slicenumpy.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         "flag"
  11         "fmt"
  12         "io"
  13         "io/ioutil"
  14         "net/http"
  15         _ "net/http/pprof"
  16         "os"
  17         "regexp"
  18         "runtime"
  19         "sort"
  20         "strconv"
  21         "strings"
  22         "sync/atomic"
  23
  24         "git.arvados.org/arvados.git/sdk/go/arvados"
  25         "github.com/arvados/lightning/hgvs"
  26         "github.com/kshedden/gonpy"
  27         log "github.com/sirupsen/logrus"
  28         "golang.org/x/crypto/blake2b"
  29 )
  30
  31 type sliceNumpy struct {
  32         filter  filter
  33         threads int
  34 }
  35
  36 func (cmd *sliceNumpy) RunCommand(prog string, args []string, stdin io.Reader, stdout, stderr io.Writer) int {
  37         var err error
  38         defer func() {
  39                 if err != nil {
  40                         fmt.Fprintf(stderr, "%s\n", err)
  41                 }
  42         }()
  43         flags := flag.NewFlagSet("", flag.ContinueOnError)
  44         flags.SetOutput(stderr)
  45         pprof := flags.String("pprof", "", "serve Go profile data at http://`[addr]:port`")
  46         runlocal := flags.Bool("local", false, "run on local host (default: run in an arvados container)")
  47         projectUUID := flags.String("project", "", "project `UUID` for output data")
  48         priority := flags.Int("priority", 500, "container request priority")
  49         inputDir := flags.String("input-dir", "./in", "input `directory`")
  50         outputDir := flags.String("output-dir", "./out", "output `directory`")
  51         ref := flags.String("ref", "", "reference name (if blank, choose last one that appears in input)")
  52         regionsFilename := flags.String("regions", "", "only output columns/annotations that intersect regions in specified bed `file`")
  53         expandRegions := flags.Int("expand-regions", 0, "expand specified regions by `N` base pairs on each side`")
  54         mergeOutput := flags.Bool("merge-output", false, "merge output into one matrix.npy and one matrix.annotations.csv")
  55         hgvsSingle := flags.Bool("single-hgvs-matrix", false, "also generate hgvs-based matrix")
  56         hgvsChunked := flags.Bool("chunked-hgvs-matrix", false, "also generate hgvs-based matrix per chromosome")
  57         flags.IntVar(&cmd.threads, "threads", 16, "number of memory-hungry assembly threads")
  58         cmd.filter.Flags(flags)
  59         err = flags.Parse(args)
  60         if err == flag.ErrHelp {
  61                 err = nil
  62                 return 0
  63         } else if err != nil {
  64                 return 2
  65         }
  66
  67         if *pprof != "" {
  68                 go func() {
  69                         log.Println(http.ListenAndServe(*pprof, nil))
  70                 }()
  71         }
  72
  73         if !*runlocal {
  74                 runner := arvadosContainerRunner{
  75                         Name:        "lightning slice-numpy",
  76                         Client:      arvados.NewClientFromEnv(),
  77                         ProjectUUID: *projectUUID,
  78                         RAM:         750000000000,
  79                         VCPUs:       96,
  80                         Priority:    *priority,
  81                         KeepCache:   2,
  82                         APIAccess:   true,
  83                 }
  84                 err = runner.TranslatePaths(inputDir, regionsFilename)
  85                 if err != nil {
  86                         return 1
  87                 }
  88                 runner.Args = []string{"slice-numpy", "-local=true",
  89                         "-pprof=:6060",
  90                         "-input-dir=" + *inputDir,
  91                         "-output-dir=/mnt/output",
  92                         "-threads=" + fmt.Sprintf("%d", cmd.threads),
  93                         "-regions=" + *regionsFilename,
  94                         "-expand-regions=" + fmt.Sprintf("%d", *expandRegions),
  95                         "-merge-output=" + fmt.Sprintf("%v", *mergeOutput),
  96                         "-single-hgvs-matrix=" + fmt.Sprintf("%v", *hgvsSingle),
  97                         "-chunked-hgvs-matrix=" + fmt.Sprintf("%v", *hgvsChunked),
  98                 }
  99                 runner.Args = append(runner.Args, cmd.filter.Args()...)
