 432                                                 refstr := strings.ToUpper(string(refSequence))
 433                                                 genomestr := strings.ToUpper(string(genomeseq))
 434                                                 vars, _ = hgvs.Diff(refstr, genomestr, time.Second)
 435                                         }
 436                                         diffs[glibref] = vars
 437                                 }
 438                                 for _, v := range vars {
 439                                         if padLeft {
 440                                                 v = v.PadLeft()
 441                                         }
 442                                         v.Position += refpos
 443                                         varslice := variantAt[v.Position]
 444                                         if varslice == nil {
 445                                                 varslice = make([]tvVariant, len(cgs)*2)
 446                                                 variantAt[v.Position] = varslice
 447                                         }
 448                                         varslice[cgidx*2+phase].Variant = v
 449                                         if varslice[cgidx*2+phase].librefs == nil {
 450                                                 varslice[cgidx*2+phase].librefs = map[tileLibRef]bool{glibref: true}
 451                                         } else {
 452                                                 varslice[cgidx*2+phase].librefs[glibref] = true
 453                                         }
 454                                 }
 455                         }
 456                 }
 457                 refpos += len(refseq) - taglen
 458
 459                 // Flush entries from variantAt that are behind
 460                 // refpos. Flush all entries if this is the last
 461                 // reftile of the path/chromosome.
 462                 flushpos := make([]int, 0, len(variantAt))
 463                 lastrefstep := refstep == len(reftiles)-1
 464                 for pos := range variantAt {
 465                         if lastrefstep || pos <= refpos {
 466                                 flushpos = append(flushpos, pos)
 467                         }
 468                 }
 469                 sort.Slice(flushpos, func(i, j int) bool { return flushpos[i] < flushpos[j] })
 470                 flushvariants := make([][]tvVariant, len(flushpos))
 471                 for i, pos := range flushpos {
 472                         varslice := variantAt[pos]
 473                         delete(variantAt, pos)
 474                         for i := range varslice {
 475                                 if varslice[i].Position == 0 {
 476                                         varslice[i].Position = pos
 477                                 }
 478                         }
 479                         flushvariants[i] = varslice
 480                 }
 481                 outmtx.Lock()
 482                 go func() {
 483                         defer outmtx.Unlock()
 484                         for _, varslice := range flushvariants {
 485                                 callback(varslice)
 486                         }
 487                 }()
 488                 if bedw != nil && len(refseq) > 0 {
 489                         tilestart := refpos - len(refseq) + taglen
 490                         tileend := refpos
 491                         if !lastrefstep {
 492                                 tileend += taglen
 493                         }
 494                         thickstart := tilestart + taglen
 495                         if refstep == 0 {
 496                                 thickstart = 0
 497                         }
 498                         thickend := refpos
 499
 500                         // coverage score, 0 to 1000
 501                         score := 1000
 502                         if len(cgs) > 0 {
 503                                 score = 1000 * tagcoverage / len(cgs) / 2
 504                         }
 505
 506                         fmt.Fprintf(bedw, "%s %d %d %d %d . %d %d\n",
 507                                 seqname, tilestart, tileend,
 508                                 libref.Tag,
 509                                 score,
 510                                 thickstart, thickend)
 511                 }
 512         }
 513 }
 514
 515 func bucketVarsliceByRef(varslice []tvVariant) map[string]map[string]int {
 516         byref := map[string]map[string]int{}
 517         for _, v := range varslice {
 518                 if v.Ref == "" && v.New == "" {
 519                         continue
 520                 }
 521                 alts := byref[v.Ref]
 522                 if alts == nil {
 523                         alts = map[string]int{}
 524                         byref[v.Ref] = alts
 525                 }
 526                 alts[v.New]++
 527         }
 528         return byref
 529 }
 530
 531 type formatVCF struct{}
 532
 533 func (formatVCF) MaxGoroutines() int                     { return 0 }
 534 func (formatVCF) Filename() string                       { return "out.vcf" }
 535 func (formatVCF) PadLeft() bool                          { return true }
 536 func (formatVCF) Finish(string, io.Writer, string) error { return nil }
 537 func (formatVCF) Head(out io.Writer, cgs []CompactGenome) error {
 538         _, err := fmt.Fprint(out, "#CHROM\tPOS\tID\tREF\tALT\tQUAL\tFILTER\tINFO\n")
 539         return err
 540 }
 541 func (formatVCF) Print(out io.Writer, seqname string, varslice []tvVariant) error {
