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, cases []bool, p float64) 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         maxPValue      float64
  65         cases          []bool
  66 }
  67
  68 func (cmd *exporter) RunCommand(prog string, args []string, stdin io.Reader, stdout, stderr io.Writer) int {
  69         var err error
  70         defer func() {
  71                 if err != nil {
  72                         fmt.Fprintf(stderr, "%s\n", err)
  73                 }
  74         }()
  75         flags := flag.NewFlagSet("", flag.ContinueOnError)
  76         flags.SetOutput(stderr)
  77         pprof := flags.String("pprof", "", "serve Go profile data at http://`[addr]:port`")
  78         pprofdir := flags.String("pprof-dir", "", "write Go profile data to `directory` periodically")
  79         runlocal := flags.Bool("local", false, "run on local host (default: run in an arvados container)")
  80         projectUUID := flags.String("project", "", "project `UUID` for output data")
  81         priority := flags.Int("priority", 500, "container request priority")
  82         refname := flags.String("ref", "", "reference genome `name`")
  83         inputDir := flags.String("input-dir", ".", "input `directory`")
  84         cases := flags.String("cases", "", "file indicating which genomes are positive cases (for computing p-values)")
  85         flags.Float64Var(&cmd.maxPValue, "p-value", 1, "do chi square test and omit columns with p-value above this threshold")
  86         outputDir := flags.String("output-dir", ".", "output `directory`")
  87         outputFormatStr := flags.String("output-format", "hgvs", "output `format`: hgvs, pvcf, or vcf")
  88         outputBed := flags.String("output-bed", "", "also output bed `file`")
  89         flags.BoolVar(&cmd.outputPerChrom, "output-per-chromosome", true, "output one file per chromosome")
  90         flags.BoolVar(&cmd.compress, "z", false, "write gzip-compressed output files")
  91         labelsFilename := flags.String("output-labels", "", "also output genome labels csv `file`")
  92         flags.IntVar(&cmd.maxTileSize, "max-tile-size", 50000, "don't try to make annotations for tiles bigger than given `size`")
  93         cmd.filter.Flags(flags)
  94         err = flags.Parse(args)
  95         if err == flag.ErrHelp {
  96                 err = nil
  97                 return 0
  98         } else if err != nil {
  99                 return 2
 100         }
 101         if flag.NArg() > 0 {
 102                 err = fmt.Errorf("extra unparsed command line arguments: %q", flag.Args())
 103                 return 2
 104         }
 105
 106         if f, ok := outputFormats[*outputFormatStr]; !ok {
 107                 err = fmt.Errorf("invalid output format %q", *outputFormatStr)
 108                 return 2
 109         } else {
 110                 cmd.outputFormat = f()
 111         }
 112
 113         if *pprof != "" {
 114                 go func() {
 115                         log.Println(http.ListenAndServe(*pprof, nil))
 116                 }()
 117         }
 118         if *pprofdir != "" {
 119                 go writeProfilesPeriodically(*pprofdir)
 120         }
 121
 122         if !*runlocal {
 123                 if *outputDir != "." {
 124                         err = errors.New("cannot specify output directory in container mode: not implemented")
 125                         return 1
 126                 }
 127                 runner := arvadosContainerRunner{
 128                         Name:        "lightning export",
 129                         Client:      arvados.NewClientFromEnv(),
 130                         ProjectUUID: *projectUUID,
 131                         RAM:         750000000000,
 132                         VCPUs:       96,
 133                         Priority:    *priority,
 134                         APIAccess:   true,
 135                 }
 136                 err = runner.TranslatePaths(inputDir)
 137                 if err != nil {
 138                         return 1
 139                 }
 140                 if *outputBed != "" {
 141                         if strings.Contains(*outputBed, "/") {
 142                                 err = fmt.Errorf("cannot use -output-bed filename %q containing '/' char", *outputBed)
 143                                 return 1
 144                         }
 145                         *outputBed = "/mnt/output/" + *outputBed
 146                 }
 147                 runner.Args = []string{"export", "-local=true",
 148                         "-pprof", ":6000",
 149                         "-pprof-dir", "/mnt/output",
 150                         "-ref", *refname,
 151                         "-cases", *cases,
 152                         "-p-value", fmt.Sprintf("%f", cmd.maxPValue),
 153                         "-output-format", *outputFormatStr,
 154                         "-output-bed", *outputBed,
 155                         "-output-labels", "/mnt/output/labels.csv",
 156                         "-output-per-chromosome=" + fmt.Sprintf("%v", cmd.outputPerChrom),
 157                         "-max-tile-size", fmt.Sprintf("%d", cmd.maxTileSize),
 158                         "-input-dir", *inputDir,
 159                         "-output-dir", "/mnt/output",
 160                         "-z=" + fmt.Sprintf("%v", cmd.compress),
 161                 }
 162                 runner.Args = append(runner.Args, cmd.filter.Args()...)
