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         "unsafe"
  27
  28         "git.arvados.org/arvados.git/sdk/go/arvados"
  29         "github.com/arvados/lightning/hgvs"
  30         "github.com/kshedden/gonpy"
  31         log "github.com/sirupsen/logrus"
  32         "golang.org/x/crypto/blake2b"
  33 )
  34
  35 type sliceNumpy struct {
  36         filter                filter
  37         threads               int
  38         chi2CaseControlColumn string
  39         chi2CaseControlFile   string
  40         chi2Cases             []bool
  41         chi2PValue            float64
  42         minCoverage           int
  43         cgnames               []string
  44         includeVariant1       bool
  45 }
  46
  47 func (cmd *sliceNumpy) RunCommand(prog string, args []string, stdin io.Reader, stdout, stderr io.Writer) int {
  48         var err error
  49         defer func() {
  50                 if err != nil {
  51                         fmt.Fprintf(stderr, "%s\n", err)
  52                 }
  53         }()
  54         flags := flag.NewFlagSet("", flag.ContinueOnError)
  55         flags.SetOutput(stderr)
  56         pprof := flags.String("pprof", "", "serve Go profile data at http://`[addr]:port`")
  57         runlocal := flags.Bool("local", false, "run on local host (default: run in an arvados container)")
  58         projectUUID := flags.String("project", "", "project `UUID` for output data")
  59         priority := flags.Int("priority", 500, "container request priority")
  60         inputDir := flags.String("input-dir", "./in", "input `directory`")
  61         outputDir := flags.String("output-dir", "./out", "output `directory`")
  62         ref := flags.String("ref", "", "reference name (if blank, choose last one that appears in input)")
  63         regionsFilename := flags.String("regions", "", "only output columns/annotations that intersect regions in specified bed `file`")
  64         expandRegions := flags.Int("expand-regions", 0, "expand specified regions by `N` base pairs on each side`")
  65         mergeOutput := flags.Bool("merge-output", false, "merge output into one matrix.npy and one matrix.annotations.csv")
  66         hgvsSingle := flags.Bool("single-hgvs-matrix", false, "also generate hgvs-based matrix")
  67         hgvsChunked := flags.Bool("chunked-hgvs-matrix", false, "also generate hgvs-based matrix per chromosome")
  68         onehotSingle := flags.Bool("single-onehot", false, "generate one-hot tile-based matrix")
  69         onehotChunked := flags.Bool("chunked-onehot", false, "generate one-hot tile-based matrix per input chunk")
  70         flags.IntVar(&cmd.threads, "threads", 16, "number of memory-hungry assembly threads")
  71         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)")
  72         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)")
  73         flags.Float64Var(&cmd.chi2PValue, "chi2-p-value", 1, "do Χ² test and omit columns with p-value above this threshold")
  74         flags.BoolVar(&cmd.includeVariant1, "include-variant-1", false, "include most common variant when building one-hot matrix")
  75         cmd.filter.Flags(flags)
  76         err = flags.Parse(args)
  77         if err == flag.ErrHelp {
  78                 err = nil
  79                 return 0
  80         } else if err != nil {
  81                 return 2
  82         }
  83
  84         if *pprof != "" {
  85                 go func() {
  86                         log.Println(http.ListenAndServe(*pprof, nil))
  87                 }()
  88         }
  89
  90         if cmd.chi2PValue != 1 && (cmd.chi2CaseControlFile == "" || cmd.chi2CaseControlColumn == "") {
  91                 log.Errorf("cannot use provided -chi2-p-value=%f because -chi2-case-control-file= or -chi2-case-control-column= value is empty", cmd.chi2PValue)
  92                 return 2
  93         }
  94
  95         if !*runlocal {
  96                 runner := arvadosContainerRunner{
  97                         Name:        "lightning slice-numpy",
  98                         Client:      arvados.NewClientFromEnv(),
  99                         ProjectUUID: *projectUUID,
 100                         RAM:         750000000000,
 101                         VCPUs:       96,
 102                         Priority:    *priority,
 103                         KeepCache:   2,
 104                         APIAccess:   true,
 105                 }
 106                 err = runner.TranslatePaths(inputDir, regionsFilename, &cmd.chi2CaseControlFile)
