export.go

   1 // Copyright (C) The Lightning Authors. All rights reserved.
   2 //
   3 // SPDX-License-Identifier: AGPL-3.0
   4
   5 package lightning
   6
   7 import (
   8         "bufio"
   9         "bytes"
  10         "context"
  11         "errors"
  12         "flag"
  13         "fmt"
  14         "io"
  15         "net/http"
  16         _ "net/http/pprof"
  17         "os"
  18         "path/filepath"
  19         "runtime"
  20         "sort"
  21         "strconv"
  22         "strings"
  23         "sync"
  24         "time"
  25
  26         "git.arvados.org/arvados.git/sdk/go/arvados"
  27         "github.com/arvados/lightning/hgvs"
  28         "github.com/klauspost/pgzip"
  29         "github.com/kshedden/gonpy"
  30         "github.com/sirupsen/logrus"
  31         log "github.com/sirupsen/logrus"
  32 )
  33
  34 type tvVariant struct {
  35         hgvs.Variant
  36         librefs map[tileLibRef]bool
  37 }
  38
  39 type outputFormat interface {
  40         Filename() string
  41         PadLeft() bool
  42         Head(out io.Writer, cgs []CompactGenome) error
  43         Print(out io.Writer, seqname string, varslice []tvVariant) error
  44         Finish(outdir string, out io.Writer, seqname string) error
  45         MaxGoroutines() int
  46 }
  47
  48 var outputFormats = map[string]func() outputFormat{
  49         "hgvs-numpy": func() outputFormat {
  50                 return &formatHGVSNumpy{alleles: map[string][][]bool{}}
  51         },
  52         "hgvs-onehot": func() outputFormat { return formatHGVSOneHot{} },
  53         "hgvs":        func() outputFormat { return formatHGVS{} },
  54         "pvcf":        func() outputFormat { return formatPVCF{} },
  55         "vcf":         func() outputFormat { return formatVCF{} },
  56 }
  57
  58 type exporter struct {
  59         outputFormat   outputFormat
  60         outputPerChrom bool
  61         compress       bool
  62         maxTileSize    int
  63         filter         filter
  64 }
  65
  66 func (cmd *exporter) RunCommand(prog string, args []string, stdin io.Reader, stdout, stderr io.Writer) int {
  67         var err error
  68         defer func() {
  69                 if err != nil {
  70                         fmt.Fprintf(stderr, "%s\n", err)
  71                 }
  72         }()
  73         flags := flag.NewFlagSet("", flag.ContinueOnError)
  74         flags.SetOutput(stderr)
  75         pprof := flags.String("pprof", "", "serve Go profile data at http://`[addr]:port`")
  76         pprofdir := flags.String("pprof-dir", "", "write Go profile data to `directory` periodically")
  77         runlocal := flags.Bool("local", false, "run on local host (default: run in an arvados container)")
  78         projectUUID := flags.String("project", "", "project `UUID` for output data")
  79         priority := flags.Int("priority", 500, "container request priority")
  80         refname := flags.String("ref", "", "reference genome `name`")
  81         inputDir := flags.String("input-dir", ".", "input `directory`")
  82         outputDir := flags.String("output-dir", ".", "output `directory`")
  83         outputFormatStr := flags.String("output-format", "hgvs", "output `format`: hgvs, pvcf, or vcf")
  84         outputBed := flags.String("output-bed", "", "also output bed `file`")
  85         flags.BoolVar(&cmd.outputPerChrom, "output-per-chromosome", true, "output one file per chromosome")
  86         flags.BoolVar(&cmd.compress, "z", false, "write gzip-compressed output files")
  87         labelsFilename := flags.String("output-labels", "", "also output genome labels csv `file`")
  88         flags.IntVar(&cmd.maxTileSize, "max-tile-size", 50000, "don't try to make annotations for tiles bigger than given `size`")
  89         cmd.filter.Flags(flags)
  90         err = flags.Parse(args)
  91         if err == flag.ErrHelp {
  92                 err = nil
  93                 return 0
  94         } else if err != nil {
  95                 return 2
  96         }
  97         if flag.NArg() > 0 {
  98                 err = fmt.Errorf("extra unparsed command line arguments: %q", flag.Args())
  99                 return 2
 100         }
 101
 102         if f, ok := outputFormats[*outputFormatStr]; !ok {
 103                 err = fmt.Errorf("invalid output format %q", *outputFormatStr)
 104                 return 2
 105         } else {
 106                 cmd.outputFormat = f()
 107         }
 108
 109         if *pprof != "" {
 110                 go func() {
 111                         log.Println(http.ListenAndServe(*pprof, nil))
 112                 }()
 113         }
 114         if *pprofdir != "" {
 115                 go writeProfilesPeriodically(*pprofdir)
 116         }
 117
 118         if !*runlocal {
 119                 if *outputDir != "." {
 120                         err = errors.New("cannot specify output directory in container mode: not implemented")
 121                         return 1
 122                 }