 163                 var output string
 164                 output, err = runner.Run()
 165                 if err != nil {
 166                         return 1
 167                 }
 168                 fmt.Fprintln(stdout, output)
 169                 return 0
 170         }
 171
 172         var cgs []CompactGenome
 173         tilelib := &tileLibrary{
 174                 retainNoCalls:       true,
 175                 retainTileSequences: true,
 176                 compactGenomes:      map[string][]tileVariantID{},
 177         }
 178         err = tilelib.LoadDir(context.Background(), *inputDir, nil)
 179         if err != nil {
 180                 return 1
 181         }
 182
 183         refseq, ok := tilelib.refseqs[*refname]
 184         if !ok {
 185                 err = fmt.Errorf("reference name %q not found in input; have %v", *refname, func() (names []string) {
 186                         for name := range tilelib.refseqs {
 187                                 names = append(names, name)
 188                         }
 189                         return
 190                 }())
 191                 return 1
 192         }
 193
 194         log.Infof("filtering: %+v", cmd.filter)
 195         cmd.filter.Apply(tilelib)
 196
 197         names := cgnames(tilelib)
 198         for _, name := range names {
 199                 cgs = append(cgs, CompactGenome{Name: name, Variants: tilelib.compactGenomes[name]})
 200         }
 201         if *labelsFilename != "" {
 202                 log.Infof("writing labels to %s", *labelsFilename)
 203                 var f *os.File
 204                 f, err = os.OpenFile(*labelsFilename, os.O_CREATE|os.O_WRONLY, 0777)
 205                 if err != nil {
 206                         return 1
 207                 }
 208                 defer f.Close()
 209                 for i, name := range names {
 210                         _, err = fmt.Fprintf(f, "%d,%q,%q\n", i, trimFilenameForLabel(name), cmd.outputFormat.Filename())
 211                         if err != nil {
 212                                 err = fmt.Errorf("write %s: %w", *labelsFilename, err)
 213                                 return 1
 214                         }
 215                 }
 216                 err = f.Close()
 217                 if err != nil {
 218                         err = fmt.Errorf("close %s: %w", *labelsFilename, err)
 219                         return 1
 220                 }
 221         }
 222
 223         cmd.cases = make([]bool, len(names))
 224         if *cases != "" {
 225                 log.Infof("reading cases file: %s", *cases)
 226                 f, err := open(*cases)
 227                 if err != nil {
 228                         return 1
 229                 }
 230                 buf, err := io.ReadAll(f)
 231                 if err != nil {
 232                         return 1
 233                 }
 234                 for _, pattern := range bytes.Split(buf, []byte("\n")) {
 235                         if len(pattern) == 0 {
 236                                 continue
 237                         }
 238                         pattern := string(pattern)
 239                         idx := -1
 240                         for i, name := range names {
 241                                 if !strings.Contains(name, pattern) {
 242                                         continue
 243                                 } else if idx >= 0 {
 244                                         err = fmt.Errorf("pattern %q in cases file matches multiple genome IDs: %q, %q", pattern, names[idx], name)
 245                                         return 1
 246                                 } else {
 247                                         idx = i
 248                                 }
 249                         }
 250                         if idx < 0 {
 251                                 log.Warnf("pattern %q in cases file does not match any genome IDs", pattern)
 252                                 continue
 253                         }
 254                         cmd.cases[idx] = true
 255                 }
 256         }
 257
 258         var bedout io.Writer
 259         var bedfile *os.File
 260         var bedbufw *bufio.Writer
 261         if *outputBed != "" {
 262                 bedfile, err = os.OpenFile(*outputBed, os.O_CREATE|os.O_WRONLY, 0666)
 263                 if err != nil {
 264                         return 1
 265                 }
 266                 defer bedfile.Close()
 267                 bedbufw = bufio.NewWriterSize(bedfile, 16*1024*1024)
 268                 bedout = bedbufw
 269         }
 270
 271         err = cmd.export(*outputDir, bedout, tilelib, refseq, cgs)
 272         if err != nil {
 273                 return 1
 274         }
 275         if bedout != nil {
 276                 err = bedbufw.Flush()
 277                 if err != nil {
 278                         return 1
 279                 }
 280                 err = bedfile.Close()
 281                 if err != nil {
 282                         return 1
 283                 }
 284         }
 285         return 0
 286 }
 287
 288 func (cmd *exporter) export(outdir string, bedout io.Writer, tilelib *tileLibrary, refseq map[string][]tileLibRef, cgs []CompactGenome) error {
 289         var seqnames []string
 290         var missing []tileLibRef
 291         for seqname, librefs := range refseq {
 292                 seqnames = append(seqnames, seqname)
 293                 for _, libref := range librefs {
 294                         if libref.Variant != 0 && tilelib.TileVariantSequence(libref) == nil {
 295                                 missing = append(missing, libref)
 296                         }
