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