 100                 var output string
 101                 output, err = runner.Run()
 102                 if err != nil {
 103                         return 1
 104                 }
 105                 fmt.Fprintln(stdout, output)
 106                 return 0
 107         }
 108
 109         infiles, err := allGobFiles(*inputDir)
 110         if err != nil {
 111                 return 1
 112         }
 113         if len(infiles) == 0 {
 114                 err = fmt.Errorf("no input files found in %s", *inputDir)
 115                 return 1
 116         }
 117         sort.Strings(infiles)
 118
 119         var cgnames []string
 120         var refseq map[string][]tileLibRef
 121         var reftiledata = make(map[tileLibRef][]byte, 11000000)
 122         in0, err := open(infiles[0])
 123         if err != nil {
 124                 return 1
 125         }
 126
 127         matchGenome, err := regexp.Compile(cmd.filter.MatchGenome)
 128         if err != nil {
 129                 err = fmt.Errorf("-match-genome: invalid regexp: %q", cmd.filter.MatchGenome)
 130                 return 1
 131         }
 132
 133         taglen := -1
 134         DecodeLibrary(in0, strings.HasSuffix(infiles[0], ".gz"), func(ent *LibraryEntry) error {
 135                 if len(ent.TagSet) > 0 {
 136                         taglen = len(ent.TagSet[0])
 137                 }
 138                 for _, cseq := range ent.CompactSequences {
 139                         if cseq.Name == *ref || *ref == "" {
 140                                 refseq = cseq.TileSequences
 141                         }
 142                 }
 143                 for _, cg := range ent.CompactGenomes {
 144                         if matchGenome.MatchString(cg.Name) {
 145                                 cgnames = append(cgnames, cg.Name)
 146                         }
 147                 }
 148                 for _, tv := range ent.TileVariants {
 149                         if tv.Ref {
 150                                 reftiledata[tileLibRef{tv.Tag, tv.Variant}] = tv.Sequence
 151                         }
 152                 }
 153                 return nil
 154         })
 155         if err != nil {
 156                 return 1
 157         }
 158         in0.Close()
 159         if refseq == nil {
 160                 err = fmt.Errorf("%s: reference sequence not found", infiles[0])
 161                 return 1
 162         }
 163         if taglen < 0 {
 164                 err = fmt.Errorf("tagset not found")
 165                 return 1
 166         }
 167         if len(cgnames) == 0 {
 168                 err = fmt.Errorf("no genomes found matching regexp %q", cmd.filter.MatchGenome)
 169                 return 1
 170         }
 171         sort.Strings(cgnames)
 172
 173         {
 174                 labelsFilename := *outputDir + "/labels.csv"
 175                 log.Infof("writing labels to %s", labelsFilename)
 176                 var f *os.File
 177                 f, err = os.Create(labelsFilename)
 178                 if err != nil {
 179                         return 1
 180                 }
 181                 defer f.Close()
 182                 for i, name := range cgnames {
 183                         _, err = fmt.Fprintf(f, "%d,%q\n", i, trimFilenameForLabel(name))
 184                         if err != nil {
 185                                 err = fmt.Errorf("write %s: %w", labelsFilename, err)
 186                                 return 1
 187                         }
 188                 }
 189                 err = f.Close()
 190                 if err != nil {
 191                         err = fmt.Errorf("close %s: %w", labelsFilename, err)
 192                         return 1
 193                 }
 194         }
 195
 196         log.Info("indexing reference tiles")
 197         type reftileinfo struct {
 198                 variant  tileVariantID
 199                 seqname  string // chr1
 200                 pos      int    // distance from start of chromosome to starttag
 201                 tiledata []byte // acgtggcaa...