 297                 }
 298         }
 299         sort.Strings(seqnames)
 300
 301         if len(missing) > 0 {
 302                 if limit := 100; len(missing) > limit {
 303                         log.Warnf("first %d missing tiles: %v", limit, missing[:limit])
 304                 } else {
 305                         log.Warnf("missing tiles: %v", missing)
 306                 }
 307                 return fmt.Errorf("%d needed tiles are missing from library", len(missing))
 308         }
 309
 310         outw := make([]io.WriteCloser, len(seqnames))
 311         bedw := make([]io.WriteCloser, len(seqnames))
 312
 313         var merges sync.WaitGroup
 314         merge := func(dst io.Writer, src []io.WriteCloser, label string) {
 315                 var mtx sync.Mutex
 316                 for i, seqname := range seqnames {
 317                         pr, pw := io.Pipe()
 318                         src[i] = pw
 319                         merges.Add(1)
 320                         seqname := seqname
 321                         go func() {
 322                                 defer merges.Done()
 323                                 log.Infof("writing %s %s", seqname, label)
 324                                 scanner := bufio.NewScanner(pr)
 325                                 for scanner.Scan() {
 326                                         mtx.Lock()
 327                                         dst.Write(scanner.Bytes())
 328                                         dst.Write([]byte{'\n'})
 329                                         mtx.Unlock()
 330                                 }
 331                                 log.Infof("writing %s %s done", seqname, label)
 332                         }()
 333                 }
 334         }
 335         if cmd.outputPerChrom {
 336                 for i, seqname := range seqnames {
 337                         fnm := filepath.Join(outdir, strings.Replace(cmd.outputFormat.Filename(), ".", "."+seqname+".", 1))
 338                         if cmd.compress {
 339                                 fnm += ".gz"
 340                         }
 341                         f, err := os.OpenFile(fnm, os.O_CREATE|os.O_WRONLY|os.O_TRUNC, 0666)
 342                         if err != nil {
 343                                 return err
 344                         }
 345                         defer f.Close()
 346                         log.Infof("writing %q", f.Name())
 347                         outw[i] = f
 348                         if cmd.compress {
 349                                 z := pgzip.NewWriter(f)
 350                                 defer z.Close()
 351                                 outw[i] = z
 352                         }
 353                         err = cmd.outputFormat.Head(outw[i], cgs, cmd.cases, cmd.maxPValue)
 354                         if err != nil {
 355                                 return err
 356                         }
 357                 }
 358         } else {
 359                 fnm := filepath.Join(outdir, cmd.outputFormat.Filename())
 360                 if cmd.compress {
 361                         fnm += ".gz"
 362                 }
 363                 f, err := os.OpenFile(fnm, os.O_CREATE|os.O_WRONLY|os.O_TRUNC, 0666)
 364                 if err != nil {
 365                         return err
 366                 }
 367                 defer f.Close()
 368                 log.Infof("writing %q", fnm)
 369                 var out io.Writer = f
 370                 if cmd.compress {
 371                         z := pgzip.NewWriter(out)
 372                         defer z.Close()
 373                         out = z
 374                 }
 375                 cmd.outputFormat.Head(out, cgs, cmd.cases, cmd.maxPValue)
 376                 merge(out, outw, "output")
 377         }
 378         if bedout != nil {
 379                 merge(bedout, bedw, "bed")
 380         }
 381
 382         throttle := throttle{Max: runtime.NumCPU()}
 383         if max := cmd.outputFormat.MaxGoroutines(); max > 0 {
 384                 throttle.Max = max
 385         }
 386         log.Infof("assembling %d sequences in %d goroutines", len(seqnames), throttle.Max)
 387         for seqidx, seqname := range seqnames {
 388                 seqidx, seqname := seqidx, seqname
 389                 outw := outw[seqidx]
 390                 bedw := bedw[seqidx]
 391                 throttle.Acquire()
 392                 go func() {
 393                         defer throttle.Release()
 394                         if bedw != nil {
 395                                 defer bedw.Close()
 396                         }
 397                         outwb := bufio.NewWriterSize(outw, 8*1024*1024)
 398                         eachVariant(bedw, tilelib.taglib.keylen, seqname, refseq[seqname], tilelib, cgs, cmd.outputFormat.PadLeft(), cmd.maxTileSize, func(varslice []tvVariant) {
 399                                 err := cmd.outputFormat.Print(outwb, seqname, varslice)
 400                                 throttle.Report(err)
 401                         })
 402                         err := cmd.outputFormat.Finish(outdir, outwb, seqname)
 403                         throttle.Report(err)
 404                         err = outwb.Flush()
 405                         throttle.Report(err)
 406                         err = outw.Close()
 407                         throttle.Report(err)
 408                 }()
 409         }
 410
 411         merges.Wait()
 412         throttle.Wait()
 413         return throttle.Err()
 414 }
 415
 416 // Align genome tiles to reference tiles, call callback func on each
 417 // variant, and (if bedw is not nil) write tile coverage to bedw.
