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         "math"
  16         "net/http"
  17         _ "net/http/pprof"
  18         "os"
  19         "regexp"
  20         "runtime"
  21         "runtime/debug"
  22         "sort"
  23         "strconv"
  24         "strings"
  25         "sync/atomic"
  26
  27         "git.arvados.org/arvados.git/sdk/go/arvados"
  28         "github.com/arvados/lightning/hgvs"
  29         "github.com/kshedden/gonpy"
  30         log "github.com/sirupsen/logrus"
  31         "golang.org/x/crypto/blake2b"
  32 )
  33
  34 type sliceNumpy struct {
  35         filter                filter
  36         threads               int
  37         chi2CaseControlColumn string
  38         chi2CaseControlFile   string
  39         chi2Cases             []bool
  40         chi2PValue            float64
  41         minCoverage           int
  42         cgnames               []string
  43 }
  44
  45 func (cmd *sliceNumpy) RunCommand(prog string, args []string, stdin io.Reader, stdout, stderr io.Writer) int {
  46         var err error
  47         defer func() {
  48                 if err != nil {
  49                         fmt.Fprintf(stderr, "%s\n", err)
  50                 }
  51         }()
  52         flags := flag.NewFlagSet("", flag.ContinueOnError)
  53         flags.SetOutput(stderr)
  54         pprof := flags.String("pprof", "", "serve Go profile data at http://`[addr]:port`")
  55         runlocal := flags.Bool("local", false, "run on local host (default: run in an arvados container)")
  56         projectUUID := flags.String("project", "", "project `UUID` for output data")
  57         priority := flags.Int("priority", 500, "container request priority")
  58         inputDir := flags.String("input-dir", "./in", "input `directory`")
  59         outputDir := flags.String("output-dir", "./out", "output `directory`")
  60         ref := flags.String("ref", "", "reference name (if blank, choose last one that appears in input)")
  61         regionsFilename := flags.String("regions", "", "only output columns/annotations that intersect regions in specified bed `file`")
  62         expandRegions := flags.Int("expand-regions", 0, "expand specified regions by `N` base pairs on each side`")
  63         mergeOutput := flags.Bool("merge-output", false, "merge output into one matrix.npy and one matrix.annotations.csv")
  64         hgvsSingle := flags.Bool("single-hgvs-matrix", false, "also generate hgvs-based matrix")
  65         hgvsChunked := flags.Bool("chunked-hgvs-matrix", false, "also generate hgvs-based matrix per chromosome")
  66         onehotSingle := flags.Bool("single-onehot", false, "generate one-hot tile-based matrix")
  67         onehotChunked := flags.Bool("chunked-onehot", false, "generate one-hot tile-based matrix per input chunk")
  68         flags.IntVar(&cmd.threads, "threads", 16, "number of memory-hungry assembly threads")
  69         flags.StringVar(&cmd.chi2CaseControlFile, "chi2-case-control-file", "", "tsv file or directory indicating cases and controls for Χ² test (if directory, all .tsv files will be read)")
  70         flags.StringVar(&cmd.chi2CaseControlColumn, "chi2-case-control-column", "", "name of case/control column in case-control files for Χ² test (value must be 0 for control, 1 for case)")
  71         flags.Float64Var(&cmd.chi2PValue, "chi2-p-value", 1, "do Χ² test and omit columns with p-value above this threshold")
  72         cmd.filter.Flags(flags)
  73         err = flags.Parse(args)
  74         if err == flag.ErrHelp {
  75                 err = nil
  76                 return 0
  77         } else if err != nil {
  78                 return 2
  79         }
  80
  81         if *pprof != "" {
  82                 go func() {
  83                         log.Println(http.ListenAndServe(*pprof, nil))
  84                 }()
  85         }
  86
  87         if cmd.chi2PValue != 1 && (cmd.chi2CaseControlFile == "" || cmd.chi2CaseControlColumn == "") {
  88                 log.Errorf("cannot use provided -chi2-p-value=%f because -chi2-case-control-file= or -chi2-case-control-column= value is empty", cmd.chi2PValue)
  89                 return 2
  90         }
  91
  92         if !*runlocal {
  93                 runner := arvadosContainerRunner{
  94                         Name:        "lightning slice-numpy",
  95                         Client:      arvados.NewClientFromEnv(),
  96                         ProjectUUID: *projectUUID,
  97                         RAM:         750000000000,
  98                         VCPUs:       96,
  99                         Priority:    *priority,
 100                         KeepCache:   2,
 101                         APIAccess:   true,
 102                 }
 103                 err = runner.TranslatePaths(inputDir, regionsFilename, &cmd.chi2CaseControlFile)
 104                 if err != nil {
 105                         return 1
 106                 }
 107                 runner.Args = []string{"slice-numpy", "-local=true",
 108                         "-pprof=:6060",
 109                         "-input-dir=" + *inputDir,
 110                         "-output-dir=/mnt/output",
 111                         "-threads=" + fmt.Sprintf("%d", cmd.threads),
 112                         "-regions=" + *regionsFilename,
 113                         "-expand-regions=" + fmt.Sprintf("%d", *expandRegions),
 114                         "-merge-output=" + fmt.Sprintf("%v", *mergeOutput),
 115                         "-single-hgvs-matrix=" + fmt.Sprintf("%v", *hgvsSingle),
 116                         "-chunked-hgvs-matrix=" + fmt.Sprintf("%v", *hgvsChunked),
 117                         "-single-onehot=" + fmt.Sprintf("%v", *onehotSingle),
 118                         "-chunked-onehot=" + fmt.Sprintf("%v", *onehotChunked),
 119                         "-chi2-case-control-file=" + cmd.chi2CaseControlFile,
 120                         "-chi2-case-control-column=" + cmd.chi2CaseControlColumn,
 121                         "-chi2-p-value=" + fmt.Sprintf("%f", cmd.chi2PValue),
 122                 }
 123                 runner.Args = append(runner.Args, cmd.filter.Args()...)