 202         }
 203         isdup := map[tagID]bool{}
 204         reftile := map[tagID]*reftileinfo{}
 205         for seqname, cseq := range refseq {
 206                 pos := 0
 207                 for _, libref := range cseq {
 208                         tiledata := reftiledata[libref]
 209                         if len(tiledata) == 0 {
 210                                 err = fmt.Errorf("missing tiledata for tag %d variant %d in %s in ref", libref.Tag, libref.Variant, seqname)
 211                                 return 1
 212                         }
 213                         if isdup[libref.Tag] {
 214                                 log.Printf("dropping reference tile %+v from %s @ %d, tag not unique", libref, seqname, pos)
 215                         } else if reftile[libref.Tag] != nil {
 216                                 log.Printf("dropping reference tile %+v from %s @ %d, tag not unique", tileLibRef{Tag: libref.Tag, Variant: reftile[libref.Tag].variant}, reftile[libref.Tag].seqname, reftile[libref.Tag].pos)
 217                                 delete(reftile, libref.Tag)
 218                                 log.Printf("dropping reference tile %+v from %s @ %d, tag not unique", libref, seqname, pos)
 219                                 isdup[libref.Tag] = true
 220                         } else {
 221                                 reftile[libref.Tag] = &reftileinfo{
 222                                         seqname:  seqname,
 223                                         variant:  libref.Variant,
 224                                         tiledata: tiledata,
 225                                         pos:      pos,
 226                                 }
 227                         }
 228                         pos += len(tiledata) - taglen
 229                 }
 230                 log.Printf("... %s done, len %d", seqname, pos+taglen)
 231         }
 232
 233         var mask *mask
 234         if *regionsFilename != "" {
 235                 log.Printf("loading regions from %s", *regionsFilename)
 236                 mask, err = makeMask(*regionsFilename, *expandRegions)
 237                 if err != nil {
 238                         return 1
 239                 }
 240                 log.Printf("before applying mask, len(reftile) == %d", len(reftile))
 241                 log.Printf("deleting reftile entries for regions outside %d intervals", mask.Len())
 242                 for tag, rt := range reftile {
 243                         if !mask.Check(strings.TrimPrefix(rt.seqname, "chr"), rt.pos, rt.pos+len(rt.tiledata)) {
 244                                 delete(reftile, tag)
 245                         }
 246                 }
 247                 log.Printf("after applying mask, len(reftile) == %d", len(reftile))
 248         }
 249
 250         var toMerge [][]int16
 251         if *mergeOutput || *hgvsSingle || *hgvsChunked {
 252                 toMerge = make([][]int16, len(infiles))
 253         }
 254
 255         throttleMem := throttle{Max: cmd.threads} // TODO: estimate using mem and data size
 256         throttleNumpyMem := throttle{Max: cmd.threads/2 + 1}
 257         log.Info("generating annotations and numpy matrix for each slice")
 258         var done int64
 259         for infileIdx, infile := range infiles {
 260                 infileIdx, infile := infileIdx, infile
 261                 throttleMem.Go(func() error {
 262                         seq := make(map[tagID][]TileVariant, 50000)
 263                         cgs := make(map[string]CompactGenome, len(cgnames))
 264                         f, err := open(infile)
 265                         if err != nil {
 266                                 return err
 267                         }
 268                         defer f.Close()
 269                         log.Infof("%04d: reading %s", infileIdx, infile)
 270                         err = DecodeLibrary(f, strings.HasSuffix(infile, ".gz"), func(ent *LibraryEntry) error {
 271                                 for _, tv := range ent.TileVariants {
 272                                         if tv.Ref {
 273                                                 continue
 274                                         }
 275                                         if mask != nil && reftile[tv.Tag] == nil {
 276                                                 // Don't waste
 277                                                 // time/memory on
 278                                                 // masked-out tiles.