 418 func eachVariant(bedw io.Writer, taglen int, seqname string, reftiles []tileLibRef, tilelib *tileLibrary, cgs []CompactGenome, padLeft bool, maxTileSize int, callback func(varslice []tvVariant)) {
 419         t0 := time.Now()
 420         progressbar := time.NewTicker(time.Minute)
 421         defer progressbar.Stop()
 422         var outmtx sync.Mutex
 423         defer outmtx.Lock()
 424         refpos := 0
 425         variantAt := map[int][]tvVariant{} // variantAt[chromOffset][genomeIndex*2+phase]
 426         for refstep, libref := range reftiles {
 427                 select {
 428                 case <-progressbar.C:
 429                         var eta interface{}
 430                         if refstep > 0 {
 431                                 fin := t0.Add(time.Duration(float64(time.Now().Sub(t0)) * float64(len(reftiles)) / float64(refstep)))
 432                                 eta = fmt.Sprintf("%v (%v)", fin.Format(time.RFC3339), fin.Sub(time.Now()))
 433                         } else {
 434                                 eta = "N/A"
 435                         }
 436                         log.Printf("exportSeq: %s: refstep %d of %d, %.0f/s, ETA %v", seqname, refstep, len(reftiles), float64(refstep)/time.Now().Sub(t0).Seconds(), eta)
 437                 default:
 438                 }
 439                 diffs := map[tileLibRef][]hgvs.Variant{}
 440                 refseq := tilelib.TileVariantSequence(libref)
 441                 tagcoverage := 0 // number of times the start tag was found in genomes -- max is len(cgs)*2
 442                 for cgidx, cg := range cgs {
 443                         for phase := 0; phase < 2; phase++ {
 444                                 var variant tileVariantID
 445                                 if i := int(libref.Tag)*2 + phase; len(cg.Variants) > i {
 446                                         variant = cg.Variants[i]
 447                                 }
 448                                 if variant > 0 {
 449                                         tagcoverage++
 450                                 }
 451                                 if variant == libref.Variant || variant == 0 {
 452                                         continue
 453                                 }
 454                                 glibref := tileLibRef{Tag: libref.Tag, Variant: variant}
 455                                 vars, ok := diffs[glibref]
 456                                 if !ok {
 457                                         genomeseq := tilelib.TileVariantSequence(glibref)
 458                                         if len(genomeseq) == 0 {
 459                                                 // Hash is known but sequence
 460                                                 // is not, e.g., retainNoCalls
 461                                                 // was false during import
 462                                                 continue
 463                                         }
 464                                         if len(genomeseq) > maxTileSize {
 465                                                 continue
 466                                         }
 467                                         refSequence := refseq
 468                                         // If needed, extend the
 469                                         // reference sequence up to
 470                                         // the tag at the end of the
 471                                         // genomeseq sequence.
 472                                         refstepend := refstep + 1
 473                                         for refstepend < len(reftiles) && len(refSequence) >= taglen && !bytes.EqualFold(refSequence[len(refSequence)-taglen:], genomeseq[len(genomeseq)-taglen:]) && len(refSequence) <= maxTileSize {
 474                                                 if &refSequence[0] == &refseq[0] {
 475                                                         refSequence = append([]byte(nil), refSequence...)