 542         for ref, alts := range bucketVarsliceByRef(varslice) {
 543                 altslice := make([]string, 0, len(alts))
 544                 for alt := range alts {
 545                         altslice = append(altslice, alt)
 546                 }
 547                 sort.Strings(altslice)
 548
 549                 info := "AC="
 550                 for i, a := range altslice {
 551                         if i > 0 {
 552                                 info += ","
 553                         }
 554                         info += strconv.Itoa(alts[a])
 555                 }
 556                 _, err := fmt.Fprintf(out, "%s\t%d\t.\t%s\t%s\t.\t.\t%s\n", seqname, varslice[0].Position, ref, strings.Join(altslice, ","), info)
 557                 if err != nil {
 558                         return err
 559                 }
 560         }
 561         return nil
 562 }
 563
 564 type formatPVCF struct{}
 565
 566 func (formatPVCF) MaxGoroutines() int                     { return 0 }
 567 func (formatPVCF) Filename() string                       { return "out.vcf" }
 568 func (formatPVCF) PadLeft() bool                          { return true }
 569 func (formatPVCF) Finish(string, io.Writer, string) error { return nil }
 570 func (formatPVCF) Head(out io.Writer, cgs []CompactGenome) error {
 571         fmt.Fprintln(out, `##FORMAT=<ID=GT,Number=1,Type=String,Description="Genotype">`)
 572         fmt.Fprintf(out, "#CHROM\tPOS\tID\tREF\tALT\tQUAL\tFILTER\tINFO\tFORMAT")
 573         for _, cg := range cgs {
 574                 fmt.Fprintf(out, "\t%s", cg.Name)
 575         }
 576         _, err := fmt.Fprintf(out, "\n")
 577         return err
 578 }
 579
 580 func (formatPVCF) Print(out io.Writer, seqname string, varslice []tvVariant) error {
 581         for ref, alts := range bucketVarsliceByRef(varslice) {
 582                 altslice := make([]string, 0, len(alts))
 583                 for alt := range alts {
 584                         altslice = append(altslice, alt)
 585                 }
 586                 sort.Strings(altslice)
 587                 for i, a := range altslice {
 588                         alts[a] = i + 1
 589                 }
 590                 _, err := fmt.Fprintf(out, "%s\t%d\t.\t%s\t%s\t.\t.\t.\tGT", seqname, varslice[0].Position, ref, strings.Join(altslice, ","))
 591                 if err != nil {
 592                         return err
 593                 }
 594                 for i := 0; i < len(varslice); i += 2 {
 595                         v1, v2 := varslice[i], varslice[i+1]
 596                         a1, a2 := alts[v1.New], alts[v2.New]
 597                         if v1.Ref != ref {
 598                                 // variant on allele 0 belongs on a
 599                                 // different output line -- same
 600                                 // chr,pos but different "ref" length
 601                                 a1 = 0
 602                         }
 603                         if v2.Ref != ref {
 604                                 a2 = 0
 605                         }
 606                         _, err := fmt.Fprintf(out, "\t%d/%d", a1, a2)
 607                         if err != nil {
 608                                 return err
 609                         }
 610                 }
 611                 _, err = out.Write([]byte{'\n'})
 612                 if err != nil {
 613                         return err
 614                 }
 615         }
 616         return nil
 617 }
 618
 619 type formatHGVS struct{}
 620
 621 func (formatHGVS) MaxGoroutines() int                            { return 0 }
 622 func (formatHGVS) Filename() string                              { return "out.tsv" }
 623 func (formatHGVS) PadLeft() bool                                 { return false }
 624 func (formatHGVS) Head(out io.Writer, cgs []CompactGenome) error { return nil }
 625 func (formatHGVS) Finish(string, io.Writer, string) error        { return nil }
 626 func (formatHGVS) Print(out io.Writer, seqname string, varslice []tvVariant) error {
 627         for i := 0; i < len(varslice)/2; i++ {
 628                 if i > 0 {
 629                         out.Write([]byte{'\t'})
 630                 }
 631                 var1, var2 := varslice[i*2], varslice[i*2+1]
 632                 if var1.Variant == var2.Variant {
 633                         if var1.Ref == var1.New {
 634                                 _, err := out.Write([]byte{'.'})
 635                                 if err != nil {
 636                                         return err
 637                                 }
 638                         } else {
 639                                 _, err := fmt.Fprintf(out, "%s:g.%s", seqname, var1.String())
 640                                 if err != nil {
 641                                         return err
 642                                 }
 643                         }
 644                 } else {
 645                         _, err := fmt.Fprintf(out, "%s:g.[%s];[%s]", seqname, var1.String(), var2.String())
 646                         if err != nil {
 647                                 return err
 648                         }
 649                 }
 650         }
 651         _, err := out.Write([]byte{'\n'})
 652         return err
 653 }
 654
 655 type formatHGVSOneHot struct{}
 656
 657 func (formatHGVSOneHot) MaxGoroutines() int                            { return 0 }
 658 func (formatHGVSOneHot) Filename() string                              { return "out.tsv" }
 659 func (formatHGVSOneHot) PadLeft() bool                                 { return false }
 660 func (formatHGVSOneHot) Head(out io.Writer, cgs []CompactGenome) error { return nil }