 279                                                 continue
 280                                         }
 281                                         variants := seq[tv.Tag]
 282                                         if len(variants) == 0 {
 283                                                 variants = make([]TileVariant, 100)
 284                                         }
 285                                         for len(variants) <= int(tv.Variant) {
 286                                                 variants = append(variants, TileVariant{})
 287                                         }
 288                                         variants[int(tv.Variant)] = tv
 289                                         seq[tv.Tag] = variants
 290                                 }
 291                                 for _, cg := range ent.CompactGenomes {
 292                                         if matchGenome.MatchString(cg.Name) {
 293                                                 cgs[cg.Name] = cg
 294                                         }
 295                                 }
 296                                 return nil
 297                         })
 298                         if err != nil {
 299                                 return err
 300                         }
 301                         tagstart := cgs[cgnames[0]].StartTag
 302                         tagend := cgs[cgnames[0]].EndTag
 303
 304                         // TODO: filters
 305
 306                         log.Infof("%04d: renumber/dedup variants for tags %d-%d", infileIdx, tagstart, tagend)
 307                         variantRemap := make([][]tileVariantID, tagend-tagstart)
 308                         throttleCPU := throttle{Max: runtime.GOMAXPROCS(0)}
 309                         for tag, variants := range seq {
 310                                 tag, variants := tag, variants
 311                                 throttleCPU.Acquire()
 312                                 go func() {
 313                                         defer throttleCPU.Release()
 314                                         count := make(map[[blake2b.Size256]byte]int, len(variants))
 315
 316                                         rt := reftile[tag]
 317                                         if rt != nil {
 318                                                 count[blake2b.Sum256(rt.tiledata)] = 0
 319                                         }
 320
 321                                         for _, cg := range cgs {
 322                                                 idx := int(tag-tagstart) * 2
 323                                                 if idx < len(cg.Variants) {
 324                                                         for allele := 0; allele < 2; allele++ {
 325                                                                 v := cg.Variants[idx+allele]
 326                                                                 if v > 0 && len(variants[v].Sequence) > 0 {
 327                                                                         count[variants[v].Blake2b]++
 328                                                                 }
 329                                                         }
 330                                                 }
 331                                         }
 332                                         // hash[i] will be the hash of
 333                                         // the variant(s) that should
 334                                         // be at rank i (0-based).
 335                                         hash := make([][blake2b.Size256]byte, 0, len(count))
 336                                         for b := range count {
 337                                                 hash = append(hash, b)
 338                                         }
 339                                         sort.Slice(hash, func(i, j int) bool {
 340                                                 bi, bj := &hash[i], &hash[j]
 341                                                 if ci, cj := count[*bi], count[*bj]; ci != cj {
 342                                                         return ci > cj
 343                                                 } else {
 344                                                         return bytes.Compare((*bi)[:], (*bj)[:]) < 0
 345                                                 }
 346                                         })
 347                                         // rank[b] will be the 1-based
 348                                         // new variant number for
 349                                         // variants whose hash is b.
 350                                         rank := make(map[[blake2b.Size256]byte]tileVariantID, len(hash))
 351                                         for i, h := range hash {
 352                                                 rank[h] = tileVariantID(i + 1)
 353                                         }
 354                                         // remap[v] will be the new
 355                                         // variant number for original
 356                                         // variant number v.
 357                                         remap := make([]tileVariantID, len(variants))
 358                                         for i, tv := range variants {
 359                                                 remap[i] = rank[tv.Blake2b]
 360                                         }
 361                                         variantRemap[tag-tagstart] = remap
 362                                         if rt != nil {
 363                                                 rt.variant = rank[blake2b.Sum256(rt.tiledata)]
 364                                         }
 365                                 }()
 366                         }
 367                         throttleCPU.Wait()
 368
 369                         annotationsFilename := fmt.Sprintf("%s/matrix.%04d.annotations.csv", *outputDir, infileIdx)
 370                         log.Infof("%04d: writing %s", infileIdx, annotationsFilename)
 371                         annof, err := os.Create(annotationsFilename)
 372                         if err != nil {
 373                                 return err
 374                         }
 375                         annow := bufio.NewWriterSize(annof, 1<<20)
 376                         outcol := 0
 377                         for tag := tagstart; tag < tagend; tag++ {
 378                                 rt, ok := reftile[tag]
 379                                 if !ok {
 380                                         if mask == nil {
 381                                                 outcol++
 382                                         }
 383                                         // Excluded by specified
 384                                         // regions, or reference does
 385                                         // not use any variant of this
 386                                         // tile. (TODO: log this?
 387                                         // mention it in annotations?)
