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         "encoding/gob"
  11         "flag"
  12         "fmt"
  13         "io"
  14         "io/ioutil"
  15         "net/http"
  16         _ "net/http/pprof"
  17         "os"
  18         "regexp"
  19         "runtime"
  20         "runtime/debug"
  21         "sort"
  22         "strconv"
  23         "strings"
  24         "sync/atomic"
  25
  26         "git.arvados.org/arvados.git/sdk/go/arvados"
  27         "github.com/arvados/lightning/hgvs"
  28         "github.com/kshedden/gonpy"
  29         log "github.com/sirupsen/logrus"
  30         "golang.org/x/crypto/blake2b"
  31 )
  32
  33 type sliceNumpy struct {
  34         filter  filter
  35         threads int
  36 }
  37
  38 func (cmd *sliceNumpy) RunCommand(prog string, args []string, stdin io.Reader, stdout, stderr io.Writer) int {
  39         var err error
  40         defer func() {
  41                 if err != nil {
  42                         fmt.Fprintf(stderr, "%s\n", err)
  43                 }
  44         }()
  45         flags := flag.NewFlagSet("", flag.ContinueOnError)
  46         flags.SetOutput(stderr)
  47         pprof := flags.String("pprof", "", "serve Go profile data at http://`[addr]:port`")
  48         runlocal := flags.Bool("local", false, "run on local host (default: run in an arvados container)")
  49         projectUUID := flags.String("project", "", "project `UUID` for output data")
  50         priority := flags.Int("priority", 500, "container request priority")
  51         inputDir := flags.String("input-dir", "./in", "input `directory`")
  52         outputDir := flags.String("output-dir", "./out", "output `directory`")
  53         ref := flags.String("ref", "", "reference name (if blank, choose last one that appears in input)")
  54         regionsFilename := flags.String("regions", "", "only output columns/annotations that intersect regions in specified bed `file`")
  55         expandRegions := flags.Int("expand-regions", 0, "expand specified regions by `N` base pairs on each side`")
  56         mergeOutput := flags.Bool("merge-output", false, "merge output into one matrix.npy and one matrix.annotations.csv")
  57         hgvsSingle := flags.Bool("single-hgvs-matrix", false, "also generate hgvs-based matrix")
  58         hgvsChunked := flags.Bool("chunked-hgvs-matrix", false, "also generate hgvs-based matrix per chromosome")
  59         flags.IntVar(&cmd.threads, "threads", 16, "number of memory-hungry assembly threads")
  60         cmd.filter.Flags(flags)
  61         err = flags.Parse(args)
  62         if err == flag.ErrHelp {
  63                 err = nil
  64                 return 0
  65         } else if err != nil {
  66                 return 2
  67         }
  68
  69         if *pprof != "" {
  70                 go func() {
  71                         log.Println(http.ListenAndServe(*pprof, nil))
  72                 }()
  73         }
  74
  75         if !*runlocal {
  76                 runner := arvadosContainerRunner{
  77                         Name:        "lightning slice-numpy",
  78                         Client:      arvados.NewClientFromEnv(),
  79                         ProjectUUID: *projectUUID,
  80                         RAM:         750000000000,
  81                         VCPUs:       96,
  82                         Priority:    *priority,
  83                         KeepCache:   2,
  84                         APIAccess:   true,
  85                 }
  86                 err = runner.TranslatePaths(inputDir, regionsFilename)
  87                 if err != nil {
  88                         return 1
  89                 }
  90                 runner.Args = []string{"slice-numpy", "-local=true",
  91                         "-pprof=:6060",
  92                         "-input-dir=" + *inputDir,
  93                         "-output-dir=/mnt/output",
  94                         "-threads=" + fmt.Sprintf("%d", cmd.threads),
  95                         "-regions=" + *regionsFilename,
  96                         "-expand-regions=" + fmt.Sprintf("%d", *expandRegions),
  97                         "-merge-output=" + fmt.Sprintf("%v", *mergeOutput),
  98                         "-single-hgvs-matrix=" + fmt.Sprintf("%v", *hgvsSingle),
  99                         "-chunked-hgvs-matrix=" + fmt.Sprintf("%v", *hgvsChunked),
 100                 }
 101                 runner.Args = append(runner.Args, cmd.filter.Args()...)