 124                 var output string
 125                 output, err = runner.Run()
 126                 if err != nil {
 127                         return 1
 128                 }
 129                 fmt.Fprintln(stdout, output)
 130                 return 0
 131         }
 132
 133         infiles, err := allFiles(*inputDir, matchGobFile)
 134         if err != nil {
 135                 return 1
 136         }
 137         if len(infiles) == 0 {
 138                 err = fmt.Errorf("no input files found in %s", *inputDir)
 139                 return 1
 140         }
 141         sort.Strings(infiles)
 142
 143         var refseq map[string][]tileLibRef
 144         var reftiledata = make(map[tileLibRef][]byte, 11000000)
 145         in0, err := open(infiles[0])
 146         if err != nil {
 147                 return 1
 148         }
 149
 150         matchGenome, err := regexp.Compile(cmd.filter.MatchGenome)
 151         if err != nil {
 152                 err = fmt.Errorf("-match-genome: invalid regexp: %q", cmd.filter.MatchGenome)
 153                 return 1
 154         }
 155
 156         cmd.cgnames = nil
 157         taglen := -1
 158         DecodeLibrary(in0, strings.HasSuffix(infiles[0], ".gz"), func(ent *LibraryEntry) error {
 159                 if len(ent.TagSet) > 0 {
 160                         taglen = len(ent.TagSet[0])
 161                 }
 162                 for _, cseq := range ent.CompactSequences {
 163                         if cseq.Name == *ref || *ref == "" {
 164                                 refseq = cseq.TileSequences
 165                         }
 166                 }
 167                 for _, cg := range ent.CompactGenomes {
 168                         if matchGenome.MatchString(cg.Name) {
 169                                 cmd.cgnames = append(cmd.cgnames, cg.Name)
 170                         }
 171                 }
 172                 for _, tv := range ent.TileVariants {
 173                         if tv.Ref {
 174                                 reftiledata[tileLibRef{tv.Tag, tv.Variant}] = tv.Sequence
 175                         }
 176                 }
 177                 return nil
 178         })
 179         if err != nil {
 180                 return 1
 181         }
 182         in0.Close()
 183         if refseq == nil {
 184                 err = fmt.Errorf("%s: reference sequence not found", infiles[0])
 185                 return 1
 186         }
 187         if taglen < 0 {
 188                 err = fmt.Errorf("tagset not found")
 189                 return 1
 190         }
 191         if len(cmd.cgnames) == 0 {
 192                 err = fmt.Errorf("no genomes found matching regexp %q", cmd.filter.MatchGenome)
 193                 return 1
 194         }
 195         sort.Strings(cmd.cgnames)
 196         err = cmd.useCaseControlFiles()
 197         if err != nil {
 198                 return 1
 199         }
 200         cmd.minCoverage = int(math.Ceil(cmd.filter.MinCoverage * float64(len(cmd.cgnames))))
 201
 202         {
 203                 labelsFilename := *outputDir + "/samples.csv"
 204                 log.Infof("writing labels to %s", labelsFilename)
 205                 var f *os.File
 206                 f, err = os.Create(labelsFilename)
 207                 if err != nil {
 208                         return 1
 209                 }
 210                 defer f.Close()
 211                 for i, name := range cmd.cgnames {
 212                         cc := 0
 213                         if cmd.chi2Cases != nil && cmd.chi2Cases[i] {
 214                                 cc = 1
 215                         }
 216                         _, err = fmt.Fprintf(f, "%d,%q,%d\n", i, trimFilenameForLabel(name), cc)
 217                         if err != nil {
 218                                 err = fmt.Errorf("write %s: %w", labelsFilename, err)
 219                                 return 1
 220                         }
 221                 }
 222                 err = f.Close()
 223                 if err != nil {
 224                         err = fmt.Errorf("close %s: %w", labelsFilename, err)
 225                         return 1
 226                 }
 227         }
 228
 229         log.Info("indexing reference tiles")
 230         type reftileinfo struct {
 231                 variant  tileVariantID
 232                 seqname  string // chr1
 233                 pos      int    // distance from start of chromosome to starttag
 234                 tiledata []byte // acgtggcaa...
 235         }
 236         isdup := map[tagID]bool{}
 237         reftile := map[tagID]*reftileinfo{}
 238         for seqname, cseq := range refseq {
 239                 pos := 0
 240                 for _, libref := range cseq {
 241                         tiledata := reftiledata[libref]
 242                         if len(tiledata) == 0 {
 243                                 err = fmt.Errorf("missing tiledata for tag %d variant %d in %s in ref", libref.Tag, libref.Variant, seqname)
 244                                 return 1
 245                         }
 246                         if isdup[libref.Tag] {
 247                                 log.Printf("dropping reference tile %+v from %s @ %d, tag not unique", libref, seqname, pos)
 248                         } else if reftile[libref.Tag] != nil {
 249                                 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)
 250                                 delete(reftile, libref.Tag)
 251                                 log.Printf("dropping reference tile %+v from %s @ %d, tag not unique", libref, seqname, pos)
 252                                 isdup[libref.Tag] = true
 253                         } else {
 254                                 reftile[libref.Tag] = &reftileinfo{
 255                                         seqname:  seqname,
 256                                         variant:  libref.Variant,
 257                                         tiledata: tiledata,
 258                                         pos:      pos,
 259                                 }
 260                         }
 261                         pos += len(tiledata) - taglen
 262                 }
 263                 log.Printf("... %s done, len %d", seqname, pos+taglen)
 264         }
 265
 266         var mask *mask
 267         if *regionsFilename != "" {
 268                 log.Printf("loading regions from %s", *regionsFilename)
 269                 mask, err = makeMask(*regionsFilename, *expandRegions)
 270                 if err != nil {
 271                         return 1
 272                 }
 273                 log.Printf("before applying mask, len(reftile) == %d", len(reftile))
 274                 log.Printf("deleting reftile entries for regions outside %d intervals", mask.Len())
 275                 for tag, rt := range reftile {
 276                         if !mask.Check(strings.TrimPrefix(rt.seqname, "chr"), rt.pos, rt.pos+len(rt.tiledata)) {
 277                                 delete(reftile, tag)
 278                         }
 279                 }
 280                 log.Printf("after applying mask, len(reftile) == %d", len(reftile))
 281         }
 282
 283         type hgvsColSet map[hgvs.Variant][2][]int8
 284         encodeHGVS := throttle{Max: len(refseq)}
 285         encodeHGVSTodo := map[string]chan hgvsColSet{}
 286         tmpHGVSCols := map[string]*os.File{}
 287         if *hgvsChunked {
 288                 for seqname := range refseq {
 289                         var f *os.File
 290                         f, err = os.Create(*outputDir + "/tmp." + seqname + ".gob")
 291                         if err != nil {
 292                                 return 1
 293                         }
 294                         defer os.Remove(f.Name())
 295                         bufw := bufio.NewWriterSize(f, 1<<24)
 296                         enc := gob.NewEncoder(bufw)
 297                         tmpHGVSCols[seqname] = f
 298                         todo := make(chan hgvsColSet, 128)
 299                         encodeHGVSTodo[seqname] = todo
 300                         encodeHGVS.Go(func() error {