 123                 runner := arvadosContainerRunner{
 124                         Name:        "lightning export",
 125                         Client:      arvados.NewClientFromEnv(),
 126                         ProjectUUID: *projectUUID,
 127                         RAM:         750000000000,
 128                         VCPUs:       96,
 129                         Priority:    *priority,
 130                         APIAccess:   true,
 131                 }
 132                 err = runner.TranslatePaths(inputDir)
 133                 if err != nil {
 134                         return 1
 135                 }
 136                 if *outputBed != "" {
 137                         if strings.Contains(*outputBed, "/") {
 138                                 err = fmt.Errorf("cannot use -output-bed filename %q containing '/' char", *outputBed)
 139                                 return 1
 140                         }
 141                         *outputBed = "/mnt/output/" + *outputBed
 142                 }
 143                 runner.Args = []string{"export", "-local=true",
 144                         "-pprof", ":6000",
 145                         "-pprof-dir", "/mnt/output",
 146                         "-ref", *refname,
 147                         "-output-format", *outputFormatStr,
 148                         "-output-bed", *outputBed,
 149                         "-output-labels", "/mnt/output/labels.csv",
 150                         "-output-per-chromosome=" + fmt.Sprintf("%v", cmd.outputPerChrom),
 151                         "-max-tile-size", fmt.Sprintf("%d", cmd.maxTileSize),
 152                         "-input-dir", *inputDir,
 153                         "-output-dir", "/mnt/output",
 154                         "-z=" + fmt.Sprintf("%v", cmd.compress),
 155                 }
 156                 runner.Args = append(runner.Args, cmd.filter.Args()...)
 157                 var output string
 158                 output, err = runner.Run()
 159                 if err != nil {
 160                         return 1
 161                 }
 162                 fmt.Fprintln(stdout, output)
 163                 return 0
 164         }
 165
 166         var cgs []CompactGenome
 167         tilelib := &tileLibrary{
 168                 retainNoCalls:       true,
 169                 retainTileSequences: true,
 170                 compactGenomes:      map[string][]tileVariantID{},
 171         }
 172         err = tilelib.LoadDir(context.Background(), *inputDir, nil)
 173         if err != nil {
 174                 return 1
 175         }
 176
 177         refseq, ok := tilelib.refseqs[*refname]
 178         if !ok {
 179                 err = fmt.Errorf("reference name %q not found in input; have %v", *refname, func() (names []string) {
 180                         for name := range tilelib.refseqs {
 181                                 names = append(names, name)
 182                         }
 183                         return
 184                 }())
 185                 return 1
 186         }
 187
 188         log.Infof("filtering: %+v", cmd.filter)
 189         cmd.filter.Apply(tilelib)
 190
 191         names := cgnames(tilelib)
 192         for _, name := range names {
 193                 cgs = append(cgs, CompactGenome{Name: name, Variants: tilelib.compactGenomes[name]})
 194         }
 195         if *labelsFilename != "" {
 196                 log.Infof("writing labels to %s", *labelsFilename)
 197                 var f *os.File
 198                 f, err = os.OpenFile(*labelsFilename, os.O_CREATE|os.O_WRONLY, 0777)
 199                 if err != nil {
 200                         return 1
 201                 }
 202                 defer f.Close()
 203                 for i, name := range names {
 204                         _, err = fmt.Fprintf(f, "%d,%q,%q\n", i, trimFilenameForLabel(name), cmd.outputFormat.Filename())
 205                         if err != nil {
 206                                 err = fmt.Errorf("write %s: %w", *labelsFilename, err)
 207                                 return 1
 208                         }
 209                 }
 210                 err = f.Close()
 211                 if err != nil {
 212                         err = fmt.Errorf("close %s: %w", *labelsFilename, err)
 213                         return 1
 214                 }
 215         }
 216
 217         var bedout io.Writer
 218         var bedfile *os.File
 219         var bedbufw *bufio.Writer
 220         if *outputBed != "" {
 221                 bedfile, err = os.OpenFile(*outputBed, os.O_CREATE|os.O_WRONLY, 0666)
 222                 if err != nil {
 223                         return 1
 224                 }
 225                 defer bedfile.Close()
 226                 bedbufw = bufio.NewWriterSize(bedfile, 16*1024*1024)
 227                 bedout = bedbufw
 228         }
 229
 230         err = cmd.export(*outputDir, bedout, tilelib, refseq, cgs)
 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 = bedfile.Close()