 661 func (formatHGVSOneHot) Finish(string, io.Writer, string) error        { return nil }
 662 func (formatHGVSOneHot) Print(out io.Writer, seqname string, varslice []tvVariant) error {
 663         vars := map[hgvs.Variant]bool{}
 664         for _, v := range varslice {
 665                 if v.Ref != v.New {
 666                         vars[v.Variant] = true
 667                 }
 668         }
 669
 670         // sort variants to ensure output is deterministic
 671         sorted := make([]hgvs.Variant, 0, len(vars))
 672         for v := range vars {
 673                 sorted = append(sorted, v)
 674         }
 675         sort.Slice(sorted, func(a, b int) bool { return hgvs.Less(sorted[a], sorted[b]) })
 676
 677         for _, v := range sorted {
 678                 fmt.Fprintf(out, "%s.%s", seqname, v.String())
 679                 for i := 0; i < len(varslice); i += 2 {
 680                         if varslice[i].Variant == v || varslice[i+1].Variant == v {
 681                                 out.Write([]byte("\t1"))
 682                         } else {
 683                                 out.Write([]byte("\t0"))
 684                         }
 685                 }
 686                 _, err := out.Write([]byte{'\n'})
 687                 if err != nil {
 688                         return err
 689                 }
 690         }
 691         return nil
 692 }
 693
 694 type formatHGVSNumpy struct {
 695         sync.Mutex
 696         alleles map[string][][]bool // alleles[seqname][variantidx][genomeidx*2+phase]
 697 }
 698
 699 func (*formatHGVSNumpy) MaxGoroutines() int                            { return 8 }
 700 func (*formatHGVSNumpy) Filename() string                              { return "annotations.csv" }
 701 func (*formatHGVSNumpy) PadLeft() bool                                 { return false }
 702 func (*formatHGVSNumpy) Head(out io.Writer, cgs []CompactGenome) error { return nil }
 703 func (f *formatHGVSNumpy) Print(outw io.Writer, seqname string, varslice []tvVariant) error {
 704         // sort variants to ensure output is deterministic
 705         sorted := make([]hgvs.Variant, 0, len(varslice))
 706         for _, v := range varslice {
 707                 sorted = append(sorted, v.Variant)
 708         }
 709         sort.Slice(sorted, func(a, b int) bool { return hgvs.Less(sorted[a], sorted[b]) })
 710
 711         f.Lock()
 712         seqalleles := f.alleles[seqname]
 713         f.Unlock()
 714
 715         // append a row to seqvariants and seqalleles for each unique
 716         // non-ref variant in varslice.
 717         var previous hgvs.Variant
 718         for _, v := range sorted {
 719                 if previous == v || v.Ref == v.New {
 720                         continue
 721                 }
 722                 previous = v
 723                 newrow := make([]bool, len(varslice))
 724                 for i, allele := range varslice {
 725                         if allele.Variant == v {
 726                                 newrow[i] = true
 727                         }
 728                 }
 729                 seqalleles = append(seqalleles, newrow)
 730                 _, err := fmt.Fprintf(outw, "%d,%q\n", len(seqalleles)-1, seqname+"."+v.String())
 731                 if err != nil {
 732                         return err
 733                 }
 734         }
 735
 736         f.Lock()
 737         f.alleles[seqname] = seqalleles
 738         f.Unlock()
 739         return nil
 740 }
 741 func (f *formatHGVSNumpy) Finish(outdir string, _ io.Writer, seqname string) error {
 742         // Write seqname's data to a .npy matrix with one row per
 743         // genome and 2 columns per variant.
 744         seqalleles := f.alleles[seqname]
 745         f.Lock()
 746         delete(f.alleles, seqname)
 747         f.Unlock()
 748         if len(seqalleles) == 0 {
 749                 return nil
 750         }
 751         out := make([]int8, len(seqalleles)*len(seqalleles[0]))
 752         rows := len(seqalleles[0]) / 2
 753         cols := len(seqalleles) * 2
 754         // copy seqalleles[varidx][genome*2+phase] to
 755         // out[genome*nvars*2 + varidx*2 + phase]
 756         for varidx, alleles := range seqalleles {
 757                 for g := 0; g < len(alleles)/2; g++ {
 758                         aa, ab := alleles[g*2], alleles[g*2+1]
 759                         if aa && ab {
 760                                 // hom
 761                                 out[g*cols+varidx*2] = 1
 762                         } else if aa || ab {
 763                                 // het
 764                                 out[g*cols+varidx*2+1] = 1
 765                         }
 766                 }
 767         }
 768         outf, err := os.OpenFile(outdir+"/matrix."+seqname+".npy", os.O_CREATE|os.O_EXCL|os.O_WRONLY, 0777)
 769         if err != nil {
 770                 return err
 771         }
 772         defer outf.Close()
 773         bufw := bufio.NewWriter(outf)
 774         npw, err := gonpy.NewWriter(nopCloser{bufw})
 775         if err != nil {
 776                 return err
 777         }
 778         log.WithFields(logrus.Fields{
 779                 "seqname": seqname,
 780                 "rows":    rows,
 781                 "cols":    cols,
 782         }).Info("writing numpy")
 783         npw.Shape = []int{rows, cols}
 784         npw.WriteInt8(out)
 785         err = bufw.Flush()
 786         if err != nil {
 787                 return err
 788         }
 789         err = outf.Close()
 790         if err != nil {
 791                 return err
 792         }
 793         return nil
 794 }