 388                                         continue
 389                                 }
 390                                 fmt.Fprintf(annow, "%d,%d,%d,=,%s,%d,,,\n", tag, outcol, rt.variant, rt.seqname, rt.pos)
 391                                 variants := seq[tag]
 392                                 reftilestr := strings.ToUpper(string(rt.tiledata))
 393                                 remap := variantRemap[tag-tagstart]
 394                                 done := make([]bool, len(variants))
 395                                 for v, tv := range variants {
 396                                         v := remap[v]
 397                                         if v == rt.variant || done[v] {
 398                                                 continue
 399                                         } else {
 400                                                 done[v] = true
 401                                         }
 402                                         if len(tv.Sequence) < taglen || !bytes.HasSuffix(rt.tiledata, tv.Sequence[len(tv.Sequence)-taglen:]) {
 403                                                 fmt.Fprintf(annow, "%d,%d,%d,,%s,%d,,,\n", tag, outcol, v, rt.seqname, rt.pos)
 404                                                 continue
 405                                         }
 406                                         if lendiff := len(rt.tiledata) - len(tv.Sequence); lendiff < -1000 || lendiff > 1000 {
 407                                                 fmt.Fprintf(annow, "%d,%d,%d,,%s,%d,,,\n", tag, outcol, v, rt.seqname, rt.pos)
 408                                                 continue
 409                                         }
 410                                         diffs, _ := hgvs.Diff(reftilestr, strings.ToUpper(string(tv.Sequence)), 0)
 411                                         for _, diff := range diffs {
 412                                                 diff.Position += rt.pos
 413                                                 fmt.Fprintf(annow, "%d,%d,%d,%s:g.%s,%s,%d,%s,%s,%s\n", tag, outcol, v, rt.seqname, diff.String(), rt.seqname, diff.Position, diff.Ref, diff.New, diff.Left)
 414                                         }
 415                                 }
 416                                 outcol++
 417                         }
 418                         err = annow.Flush()
 419                         if err != nil {
 420                                 return err
 421                         }
 422                         err = annof.Close()
 423                         if err != nil {
 424                                 return err
 425                         }
 426
 427                         log.Infof("%04d: preparing numpy", infileIdx)
 428                         throttleNumpyMem.Acquire()
 429                         rows := len(cgnames)
 430                         cols := 2 * outcol
 431                         out := make([]int16, rows*cols)
 432                         for row, name := range cgnames {
 433                                 out := out[row*cols:]
 434                                 outcol := 0
 435                                 for col, v := range cgs[name].Variants {
 436                                         tag := tagstart + tagID(col/2)
 437                                         if mask != nil && reftile[tag] == nil {
 438                                                 continue
 439                                         }
 440                                         if variants, ok := seq[tag]; ok && len(variants) > int(v) && len(variants[v].Sequence) > 0 {
 441                                                 out[outcol] = int16(variantRemap[tag-tagstart][v])
 442                                         } else {
 443                                                 out[outcol] = -1
 444                                         }
 445                                         outcol++
 446                                 }
 447                         }
 448                         seq = nil
 449                         throttleNumpyMem.Release()
 450
 451                         if *mergeOutput || *hgvsSingle || *hgvsChunked {
 452                                 log.Infof("%04d: matrix fragment %d rows x %d cols", infileIdx, rows, cols)
 453                                 toMerge[infileIdx] = out
 454                         }
 455                         if !*mergeOutput {
 456                                 fnm := fmt.Sprintf("%s/matrix.%04d.npy", *outputDir, infileIdx)
 457                                 err = writeNumpyInt16(fnm, out, rows, cols)
 458                                 if err != nil {
 459                                         return err
 460                                 }
 461                         }
 462                         log.Infof("%s: done (%d/%d)", infile, int(atomic.AddInt64(&done, 1)), len(infiles))
 463                         return nil
 464                 })
 465         }
 466         if err = throttleMem.Wait(); err != nil {
 467                 return 1
 468         }
 469         if *mergeOutput || *hgvsSingle || *hgvsChunked {
 470                 var annow *bufio.Writer
 471                 var annof *os.File
 472                 if *mergeOutput {
 473                         annoFilename := fmt.Sprintf("%s/matrix.annotations.csv", *outputDir)
 474                         annof, err = os.Create(annoFilename)
 475                         if err != nil {
 476                                 return 1
 477                         }
 478                         annow = bufio.NewWriterSize(annof, 1<<20)
 479                 }
 480
 481                 rows := len(cgnames)
 482                 cols := 0
 483                 for _, chunk := range toMerge {