 240                 if err != nil {
 241                         return 1
 242                 }
 243         }
 244         return 0
 245 }
 246
 247 func (cmd *exporter) export(outdir string, bedout io.Writer, tilelib *tileLibrary, refseq map[string][]tileLibRef, cgs []CompactGenome) error {
 248         var seqnames []string
 249         var missing []tileLibRef
 250         for seqname, librefs := range refseq {
 251                 seqnames = append(seqnames, seqname)
 252                 for _, libref := range librefs {
 253                         if libref.Variant != 0 && tilelib.TileVariantSequence(libref) == nil {
 254                                 missing = append(missing, libref)
 255                         }
 256                 }
 257         }
 258         sort.Strings(seqnames)
 259
 260         if len(missing) > 0 {
 261                 if limit := 100; len(missing) > limit {
 262                         log.Warnf("first %d missing tiles: %v", limit, missing[:limit])
 263                 } else {
 264                         log.Warnf("missing tiles: %v", missing)
 265                 }
 266                 return fmt.Errorf("%d needed tiles are missing from library", len(missing))
 267         }
 268
 269         outw := make([]io.WriteCloser, len(seqnames))
 270         bedw := make([]io.WriteCloser, len(seqnames))
 271
 272         var merges sync.WaitGroup
 273         merge := func(dst io.Writer, src []io.WriteCloser, label string) {
 274                 var mtx sync.Mutex
 275                 for i, seqname := range seqnames {
 276                         pr, pw := io.Pipe()
 277                         src[i] = pw
 278                         merges.Add(1)
 279                         seqname := seqname
 280                         go func() {
 281                                 defer merges.Done()
 282                                 log.Infof("writing %s %s", seqname, label)
 283                                 scanner := bufio.NewScanner(pr)
 284                                 for scanner.Scan() {
 285                                         mtx.Lock()
 286                                         dst.Write(scanner.Bytes())
 287                                         dst.Write([]byte{'\n'})
 288                                         mtx.Unlock()
 289                                 }
 290                                 log.Infof("writing %s %s done", seqname, label)
 291                         }()
 292                 }
 293         }
 294         if cmd.outputPerChrom {
 295                 for i, seqname := range seqnames {
 296                         fnm := filepath.Join(outdir, strings.Replace(cmd.outputFormat.Filename(), ".", "."+seqname+".", 1))
 297                         if cmd.compress {
 298                                 fnm += ".gz"
 299                         }
 300                         f, err := os.OpenFile(fnm, os.O_CREATE|os.O_WRONLY|os.O_TRUNC, 0666)
 301                         if err != nil {
 302                                 return err
 303                         }
 304                         defer f.Close()
 305                         log.Infof("writing %q", f.Name())
 306                         outw[i] = f
 307                         if cmd.compress {
 308                                 z := pgzip.NewWriter(f)
 309                                 defer z.Close()
 310                                 outw[i] = z
 311                         }
 312                         err = cmd.outputFormat.Head(outw[i], cgs)
 313                         if err != nil {
 314                                 return err
 315                         }
 316                 }
 317         } else {
 318                 fnm := filepath.Join(outdir, cmd.outputFormat.Filename())
 319                 if cmd.compress {
 320                         fnm += ".gz"
 321                 }
 322                 f, err := os.OpenFile(fnm, os.O_CREATE|os.O_WRONLY|os.O_TRUNC, 0666)
 323                 if err != nil {
 324                         return err
 325                 }
 326                 defer f.Close()
 327                 log.Infof("writing %q", fnm)
 328                 var out io.Writer = f
 329                 if cmd.compress {
 330                         z := pgzip.NewWriter(out)
 331                         defer z.Close()
 332                         out = z
 333                 }
 334                 cmd.outputFormat.Head(out, cgs)
 335                 merge(out, outw, "output")
 336         }
 337         if bedout != nil {
 338                 merge(bedout, bedw, "bed")
 339         }
 340
 341         throttle := throttle{Max: runtime.NumCPU()}
 342         if max := cmd.outputFormat.MaxGoroutines(); max > 0 {
 343                 throttle.Max = max
 344         }
 345         log.Infof("assembling %d sequences in %d goroutines", len(seqnames), throttle.Max)
 346         for seqidx, seqname := range seqnames {