 102                 var output string
 103                 output, err = runner.Run()
 104                 if err != nil {
 105                         return 1
 106                 }
 107                 fmt.Fprintln(stdout, output)
 108                 return 0
 109         }
 110
 111         infiles, err := allGobFiles(*inputDir)
 112         if err != nil {
 113                 return 1
 114         }
 115         if len(infiles) == 0 {
 116                 err = fmt.Errorf("no input files found in %s", *inputDir)
 117                 return 1
 118         }
 119         sort.Strings(infiles)
 120
 121         var cgnames []string
 122         var refseq map[string][]tileLibRef
 123         var reftiledata = make(map[tileLibRef][]byte, 11000000)
 124         in0, err := open(infiles[0])
 125         if err != nil {
 126                 return 1
 127         }
 128
 129         matchGenome, err := regexp.Compile(cmd.filter.MatchGenome)
 130         if err != nil {
 131                 err = fmt.Errorf("-match-genome: invalid regexp: %q", cmd.filter.MatchGenome)
 132                 return 1
 133         }
 134
 135         taglen := -1
 136         DecodeLibrary(in0, strings.HasSuffix(infiles[0], ".gz"), func(ent *LibraryEntry) error {
 137                 if len(ent.TagSet) > 0 {
 138                         taglen = len(ent.TagSet[0])
 139                 }
 140                 for _, cseq := range ent.CompactSequences {
 141                         if cseq.Name == *ref || *ref == "" {
 142                                 refseq = cseq.TileSequences
 143                         }
 144                 }
 145                 for _, cg := range ent.CompactGenomes {
 146                         if matchGenome.MatchString(cg.Name) {
 147                                 cgnames = append(cgnames, cg.Name)
 148                         }
 149                 }
 150                 for _, tv := range ent.TileVariants {
 151                         if tv.Ref {
 152                                 reftiledata[tileLibRef{tv.Tag, tv.Variant}] = tv.Sequence
 153                         }
 154                 }
 155                 return nil
 156         })
 157         if err != nil {
 158                 return 1
 159         }
 160         in0.Close()
 161         if refseq == nil {
 162                 err = fmt.Errorf("%s: reference sequence not found", infiles[0])
 163                 return 1
 164         }
 165         if taglen < 0 {
 166                 err = fmt.Errorf("tagset not found")
 167                 return 1
 168         }
 169         if len(cgnames) == 0 {
 170                 err = fmt.Errorf("no genomes found matching regexp %q", cmd.filter.MatchGenome)
 171                 return 1
 172         }
 173         sort.Strings(cgnames)
 174
 175         {
 176                 labelsFilename := *outputDir + "/labels.csv"
 177                 log.Infof("writing labels to %s", labelsFilename)
 178                 var f *os.File
 179                 f, err = os.Create(labelsFilename)
 180                 if err != nil {
 181                         return 1
 182                 }
 183                 defer f.Close()
 184                 for i, name := range cgnames {
 185                         _, err = fmt.Fprintf(f, "%d,%q\n", i, trimFilenameForLabel(name))
 186                         if err != nil {
 187                                 err = fmt.Errorf("write %s: %w", labelsFilename, err)
 188                                 return 1
 189                         }
 190                 }
 191                 err = f.Close()
 192                 if err != nil {
 193                         err = fmt.Errorf("close %s: %w", labelsFilename, err)
 194                         return 1
 195                 }
 196         }
 197
 198         log.Info("indexing reference tiles")
 199         type reftileinfo struct {
 200                 variant  tileVariantID
 201                 seqname  string // chr1
 202                 pos      int    // distance from start of chromosome to starttag
 203                 tiledata []byte // acgtggcaa...