 476                                                 }
 477                                                 refSequence = append(refSequence, tilelib.TileVariantSequence(reftiles[refstepend])...)
 478                                                 refstepend++
 479                                         }
 480                                         // (TODO: handle no-calls)
 481                                         if len(refSequence) <= maxTileSize {
 482                                                 refstr := strings.ToUpper(string(refSequence))
 483                                                 genomestr := strings.ToUpper(string(genomeseq))
 484                                                 vars, _ = hgvs.Diff(refstr, genomestr, time.Second)
 485                                         }
 486                                         diffs[glibref] = vars
 487                                 }
 488                                 for _, v := range vars {
 489                                         if padLeft {
 490                                                 v = v.PadLeft()
 491                                         }
 492                                         v.Position += refpos
 493                                         varslice := variantAt[v.Position]
 494                                         if varslice == nil {
 495                                                 varslice = make([]tvVariant, len(cgs)*2)
 496                                                 variantAt[v.Position] = varslice
 497                                         }
 498                                         varslice[cgidx*2+phase].Variant = v
 499                                         if varslice[cgidx*2+phase].librefs == nil {
 500                                                 varslice[cgidx*2+phase].librefs = map[tileLibRef]bool{glibref: true}
 501                                         } else {
 502                                                 varslice[cgidx*2+phase].librefs[glibref] = true
 503                                         }
 504                                 }
 505                         }
 506                 }
 507                 refpos += len(refseq) - taglen
 508
 509                 // Flush entries from variantAt that are behind
 510                 // refpos. Flush all entries if this is the last
 511                 // reftile of the path/chromosome.
 512                 flushpos := make([]int, 0, len(variantAt))
 513                 lastrefstep := refstep == len(reftiles)-1
 514                 for pos := range variantAt {
 515                         if lastrefstep || pos <= refpos {
 516                                 flushpos = append(flushpos, pos)
 517                         }
 518                 }
 519                 sort.Slice(flushpos, func(i, j int) bool { return flushpos[i] < flushpos[j] })
 520                 flushvariants := make([][]tvVariant, len(flushpos))
 521                 for i, pos := range flushpos {
 522                         varslice := variantAt[pos]
 523                         delete(variantAt, pos)
 524                         // Check for uninitialized (zero-value)
 525                         // elements in varslice
 526                         for i := range varslice {
 527                                 if varslice[i].Position != 0 {
 528                                         // Not a zero-value element
 529                                         continue
 530                                 }
 531                                 // Set the position so
 532                                 // varslice[*].Position are all equal
 533                                 varslice[i].Position = pos
 534                                 // This could be either =ref or a
 535                                 // missing/low-quality tile. Figure
 536                                 // out which.
 537                                 vidx := int(libref.Tag)*2 + i%2
 538                                 if vidx >= len(cgs[i/2].Variants) {
 539                                         // Missing tile.
 540                                         varslice[i].New = "-"
 541                                         continue
 542                                 }
 543                                 v := cgs[i/2].Variants[vidx]
 544                                 if v < 1 || len(tilelib.TileVariantSequence(tileLibRef{Tag: libref.Tag, Variant: v})) == 0 {
 545                                         // Missing/low-quality tile.