 347                 seqidx, seqname := seqidx, seqname
 348                 outw := outw[seqidx]
 349                 bedw := bedw[seqidx]
 350                 throttle.Acquire()
 351                 go func() {
 352                         defer throttle.Release()
 353                         if bedw != nil {
 354                                 defer bedw.Close()
 355                         }
 356                         outwb := bufio.NewWriterSize(outw, 8*1024*1024)
 357                         eachVariant(bedw, tilelib.taglib.keylen, seqname, refseq[seqname], tilelib, cgs, cmd.outputFormat.PadLeft(), cmd.maxTileSize, func(varslice []tvVariant) {
 358                                 err := cmd.outputFormat.Print(outwb, seqname, varslice)
 359                                 throttle.Report(err)
 360                         })
 361                         err := cmd.outputFormat.Finish(outdir, outwb, seqname)
 362                         throttle.Report(err)
 363                         err = outwb.Flush()
 364                         throttle.Report(err)
 365                         err = outw.Close()
 366                         throttle.Report(err)
 367                 }()
 368         }
 369
 370         merges.Wait()
 371         throttle.Wait()
 372         return throttle.Err()
 373 }
 374
 375 // Align genome tiles to reference tiles, call callback func on each
 376 // variant, and (if bedw is not nil) write tile coverage to bedw.
 377 func eachVariant(bedw io.Writer, taglen int, seqname string, reftiles []tileLibRef, tilelib *tileLibrary, cgs []CompactGenome, padLeft bool, maxTileSize int, callback func(varslice []tvVariant)) {
 378         t0 := time.Now()
 379         progressbar := time.NewTicker(time.Minute)
 380         defer progressbar.Stop()
 381         var outmtx sync.Mutex
 382         defer outmtx.Lock()
 383         refpos := 0
 384         variantAt := map[int][]tvVariant{} // variantAt[chromOffset][genomeIndex*2+phase]
 385         for refstep, libref := range reftiles {
 386                 select {
 387                 case <-progressbar.C:
 388                         var eta interface{}
 389                         if refstep > 0 {
 390                                 fin := t0.Add(time.Duration(float64(time.Now().Sub(t0)) * float64(len(reftiles)) / float64(refstep)))
 391                                 eta = fmt.Sprintf("%v (%v)", fin.Format(time.RFC3339), fin.Sub(time.Now()))
 392                         } else {
 393                                 eta = "N/A"
 394                         }
 395                         log.Printf("exportSeq: %s: refstep %d of %d, %.0f/s, ETA %v", seqname, refstep, len(reftiles), float64(refstep)/time.Now().Sub(t0).Seconds(), eta)
 396                 default:
 397                 }
 398                 diffs := map[tileLibRef][]hgvs.Variant{}
 399                 refseq := tilelib.TileVariantSequence(libref)
 400                 tagcoverage := 0 // number of times the start tag was found in genomes -- max is len(cgs)*2
 401                 for cgidx, cg := range cgs {
 402                         for phase := 0; phase < 2; phase++ {
 403                                 if len(cg.Variants) <= int(libref.Tag)*2+phase {
 404                                         continue
 405                                 }
 406                                 variant := cg.Variants[int(libref.Tag)*2+phase]
 407                                 if variant == 0 {
 408                                         continue
 409                                 }
 410                                 tagcoverage++
 411                                 if variant == libref.Variant {
 412                                         continue
 413                                 }
 414                                 glibref := tileLibRef{Tag: libref.Tag, Variant: variant}
 415                                 vars, ok := diffs[glibref]
 416                                 if !ok {
 417                                         genomeseq := tilelib.TileVariantSequence(glibref)
 418                                         if len(genomeseq) == 0 {
 419                                                 // Hash is known but sequence
 420                                                 // is not, e.g., retainNoCalls
 421                                                 // was false during import
 422                                                 continue
 423                                         }
 424                                         if len(genomeseq) > maxTileSize {
 425                                                 continue
 426                                         }
 427                                         refSequence := refseq
 428                                         // If needed, extend the
 429                                         // reference sequence up to
 430                                         // the tag at the end of the
 431                                         // genomeseq sequence.