 204         }
 205         isdup := map[tagID]bool{}
 206         reftile := map[tagID]*reftileinfo{}
 207         for seqname, cseq := range refseq {
 208                 pos := 0
 209                 for _, libref := range cseq {
 210                         tiledata := reftiledata[libref]
 211                         if len(tiledata) == 0 {
 212                                 err = fmt.Errorf("missing tiledata for tag %d variant %d in %s in ref", libref.Tag, libref.Variant, seqname)
 213                                 return 1
 214                         }
 215                         if isdup[libref.Tag] {
 216                                 log.Printf("dropping reference tile %+v from %s @ %d, tag not unique", libref, seqname, pos)
 217                         } else if reftile[libref.Tag] != nil {
 218                                 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)
 219                                 delete(reftile, libref.Tag)
 220                                 log.Printf("dropping reference tile %+v from %s @ %d, tag not unique", libref, seqname, pos)
 221                                 isdup[libref.Tag] = true
 222                         } else {
 223                                 reftile[libref.Tag] = &reftileinfo{
 224                                         seqname:  seqname,
 225                                         variant:  libref.Variant,
 226                                         tiledata: tiledata,
 227                                         pos:      pos,
 228                                 }
 229                         }
 230                         pos += len(tiledata) - taglen
 231                 }
 232                 log.Printf("... %s done, len %d", seqname, pos+taglen)
 233         }
 234
 235         var mask *mask
 236         if *regionsFilename != "" {
 237                 log.Printf("loading regions from %s", *regionsFilename)
 238                 mask, err = makeMask(*regionsFilename, *expandRegions)
 239                 if err != nil {
 240                         return 1
 241                 }
 242                 log.Printf("before applying mask, len(reftile) == %d", len(reftile))
 243                 log.Printf("deleting reftile entries for regions outside %d intervals", mask.Len())
 244                 for tag, rt := range reftile {
 245                         if !mask.Check(strings.TrimPrefix(rt.seqname, "chr"), rt.pos, rt.pos+len(rt.tiledata)) {
 246                                 delete(reftile, tag)
 247                         }
 248                 }
 249                 log.Printf("after applying mask, len(reftile) == %d", len(reftile))
 250         }
 251
 252         tmpHGVSCols := map[string]*os.File{}
 253         bufHGVSCols := map[string]*bufio.Writer{}
 254         encodeHGVSCols := map[string]*gob.Encoder{}
 255         if *hgvsChunked {
 256                 for seqname := range refseq {
 257                         var f *os.File
 258                         f, err = os.Create(*outputDir + "/tmp." + seqname + ".gob")
 259                         if err != nil {
 260                                 return 1
 261                         }
 262                         defer os.Remove(f.Name())
 263                         bufw := bufio.NewWriterSize(f, 1<<24)
 264                         enc := gob.NewEncoder(bufw)
 265                         tmpHGVSCols[seqname] = f
 266                         bufHGVSCols[seqname] = bufw
 267                         encodeHGVSCols[seqname] = enc
 268                 }
 269         }
 270
 271         var toMerge [][]int16
 272         if *mergeOutput || *hgvsSingle {
 273                 toMerge = make([][]int16, len(infiles))
 274         }
 275
 276         throttleMem := throttle{Max: cmd.threads} // TODO: estimate using mem and data size
 277         throttleNumpyMem := throttle{Max: cmd.threads/2 + 1}
 278         log.Info("generating annotations and numpy matrix for each slice")
 279         var done int64
 280         for infileIdx, infile := range infiles {
 281                 infileIdx, infile := infileIdx, infile
 282                 throttleMem.Go(func() error {
 283                         seq := make(map[tagID][]TileVariant, 50000)
 284                         cgs := make(map[string]CompactGenome, len(cgnames))
 285                         f, err := open(infile)
 286                         if err != nil {
 287                                 return err
 288                         }
 289                         defer f.Close()
 290                         log.Infof("%04d: reading %s", infileIdx, infile)
 291                         err = DecodeLibrary(f, strings.HasSuffix(infile, ".gz"), func(ent *LibraryEntry) error {
 292                                 for _, tv := range ent.TileVariants {
 293                                         if tv.Ref {
 294                                                 continue
 295                                         }
 296                                         if mask != nil && reftile[tv.Tag] == nil {
 297                                                 // Don't waste
 298                                                 // time/memory on
 299                                                 // masked-out tiles.
 300                                                 continue
 301                                         }
 302                                         variants := seq[tv.Tag]
 303                                         if len(variants) == 0 {
 304                                                 variants = make([]TileVariant, 100)
 305                                         }
 306                                         for len(variants) <= int(tv.Variant) {
 307                                                 variants = append(variants, TileVariant{})
 308                                         }
 309                                         variants[int(tv.Variant)] = tv
 310                                         seq[tv.Tag] = variants
 311                                 }
 312                                 for _, cg := range ent.CompactGenomes {
 313                                         if !matchGenome.MatchString(cg.Name) {
 314                                                 continue
 315                                         }
 316                                         // pad to full slice size
 317                                         // to avoid out-of-bounds
 318                                         // checks later
 319                                         if sliceSize := int(cg.EndTag - cg.StartTag); len(cg.Variants) < sliceSize {
 320                                                 cg.Variants = append(cg.Variants, make([]tileVariantID, sliceSize-len(cg.Variants))...)
