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][][]int8{}}
  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                                 var variant tileVariantID
 404                                 if i := int(libref.Tag)*2 + phase; len(cg.Variants) > i {
 405                                         variant = cg.Variants[i]
 406                                 }
 407                                 if variant > 0 {
 408                                         tagcoverage++
 409                                 }
 410                                 if variant == libref.Variant || variant == 0 {
 411                                         continue
 412                                 }
 413                                 glibref := tileLibRef{Tag: libref.Tag, Variant: variant}
 414                                 vars, ok := diffs[glibref]
 415                                 if !ok {
 416                                         genomeseq := tilelib.TileVariantSequence(glibref)
 417                                         if len(genomeseq) == 0 {
 418                                                 // Hash is known but sequence
 419                                                 // is not, e.g., retainNoCalls
 420                                                 // was false during import
 421                                                 continue
 422                                         }
 423                                         if len(genomeseq) > maxTileSize {
 424                                                 continue
 425                                         }
 426                                         refSequence := refseq
 427                                         // If needed, extend the
 428                                         // reference sequence up to
 429                                         // the tag at the end of the
 430                                         // genomeseq sequence.
 431                                         refstepend := refstep + 1
 432                                         for refstepend < len(reftiles) && len(refSequence) >= taglen && !bytes.EqualFold(refSequence[len(refSequence)-taglen:], genomeseq[len(genomeseq)-taglen:]) && len(refSequence) <= maxTileSize {
 433                                                 if &refSequence[0] == &refseq[0] {
 434                                                         refSequence = append([]byte(nil), refSequence...)
 435                                                 }
 436                                                 refSequence = append(refSequence, tilelib.TileVariantSequence(reftiles[refstepend])...)
 437                                                 refstepend++
 438                                         }
 439                                         // (TODO: handle no-calls)
 440                                         if len(refSequence) <= maxTileSize {
 441                                                 refstr := strings.ToUpper(string(refSequence))
 442                                                 genomestr := strings.ToUpper(string(genomeseq))
 443                                                 vars, _ = hgvs.Diff(refstr, genomestr, time.Second)
 444                                         }
 445                                         diffs[glibref] = vars
 446                                 }
 447                                 for _, v := range vars {
 448                                         if padLeft {
 449                                                 v = v.PadLeft()
 450                                         }
 451                                         v.Position += refpos
 452                                         varslice := variantAt[v.Position]
 453                                         if varslice == nil {
 454                                                 varslice = make([]tvVariant, len(cgs)*2)
 455                                                 variantAt[v.Position] = varslice
 456                                         }
 457                                         varslice[cgidx*2+phase].Variant = v
 458                                         if varslice[cgidx*2+phase].librefs == nil {
 459                                                 varslice[cgidx*2+phase].librefs = map[tileLibRef]bool{glibref: true}
 460                                         } else {
 461                                                 varslice[cgidx*2+phase].librefs[glibref] = true
 462                                         }
 463                                 }
 464                         }
 465                 }
 466                 refpos += len(refseq) - taglen
 467
 468                 // Flush entries from variantAt that are behind
 469                 // refpos. Flush all entries if this is the last
 470                 // reftile of the path/chromosome.
 471                 flushpos := make([]int, 0, len(variantAt))
 472                 lastrefstep := refstep == len(reftiles)-1
 473                 for pos := range variantAt {
 474                         if lastrefstep || pos <= refpos {
 475                                 flushpos = append(flushpos, pos)
 476                         }
 477                 }
 478                 sort.Slice(flushpos, func(i, j int) bool { return flushpos[i] < flushpos[j] })
 479                 flushvariants := make([][]tvVariant, len(flushpos))
 480                 for i, pos := range flushpos {
 481                         varslice := variantAt[pos]
 482                         delete(variantAt, pos)
 483                         // Check for uninitialized (zero-value)
 484                         // elements in varslice
 485                         for i := range varslice {
 486                                 if varslice[i].Position != 0 {
 487                                         // Not a zero-value element
 488                                         continue
 489                                 }
 490                                 // Set the position so
 491                                 // varslice[*].Position are all equal
 492                                 varslice[i].Position = pos
 493                                 // This could be either =ref or a
 494                                 // missing/low-quality tile. Figure
 495                                 // out which.
 496                                 vidx := int(libref.Tag)*2 + i%2
 497                                 if vidx >= len(cgs[i/2].Variants) {
 498                                         // Missing tile.
 499                                         varslice[i].New = "-"
 500                                         continue
 501                                 }
 502                                 v := cgs[i/2].Variants[vidx]
 503                                 if v < 1 || len(tilelib.TileVariantSequence(tileLibRef{Tag: libref.Tag, Variant: v})) == 0 {
 504                                         // Missing/low-quality tile.