 301                                 for colset := range todo {
 302                                         err := enc.Encode(colset)
 303                                         if err != nil {
 304                                                 encodeHGVS.Report(err)
 305                                                 for range todo {
 306                                                 }
 307                                                 return err
 308                                         }
 309                                 }
 310                                 return bufw.Flush()
 311                         })
 312                 }
 313         }
 314
 315         var toMerge [][]int16
 316         if *mergeOutput || *hgvsSingle {
 317                 toMerge = make([][]int16, len(infiles))
 318         }
 319         var onehotChunks [][][]int8
 320         var onehotXrefs [][]onehotXref
 321         if *onehotSingle {
 322                 onehotChunks = make([][][]int8, len(infiles))
 323                 onehotXrefs = make([][]onehotXref, len(infiles))
 324         }
 325
 326         throttleMem := throttle{Max: cmd.threads} // TODO: estimate using mem and data size
 327         throttleNumpyMem := throttle{Max: cmd.threads/2 + 1}
 328         log.Info("generating annotations and numpy matrix for each slice")
 329         var done int64
 330         for infileIdx, infile := range infiles {
 331                 infileIdx, infile := infileIdx, infile
 332                 throttleMem.Go(func() error {
 333                         seq := make(map[tagID][]TileVariant, 50000)
 334                         cgs := make(map[string]CompactGenome, len(cmd.cgnames))
 335                         f, err := open(infile)
 336                         if err != nil {
 337                                 return err
 338                         }
 339                         defer f.Close()
 340                         log.Infof("%04d: reading %s", infileIdx, infile)
 341                         err = DecodeLibrary(f, strings.HasSuffix(infile, ".gz"), func(ent *LibraryEntry) error {
 342                                 for _, tv := range ent.TileVariants {
 343                                         if tv.Ref {
 344                                                 continue
 345                                         }
 346                                         if mask != nil && reftile[tv.Tag] == nil {
 347                                                 // Don't waste
 348                                                 // time/memory on
 349                                                 // masked-out tiles.
 350                                                 continue
 351                                         }
 352                                         variants := seq[tv.Tag]
 353                                         if len(variants) == 0 {
 354                                                 variants = make([]TileVariant, 100)
 355                                         }
 356                                         for len(variants) <= int(tv.Variant) {
 357                                                 variants = append(variants, TileVariant{})
 358                                         }
 359                                         variants[int(tv.Variant)] = tv
 360                                         seq[tv.Tag] = variants
 361                                 }
 362                                 for _, cg := range ent.CompactGenomes {
 363                                         if !matchGenome.MatchString(cg.Name) {
 364                                                 continue
 365                                         }
 366                                         // pad to full slice size
 367                                         // to avoid out-of-bounds
 368                                         // checks later
 369                                         if sliceSize := 2 * int(cg.EndTag-cg.StartTag); len(cg.Variants) < sliceSize {
 370                                                 cg.Variants = append(cg.Variants, make([]tileVariantID, sliceSize-len(cg.Variants))...)
 371                                         }
 372                                         cgs[cg.Name] = cg
 373                                 }
 374                                 return nil
 375                         })
 376                         if err != nil {
 377                                 return err
 378                         }
 379                         tagstart := cgs[cmd.cgnames[0]].StartTag
 380                         tagend := cgs[cmd.cgnames[0]].EndTag
 381
 382                         // TODO: filters
 383
 384                         log.Infof("%04d: renumber/dedup variants for tags %d-%d", infileIdx, tagstart, tagend)
 385                         variantRemap := make([][]tileVariantID, tagend-tagstart)
 386                         throttleCPU := throttle{Max: runtime.GOMAXPROCS(0)}
 387                         for tag, variants := range seq {
 388                                 tag, variants := tag, variants
 389                                 throttleCPU.Acquire()
 390                                 go func() {
 391                                         defer throttleCPU.Release()
 392                                         count := make(map[[blake2b.Size256]byte]int, len(variants))
 393
 394                                         rt := reftile[tag]
 395                                         if rt != nil {
 396                                                 count[blake2b.Sum256(rt.tiledata)] = 0
 397                                         }
 398
 399                                         for _, cg := range cgs {
 400                                                 idx := int(tag-tagstart) * 2
 401                                                 for allele := 0; allele < 2; allele++ {
 402                                                         v := cg.Variants[idx+allele]
 403                                                         if v > 0 && len(variants[v].Sequence) > 0 {
 404                                                                 count[variants[v].Blake2b]++
 405                                                         }
 406                                                 }
 407                                         }
 408                                         // hash[i] will be the hash of
 409                                         // the variant(s) that should
 410                                         // be at rank i (0-based).
 411                                         hash := make([][blake2b.Size256]byte, 0, len(count))
 412                                         for b := range count {
 413                                                 hash = append(hash, b)
 414                                         }
 415                                         sort.Slice(hash, func(i, j int) bool {
 416                                                 bi, bj := &hash[i], &hash[j]
 417                                                 if ci, cj := count[*bi], count[*bj]; ci != cj {
 418                                                         return ci > cj
 419                                                 } else {
 420                                                         return bytes.Compare((*bi)[:], (*bj)[:]) < 0
 421                                                 }
 422                                         })
 423                                         // rank[b] will be the 1-based
 424                                         // new variant number for
 425                                         // variants whose hash is b.
 426                                         rank := make(map[[blake2b.Size256]byte]tileVariantID, len(hash))
 427                                         for i, h := range hash {
 428                                                 rank[h] = tileVariantID(i + 1)
 429                                         }
 430                                         // remap[v] will be the new
 431                                         // variant number for original
 432                                         // variant number v.