 321                                         }
 322                                         cgs[cg.Name] = cg
 323                                 }
 324                                 return nil
 325                         })
 326                         if err != nil {
 327                                 return err
 328                         }
 329                         tagstart := cgs[cgnames[0]].StartTag
 330                         tagend := cgs[cgnames[0]].EndTag
 331
 332                         // TODO: filters
 333
 334                         log.Infof("%04d: renumber/dedup variants for tags %d-%d", infileIdx, tagstart, tagend)
 335                         variantRemap := make([][]tileVariantID, tagend-tagstart)
 336                         throttleCPU := throttle{Max: runtime.GOMAXPROCS(0)}
 337                         for tag, variants := range seq {
 338                                 tag, variants := tag, variants
 339                                 throttleCPU.Acquire()
 340                                 go func() {
 341                                         defer throttleCPU.Release()
 342                                         count := make(map[[blake2b.Size256]byte]int, len(variants))
 343
 344                                         rt := reftile[tag]
 345                                         if rt != nil {
 346                                                 count[blake2b.Sum256(rt.tiledata)] = 0
 347                                         }
 348
 349                                         for _, cg := range cgs {
 350                                                 idx := int(tag-tagstart) * 2
 351                                                 for allele := 0; allele < 2; allele++ {
 352                                                         v := cg.Variants[idx+allele]
 353                                                         if v > 0 && len(variants[v].Sequence) > 0 {
 354                                                                 count[variants[v].Blake2b]++
 355                                                         }
 356                                                 }
 357                                         }
 358                                         // hash[i] will be the hash of
 359                                         // the variant(s) that should
 360                                         // be at rank i (0-based).
 361                                         hash := make([][blake2b.Size256]byte, 0, len(count))
 362                                         for b := range count {
 363                                                 hash = append(hash, b)
 364                                         }
 365                                         sort.Slice(hash, func(i, j int) bool {
 366                                                 bi, bj := &hash[i], &hash[j]
 367                                                 if ci, cj := count[*bi], count[*bj]; ci != cj {
 368                                                         return ci > cj
 369                                                 } else {
 370                                                         return bytes.Compare((*bi)[:], (*bj)[:]) < 0
 371                                                 }
 372                                         })
 373                                         // rank[b] will be the 1-based
 374                                         // new variant number for
 375                                         // variants whose hash is b.
 376                                         rank := make(map[[blake2b.Size256]byte]tileVariantID, len(hash))
 377                                         for i, h := range hash {
 378                                                 rank[h] = tileVariantID(i + 1)
 379                                         }
 380                                         // remap[v] will be the new
 381                                         // variant number for original
 382                                         // variant number v.
 383                                         remap := make([]tileVariantID, len(variants))
 384                                         for i, tv := range variants {
 385                                                 remap[i] = rank[tv.Blake2b]
 386                                         }
 387                                         variantRemap[tag-tagstart] = remap
 388                                         if rt != nil {
 389                                                 rt.variant = rank[blake2b.Sum256(rt.tiledata)]
 390                                         }
 391                                 }()
 392                         }
 393                         throttleCPU.Wait()
 394
 395                         annotationsFilename := fmt.Sprintf("%s/matrix.%04d.annotations.csv", *outputDir, infileIdx)
 396                         log.Infof("%04d: writing %s", infileIdx, annotationsFilename)
 397                         annof, err := os.Create(annotationsFilename)
 398                         if err != nil {
 399                                 return err
 400                         }
 401                         annow := bufio.NewWriterSize(annof, 1<<20)
 402                         outcol := 0
 403                         for tag := tagstart; tag < tagend; tag++ {
 404                                 rt, ok := reftile[tag]
 405                                 if !ok {
 406                                         if mask == nil {
 407                                                 outcol++
 408                                         }
 409                                         // Excluded by specified
 410                                         // regions, or reference does
 411                                         // not use any variant of this
 412                                         // tile. (TODO: log this?
 413                                         // mention it in annotations?)