 432                                         refstepend := refstep + 1
 433                                         for refstepend < len(reftiles) && len(refSequence) >= taglen && !bytes.EqualFold(refSequence[len(refSequence)-taglen:], genomeseq[len(genomeseq)-taglen:]) && len(refSequence) <= maxTileSize {
 434                                                 if &refSequence[0] == &refseq[0] {
 435                                                         refSequence = append([]byte(nil), refSequence...)
 436                                                 }
 437                                                 refSequence = append(refSequence, tilelib.TileVariantSequence(reftiles[refstepend])...)
 438                                                 refstepend++
 439                                         }
 440                                         // (TODO: handle no-calls)
 441                                         if len(refSequence) <= maxTileSize {
 442                                                 refstr := strings.ToUpper(string(refSequence))
 443                                                 genomestr := strings.ToUpper(string(genomeseq))
 444                                                 vars, _ = hgvs.Diff(refstr, genomestr, time.Second)
 445                                         }
 446                                         diffs[glibref] = vars
 447                                 }
 448                                 for _, v := range vars {
 449                                         if padLeft {
 450                                                 v = v.PadLeft()
 451                                         }
 452                                         v.Position += refpos
 453                                         varslice := variantAt[v.Position]
 454                                         if varslice == nil {
 455                                                 varslice = make([]tvVariant, len(cgs)*2)
 456                                                 variantAt[v.Position] = varslice
 457                                         }
 458                                         varslice[cgidx*2+phase].Variant = v
 459                                         if varslice[cgidx*2+phase].librefs == nil {
 460                                                 varslice[cgidx*2+phase].librefs = map[tileLibRef]bool{glibref: true}
 461                                         } else {
 462                                                 varslice[cgidx*2+phase].librefs[glibref] = true
 463                                         }
 464                                 }
 465                         }
 466                 }
 467                 refpos += len(refseq) - taglen
 468
 469                 // Flush entries from variantAt that are behind
 470                 // refpos. Flush all entries if this is the last
 471                 // reftile of the path/chromosome.