 433                                         remap := make([]tileVariantID, len(variants))
 434                                         for i, tv := range variants {
 435                                                 remap[i] = rank[tv.Blake2b]
 436                                         }
 437                                         variantRemap[tag-tagstart] = remap
 438                                         if rt != nil {
 439                                                 rt.variant = rank[blake2b.Sum256(rt.tiledata)]
 440                                         }
 441                                 }()
 442                         }
 443                         throttleCPU.Wait()
 444
 445                         var onehotChunk [][]int8
 446                         var onehotXref []onehotXref
 447
 448                         annotationsFilename := fmt.Sprintf("%s/matrix.%04d.annotations.csv", *outputDir, infileIdx)
 449                         log.Infof("%04d: writing %s", infileIdx, annotationsFilename)
 450                         annof, err := os.Create(annotationsFilename)
 451                         if err != nil {
 452                                 return err
 453                         }
 454                         annow := bufio.NewWriterSize(annof, 1<<20)
 455                         outcol := 0
 456                         for tag := tagstart; tag < tagend; tag++ {
 457                                 rt, ok := reftile[tag]
 458                                 if !ok {
 459                                         if mask == nil {
 460                                                 outcol++
 461                                         }
 462                                         // Excluded by specified
 463                                         // regions, or reference does
 464                                         // not use any variant of this
 465                                         // tile. (TODO: log this?
 466                                         // mention it in annotations?)
 467                                         continue
 468                                 }
 469                                 remap := variantRemap[tag-tagstart]
 470                                 maxv := tileVariantID(0)
 471                                 for _, v := range remap {
 472                                         if maxv < v {
 473                                                 maxv = v
 474                                         }
 475                                 }
 476                                 if *onehotChunked || *onehotSingle {
 477                                         onehot, xrefs := cmd.tv2homhet(cgs, maxv, remap, tag, tagstart)
 478                                         onehotChunk = append(onehotChunk, onehot...)
 479                                         onehotXref = append(onehotXref, xrefs...)
 480                                 }
 481                                 fmt.Fprintf(annow, "%d,%d,%d,=,%s,%d,,,\n", tag, outcol, rt.variant, rt.seqname, rt.pos)
 482                                 variants := seq[tag]
 483                                 reftilestr := strings.ToUpper(string(rt.tiledata))
 484
 485                                 done := make([]bool, maxv+1)
 486                                 variantDiffs := make([][]hgvs.Variant, maxv+1)
 487                                 for v, tv := range variants {
 488                                         v := remap[v]
 489                                         if v == rt.variant || done[v] {
 490                                                 continue
 491                                         } else {
 492                                                 done[v] = true
 493                                         }
 494                                         if len(tv.Sequence) < taglen || !bytes.HasSuffix(rt.tiledata, tv.Sequence[len(tv.Sequence)-taglen:]) {
 495                                                 fmt.Fprintf(annow, "%d,%d,%d,,%s,%d,,,\n", tag, outcol, v, rt.seqname, rt.pos)
 496                                                 continue
 497                                         }
 498                                         if lendiff := len(rt.tiledata) - len(tv.Sequence); lendiff < -1000 || lendiff > 1000 {
 499                                                 fmt.Fprintf(annow, "%d,%d,%d,,%s,%d,,,\n", tag, outcol, v, rt.seqname, rt.pos)
 500                                                 continue
 501                                         }
 502                                         diffs, _ := hgvs.Diff(reftilestr, strings.ToUpper(string(tv.Sequence)), 0)
 503                                         for i := range diffs {
 504                                                 diffs[i].Position += rt.pos
 505                                         }
 506                                         for _, diff := range diffs {
 507                                                 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)
 508                                         }
 509                                         if *hgvsChunked {
 510                                                 variantDiffs[v] = diffs
 511                                         }
 512                                 }
 513                                 if *hgvsChunked {
 514                                         // We can now determine, for each HGVS
 515                                         // variant (diff) in this reftile
 516                                         // region, whether a given genome
 517                                         // phase/allele (1) has the variant, (0) has
 518                                         // =ref or a different variant in that
 519                                         // position, or (-1) is lacking
 520                                         // coverage / couldn't be diffed.
 521                                         hgvsCol := hgvsColSet{}
 522                                         for _, diffs := range variantDiffs {
 523                                                 for _, diff := range diffs {
 524                                                         if _, ok := hgvsCol[diff]; ok {
 525                                                                 continue
 526                                                         }
 527                                                         hgvsCol[diff] = [2][]int8{
 528                                                                 make([]int8, len(cmd.cgnames)),
 529                                                                 make([]int8, len(cmd.cgnames)),
 530                                                         }
 531                                                 }
 532                                         }
 533                                         for row, name := range cmd.cgnames {
 534                                                 variants := cgs[name].Variants[(tag-tagstart)*2:]
 535                                                 for ph := 0; ph < 2; ph++ {
 536                                                         v := variants[ph]
 537                                                         if int(v) >= len(remap) {
 538                                                                 v = 0
 539                                                         } else {
 540                                                                 v = remap[v]
 541                                                         }
 542                                                         if v == rt.variant {
 543                                                                 // hgvsCol[*][ph][row] is already 0
 544                                                         } else if len(variantDiffs[v]) == 0 {
 545                                                                 // lacking coverage / couldn't be diffed
 546                                                                 for _, col := range hgvsCol {
 547                                                                         col[ph][row] = -1
 548                                                                 }
 549                                                         } else {
 550                                                                 for _, diff := range variantDiffs[v] {
 551                                                                         hgvsCol[diff][ph][row] = 1
 552                                                                 }
 553                                                         }
 554                                                 }
 555                                         }
 556                                         for diff, colpair := range hgvsCol {
 557                                                 allele2homhet(colpair)
 558                                                 if !cmd.filterHGVScolpair(colpair) {
 559                                                         delete(hgvsCol, diff)
 560                                                 }
 561                                         }
 562                                         if len(hgvsCol) > 0 {
 563                                                 encodeHGVSTodo[rt.seqname] <- hgvsCol
 564                                         }
 565                                 }
 566                                 outcol++
 567                         }
 568                         err = annow.Flush()