 414                                         continue
 415                                 }
 416                                 fmt.Fprintf(annow, "%d,%d,%d,=,%s,%d,,,\n", tag, outcol, rt.variant, rt.seqname, rt.pos)
 417                                 variants := seq[tag]
 418                                 reftilestr := strings.ToUpper(string(rt.tiledata))
 419                                 remap := variantRemap[tag-tagstart]
 420                                 maxv := tileVariantID(0)
 421                                 for _, v := range remap {
 422                                         if maxv < v {
 423                                                 maxv = v
 424                                         }
 425                                 }
 426                                 done := make([]bool, maxv+1)
 427                                 variantDiffs := make([][]hgvs.Variant, maxv+1)
 428                                 for v, tv := range variants {
 429                                         v := remap[v]
 430                                         if v == rt.variant || done[v] {
 431                                                 continue
 432                                         } else {
 433                                                 done[v] = true
 434                                         }
 435                                         if len(tv.Sequence) < taglen || !bytes.HasSuffix(rt.tiledata, tv.Sequence[len(tv.Sequence)-taglen:]) {
 436                                                 fmt.Fprintf(annow, "%d,%d,%d,,%s,%d,,,\n", tag, outcol, v, rt.seqname, rt.pos)
 437                                                 continue
 438                                         }
 439                                         if lendiff := len(rt.tiledata) - len(tv.Sequence); lendiff < -1000 || lendiff > 1000 {
 440                                                 fmt.Fprintf(annow, "%d,%d,%d,,%s,%d,,,\n", tag, outcol, v, rt.seqname, rt.pos)
 441                                                 continue
 442                                         }
 443                                         diffs, _ := hgvs.Diff(reftilestr, strings.ToUpper(string(tv.Sequence)), 0)
 444                                         for _, diff := range diffs {
 445                                                 diff.Position += rt.pos
 446                                                 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)
 447                                         }
 448                                         if *hgvsChunked {
 449                                                 variantDiffs[v] = diffs
 450                                         }
 451                                 }
 452                                 if *hgvsChunked {
 453                                         // We can now determine, for each HGVS
 454                                         // variant (diff) in this reftile
 455                                         // region, whether a given genome
 456                                         // phase/allele (1) has the variant, (0) has
 457                                         // =ref or a different variant in that
 458                                         // position, or (-1) is lacking
 459                                         // coverage / couldn't be diffed.
 460                                         hgvsCol := map[hgvs.Variant][2][]int8{}
 461                                         for _, diffs := range variantDiffs {
 462                                                 for _, diff := range diffs {
 463                                                         if _, ok := hgvsCol[diff]; ok {
 464                                                                 continue
 465                                                         }
 466                                                         hgvsCol[diff] = [2][]int8{
 467                                                                 make([]int8, len(cgnames)),
 468                                                                 make([]int8, len(cgnames)),
 469                                                         }
 470                                                 }
 471                                         }
 472                                         for row, name := range cgnames {
 473                                                 variants := cgs[name].Variants[(tag-tagstart)*2:]
 474                                                 for ph := 0; ph < 2; ph++ {
 475                                                         v := variants[ph]
 476                                                         if int(v) >= len(remap) {
 477                                                                 v = 0
 478                                                         } else {
 479                                                                 v = remap[v]
 480                                                         }
 481                                                         if v == rt.variant {
 482                                                                 // hgvsCol[*][ph][row] is already 0
 483                                                         } else if len(variantDiffs[v]) == 0 {
 484                                                                 // lacking coverage / couldn't be diffed
 485                                                                 for _, col := range hgvsCol {
 486                                                                         col[ph][row] = -1
 487                                                                 }
 488                                                         } else {
 489                                                                 for _, diff := range variantDiffs[v] {
 490                                                                         hgvsCol[diff][ph][row] = 1
 491                                                                 }