 107                 if err != nil {
 108                         return 1
 109                 }
 110                 runner.Args = []string{"slice-numpy", "-local=true",
 111                         "-pprof=:6060",
 112                         "-input-dir=" + *inputDir,
 113                         "-output-dir=/mnt/output",
 114                         "-threads=" + fmt.Sprintf("%d", cmd.threads),
 115                         "-regions=" + *regionsFilename,
 116                         "-expand-regions=" + fmt.Sprintf("%d", *expandRegions),
 117                         "-merge-output=" + fmt.Sprintf("%v", *mergeOutput),
 118                         "-single-hgvs-matrix=" + fmt.Sprintf("%v", *hgvsSingle),
 119                         "-chunked-hgvs-matrix=" + fmt.Sprintf("%v", *hgvsChunked),
 120                         "-single-onehot=" + fmt.Sprintf("%v", *onehotSingle),
 121                         "-chunked-onehot=" + fmt.Sprintf("%v", *onehotChunked),
 122                         "-chi2-case-control-file=" + cmd.chi2CaseControlFile,
 123                         "-chi2-case-control-column=" + cmd.chi2CaseControlColumn,
 124                         "-chi2-p-value=" + fmt.Sprintf("%f", cmd.chi2PValue),
 125                         "-include-variant-1=" + fmt.Sprintf("%v", cmd.includeVariant1),
 126                 }
 127                 runner.Args = append(runner.Args, cmd.filter.Args()...)
 128                 var output string
 129                 output, err = runner.Run()
 130                 if err != nil {
 131                         return 1
 132                 }
 133                 fmt.Fprintln(stdout, output)
 134                 return 0
 135         }
 136
 137         infiles, err := allFiles(*inputDir, matchGobFile)
 138         if err != nil {
 139                 return 1
 140         }
 141         if len(infiles) == 0 {
 142                 err = fmt.Errorf("no input files found in %s", *inputDir)
 143                 return 1
 144         }
 145         sort.Strings(infiles)
 146
 147         var refseq map[string][]tileLibRef
 148         var reftiledata = make(map[tileLibRef][]byte, 11000000)
 149         in0, err := open(infiles[0])
 150         if err != nil {
 151                 return 1
 152         }
 153
 154         matchGenome, err := regexp.Compile(cmd.filter.MatchGenome)
 155         if err != nil {
 156                 err = fmt.Errorf("-match-genome: invalid regexp: %q", cmd.filter.MatchGenome)
 157                 return 1
 158         }
 159
 160         cmd.cgnames = nil
 161         var tagset [][]byte
 162         DecodeLibrary(in0, strings.HasSuffix(infiles[0], ".gz"), func(ent *LibraryEntry) error {
 163                 if len(ent.TagSet) > 0 {
 164                         tagset = ent.TagSet
 165                 }
 166                 for _, cseq := range ent.CompactSequences {
 167                         if cseq.Name == *ref || *ref == "" {
 168                                 refseq = cseq.TileSequences
 169                         }
 170                 }
 171                 for _, cg := range ent.CompactGenomes {
 172                         if matchGenome.MatchString(cg.Name) {
 173                                 cmd.cgnames = append(cmd.cgnames, cg.Name)
 174                         }
 175                 }
 176                 for _, tv := range ent.TileVariants {
 177                         if tv.Ref {
 178                                 reftiledata[tileLibRef{tv.Tag, tv.Variant}] = tv.Sequence
 179                         }
 180                 }
 181                 return nil
 182         })
 183         if err != nil {
 184                 return 1
 185         }
 186         in0.Close()
 187         if refseq == nil {
 188                 err = fmt.Errorf("%s: reference sequence not found", infiles[0])
 189                 return 1
 190         }
 191         if len(tagset) == 0 {
 192                 err = fmt.Errorf("tagset not found")
 193                 return 1
 194         }
 195
 196         taglib := &tagLibrary{}
 197         err = taglib.setTags(tagset)
 198         if err != nil {
 199                 return 1
 200         }
 201         taglen := taglib.TagLen()
 202
 203         if len(cmd.cgnames) == 0 {
 204                 err = fmt.Errorf("no genomes found matching regexp %q", cmd.filter.MatchGenome)
 205                 return 1
 206         }
 207         sort.Strings(cmd.cgnames)