 546                                         varslice[i].New = "-" // fasta "gap of indeterminate length"
 547                                 }
 548                         }
 549                         flushvariants[i] = varslice
 550                 }
 551                 outmtx.Lock()
 552                 go func() {
 553                         defer outmtx.Unlock()
 554                         for _, varslice := range flushvariants {
 555                                 callback(varslice)
 556                         }
 557                 }()
 558                 if bedw != nil && len(refseq) > 0 {
 559                         tilestart := refpos - len(refseq) + taglen
 560                         tileend := refpos
 561                         if !lastrefstep {
 562                                 tileend += taglen
 563                         }
 564                         thickstart := tilestart + taglen
 565                         if refstep == 0 {
 566                                 thickstart = 0
 567                         }
 568                         thickend := refpos
 569
 570                         // coverage score, 0 to 1000
 571                         score := 1000
 572                         if len(cgs) > 0 {
 573                                 score = 1000 * tagcoverage / len(cgs) / 2
 574                         }
 575
 576                         fmt.Fprintf(bedw, "%s %d %d %d %d . %d %d\n",
 577                                 seqname, tilestart, tileend,
 578                                 libref.Tag,
 579                                 score,
 580                                 thickstart, thickend)
 581                 }
 582         }
 583 }
 584
 585 func bucketVarsliceByRef(varslice []tvVariant) map[string]map[string]int {
 586         byref := map[string]map[string]int{}
 587         for _, v := range varslice {
 588                 if v.Ref == "" && v.New == "" {
 589                         // =ref
 590                         continue
 591                 }
 592                 if v.New == "-" {
 593                         // no-call
 594                         continue
 595                 }
 596                 alts := byref[v.Ref]
 597                 if alts == nil {
 598                         alts = map[string]int{}
 599                         byref[v.Ref] = alts
 600                 }
 601                 alts[v.New]++
 602         }
 603         return byref
 604 }
 605
 606 type formatVCF struct{}
 607
 608 func (formatVCF) MaxGoroutines() int                     { return 0 }
 609 func (formatVCF) Filename() string                       { return "out.vcf" }
 610 func (formatVCF) PadLeft() bool                          { return true }
 611 func (formatVCF) Finish(string, io.Writer, string) error { return nil }
 612 func (formatVCF) Head(out io.Writer, cgs []CompactGenome, cases []bool, p float64) error {
 613         _, err := fmt.Fprint(out, "#CHROM\tPOS\tID\tREF\tALT\tQUAL\tFILTER\tINFO\n")
 614         return err
 615 }
 616 func (formatVCF) Print(out io.Writer, seqname string, varslice []tvVariant) error {
 617         for ref, alts := range bucketVarsliceByRef(varslice) {
 618                 altslice := make([]string, 0, len(alts))
 619                 for alt := range alts {
 620                         altslice = append(altslice, alt)
 621                 }
 622                 sort.Strings(altslice)
 623
 624                 info := "AC="
 625                 for i, a := range altslice {
 626                         if i > 0 {
 627                                 info += ","
 628                         }
 629                         info += strconv.Itoa(alts[a])
 630                 }
 631                 _, 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)
 632                 if err != nil {
 633                         return err
 634                 }
 635         }
 636         return nil
 637 }
 638
 639 type formatPVCF struct{}
 640
 641 func (formatPVCF) MaxGoroutines() int                     { return 0 }
 642 func (formatPVCF) Filename() string                       { return "out.vcf" }
 643 func (formatPVCF) PadLeft() bool                          { return true }
 644 func (formatPVCF) Finish(string, io.Writer, string) error { return nil }
 645 func (formatPVCF) Head(out io.Writer, cgs []CompactGenome, cases []bool, p float64) error {
 646         fmt.Fprintln(out, `##FORMAT=<ID=GT,Number=1,Type=String,Description="Genotype">`)
 647         fmt.Fprintf(out, "#CHROM\tPOS\tID\tREF\tALT\tQUAL\tFILTER\tINFO\tFORMAT")
 648         for _, cg := range cgs {
 649                 fmt.Fprintf(out, "\t%s", cg.Name)
 650         }
 651         _, err := fmt.Fprintf(out, "\n")
 652         return err
 653 }
 654
 655 func (formatPVCF) Print(out io.Writer, seqname string, varslice []tvVariant) error {
 656         for ref, alts := range bucketVarsliceByRef(varslice) {
 657                 altslice := make([]string, 0, len(alts))
 658                 for alt := range alts {
 659                         altslice = append(altslice, alt)
 660                 }
 661                 sort.Strings(altslice)
 662                 for i, a := range altslice {
 663                         alts[a] = i + 1
 664                 }
 665                 _, err := fmt.Fprintf(out, "%s\t%d\t.\t%s\t%s\t.\t.\t.\tGT", seqname, varslice[0].Position, ref, strings.Join(altslice, ","))
 666                 if err != nil {
 667                         return err
 668                 }
 669                 for i := 0; i < len(varslice); i += 2 {
 670                         v1, v2 := varslice[i], varslice[i+1]
 671                         a1, a2 := alts[v1.New], alts[v2.New]
 672                         if v1.Ref != ref {
 673                                 // variant on allele 0 belongs on a
 674                                 // different output line -- same
 675                                 // chr,pos but different "ref" length
 676                                 a1 = 0
 677                         }