 492                                                         }
 493                                                 }
 494                                         }
 495                                         encodeHGVSCols[rt.seqname].Encode(hgvsCol)
 496                                 }
 497                                 outcol++
 498                         }
 499                         err = annow.Flush()
 500                         if err != nil {
 501                                 return err
 502                         }
 503                         err = annof.Close()
 504                         if err != nil {
 505                                 return err
 506                         }
 507
 508                         log.Infof("%04d: preparing numpy", infileIdx)
 509                         throttleNumpyMem.Acquire()
 510                         rows := len(cgnames)
 511                         cols := 2 * outcol
 512                         out := make([]int16, rows*cols)
 513                         for row, name := range cgnames {
 514                                 out := out[row*cols:]
 515                                 outcol := 0
 516                                 for col, v := range cgs[name].Variants {
 517                                         tag := tagstart + tagID(col/2)
 518                                         if mask != nil && reftile[tag] == nil {
 519                                                 continue
 520                                         }
 521                                         if variants, ok := seq[tag]; ok && len(variants) > int(v) && len(variants[v].Sequence) > 0 {
 522                                                 out[outcol] = int16(variantRemap[tag-tagstart][v])
 523                                         } else {
 524                                                 out[outcol] = -1
 525                                         }
 526                                         outcol++
 527                                 }
 528                         }
 529                         seq = nil
 530                         cgs = nil
 531                         debug.FreeOSMemory()
 532                         throttleNumpyMem.Release()
 533
 534                         if *mergeOutput || *hgvsSingle {
 535                                 log.Infof("%04d: matrix fragment %d rows x %d cols", infileIdx, rows, cols)
 536                                 toMerge[infileIdx] = out
 537                         }
 538                         if !*mergeOutput {
 539                                 fnm := fmt.Sprintf("%s/matrix.%04d.npy", *outputDir, infileIdx)
 540                                 err = writeNumpyInt16(fnm, out, rows, cols)
 541                                 if err != nil {
 542                                         return err
 543                                 }
 544                                 debug.FreeOSMemory()
 545                         }
 546                         log.Infof("%s: done (%d/%d)", infile, int(atomic.AddInt64(&done, 1)), len(infiles))
 547                         return nil
 548                 })
 549         }
 550         if err = throttleMem.Wait(); err != nil {
 551                 return 1
 552         }
 553
 554         if *hgvsChunked {
 555                 log.Info("flushing hgvsCols temp files")
 556                 for seqname := range refseq {
 557                         err = bufHGVSCols[seqname].Flush()
 558                         if err != nil {
 559                                 return 1
 560                         }
 561                         bufHGVSCols[seqname] = nil // free buffer memory
 562                 }
 563                 for seqname := range refseq {
 564                         log.Infof("%s: reading hgvsCols from temp file", seqname)
 565                         f := tmpHGVSCols[seqname]
 566                         _, err = f.Seek(0, io.SeekStart)
 567                         if err != nil {
 568                                 return 1
 569                         }
 570                         var hgvsCols map[hgvs.Variant][2][]int8
 571                         dec := gob.NewDecoder(bufio.NewReaderSize(f, 1<<24))
 572                         for err == nil {
 573                                 err = dec.Decode(&hgvsCols)
 574                         }
 575                         if err != io.EOF {
 576                                 return 1
 577                         }
 578                         log.Infof("%s: sorting %d hgvs variants", seqname, len(hgvsCols))
 579                         variants := make([]hgvs.Variant, 0, len(hgvsCols))
 580                         for v := range hgvsCols {
 581                                 variants = append(variants, v)
 582                         }
 583                         sort.Slice(variants, func(i, j int) bool {
 584                                 vi, vj := &variants[i], &variants[j]
 585                                 if vi.Position != vj.Position {
 586                                         return vi.Position < vj.Position
 587                                 } else if vi.Ref != vj.Ref {
 588                                         return vi.Ref < vj.Ref
 589                                 } else {
 590                                         return vi.New < vj.New
 591                                 }
 592                         })
 593                         rows := len(cgnames)
 594                         cols := len(variants) * 2
 595                         log.Infof("%s: building hgvs matrix (rows=%d, cols=%d, mem=%d)", seqname, rows, cols, rows*cols)
 596                         out := make([]int8, rows*cols)
 597                         for varIdx, variant := range variants {
 598                                 hgvsCols := hgvsCols[variant]
 599                                 for row := range cgnames {
 600                                         for ph := 0; ph < 2; ph++ {