 505                                         varslice[i].New = "-" // fasta "gap of indeterminate length"
 506                                 }
 507                         }
 508                         flushvariants[i] = varslice
 509                 }
 510                 outmtx.Lock()
 511                 go func() {
 512                         defer outmtx.Unlock()
 513                         for _, varslice := range flushvariants {
 514                                 callback(varslice)
 515                         }
 516                 }()
 517                 if bedw != nil && len(refseq) > 0 {
 518                         tilestart := refpos - len(refseq) + taglen
 519                         tileend := refpos
 520                         if !lastrefstep {
 521                                 tileend += taglen
 522                         }
 523                         thickstart := tilestart + taglen
 524                         if refstep == 0 {
 525                                 thickstart = 0
 526                         }
 527                         thickend := refpos
 528
 529                         // coverage score, 0 to 1000
 530                         score := 1000
 531                         if len(cgs) > 0 {
 532                                 score = 1000 * tagcoverage / len(cgs) / 2
 533                         }
 534
 535                         fmt.Fprintf(bedw, "%s %d %d %d %d . %d %d\n",
 536                                 seqname, tilestart, tileend,
 537                                 libref.Tag,
 538                                 score,
 539                                 thickstart, thickend)
 540                 }
 541         }
 542 }
 543
 544 func bucketVarsliceByRef(varslice []tvVariant) map[string]map[string]int {
 545         byref := map[string]map[string]int{}
 546         for _, v := range varslice {
 547                 if v.Ref == "" && v.New == "" {
 548                         // =ref
 549                         continue
 550                 }
 551                 if v.New == "-" {
 552                         // no-call
 553                         continue
 554                 }
 555                 alts := byref[v.Ref]
 556                 if alts == nil {
 557                         alts = map[string]int{}
 558                         byref[v.Ref] = alts
 559                 }
 560                 alts[v.New]++
 561         }
 562         return byref
 563 }
 564
 565 type formatVCF struct{}
 566
 567 func (formatVCF) MaxGoroutines() int                     { return 0 }
 568 func (formatVCF) Filename() string                       { return "out.vcf" }
 569 func (formatVCF) PadLeft() bool                          { return true }
 570 func (formatVCF) Finish(string, io.Writer, string) error { return nil }
 571 func (formatVCF) Head(out io.Writer, cgs []CompactGenome) error {
 572         _, err := fmt.Fprint(out, "#CHROM\tPOS\tID\tREF\tALT\tQUAL\tFILTER\tINFO\n")
 573         return err
 574 }
 575 func (formatVCF) Print(out io.Writer, seqname string, varslice []tvVariant) error {
 576         for ref, alts := range bucketVarsliceByRef(varslice) {
 577                 altslice := make([]string, 0, len(alts))
 578                 for alt := range alts {
 579                         altslice = append(altslice, alt)
 580                 }
 581                 sort.Strings(altslice)
 582
 583                 info := "AC="
 584                 for i, a := range altslice {
 585                         if i > 0 {
 586                                 info += ","
 587                         }
 588                         info += strconv.Itoa(alts[a])
 589                 }
 590                 _, 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)
 591                 if err != nil {
 592                         return err
 593                 }
 594         }
 595         return nil
 596 }
 597
 598 type formatPVCF struct{}
 599
 600 func (formatPVCF) MaxGoroutines() int                     { return 0 }
 601 func (formatPVCF) Filename() string                       { return "out.vcf" }
 602 func (formatPVCF) PadLeft() bool                          { return true }
 603 func (formatPVCF) Finish(string, io.Writer, string) error { return nil }
 604 func (formatPVCF) Head(out io.Writer, cgs []CompactGenome) error {
 605         fmt.Fprintln(out, `##FORMAT=<ID=GT,Number=1,Type=String,Description="Genotype">`)
 606         fmt.Fprintf(out, "#CHROM\tPOS\tID\tREF\tALT\tQUAL\tFILTER\tINFO\tFORMAT")
 607         for _, cg := range cgs {
 608                 fmt.Fprintf(out, "\t%s", cg.Name)
 609         }
 610         _, err := fmt.Fprintf(out, "\n")
 611         return err
 612 }
 613
 614 func (formatPVCF) Print(out io.Writer, seqname string, varslice []tvVariant) error {
 615         for ref, alts := range bucketVarsliceByRef(varslice) {
 616                 altslice := make([]string, 0, len(alts))
 617                 for alt := range alts {
 618                         altslice = append(altslice, alt)
 619                 }
 620                 sort.Strings(altslice)
 621                 for i, a := range altslice {
 622                         alts[a] = i + 1
 623                 }
 624                 _, err := fmt.Fprintf(out, "%s\t%d\t.\t%s\t%s\t.\t.\t.\tGT", seqname, varslice[0].Position, ref, strings.Join(altslice, ","))
 625                 if err != nil {
 626                         return err
 627                 }
 628                 for i := 0; i < len(varslice); i += 2 {
 629                         v1, v2 := varslice[i], varslice[i+1]
 630                         a1, a2 := alts[v1.New], alts[v2.New]
 631                         if v1.Ref != ref {
 632                                 // variant on allele 0 belongs on a
 633                                 // different output line -- same
 634                                 // chr,pos but different "ref" length