 484                         cols += len(chunk) / rows
 485                 }
 486                 log.Infof("merging output matrix (rows=%d, cols=%d, mem=%d) and annotations", rows, cols, rows*cols*2)
 487                 var out []int16
 488                 if *mergeOutput {
 489                         out = make([]int16, rows*cols)
 490                 }
 491                 hgvsCols := map[string][2][]int16{} // hgvs -> [[g0,g1,g2,...], [g0,g1,g2,...]] (slice of genomes for each phase)
 492                 startcol := 0
 493                 for outIdx, chunk := range toMerge {
 494                         chunkcols := len(chunk) / rows
 495                         if *mergeOutput {
 496                                 for row := 0; row < rows; row++ {
 497                                         copy(out[row*cols+startcol:], chunk[row*chunkcols:(row+1)*chunkcols])
 498                                 }
 499                         }
 500                         toMerge[outIdx] = nil
 501
 502                         annotationsFilename := fmt.Sprintf("%s/matrix.%04d.annotations.csv", *outputDir, outIdx)
 503                         log.Infof("reading %s", annotationsFilename)
 504                         buf, err := os.ReadFile(annotationsFilename)
 505                         if err != nil {
 506                                 return 1
 507                         }
 508                         if *mergeOutput {
 509                                 err = os.Remove(annotationsFilename)
 510                                 if err != nil {
 511                                         return 1
 512                                 }
 513                         }
 514                         for _, line := range bytes.Split(buf, []byte{'\n'}) {
 515                                 if len(line) == 0 {
 516                                         continue
 517                                 }
 518                                 fields := bytes.SplitN(line, []byte{','}, 9)
 519                                 tag, _ := strconv.Atoi(string(fields[0]))
 520                                 incol, _ := strconv.Atoi(string(fields[1]))
 521                                 tileVariant, _ := strconv.Atoi(string(fields[2]))
 522                                 hgvsID := string(fields[3])
 523                                 seqname := string(fields[4])
 524                                 pos, _ := strconv.Atoi(string(fields[5]))
 525                                 refseq := fields[6]
 526                                 if hgvsID == "" {
 527                                         // Null entry for un-diffable
 528                                         // tile variant
 529                                         continue
 530                                 }
 531                                 if hgvsID == "=" {
 532                                         // Null entry for ref tile
 533                                         continue
 534                                 }
 535                                 if mask != nil && !mask.Check(strings.TrimPrefix(seqname, "chr"), pos, pos+len(refseq)) {
 536                                         // The tile intersects one of
 537                                         // the selected regions, but
 538                                         // this particular HGVS
 539                                         // variant does not.
 540                                         continue
 541                                 }
 542                                 hgvsColPair := hgvsCols[hgvsID]
 543                                 if hgvsColPair[0] == nil {
 544                                         // values in new columns start
 545                                         // out as -1 ("no data yet")
 546                                         // or 0 ("=ref") here, may
 547                                         // change to 1 ("hgvs variant
 548                                         // present") below, either on
 549                                         // this line or a future line.
 550                                         hgvsColPair = [2][]int16{make([]int16, len(cgnames)), make([]int16, len(cgnames))}
 551                                         rt, ok := reftile[tagID(tag)]
 552                                         if !ok {
 553                                                 err = fmt.Errorf("bug: seeing annotations for tag %d, but it has no reftile entry", tag)
 554                                                 return 1
 555                                         }
 556                                         for ph := 0; ph < 2; ph++ {
 557                                                 for row := 0; row < rows; row++ {
 558                                                         v := chunk[row*chunkcols+incol*2+ph]
 559                                                         if tileVariantID(v) == rt.variant {
 560                                                                 hgvsColPair[ph][row] = 0
 561                                                         } else {
 562                                                                 hgvsColPair[ph][row] = -1
 563                                                         }
 564                                                 }
 565                                         }
 566                                         hgvsCols[hgvsID] = hgvsColPair
 567                                         hgvsref := hgvs.Variant{
 568                                                 Position: pos,
 569                                                 Ref:      string(refseq),
 570                                                 New:      string(refseq),
 571                                         }
 572                                         if annow != nil {
