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