 635                                 a1 = 0
 636                         }
 637                         if v2.Ref != ref {
 638                                 a2 = 0
 639                         }
 640                         _, err := fmt.Fprintf(out, "\t%d/%d", a1, a2)
 641                         if err != nil {
 642                                 return err
 643                         }
 644                 }
 645                 _, err = out.Write([]byte{'\n'})
 646                 if err != nil {
 647                         return err
 648                 }
 649         }
 650         return nil
 651 }
 652
 653 type formatHGVS struct{}
 654
 655 func (formatHGVS) MaxGoroutines() int                            { return 0 }
 656 func (formatHGVS) Filename() string                              { return "out.tsv" }
 657 func (formatHGVS) PadLeft() bool                                 { return false }
 658 func (formatHGVS) Head(out io.Writer, cgs []CompactGenome) error { return nil }
 659 func (formatHGVS) Finish(string, io.Writer, string) error        { return nil }
 660 func (formatHGVS) Print(out io.Writer, seqname string, varslice []tvVariant) error {
 661         for i := 0; i < len(varslice)/2; i++ {
 662                 if i > 0 {
 663                         out.Write([]byte{'\t'})
 664                 }
 665                 var1, var2 := varslice[i*2], varslice[i*2+1]
 666                 if var1.New == "-" || var2.New == "-" {
 667                         _, err := out.Write([]byte{'N'})
 668                         if err != nil {
 669                                 return err
 670                         }
 671                         continue
 672                 }
 673                 if var1.Variant == var2.Variant {
 674                         if var1.Ref == var1.New {
 675                                 _, err := out.Write([]byte{'.'})
 676                                 if err != nil {
 677                                         return err
 678                                 }
 679                         } else {
 680                                 _, err := fmt.Fprintf(out, "%s:g.%s", seqname, var1.String())
 681                                 if err != nil {
 682                                         return err
 683                                 }
 684                         }
 685                 } else {
 686                         _, err := fmt.Fprintf(out, "%s:g.[%s];[%s]", seqname, var1.String(), var2.String())
 687                         if err != nil {
 688                                 return err
 689                         }
 690                 }
 691         }
 692         _, err := out.Write([]byte{'\n'})
 693         return err
 694 }
 695
 696 type formatHGVSOneHot struct{}
 697
 698 func (formatHGVSOneHot) MaxGoroutines() int                            { return 0 }
 699 func (formatHGVSOneHot) Filename() string                              { return "out.tsv" }
 700 func (formatHGVSOneHot) PadLeft() bool                                 { return false }
 701 func (formatHGVSOneHot) Head(out io.Writer, cgs []CompactGenome) error { return nil }
 702 func (formatHGVSOneHot) Finish(string, io.Writer, string) error        { return nil }
 703 func (formatHGVSOneHot) Print(out io.Writer, seqname string, varslice []tvVariant) error {
 704         vars := map[hgvs.Variant]bool{}
 705         for _, v := range varslice {
 706                 if v.Ref != v.New {
 707                         vars[v.Variant] = true
 708                 }
 709         }
 710
 711         // sort variants to ensure output is deterministic
 712         sorted := make([]hgvs.Variant, 0, len(vars))
 713         for v := range vars {
 714                 sorted = append(sorted, v)
 715         }
 716         sort.Slice(sorted, func(a, b int) bool { return hgvs.Less(sorted[a], sorted[b]) })
 717
 718         for _, v := range sorted {
 719                 if v.New == "-" {
 720                         continue
 721                 }
 722                 fmt.Fprintf(out, "%s.%s", seqname, v.String())
 723                 for i := 0; i < len(varslice); i += 2 {
 724                         if varslice[i].Variant == v || varslice[i+1].Variant == v {
 725                                 out.Write([]byte("\t1"))
 726                         } else {
 727                                 out.Write([]byte("\t0"))
 728                         }
 729                 }
 730                 _, err := out.Write([]byte{'\n'})
 731                 if err != nil {
 732                         return err
 733                 }
 734         }
 735         return nil
 736 }
 737
 738 type formatHGVSNumpy struct {
 739         sync.Mutex
 740         writelock sync.Mutex
 741         alleles   map[string][][]int8 // alleles[seqname][variantidx][genomeidx*2+phase]
 742 }
 743
 744 func (*formatHGVSNumpy) MaxGoroutines() int                            { return 4 }
 745 func (*formatHGVSNumpy) Filename() string                              { return "annotations.csv" }
 746 func (*formatHGVSNumpy) PadLeft() bool                                 { return false }
 747 func (*formatHGVSNumpy) Head(out io.Writer, cgs []CompactGenome) error { return nil }
 748 func (f *formatHGVSNumpy) Print(outw io.Writer, seqname string, varslice []tvVariant) error {
 749         // sort variants to ensure output is deterministic
 750         sorted := make([]hgvs.Variant, 0, len(varslice))
 751         for _, v := range varslice {
 752                 sorted = append(sorted, v.Variant)
 753         }
 754         sort.Slice(sorted, func(a, b int) bool { return hgvs.Less(sorted[a], sorted[b]) })
 755
 756         f.Lock()
 757         seqalleles := f.alleles[seqname]
 758         f.Unlock()
 759
 760         // append a row to seqalleles for each unique non-ref variant
 761         // in varslice.