 208         err = cmd.useCaseControlFiles()
 209         if err != nil {
 210                 return 1
 211         }
 212         cmd.minCoverage = int(math.Ceil(cmd.filter.MinCoverage * float64(len(cmd.cgnames))))
 213
 214         {
 215                 labelsFilename := *outputDir + "/samples.csv"
 216                 log.Infof("writing labels to %s", labelsFilename)
 217                 var f *os.File
 218                 f, err = os.Create(labelsFilename)
 219                 if err != nil {
 220                         return 1
 221                 }
 222                 defer f.Close()
 223                 for i, name := range cmd.cgnames {
 224                         cc := 0
 225                         if cmd.chi2Cases != nil && cmd.chi2Cases[i] {
 226                                 cc = 1
 227                         }
 228                         _, err = fmt.Fprintf(f, "%d,%q,%d\n", i, trimFilenameForLabel(name), cc)
 229                         if err != nil {
 230                                 err = fmt.Errorf("write %s: %w", labelsFilename, err)
 231                                 return 1
 232                         }
 233                 }
 234                 err = f.Close()
 235                 if err != nil {
 236                         err = fmt.Errorf("close %s: %w", labelsFilename, err)
 237                         return 1
 238                 }
 239         }
 240
 241         log.Info("indexing reference tiles")
 242         type reftileinfo struct {
 243                 variant  tileVariantID
 244                 seqname  string // chr1
 245                 pos      int    // distance from start of chromosome to starttag
 246                 tiledata []byte // acgtggcaa...
 247         }
 248         isdup := map[tagID]bool{}
 249         reftile := map[tagID]*reftileinfo{}
 250         for seqname, cseq := range refseq {
 251                 pos := 0
 252                 for _, libref := range cseq {
 253                         if cmd.filter.MaxTag >= 0 && libref.Tag > tagID(cmd.filter.MaxTag) {
 254                                 continue
 255                         }
 256                         tiledata := reftiledata[libref]
 257                         if len(tiledata) == 0 {
 258                                 err = fmt.Errorf("missing tiledata for tag %d variant %d in %s in ref", libref.Tag, libref.Variant, seqname)
 259                                 return 1
 260                         }
 261                         foundthistag := false
 262                         taglib.FindAll(tiledata[:len(tiledata)-1], func(tagid tagID, offset, _ int) {
 263                                 if !foundthistag && tagid == libref.Tag {
 264                                         foundthistag = true
 265                                         return
 266                                 }
 267                                 if dupref, ok := reftile[tagid]; ok {
 268                                         log.Printf("dropping reference tile %+v from %s @ %d, tag not unique, also found inside %+v from %s @ %d", tileLibRef{Tag: tagid, Variant: dupref.variant}, dupref.seqname, dupref.pos, libref, seqname, pos+offset+1)
 269                                         delete(reftile, tagid)
 270                                 } else {
 271                                         log.Printf("found tag %d at offset %d inside tile variant %+v on %s @ %d", tagid, offset, libref, seqname, pos+offset+1)
 272                                 }
 273                                 isdup[tagid] = true
 274                         })
 275                         if isdup[libref.Tag] {
 276                                 log.Printf("dropping reference tile %+v from %s @ %d, tag not unique", libref, seqname, pos)
 277                         } else if reftile[libref.Tag] != nil {
 278                                 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)
 279                                 delete(reftile, libref.Tag)
 280                                 log.Printf("dropping reference tile %+v from %s @ %d, tag not unique", libref, seqname, pos)
 281                                 isdup[libref.Tag] = true
 282                         } else {
 283                                 reftile[libref.Tag] = &reftileinfo{
 284                                         seqname:  seqname,
 285                                         variant:  libref.Variant,
 286                                         tiledata: tiledata,