 573                                                 fmt.Fprintf(annow, "%d,%d,%d,%s:g.%s,%s,%d,%s,%s,%s\n", tag, incol+startcol/2, rt.variant, seqname, hgvsref.String(), seqname, pos, refseq, refseq, fields[8])
 574                                         }
 575                                 }
 576                                 if annow != nil {
 577                                         fmt.Fprintf(annow, "%d,%d,%d,%s,%s,%d,%s,%s,%s\n", tag, incol+startcol/2, tileVariant, hgvsID, seqname, pos, refseq, fields[7], fields[8])
 578                                 }
 579                                 for ph := 0; ph < 2; ph++ {
 580                                         for row := 0; row < rows; row++ {
 581                                                 v := chunk[row*chunkcols+incol*2+ph]
 582                                                 if int(v) == tileVariant {
 583                                                         hgvsColPair[ph][row] = 1
 584                                                 }
 585                                         }
 586                                 }
 587                         }
 588
 589                         startcol += chunkcols
 590                 }
 591                 if *mergeOutput {
 592                         err = annow.Flush()
 593                         if err != nil {
 594                                 return 1
 595                         }
 596                         err = annof.Close()
 597                         if err != nil {
 598                                 return 1
 599                         }
 600                         err = writeNumpyInt16(fmt.Sprintf("%s/matrix.npy", *outputDir), out, rows, cols)
 601                         if err != nil {
 602                                 return 1
 603                         }
 604                 }
 605                 out = nil
 606
 607                 var seqnames []string
 608                 if *hgvsSingle {
 609                         seqnames = []string{""}
 610                 }
 611                 if *hgvsChunked {
 612                         for seqname := range refseq {
 613                                 seqnames = append(seqnames, seqname)
 614                         }
 615                 }
 616                 for _, seqname := range seqnames {
 617                         basename := "hgvs"
 618                         wantPrefix := ""
 619                         if seqname == "" {
 620                                 cols = len(hgvsCols) * 2
 621                         } else {
 622                                 basename = "hgvs." + seqname
 623                                 wantPrefix = seqname + ":"
 624                                 cols = 0
 625                                 for hgvsID := range hgvsCols {
 626                                         if strings.HasPrefix(hgvsID, wantPrefix) {
 627                                                 cols += 2
 628                                         }
 629                                 }
 630                         }
 631                         log.Printf("building hgvs-based matrix [%s]: %d rows x %d cols", seqname, rows, cols)
 632                         out = make([]int16, rows*cols)
 633                         hgvsIDs := make([]string, 0, cols/2)
 634                         for hgvsID := range hgvsCols {
 635                                 if strings.HasPrefix(hgvsID, wantPrefix) {
 636                                         hgvsIDs = append(hgvsIDs, hgvsID)
 637                                 }
 638                         }
 639                         sort.Strings(hgvsIDs)
 640                         var hgvsLabels bytes.Buffer
 641                         for idx, hgvsID := range hgvsIDs {
 642                                 fmt.Fprintf(&hgvsLabels, "%d,%s\n", idx, hgvsID)
 643                                 for ph := 0; ph < 2; ph++ {
 644                                         hgvscol := hgvsCols[hgvsID][ph]
 645                                         for row, val := range hgvscol {
 646                                                 out[row*cols+idx*2+ph] = val
 647                                         }
 648                                 }
 649                         }
 650                         err = writeNumpyInt16(fmt.Sprintf("%s/%s.npy", *outputDir, basename), out, rows, cols)
 651                         if err != nil {
 652                                 return 1
 653                         }
 654
 655                         fnm := fmt.Sprintf("%s/%s.annotations.csv", *outputDir, basename)
 656                         log.Printf("writing hgvs labels: %s", fnm)
 657                         err = ioutil.WriteFile(fnm, hgvsLabels.Bytes(), 0777)
 658                         if err != nil {
 659                                 return 1
 660                         }
 661                 }
 662         }
 663         return 0
 664 }
 665
 666 func writeNumpyInt16(fnm string, out []int16, rows, cols int) error {
 667         output, err := os.Create(fnm)
 668         if err != nil {
 669                 return err
 670         }
 671         defer output.Close()
 672         bufw := bufio.NewWriterSize(output, 1<<26)
 673         npw, err := gonpy.NewWriter(nopCloser{bufw})
 674         if err != nil {
 675                 return err
 676         }
 677         log.WithFields(log.Fields{
 678                 "filename": fnm,
 679                 "rows":     rows,
 680                 "cols":     cols,
 681         }).Infof("writing numpy: %s", fnm)
 682         npw.Shape = []int{rows, cols}
 683         npw.WriteInt16(out)
 684         err = bufw.Flush()
 685         if err != nil {
 686                 return err
 687         }
 688         return output.Close()
 689 }