 762         var previous hgvs.Variant
 763         for _, v := range sorted {
 764                 if previous == v || v.Ref == v.New || v.New == "-" {
 765                         continue
 766                 }
 767                 previous = v
 768                 newrow := make([]int8, len(varslice))
 769                 for i, allele := range varslice {
 770                         if allele.Variant == v {
 771                                 newrow[i] = 1
 772                         } else if allele.Variant.New == "-" {
 773                                 newrow[i] = -1
 774                         }
 775                 }
 776                 seqalleles = append(seqalleles, newrow)
 777                 _, err := fmt.Fprintf(outw, "%d,%q\n", len(seqalleles)-1, seqname+"."+v.String())
 778                 if err != nil {
 779                         return err
 780                 }
 781         }
 782
 783         f.Lock()
 784         f.alleles[seqname] = seqalleles
 785         f.Unlock()
 786         return nil
 787 }
 788 func (f *formatHGVSNumpy) Finish(outdir string, _ io.Writer, seqname string) error {
 789         // Write seqname's data to a .npy matrix with one row per
 790         // genome and 2 columns per variant.
 791         f.Lock()
 792         seqalleles := f.alleles[seqname]
 793         delete(f.alleles, seqname)
 794         f.Unlock()
 795         if len(seqalleles) == 0 {
 796                 return nil
 797         }
 798         out := make([]int8, len(seqalleles)*len(seqalleles[0]))
 799         rows := len(seqalleles[0]) / 2
 800         cols := len(seqalleles) * 2
 801         // copy seqalleles[varidx][genome*2+phase] to
 802         // out[genome*nvars*2 + varidx*2 + phase]
 803         for varidx, alleles := range seqalleles {
 804                 for g := 0; g < len(alleles)/2; g++ {
 805                         aa, ab := alleles[g*2], alleles[g*2+1]
 806                         if aa < 0 || ab < 0 {
 807                                 // no-call
 808                                 out[g*cols+varidx*2] = -1
 809                                 out[g*cols+varidx*2+1] = -1
 810                         } else if aa > 0 && ab > 0 {
 811                                 // hom
 812                                 out[g*cols+varidx*2] = 1
 813                         } else if aa > 0 || ab > 0 {
 814                                 // het
 815                                 out[g*cols+varidx*2+1] = 1
 816                         }
 817                 }
 818         }
 819         outf, err := os.OpenFile(outdir+"/matrix."+seqname+".npy", os.O_CREATE|os.O_EXCL|os.O_WRONLY, 0777)
 820         if err != nil {
 821                 return err
 822         }
 823         defer outf.Close()
 824         bufw := bufio.NewWriter(outf)
 825         npw, err := gonpy.NewWriter(nopCloser{bufw})
 826         if err != nil {
 827                 return err
 828         }
 829         log.WithFields(logrus.Fields{
 830                 "seqname": seqname,
 831                 "rows":    rows,
 832                 "cols":    cols,
 833         }).Info("writing numpy")
 834         npw.Shape = []int{rows, cols}
 835         f.writelock.Lock() // serialize because WriteInt8 uses lots of memory
 836         npw.WriteInt8(out)
 837         f.writelock.Unlock()
 838         err = bufw.Flush()
 839         if err != nil {
 840                 return err
 841         }
 842         err = outf.Close()
 843         if err != nil {
 844                 return err
 845         }
 846         return nil
 847 }