 601                                                 out[row*cols+varIdx+ph] = hgvsCols[ph][row]
 602                                         }
 603                                 }
 604                         }
 605                         err = writeNumpyInt8(fmt.Sprintf("%s/hgvs.%s.npy", *outputDir, seqname), out, rows, cols)
 606                         if err != nil {
 607                                 return 1
 608                         }
 609                         out = nil
 610
 611                         fnm := fmt.Sprintf("%s/hgvs.%s.annotations.csv", *outputDir, seqname)
 612                         log.Infof("%s: writing hgvs column labels to %s", seqname, fnm)
 613                         var hgvsLabels bytes.Buffer
 614                         for varIdx, variant := range variants {
 615                                 fmt.Fprintf(&hgvsLabels, "%d,%s:g.%s\n", varIdx, seqname, variant.String())
 616                         }
 617                         err = ioutil.WriteFile(fnm, hgvsLabels.Bytes(), 0666)
 618                         if err != nil {
 619                                 return 1
 620                         }
 621                 }
 622         }
 623
 624         if *mergeOutput || *hgvsSingle {
 625                 var annow *bufio.Writer
 626                 var annof *os.File
 627                 if *mergeOutput {
 628                         annoFilename := fmt.Sprintf("%s/matrix.annotations.csv", *outputDir)
 629                         annof, err = os.Create(annoFilename)
 630                         if err != nil {
 631                                 return 1
 632                         }
 633                         annow = bufio.NewWriterSize(annof, 1<<20)
 634                 }
 635
 636                 rows := len(cgnames)
 637                 cols := 0
 638                 for _, chunk := range toMerge {
 639                         cols += len(chunk) / rows
 640                 }
 641                 log.Infof("merging output matrix (rows=%d, cols=%d, mem=%d) and annotations", rows, cols, rows*cols*2)
 642                 var out []int16
 643                 if *mergeOutput {
 644                         out = make([]int16, rows*cols)
 645                 }
 646                 hgvsCols := map[string][2][]int16{} // hgvs -> [[g0,g1,g2,...], [g0,g1,g2,...]] (slice of genomes for each phase)
 647                 startcol := 0
 648                 for outIdx, chunk := range toMerge {
 649                         chunkcols := len(chunk) / rows
 650                         if *mergeOutput {
 651                                 for row := 0; row < rows; row++ {
 652                                         copy(out[row*cols+startcol:], chunk[row*chunkcols:(row+1)*chunkcols])
 653                                 }
 654                         }
 655                         toMerge[outIdx] = nil
 656
 657                         annotationsFilename := fmt.Sprintf("%s/matrix.%04d.annotations.csv", *outputDir, outIdx)
 658                         log.Infof("reading %s", annotationsFilename)
 659                         buf, err := os.ReadFile(annotationsFilename)
 660                         if err != nil {
 661                                 return 1
 662                         }
 663                         if *mergeOutput {
 664                                 err = os.Remove(annotationsFilename)
 665                                 if err != nil {
 666                                         return 1
 667                                 }
 668                         }
 669                         for _, line := range bytes.Split(buf, []byte{'\n'}) {
 670                                 if len(line) == 0 {
 671                                         continue
 672                                 }
 673                                 fields := bytes.SplitN(line, []byte{','}, 9)
 674                                 tag, _ := strconv.Atoi(string(fields[0]))
 675                                 incol, _ := strconv.Atoi(string(fields[1]))
 676                                 tileVariant, _ := strconv.Atoi(string(fields[2]))
 677                                 hgvsID := string(fields[3])
 678                                 seqname := string(fields[4])
 679                                 pos, _ := strconv.Atoi(string(fields[5]))
 680                                 refseq := fields[6]
 681                                 if hgvsID == "" {
 682                                         // Null entry for un-diffable
 683                                         // tile variant
 684                                         continue
 685                                 }
 686                                 if hgvsID == "=" {
 687                                         // Null entry for ref tile
 688                                         continue
 689                                 }
 690                                 if mask != nil && !mask.Check(strings.TrimPrefix(seqname, "chr"), pos, pos+len(refseq)) {
 691                                         // The tile intersects one of
 692                                         // the selected regions, but
 693                                         // this particular HGVS
 694                                         // variant does not.
 695                                         continue
 696                                 }
 697                                 hgvsColPair := hgvsCols[hgvsID]
 698                                 if hgvsColPair[0] == nil {
 699                                         // values in new columns start
 700                                         // out as -1 ("no data yet")
 701                                         // or 0 ("=ref") here, may
 702                                         // change to 1 ("hgvs variant
 703                                         // present") below, either on
 704                                         // this line or a future line.