 678                         if v2.Ref != ref {
 679                                 a2 = 0
 680                         }
 681                         _, err := fmt.Fprintf(out, "\t%d/%d", a1, a2)
 682                         if err != nil {
 683                                 return err
 684                         }
 685                 }
 686                 _, err = out.Write([]byte{'\n'})
 687                 if err != nil {
 688                         return err
 689                 }
 690         }
 691         return nil
 692 }
 693
 694 type formatHGVS struct{}
 695
 696 func (formatHGVS) MaxGoroutines() int                                                     { return 0 }
 697 func (formatHGVS) Filename() string                                                       { return "out.tsv" }
 698 func (formatHGVS) PadLeft() bool                                                          { return false }
 699 func (formatHGVS) Head(out io.Writer, cgs []CompactGenome, cases []bool, p float64) error { return nil }
 700 func (formatHGVS) Finish(string, io.Writer, string) error                                 { return nil }
 701 func (formatHGVS) Print(out io.Writer, seqname string, varslice []tvVariant) error {
 702         for i := 0; i < len(varslice)/2; i++ {
 703                 if i > 0 {
 704                         out.Write([]byte{'\t'})
 705                 }
 706                 var1, var2 := varslice[i*2], varslice[i*2+1]
 707                 if var1.New == "-" || var2.New == "-" {
 708                         _, err := out.Write([]byte{'N'})
 709                         if err != nil {
 710                                 return err
 711                         }
 712                         continue
 713                 }
 714                 if var1.Variant == var2.Variant {
 715                         if var1.Ref == var1.New {
 716                                 _, err := out.Write([]byte{'.'})
 717                                 if err != nil {
 718                                         return err
 719                                 }
 720                         } else {
 721                                 _, err := fmt.Fprintf(out, "%s:g.%s", seqname, var1.String())
 722                                 if err != nil {
 723                                         return err
 724                                 }
 725                         }
 726                 } else {
 727                         _, err := fmt.Fprintf(out, "%s:g.[%s];[%s]", seqname, var1.String(), var2.String())
 728                         if err != nil {
 729                                 return err
 730                         }
 731                 }
 732         }
 733         _, err := out.Write([]byte{'\n'})
 734         return err
 735 }
 736
 737 type formatHGVSOneHot struct{}
 738
 739 func (formatHGVSOneHot) MaxGoroutines() int { return 0 }
 740 func (formatHGVSOneHot) Filename() string   { return "out.tsv" }
 741 func (formatHGVSOneHot) PadLeft() bool      { return false }
 742 func (formatHGVSOneHot) Head(out io.Writer, cgs []CompactGenome, cases []bool, p float64) error {
 743         return nil
 744 }
 745 func (formatHGVSOneHot) Finish(string, io.Writer, string) error { return nil }
 746 func (formatHGVSOneHot) Print(out io.Writer, seqname string, varslice []tvVariant) error {
 747         vars := map[hgvs.Variant]bool{}
 748         for _, v := range varslice {
 749                 if v.Ref != v.New {
 750                         vars[v.Variant] = true
 751                 }
 752         }
 753
 754         // sort variants to ensure output is deterministic
 755         sorted := make([]hgvs.Variant, 0, len(vars))
 756         for v := range vars {
 757                 sorted = append(sorted, v)
 758         }
 759         sort.Slice(sorted, func(a, b int) bool { return hgvs.Less(sorted[a], sorted[b]) })
 760
 761         for _, v := range sorted {
 762                 if v.New == "-" {
 763                         continue
 764                 }
 765                 fmt.Fprintf(out, "%s.%s", seqname, v.String())
 766                 for i := 0; i < len(varslice); i += 2 {
 767                         if varslice[i].Variant == v || varslice[i+1].Variant == v {
 768                                 out.Write([]byte("\t1"))
 769                         } else {
 770                                 out.Write([]byte("\t0"))
 771                         }
 772                 }
 773                 _, err := out.Write([]byte{'\n'})
 774                 if err != nil {
 775                         return err
 776                 }
 777         }
 778         return nil
 779 }
 780
 781 type formatHGVSNumpy struct {
 782         sync.Mutex
 783         writelock sync.Mutex
 784         alleles   map[string][][]int8 // alleles[seqname][variantidx][genomeidx*2+phase]
 785         cases     []bool
 786         maxPValue float64
 787 }
 788
 789 func (*formatHGVSNumpy) MaxGoroutines() int { return 4 }
 790 func (*formatHGVSNumpy) Filename() string   { return "annotations.csv" }
 791 func (*formatHGVSNumpy) PadLeft() bool      { return false }
 792 func (f *formatHGVSNumpy) Head(out io.Writer, cgs []CompactGenome, cases []bool, p float64) error {
 793         f.cases = cases
 794         f.maxPValue = p
 795         return nil
 796 }
 797 func (f *formatHGVSNumpy) Print(outw io.Writer, seqname string, varslice []tvVariant) error {
 798         // sort variants to ensure output is deterministic
 799         sorted := make([]hgvs.Variant, 0, len(varslice))
 800         for _, v := range varslice {
 801                 sorted = append(sorted, v.Variant)
 802         }
 803         sort.Slice(sorted, func(a, b int) bool { return hgvs.Less(sorted[a], sorted[b]) })
 804
 805         f.Lock()
 806         seqalleles := f.alleles[seqname]
 807         f.Unlock()
 808
 809         chi2x := make([]bool, 0, len(varslice))
 810         chi2y := make([]bool, 0, len(varslice))
 811
 812         // append a row to seqalleles for each unique non-ref variant
 813         // in varslice.