 472                 flushpos := make([]int, 0, len(variantAt))
 473                 lastrefstep := refstep == len(reftiles)-1
 474                 for pos := range variantAt {
 475                         if lastrefstep || pos <= refpos {
 476                                 flushpos = append(flushpos, pos)
 477                         }
 478                 }
 479                 sort.Slice(flushpos, func(i, j int) bool { return flushpos[i] < flushpos[j] })
 480                 flushvariants := make([][]tvVariant, len(flushpos))
 481                 for i, pos := range flushpos {
 482                         varslice := variantAt[pos]
 483                         delete(variantAt, pos)
 484                         for i := range varslice {
 485                                 if varslice[i].Position == 0 {
 486                                         varslice[i].Position = pos
 487                                 }
 488                         }
 489                         flushvariants[i] = varslice
 490                 }
 491                 outmtx.Lock()
 492                 go func() {
 493                         defer outmtx.Unlock()
 494                         for _, varslice := range flushvariants {
 495                                 callback(varslice)
 496                         }
 497                 }()
 498                 if bedw != nil && len(refseq) > 0 {
 499                         tilestart := refpos - len(refseq) + taglen
 500                         tileend := refpos
 501                         if !lastrefstep {
 502                                 tileend += taglen
 503                         }
 504                         thickstart := tilestart + taglen
 505                         if refstep == 0 {
 506                                 thickstart = 0
 507                         }
 508                         thickend := refpos
 509
 510                         // coverage score, 0 to 1000
 511                         score := 1000
 512                         if len(cgs) > 0 {
 513                                 score = 1000 * tagcoverage / len(cgs) / 2
 514                         }
 515
 516                         fmt.Fprintf(bedw, "%s %d %d %d %d . %d %d\n",
 517                                 seqname, tilestart, tileend,
 518                                 libref.Tag,
 519                                 score,
 520                                 thickstart, thickend)
 521                 }
 522         }
 523 }
 524
 525 func bucketVarsliceByRef(varslice []tvVariant) map[string]map[string]int {
 526         byref := map[string]map[string]int{}
 527         for _, v := range varslice {
 528                 if v.Ref == "" && v.New == "" {
 529                         continue
 530                 }
 531                 alts := byref[v.Ref]
 532                 if alts == nil {
 533                         alts = map[string]int{}
 534                         byref[v.Ref] = alts
 535                 }
 536                 alts[v.New]++
 537         }
 538         return byref
 539 }
 540
 541 type formatVCF struct{}
 542
 543 func (formatVCF) MaxGoroutines() int                     { return 0 }
 544 func (formatVCF) Filename() string                       { return "out.vcf" }
 545 func (formatVCF) PadLeft() bool                          { return true }
 546 func (formatVCF) Finish(string, io.Writer, string) error { return nil }
 547 func (formatVCF) Head(out io.Writer, cgs []CompactGenome) error {
 548         _, err := fmt.Fprint(out, "#CHROM\tPOS\tID\tREF\tALT\tQUAL\tFILTER\tINFO\n")
 549         return err
 550 }
 551 func (formatVCF) Print(out io.Writer, seqname string, varslice []tvVariant) error {
 552         for ref, alts := range bucketVarsliceByRef(varslice) {
 553                 altslice := make([]string, 0, len(alts))
 554                 for alt := range alts {
 555                         altslice = append(altslice, alt)
 556                 }
 557                 sort.Strings(altslice)
 558
 559                 info := "AC="
 560                 for i, a := range altslice {
 561                         if i > 0 {
 562                                 info += ","
 563                         }
 564                         info += strconv.Itoa(alts[a])
 565                 }
 566                 _, 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)
 567                 if err != nil {
 568                         return err
 569                 }
 570         }
 571         return nil
 572 }
 573
 574 type formatPVCF struct{}
 575
 576 func (formatPVCF) MaxGoroutines() int                     { return 0 }
 577 func (formatPVCF) Filename() string                       { return "out.vcf" }
 578 func (formatPVCF) PadLeft() bool                          { return true }
 579 func (formatPVCF) Finish(string, io.Writer, string) error { return nil }
 580 func (formatPVCF) Head(out io.Writer, cgs []CompactGenome) error {
 581         fmt.Fprintln(out, `##FORMAT=<ID=GT,Number=1,Type=String,Description="Genotype">`)
 582         fmt.Fprintf(out, "#CHROM\tPOS\tID\tREF\tALT\tQUAL\tFILTER\tINFO\tFORMAT")
 583         for _, cg := range cgs {
 584                 fmt.Fprintf(out, "\t%s", cg.Name)
 585         }
 586         _, err := fmt.Fprintf(out, "\n")
 587         return err
 588 }
 589
 590 func (formatPVCF) Print(out io.Writer, seqname string, varslice []tvVariant) error {
 591         for ref, alts := range bucketVarsliceByRef(varslice) {
 592                 altslice := make([]string, 0, len(alts))
 593                 for alt := range alts {
 594                         altslice = append(altslice, alt)
 595                 }
 596                 sort.Strings(altslice)
 597                 for i, a := range altslice {
 598                         alts[a] = i + 1
 599                 }
 600                 _, err := fmt.Fprintf(out, "%s\t%d\t.\t%s\t%s\t.\t.\t.\tGT", seqname, varslice[0].Position, ref, strings.Join(altslice, ","))
 601                 if err != nil {