 705                                         hgvsColPair = [2][]int16{make([]int16, len(cgnames)), make([]int16, len(cgnames))}
 706                                         rt, ok := reftile[tagID(tag)]
 707                                         if !ok {
 708                                                 err = fmt.Errorf("bug: seeing annotations for tag %d, but it has no reftile entry", tag)
 709                                                 return 1
 710                                         }
 711                                         for ph := 0; ph < 2; ph++ {
 712                                                 for row := 0; row < rows; row++ {
 713                                                         v := chunk[row*chunkcols+incol*2+ph]
 714                                                         if tileVariantID(v) == rt.variant {
 715                                                                 hgvsColPair[ph][row] = 0
 716                                                         } else {
 717                                                                 hgvsColPair[ph][row] = -1
 718                                                         }
 719                                                 }
 720                                         }
 721                                         hgvsCols[hgvsID] = hgvsColPair
 722                                         if annow != nil {
 723                                                 hgvsref := hgvs.Variant{
 724                                                         Position: pos,
 725                                                         Ref:      string(refseq),
 726                                                         New:      string(refseq),
 727                                                 }
 728                                                 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])
 729                                         }
 730                                 }
 731                                 if annow != nil {
 732                                         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])
 733                                 }
 734                                 for ph := 0; ph < 2; ph++ {
 735                                         for row := 0; row < rows; row++ {
 736                                                 v := chunk[row*chunkcols+incol*2+ph]
 737                                                 if int(v) == tileVariant {
 738                                                         hgvsColPair[ph][row] = 1
 739                                                 }
 740                                         }
 741                                 }
 742                         }
 743
 744                         startcol += chunkcols
 745                 }
 746                 if *mergeOutput {
 747                         err = annow.Flush()
 748                         if err != nil {
 749                                 return 1
 750                         }
 751                         err = annof.Close()
 752                         if err != nil {
 753                                 return 1
 754                         }
 755                         err = writeNumpyInt16(fmt.Sprintf("%s/matrix.npy", *outputDir), out, rows, cols)
 756                         if err != nil {
 757                                 return 1
 758                         }
 759                 }
 760                 out = nil
 761
 762                 if *hgvsSingle {
 763                         cols = len(hgvsCols) * 2
 764                         log.Printf("building hgvs-based matrix: %d rows x %d cols", rows, cols)
 765                         out = make([]int16, rows*cols)
 766                         hgvsIDs := make([]string, 0, cols/2)
 767                         for hgvsID := range hgvsCols {
 768                                 hgvsIDs = append(hgvsIDs, hgvsID)
 769                         }
 770                         sort.Strings(hgvsIDs)
 771                         var hgvsLabels bytes.Buffer
 772                         for idx, hgvsID := range hgvsIDs {
 773                                 fmt.Fprintf(&hgvsLabels, "%d,%s\n", idx, hgvsID)
 774                                 for ph := 0; ph < 2; ph++ {
 775                                         hgvscol := hgvsCols[hgvsID][ph]
 776                                         for row, val := range hgvscol {
 777                                                 out[row*cols+idx*2+ph] = val
 778                                         }
 779                                 }
 780                         }
 781                         err = writeNumpyInt16(fmt.Sprintf("%s/hgvs.npy", *outputDir), out, rows, cols)
 782                         if err != nil {
 783                                 return 1
 784                         }
 785
 786                         fnm := fmt.Sprintf("%s/hgvs.annotations.csv", *outputDir)
 787                         log.Printf("writing hgvs labels: %s", fnm)
 788                         err = ioutil.WriteFile(fnm, hgvsLabels.Bytes(), 0777)
 789                         if err != nil {
 790                                 return 1
 791                         }
 792                 }
 793         }
 794         return 0
 795 }
 796
 797 func writeNumpyInt16(fnm string, out []int16, rows, cols int) error {
 798         output, err := os.Create(fnm)
 799         if err != nil {
 800                 return err
 801         }
 802         defer output.Close()
 803         bufw := bufio.NewWriterSize(output, 1<<26)
 804         npw, err := gonpy.NewWriter(nopCloser{bufw})
 805         if err != nil {
 806                 return err
 807         }
 808         log.WithFields(log.Fields{
 809                 "filename": fnm,
 810                 "rows":     rows,
 811                 "cols":     cols,
 812         }).Infof("writing numpy: %s", fnm)
 813         npw.Shape = []int{rows, cols}
 814         npw.WriteInt16(out)
 815         err = bufw.Flush()
 816         if err != nil {
 817                 return err
 818         }
 819         return output.Close()
 820 }
 821
 822 func writeNumpyInt8(fnm string, out []int8, rows, cols int) error {
 823         output, err := os.Create(fnm)
 824         if err != nil {
 825                 return err
 826         }
 827         defer output.Close()
 828         bufw := bufio.NewWriterSize(output, 1<<26)
 829         npw, err := gonpy.NewWriter(nopCloser{bufw})
 830         if err != nil {
 831                 return err
 832         }
 833         log.WithFields(log.Fields{
 834                 "filename": fnm,
 835                 "rows":     rows,
 836                 "cols":     cols,
 837         }).Infof("writing numpy: %s", fnm)
 838         npw.Shape = []int{rows, cols}
 839         npw.WriteInt8(out)
 840         err = bufw.Flush()
 841         if err != nil {
 842                 return err
 843         }
 844         return output.Close()
 845 }