 569                         if err != nil {
 570                                 return err
 571                         }
 572                         err = annof.Close()
 573                         if err != nil {
 574                                 return err
 575                         }
 576
 577                         if *onehotChunked {
 578                                 // transpose onehotChunk[col][row] to numpy[row*ncols+col]
 579                                 rows := len(cmd.cgnames)
 580                                 cols := len(onehotChunk)
 581                                 log.Infof("%04d: preparing onehot numpy (rows=%d, cols=%d, mem=%d)", infileIdx, len(cmd.cgnames), len(onehotChunk), len(cmd.cgnames)*len(onehotChunk))
 582                                 throttleNumpyMem.Acquire()
 583                                 out := onehotcols2int8(onehotChunk)
 584                                 fnm := fmt.Sprintf("%s/onehot.%04d.npy", *outputDir, infileIdx)
 585                                 err = writeNumpyInt8(fnm, out, rows, cols)
 586                                 if err != nil {
 587                                         return err
 588                                 }
 589                                 fnm = fmt.Sprintf("%s/onehot-columns.%04d.npy", *outputDir, infileIdx)
 590                                 err = writeNumpyInt32(fnm, onehotXref2int32(onehotXref), 4, len(onehotXref))
 591                                 if err != nil {
 592                                         return err
 593                                 }
 594                                 debug.FreeOSMemory()
 595                                 throttleNumpyMem.Release()
 596                         }
 597                         if *onehotSingle {
 598                                 onehotChunks[infileIdx] = onehotChunk
 599                                 onehotXrefs[infileIdx] = onehotXref
 600                         }
 601                         if !(*onehotSingle || *onehotChunked) || *mergeOutput || *hgvsSingle {
 602                                 log.Infof("%04d: preparing numpy", infileIdx)
 603                                 throttleNumpyMem.Acquire()
 604                                 rows := len(cmd.cgnames)
 605                                 cols := 2 * outcol
 606                                 out := make([]int16, rows*cols)
 607                                 for row, name := range cmd.cgnames {
 608                                         out := out[row*cols:]
 609                                         outcol := 0
 610                                         for col, v := range cgs[name].Variants {
 611                                                 tag := tagstart + tagID(col/2)
 612                                                 if mask != nil && reftile[tag] == nil {
 613                                                         continue
 614                                                 }
 615                                                 if variants, ok := seq[tag]; ok && len(variants) > int(v) && len(variants[v].Sequence) > 0 {
 616                                                         out[outcol] = int16(variantRemap[tag-tagstart][v])
 617                                                 } else {
 618                                                         out[outcol] = -1
 619                                                 }
 620                                                 outcol++
 621                                         }
 622                                 }
 623                                 seq = nil
 624                                 cgs = nil
 625                                 debug.FreeOSMemory()
 626                                 throttleNumpyMem.Release()
 627                                 if *mergeOutput || *hgvsSingle {
 628                                         log.Infof("%04d: matrix fragment %d rows x %d cols", infileIdx, rows, cols)
 629                                         toMerge[infileIdx] = out
 630                                 }
 631                                 if !*mergeOutput && !*onehotChunked && !*onehotSingle {
 632                                         fnm := fmt.Sprintf("%s/matrix.%04d.npy", *outputDir, infileIdx)
 633                                         err = writeNumpyInt16(fnm, out, rows, cols)
 634                                         if err != nil {
 635                                                 return err
 636                                         }
 637                                 }
 638                         }
 639                         debug.FreeOSMemory()
 640                         log.Infof("%s: done (%d/%d)", infile, int(atomic.AddInt64(&done, 1)), len(infiles))
 641                         return nil
 642                 })
 643         }
 644         if err = throttleMem.Wait(); err != nil {
 645                 return 1
 646         }
 647
 648         if *hgvsChunked {
 649                 log.Info("flushing hgvsCols temp files")
 650                 for seqname := range refseq {
 651                         close(encodeHGVSTodo[seqname])
 652                 }
 653                 err = encodeHGVS.Wait()
 654                 if err != nil {
 655                         return 1
 656                 }
 657                 for seqname := range refseq {
 658                         log.Infof("%s: reading hgvsCols from temp file", seqname)
 659                         f := tmpHGVSCols[seqname]
 660                         _, err = f.Seek(0, io.SeekStart)
 661                         if err != nil {
 662                                 return 1
 663                         }
 664                         var hgvsCols hgvsColSet
 665                         dec := gob.NewDecoder(bufio.NewReaderSize(f, 1<<24))
 666                         for err == nil {
 667                                 err = dec.Decode(&hgvsCols)
 668                         }
 669                         if err != io.EOF {
 670                                 return 1
 671                         }
 672                         log.Infof("%s: sorting %d hgvs variants", seqname, len(hgvsCols))
 673                         variants := make([]hgvs.Variant, 0, len(hgvsCols))
 674                         for v := range hgvsCols {
 675                                 variants = append(variants, v)
 676                         }
 677                         sort.Slice(variants, func(i, j int) bool {
 678                                 vi, vj := &variants[i], &variants[j]
 679                                 if vi.Position != vj.Position {
 680                                         return vi.Position < vj.Position
 681                                 } else if vi.Ref != vj.Ref {
 682                                         return vi.Ref < vj.Ref
 683                                 } else {
 684                                         return vi.New < vj.New
 685                                 }
 686                         })
 687                         rows := len(cmd.cgnames)
 688                         cols := len(variants) * 2
 689                         log.Infof("%s: building hgvs matrix (rows=%d, cols=%d, mem=%d)", seqname, rows, cols, rows*cols)
 690                         out := make([]int8, rows*cols)
 691                         for varIdx, variant := range variants {
 692                                 hgvsCols := hgvsCols[variant]
 693                                 for row := range cmd.cgnames {
 694                                         for ph := 0; ph < 2; ph++ {
 695                                                 out[row*cols+varIdx+ph] = hgvsCols[ph][row]
 696                                         }
 697                                 }
 698                         }
 699                         err = writeNumpyInt8(fmt.Sprintf("%s/hgvs.%s.npy", *outputDir, seqname), out, rows, cols)
 700                         if err != nil {
 701                                 return 1
 702                         }
 703                         out = nil
 704
 705                         fnm := fmt.Sprintf("%s/hgvs.%s.annotations.csv", *outputDir, seqname)
 706                         log.Infof("%s: writing hgvs column labels to %s", seqname, fnm)
 707                         var hgvsLabels bytes.Buffer
 708                         for varIdx, variant := range variants {
 709                                 fmt.Fprintf(&hgvsLabels, "%d,%s:g.%s\n", varIdx, seqname, variant.String())
 710                         }
 711                         err = ioutil.WriteFile(fnm, hgvsLabels.Bytes(), 0666)
 712                         if err != nil {
 713                                 return 1
 714                         }
 715                 }
 716         }
 717
 718         if *mergeOutput || *hgvsSingle {
 719                 var annow *bufio.Writer
 720                 var annof *os.File
 721                 if *mergeOutput {
 722                         annoFilename := fmt.Sprintf("%s/matrix.annotations.csv", *outputDir)
 723                         annof, err = os.Create(annoFilename)
 724                         if err != nil {
 725                                 return 1
 726                         }
 727                         annow = bufio.NewWriterSize(annof, 1<<20)
 728                 }
 729
 730                 rows := len(cmd.cgnames)
 731                 cols := 0
 732                 for _, chunk := range toMerge {
 733                         cols += len(chunk) / rows
 734                 }