 814         var previous hgvs.Variant
 815         for _, v := range sorted {
 816                 if previous == v || v.Ref == v.New || v.New == "-" {
 817                         continue
 818                 }
 819                 previous = v
 820                 chi2x, chi2y := chi2x, chi2y
 821                 newrow := make([]int8, len(varslice))
 822                 for i, allele := range varslice {
 823                         if allele.Variant == v {
 824                                 newrow[i] = 1
 825                                 chi2x = append(chi2x, true)
 826                                 chi2y = append(chi2y, f.cases[i/2])
 827                         } else if allele.Variant.New == "-" {
 828                                 newrow[i] = -1
 829                         } else {
 830                                 chi2x = append(chi2x, false)
 831                                 chi2y = append(chi2y, f.cases[i/2])
 832                         }
 833                 }
 834                 if f.maxPValue < 1 && pvalue(chi2x, chi2y) > f.maxPValue {
 835                         continue
 836                 }
 837                 seqalleles = append(seqalleles, newrow)
 838                 _, err := fmt.Fprintf(outw, "%d,%q\n", len(seqalleles)-1, seqname+"."+v.String())
 839                 if err != nil {
 840                         return err
 841                 }
 842         }
 843
 844         f.Lock()
 845         f.alleles[seqname] = seqalleles
 846         f.Unlock()
 847         return nil
 848 }
 849 func (f *formatHGVSNumpy) Finish(outdir string, _ io.Writer, seqname string) error {
 850         // Write seqname's data to a .npy matrix with one row per
 851         // genome and 2 columns per variant.
 852         f.Lock()
 853         seqalleles := f.alleles[seqname]
 854         delete(f.alleles, seqname)
 855         f.Unlock()
 856         if len(seqalleles) == 0 {
 857                 return nil
 858         }
 859         out := make([]int8, len(seqalleles)*len(seqalleles[0]))
 860         rows := len(seqalleles[0]) / 2
 861         cols := len(seqalleles) * 2
 862         // copy seqalleles[varidx][genome*2+phase] to
 863         // out[genome*nvars*2 + varidx*2 + phase]
 864         for varidx, alleles := range seqalleles {
 865                 for g := 0; g < len(alleles)/2; g++ {
 866                         aa, ab := alleles[g*2], alleles[g*2+1]
 867                         if aa < 0 || ab < 0 {
 868                                 // no-call
 869                                 out[g*cols+varidx*2] = -1
 870                                 out[g*cols+varidx*2+1] = -1
 871                         } else if aa > 0 && ab > 0 {
 872                                 // hom
 873                                 out[g*cols+varidx*2] = 1
 874                         } else if aa > 0 || ab > 0 {
 875                                 // het
 876                                 out[g*cols+varidx*2+1] = 1
 877                         }
 878                 }
 879         }
 880         outf, err := os.OpenFile(outdir+"/matrix."+seqname+".npy", os.O_CREATE|os.O_EXCL|os.O_WRONLY, 0777)
 881         if err != nil {
 882                 return err
 883         }
 884         defer outf.Close()
 885         bufw := bufio.NewWriter(outf)
 886         npw, err := gonpy.NewWriter(nopCloser{bufw})
 887         if err != nil {
 888                 return err
 889         }
 890         log.WithFields(logrus.Fields{
 891                 "seqname": seqname,
 892                 "rows":    rows,
 893                 "cols":    cols,
 894         }).Info("writing numpy")
 895         npw.Shape = []int{rows, cols}
 896         f.writelock.Lock() // serialize because WriteInt8 uses lots of memory
 897         npw.WriteInt8(out)
 898         f.writelock.Unlock()
 899         err = bufw.Flush()
 900         if err != nil {
 901                 return err
 902         }
 903         err = outf.Close()
 904         if err != nil {
 905                 return err
 906         }
 907         return nil
 908 }