 602                         return err
 603                 }
 604                 for i := 0; i < len(varslice); i += 2 {
 605                         v1, v2 := varslice[i], varslice[i+1]
 606                         a1, a2 := alts[v1.New], alts[v2.New]
 607                         if v1.Ref != ref {
 608                                 // variant on allele 0 belongs on a
 609                                 // different output line -- same
 610                                 // chr,pos but different "ref" length
 611                                 a1 = 0
 612                         }
 613                         if v2.Ref != ref {
 614                                 a2 = 0
 615                         }
 616                         _, err := fmt.Fprintf(out, "\t%d/%d", a1, a2)
 617                         if err != nil {
 618                                 return err
 619                         }
 620                 }
 621                 _, err = out.Write([]byte{'\n'})
 622                 if err != nil {
 623                         return err
 624                 }
 625         }
 626         return nil
 627 }
 628
 629 type formatHGVS struct{}
 630
 631 func (formatHGVS) MaxGoroutines() int                            { return 0 }
 632 func (formatHGVS) Filename() string                              { return "out.tsv" }
 633 func (formatHGVS) PadLeft() bool                                 { return false }
 634 func (formatHGVS) Head(out io.Writer, cgs []CompactGenome) error { return nil }
 635 func (formatHGVS) Finish(string, io.Writer, string) error        { return nil }
 636 func (formatHGVS) Print(out io.Writer, seqname string, varslice []tvVariant) error {
 637         for i := 0; i < len(varslice)/2; i++ {
 638                 if i > 0 {
 639                         out.Write([]byte{'\t'})
 640                 }
 641                 var1, var2 := varslice[i*2], varslice[i*2+1]
 642                 if var1.Variant == var2.Variant {
 643                         if var1.Ref == var1.New {
 644                                 _, err := out.Write([]byte{'.'})
 645                                 if err != nil {
 646                                         return err
 647                                 }
 648                         } else {
 649                                 _, err := fmt.Fprintf(out, "%s:g.%s", seqname, var1.String())
 650                                 if err != nil {
 651                                         return err
 652                                 }
 653                         }
 654                 } else {
 655                         _, err := fmt.Fprintf(out, "%s:g.[%s];[%s]", seqname, var1.String(), var2.String())
 656                         if err != nil {
 657                                 return err
 658                         }
 659                 }
 660         }
 661         _, err := out.Write([]byte{'\n'})
 662         return err
 663 }
 664
 665 type formatHGVSOneHot struct{}
 666
 667 func (formatHGVSOneHot) MaxGoroutines() int                            { return 0 }
 668 func (formatHGVSOneHot) Filename() string                              { return "out.tsv" }
 669 func (formatHGVSOneHot) PadLeft() bool                                 { return false }
 670 func (formatHGVSOneHot) Head(out io.Writer, cgs []CompactGenome) error { return nil }
 671 func (formatHGVSOneHot) Finish(string, io.Writer, string) error        { return nil }
 672 func (formatHGVSOneHot) Print(out io.Writer, seqname string, varslice []tvVariant) error {
 673         vars := map[hgvs.Variant]bool{}
 674         for _, v := range varslice {
 675                 if v.Ref != v.New {
 676                         vars[v.Variant] = true
 677                 }
 678         }
 679
 680         // sort variants to ensure output is deterministic
 681         sorted := make([]hgvs.Variant, 0, len(vars))
 682         for v := range vars {
 683                 sorted = append(sorted, v)
 684         }
 685         sort.Slice(sorted, func(a, b int) bool { return hgvs.Less(sorted[a], sorted[b]) })
 686
 687         for _, v := range sorted {
 688                 fmt.Fprintf(out, "%s.%s", seqname, v.String())
 689                 for i := 0; i < len(varslice); i += 2 {
 690                         if varslice[i].Variant == v || varslice[i+1].Variant == v {
 691                                 out.Write([]byte("\t1"))
 692                         } else {
 693                                 out.Write([]byte("\t0"))
 694                         }
 695                 }
 696                 _, err := out.Write([]byte{'\n'})
 697                 if err != nil {
 698                         return err
 699                 }
 700         }
 701         return nil
 702 }
 703
 704 type formatHGVSNumpy struct {
 705         sync.Mutex
 706         writelock sync.Mutex
 707         alleles   map[string][][]bool // alleles[seqname][variantidx][genomeidx*2+phase]
 708 }
 709
 710 func (*formatHGVSNumpy) MaxGoroutines() int                            { return 4 }
 711 func (*formatHGVSNumpy) Filename() string                              { return "annotations.csv" }
 712 func (*formatHGVSNumpy) PadLeft() bool                                 { return false }
 713 func (*formatHGVSNumpy) Head(out io.Writer, cgs []CompactGenome) error { return nil }
 714 func (f *formatHGVSNumpy) Print(outw io.Writer, seqname string, varslice []tvVariant) error {
 715         // sort variants to ensure output is deterministic
 716         sorted := make([]hgvs.Variant, 0, len(varslice))
 717         for _, v := range varslice {
 718                 sorted = append(sorted, v.Variant)
 719         }
 720         sort.Slice(sorted, func(a, b int) bool { return hgvs.Less(sorted[a], sorted[b]) })
 721
 722         f.Lock()
 723         seqalleles := f.alleles[seqname]
 724         f.Unlock()
 725
 726         // append a row to seqvariants and seqalleles for each unique
 727         // non-ref variant in varslice.