 735                 log.Infof("merging output matrix (rows=%d, cols=%d, mem=%d) and annotations", rows, cols, rows*cols*2)
 736                 var out []int16
 737                 if *mergeOutput {
 738                         out = make([]int16, rows*cols)
 739                 }
 740                 hgvsCols := map[string][2][]int16{} // hgvs -> [[g0,g1,g2,...], [g0,g1,g2,...]] (slice of genomes for each phase)
 741                 startcol := 0
 742                 for outIdx, chunk := range toMerge {
 743                         chunkcols := len(chunk) / rows
 744                         if *mergeOutput {
 745                                 for row := 0; row < rows; row++ {
 746                                         copy(out[row*cols+startcol:], chunk[row*chunkcols:(row+1)*chunkcols])
 747                                 }
 748                         }
 749                         toMerge[outIdx] = nil
 750
 751                         annotationsFilename := fmt.Sprintf("%s/matrix.%04d.annotations.csv", *outputDir, outIdx)
 752                         log.Infof("reading %s", annotationsFilename)
 753                         buf, err := os.ReadFile(annotationsFilename)
 754                         if err != nil {
 755                                 return 1
 756                         }
 757                         if *mergeOutput {
 758                                 err = os.Remove(annotationsFilename)
 759                                 if err != nil {
 760                                         return 1
 761                                 }
 762                         }
 763                         for _, line := range bytes.Split(buf, []byte{'\n'}) {
 764                                 if len(line) == 0 {
 765                                         continue
 766                                 }
 767                                 fields := bytes.SplitN(line, []byte{','}, 9)
 768                                 tag, _ := strconv.Atoi(string(fields[0]))
 769                                 incol, _ := strconv.Atoi(string(fields[1]))
 770                                 tileVariant, _ := strconv.Atoi(string(fields[2]))
 771                                 hgvsID := string(fields[3])
 772                                 seqname := string(fields[4])
 773                                 pos, _ := strconv.Atoi(string(fields[5]))
 774                                 refseq := fields[6]
 775                                 if hgvsID == "" {
 776                                         // Null entry for un-diffable
 777                                         // tile variant
 778                                         continue
 779                                 }
 780                                 if hgvsID == "=" {
 781                                         // Null entry for ref tile
 782                                         continue
 783                                 }
 784                                 if mask != nil && !mask.Check(strings.TrimPrefix(seqname, "chr"), pos, pos+len(refseq)) {
 785                                         // The tile intersects one of
 786                                         // the selected regions, but
 787                                         // this particular HGVS
 788                                         // variant does not.
 789                                         continue
 790                                 }
 791                                 hgvsColPair := hgvsCols[hgvsID]
 792                                 if hgvsColPair[0] == nil {
 793                                         // values in new columns start
 794                                         // out as -1 ("no data yet")
 795                                         // or 0 ("=ref") here, may
 796                                         // change to 1 ("hgvs variant
 797                                         // present") below, either on
 798                                         // this line or a future line.
 799                                         hgvsColPair = [2][]int16{make([]int16, len(cmd.cgnames)), make([]int16, len(cmd.cgnames))}
 800                                         rt, ok := reftile[tagID(tag)]
 801                                         if !ok {
 802                                                 err = fmt.Errorf("bug: seeing annotations for tag %d, but it has no reftile entry", tag)
 803                                                 return 1
 804                                         }
 805                                         for ph := 0; ph < 2; ph++ {
 806                                                 for row := 0; row < rows; row++ {
 807                                                         v := chunk[row*chunkcols+incol*2+ph]
 808                                                         if tileVariantID(v) == rt.variant {
 809                                                                 hgvsColPair[ph][row] = 0
 810                                                         } else {
 811                                                                 hgvsColPair[ph][row] = -1
 812                                                         }
 813                                                 }
 814                                         }
 815                                         hgvsCols[hgvsID] = hgvsColPair
 816                                         if annow != nil {
 817                                                 hgvsref := hgvs.Variant{
 818                                                         Position: pos,
 819                                                         Ref:      string(refseq),
 820                                                         New:      string(refseq),
 821                                                 }
 822                                                 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])
 823                                         }
 824                                 }
 825                                 if annow != nil {
 826                                         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])
 827                                 }
 828                                 for ph := 0; ph < 2; ph++ {
 829                                         for row := 0; row < rows; row++ {
 830                                                 v := chunk[row*chunkcols+incol*2+ph]
 831                                                 if int(v) == tileVariant {
 832                                                         hgvsColPair[ph][row] = 1
 833                                                 }
 834                                         }
 835                                 }
 836                         }
 837
 838                         startcol += chunkcols
 839                 }
 840                 if *mergeOutput {
 841                         err = annow.Flush()
 842                         if err != nil {
 843                                 return 1
 844                         }
 845                         err = annof.Close()
 846                         if err != nil {
 847                                 return 1
 848                         }
 849                         err = writeNumpyInt16(fmt.Sprintf("%s/matrix.npy", *outputDir), out, rows, cols)
 850                         if err != nil {
 851                                 return 1
 852                         }
 853                 }
 854                 out = nil
 855
 856                 if *hgvsSingle {
 857                         cols = len(hgvsCols) * 2
 858                         log.Printf("building hgvs-based matrix: %d rows x %d cols", rows, cols)
 859                         out = make([]int16, rows*cols)
 860                         hgvsIDs := make([]string, 0, cols/2)
 861                         for hgvsID := range hgvsCols {
 862                                 hgvsIDs = append(hgvsIDs, hgvsID)
 863                         }
 864                         sort.Strings(hgvsIDs)
 865                         var hgvsLabels bytes.Buffer
 866                         for idx, hgvsID := range hgvsIDs {
 867                                 fmt.Fprintf(&hgvsLabels, "%d,%s\n", idx, hgvsID)
 868                                 for ph := 0; ph < 2; ph++ {
 869                                         hgvscol := hgvsCols[hgvsID][ph]
 870                                         for row, val := range hgvscol {
 871                                                 out[row*cols+idx*2+ph] = val
 872                                         }
 873                                 }
 874                         }
 875                         err = writeNumpyInt16(fmt.Sprintf("%s/hgvs.npy", *outputDir), out, rows, cols)
 876                         if err != nil {
 877                                 return 1
 878                         }
 879
 880                         fnm := fmt.Sprintf("%s/hgvs.annotations.csv", *outputDir)
 881                         log.Printf("writing hgvs labels: %s", fnm)
 882                         err = ioutil.WriteFile(fnm, hgvsLabels.Bytes(), 0777)
 883                         if err != nil {
 884                                 return 1
 885                         }
 886                 }
 887         }
 888         if *onehotSingle {
 889                 var onehot [][]int8
 890                 var xrefs []onehotXref
 891                 for i := range onehotChunks {
 892                         onehot = append(onehot, onehotChunks[i]...)
 893                         onehotChunks[i] = nil
 894                         xrefs = append(xrefs, onehotXrefs[i]...)
 895                         onehotXrefs[i] = nil
 896                 }
 897                 fnm := fmt.Sprintf("%s/onehot.npy", *outputDir)
 898                 err = writeNumpyInt8(fnm, onehotcols2int8(onehot), len(cmd.cgnames), len(onehot))
 899                 if err != nil {
 900                         return 1
 901                 }
 902                 fnm = fmt.Sprintf("%s/onehot-columns.npy", *outputDir)
 903                 err = writeNumpyInt32(fnm, onehotXref2int32(xrefs), 4, len(xrefs))
 904                 if err != nil {
 905                         return 1
 906                 }
 907         }
 908         return 0
 909 }
 910
 911 // Read case/control files, remove non-case/control entries from
 912 // cmd.cgnames, and build cmd.chi2Cases.
 913 func (cmd *sliceNumpy) useCaseControlFiles() error {
 914         if cmd.chi2CaseControlFile == "" {
 915                 return nil
 916         }
 917         infiles, err := allFiles(cmd.chi2CaseControlFile, nil)
 918         if err != nil {
 919                 return err
 920         }
 921         // index in cmd.cgnames => case(true) / control(false)
 922         cc := map[int]bool{}
 923         for _, infile := range infiles {
 924                 f, err := open(infile)
 925                 if err != nil {
 926                         return err
 927                 }
 928                 buf, err := io.ReadAll(f)
 929                 f.Close()
 930                 if err != nil {
 931                         return err
 932                 }
 933                 ccCol := -1
 934                 for _, tsv := range bytes.Split(buf, []byte{'\n'}) {
 935                         if len(tsv) == 0 {
 936                                 continue
 937                         }
 938                         split := strings.Split(string(tsv), "\t")
 939                         if ccCol < 0 {
 940                                 // header row
 941                                 for col, name := range split {
 942                                         if name == cmd.chi2CaseControlColumn {
 943                                                 ccCol = col
 944                                                 break
 945                                         }
 946                                 }
 947                                 if ccCol < 0 {
 948                                         return fmt.Errorf("%s: no column named %q in header row %q", infile, cmd.chi2CaseControlColumn, tsv)
 949                                 }
 950                                 continue
 951                         }
 952                         if len(split) <= ccCol {
 953                                 continue
 954                         }
 955                         pattern := split[0]
 956                         found := -1
 957                         for i, name := range cmd.cgnames {
 958                                 if strings.Contains(name, pattern) {
 959                                         if found >= 0 {
 960                                                 log.Warnf("pattern %q in %s matches multiple genome IDs (%qs, %q)", pattern, infile, cmd.cgnames[found], name)
 961                                         }
 962                                         found = i
 963                                 }
 964                         }
 965                         if found < 0 {
 966                                 log.Warnf("pattern %q in %s does not match any genome IDs", pattern, infile)
 967                                 continue
 968                         }
 969                         if split[ccCol] == "0" {
 970                                 cc[found] = false
 971                         }
 972                         if split[ccCol] == "1" {
 973                                 cc[found] = true
 974                         }
 975                 }
 976         }
 977         allnames := cmd.cgnames
 978         cmd.cgnames = nil
 979         cmd.chi2Cases = nil
 980         ncases := 0
 981         for i, name := range allnames {
 982                 if cc, ok := cc[i]; ok {
 983                         cmd.cgnames = append(cmd.cgnames, name)
 984                         cmd.chi2Cases = append(cmd.chi2Cases, cc)
 985                         if cc {
 986                                 ncases++
 987                         }
 988                 }
 989         }
 990         log.Printf("%d cases, %d controls, %d neither (dropped)", ncases, len(cmd.cgnames)-ncases, len(allnames)-len(cmd.cgnames))
 991         return nil
 992 }
 993
 994 func (cmd *sliceNumpy) filterHGVScolpair(colpair [2][]int8) bool {
 995         if cmd.chi2PValue >= 1 {
 996                 return true
 997         }
 998         col0 := make([]bool, 0, len(cmd.chi2Cases))
 999         col1 := make([]bool, 0, len(cmd.chi2Cases))
1000         cases := make([]bool, 0, len(cmd.chi2Cases))
1001         for i, c := range cmd.chi2Cases {
1002                 if colpair[0][i] < 0 {
1003                         continue
1004                 }
1005                 col0 = append(col0, colpair[0][i] != 0)
1006                 col1 = append(col1, colpair[1][i] != 0)
1007                 cases = append(cases, c)
1008         }
1009         return len(cases) >= cmd.minCoverage &&
1010                 (pvalue(cases, col0) <= cmd.chi2PValue || pvalue(cases, col1) <= cmd.chi2PValue)
1011 }
1012
1013 func writeNumpyInt32(fnm string, out []int32, rows, cols int) error {
1014         output, err := os.Create(fnm)
1015         if err != nil {
1016                 return err
1017         }
1018         defer output.Close()
1019         bufw := bufio.NewWriterSize(output, 1<<26)
1020         npw, err := gonpy.NewWriter(nopCloser{bufw})
1021         if err != nil {
1022                 return err
1023         }
1024         log.WithFields(log.Fields{
1025                 "filename": fnm,
1026                 "rows":     rows,
1027                 "cols":     cols,
1028                 "bytes":    rows * cols * 4,
1029         }).Infof("writing numpy: %s", fnm)
1030         npw.Shape = []int{rows, cols}
1031         npw.WriteInt32(out)
1032         err = bufw.Flush()
1033         if err != nil {
1034                 return err
1035         }
1036         return output.Close()
1037 }
1038
1039 func writeNumpyInt16(fnm string, out []int16, rows, cols int) error {
1040         output, err := os.Create(fnm)
1041         if err != nil {
1042                 return err
1043         }
1044         defer output.Close()
1045         bufw := bufio.NewWriterSize(output, 1<<26)