 728         var previous hgvs.Variant
 729         for _, v := range sorted {
 730                 if previous == v || v.Ref == v.New {
 731                         continue
 732                 }
 733                 previous = v
 734                 newrow := make([]bool, len(varslice))
 735                 for i, allele := range varslice {
 736                         if allele.Variant == v {
 737                                 newrow[i] = true
 738                         }
 739                 }
 740                 seqalleles = append(seqalleles, newrow)
 741                 _, err := fmt.Fprintf(outw, "%d,%q\n", len(seqalleles)-1, seqname+"."+v.String())
 742                 if err != nil {
 743                         return err
 744                 }
 745         }
 746
 747         f.Lock()
 748         f.alleles[seqname] = seqalleles
 749         f.Unlock()
 750         return nil
 751 }
 752 func (f *formatHGVSNumpy) Finish(outdir string, _ io.Writer, seqname string) error {
 753         // Write seqname's data to a .npy matrix with one row per
 754         // genome and 2 columns per variant.
 755         seqalleles := f.alleles[seqname]
 756         f.Lock()
 757         delete(f.alleles, seqname)
 758         f.Unlock()
 759         if len(seqalleles) == 0 {
 760                 return nil
 761         }
 762         out := make([]int8, len(seqalleles)*len(seqalleles[0]))
 763         rows := len(seqalleles[0]) / 2
 764         cols := len(seqalleles) * 2
 765         // copy seqalleles[varidx][genome*2+phase] to
 766         // out[genome*nvars*2 + varidx*2 + phase]
 767         for varidx, alleles := range seqalleles {
 768                 for g := 0; g < len(alleles)/2; g++ {
 769                         aa, ab := alleles[g*2], alleles[g*2+1]
 770                         if aa && ab {
 771                                 // hom
 772                                 out[g*cols+varidx*2] = 1
 773                         } else if aa || ab {
 774                                 // het
 775                                 out[g*cols+varidx*2+1] = 1
 776                         }
 777                 }
 778         }
 779         outf, err := os.OpenFile(outdir+"/matrix."+seqname+".npy", os.O_CREATE|os.O_EXCL|os.O_WRONLY, 0777)
 780         if err != nil {
 781                 return err
 782         }
 783         defer outf.Close()
 784         bufw := bufio.NewWriter(outf)
 785         npw, err := gonpy.NewWriter(nopCloser{bufw})
 786         if err != nil {
 787                 return err
 788         }
 789         log.WithFields(logrus.Fields{
 790                 "seqname": seqname,
 791                 "rows":    rows,
 792                 "cols":    cols,
 793         }).Info("writing numpy")
 794         npw.Shape = []int{rows, cols}
 795         f.writelock.Lock() // serialize because WriteInt8 uses lots of memory
 796         npw.WriteInt8(out)
 797         f.writelock.Unlock()
 798         err = bufw.Flush()
 799         if err != nil {
 800                 return err
 801         }
 802         err = outf.Close()
 803         if err != nil {
 804                 return err
 805         }
 806         return nil
 807 }