1046         npw, err := gonpy.NewWriter(nopCloser{bufw})
1047         if err != nil {
1048                 return err
1049         }
1050         log.WithFields(log.Fields{
1051                 "filename": fnm,
1052                 "rows":     rows,
1053                 "cols":     cols,
1054                 "bytes":    rows * cols * 2,
1055         }).Infof("writing numpy: %s", fnm)
1056         npw.Shape = []int{rows, cols}
1057         npw.WriteInt16(out)
1058         err = bufw.Flush()
1059         if err != nil {
1060                 return err
1061         }
1062         return output.Close()
1063 }
1064
1065 func writeNumpyInt8(fnm string, out []int8, rows, cols int) error {
1066         output, err := os.Create(fnm)
1067         if err != nil {
1068                 return err
1069         }
1070         defer output.Close()
1071         bufw := bufio.NewWriterSize(output, 1<<26)
1072         npw, err := gonpy.NewWriter(nopCloser{bufw})
1073         if err != nil {
1074                 return err
1075         }
1076         log.WithFields(log.Fields{
1077                 "filename": fnm,
1078                 "rows":     rows,
1079                 "cols":     cols,
1080                 "bytes":    rows * cols,
1081         }).Infof("writing numpy: %s", fnm)
1082         npw.Shape = []int{rows, cols}
1083         npw.WriteInt8(out)
1084         err = bufw.Flush()
1085         if err != nil {
1086                 return err
1087         }
1088         return output.Close()
1089 }
1090
1091 func allele2homhet(colpair [2][]int8) {
1092         a, b := colpair[0], colpair[1]
1093         for i, av := range a {
1094                 bv := b[i]
1095                 if av < 0 || bv < 0 {
1096                         // no-call
1097                         a[i], b[i] = -1, -1
1098                 } else if av > 0 && bv > 0 {
1099                         // hom
1100                         a[i], b[i] = 1, 0
1101                 } else if av > 0 || bv > 0 {
1102                         // het
1103                         a[i], b[i] = 0, 1
1104                 } else {
1105                         // ref (or a different variant in same position)
1106                         // (this is a no-op) a[i], b[i] = 0, 0
1107                 }
1108         }
1109 }
1110
1111 type onehotXref struct {
1112         tag     tagID
1113         variant tileVariantID
1114         het     bool
1115         pvalue  float64
1116 }
1117
1118 // Build onehot matrix (m[variant*2+isHet][genome] == 0 or 1) for all
1119 // variants of a single tile/tag#.
1120 //
1121 // Return nil if no tile variant passes Χ² filter.
1122 func (cmd *sliceNumpy) tv2homhet(cgs map[string]CompactGenome, maxv tileVariantID, remap []tileVariantID, tag, chunkstarttag tagID) ([][]int8, []onehotXref) {
1123         if maxv < 2 {
1124                 // everyone has the most common variant
1125                 return nil, nil
1126         }
1127         tagoffset := tag - chunkstarttag
1128         coverage := 0
1129         for _, cg := range cgs {
1130                 if cg.Variants[tagoffset*2] > 0 && cg.Variants[tagoffset*2+1] > 0 {
1131                         coverage++
1132                 }
1133         }
1134         if coverage < cmd.minCoverage {
1135                 return nil, nil
1136         }
1137         obs := make([][]bool, (maxv+1)*2) // 2 slices (hom + het) for each variant#
1138         for i := range obs {
1139                 obs[i] = make([]bool, len(cmd.cgnames))
1140         }
1141         for cgid, name := range cmd.cgnames {
1142                 cgvars := cgs[name].Variants
1143                 for v := tileVariantID(2); v <= maxv; v++ {
1144                         if remap[cgvars[tagoffset*2]] == v && remap[cgvars[tagoffset*2+1]] == v {
1145                                 obs[v*2][cgid] = true
1146                         } else if remap[cgvars[tagoffset*2]] == v || remap[cgvars[tagoffset*2+1]] == v {
1147                                 obs[v*2+1][cgid] = true
1148                         }
1149                 }
1150         }
1151         var onehot [][]int8
1152         var xref []onehotXref
1153         for homcol := 4; homcol < len(obs); homcol += 2 {
1154                 p := [2]float64{
1155                         pvalue(cmd.chi2Cases, obs[homcol]),
1156                         pvalue(cmd.chi2Cases, obs[homcol+1]),
1157                 }
1158                 if cmd.chi2PValue < 1 && !(p[0] < cmd.chi2PValue || p[1] < cmd.chi2PValue) {
1159                         continue
1160                 }
1161                 for het := 0; het < 2; het++ {
1162                         onehot = append(onehot, bool2int8(obs[homcol+het]))
1163                         xref = append(xref, onehotXref{
1164                                 tag:     tag,
1165                                 variant: tileVariantID(homcol / 2),
1166                                 het:     het == 1,
1167                                 pvalue:  p[het],
1168                         })
1169                 }
1170         }
1171         return onehot, xref
1172 }
1173
1174 func bool2int8(in []bool) []int8 {
1175         out := make([]int8, len(in))
1176         for i, v := range in {
1177                 if v {
1178                         out[i] = 1
1179                 }
1180         }
1181         return out
1182 }
1183
1184 // convert a []onehotXref with length N to a numpy-style []int32
1185 // matrix with N columns, one row per field of onehotXref struct.
1186 //
1187 // Hom/het row contains hom=0, het=1.
1188 //
1189 // P-value row contains 1000000x actual p-value.
1190 func onehotXref2int32(xrefs []onehotXref) []int32 {
1191         xcols := len(xrefs)
1192         xdata := make([]int32, 4*xcols)
1193         for i, xref := range xrefs {
1194                 xdata[i] = int32(xref.tag)
1195                 xdata[xcols+i] = int32(xref.variant)
1196                 if xref.het {
1197                         xdata[xcols*2+i] = 1
1198                 }
1199                 xdata[xcols*3+i] = int32(xref.pvalue * 1000000)
1200         }
1201         return xdata
1202 }
1203
1204 // transpose onehot data from in[col][row] to numpy-style
1205 // out[row*cols+col].
1206 func onehotcols2int8(in [][]int8) []int8 {
1207         if len(in) == 0 {
1208                 return nil
1209         }
1210         cols := len(in)
1211         rows := len(in[0])
1212         out := make([]int8, rows*cols)
1213         for row := 0; row < rows; row++ {
1214                 outrow := out[row*cols:]
1215                 for col, incol := range in {
1216                         outrow[col] = incol[row]
1217                 }
1218         }
1219         return out
1220 }