 287                                         pos:      pos,
 288                                 }
 289                         }
 290                         pos += len(tiledata) - taglen
 291                 }
 292                 log.Printf("... %s done, len %d", seqname, pos+taglen)
 293         }
 294
 295         var mask *mask
 296         if *regionsFilename != "" {
 297                 log.Printf("loading regions from %s", *regionsFilename)
 298                 mask, err = makeMask(*regionsFilename, *expandRegions)
 299                 if err != nil {
 300                         return 1
 301                 }
 302                 log.Printf("before applying mask, len(reftile) == %d", len(reftile))
 303                 log.Printf("deleting reftile entries for regions outside %d intervals", mask.Len())
 304                 for tag, rt := range reftile {
 305                         if !mask.Check(strings.TrimPrefix(rt.seqname, "chr"), rt.pos, rt.pos+len(rt.tiledata)) {
 306                                 delete(reftile, tag)
 307                         }
 308                 }
 309                 log.Printf("after applying mask, len(reftile) == %d", len(reftile))
 310         }
 311
 312         type hgvsColSet map[hgvs.Variant][2][]int8
 313         encodeHGVS := throttle{Max: len(refseq)}
 314         encodeHGVSTodo := map[string]chan hgvsColSet{}
 315         tmpHGVSCols := map[string]*os.File{}
 316         if *hgvsChunked {
 317                 for seqname := range refseq {
 318                         var f *os.File
 319                         f, err = os.Create(*outputDir + "/tmp." + seqname + ".gob")
 320                         if err != nil {
 321                                 return 1
 322                         }
 323                         defer os.Remove(f.Name())
 324                         bufw := bufio.NewWriterSize(f, 1<<24)
 325                         enc := gob.NewEncoder(bufw)
 326                         tmpHGVSCols[seqname] = f
 327                         todo := make(chan hgvsColSet, 128)
 328                         encodeHGVSTodo[seqname] = todo
 329                         encodeHGVS.Go(func() error {
 330                                 for colset := range todo {
 331                                         err := enc.Encode(colset)
 332                                         if err != nil {
 333                                                 encodeHGVS.Report(err)
 334                                                 for range todo {
 335                                                 }
 336                                                 return err
 337                                         }
 338                                 }
 339                                 return bufw.Flush()
 340                         })
 341                 }
 342         }
 343
 344         var toMerge [][]int16
 345         if *mergeOutput || *hgvsSingle {
 346                 toMerge = make([][]int16, len(infiles))
 347         }
 348         var onehotIndirect [][2][]uint32 // [chunkIndex][axis][index]
 349         var onehotChunkSize []uint32
 350         var onehotXrefs [][]onehotXref
 351         if *onehotSingle {
 352                 onehotIndirect = make([][2][]uint32, len(infiles))
 353                 onehotChunkSize = make([]uint32, len(infiles))
 354                 onehotXrefs = make([][]onehotXref, len(infiles))
 355         }
 356
 357         throttleMem := throttle{Max: cmd.threads} // TODO: estimate using mem and data size
 358         throttleNumpyMem := throttle{Max: cmd.threads/2 + 1}
 359         log.Info("generating annotations and numpy matrix for each slice")
 360         var done int64
 361         for infileIdx, infile := range infiles {
 362                 infileIdx, infile := infileIdx, infile
 363                 throttleMem.Go(func() error {
 364                         seq := make(map[tagID][]TileVariant, 50000)
 365                         cgs := make(map[string]CompactGenome, len(cmd.cgnames))
 366                         f, err := open(infile)
 367                         if err != nil {
 368                                 return err
 369                         }
 370                         defer f.Close()
 371                         log.Infof("%04d: reading %s", infileIdx, infile)
 372                         err = DecodeLibrary(f, strings.HasSuffix(infile, ".gz"), func(ent *LibraryEntry) error {
 373                                 for _, tv := range ent.TileVariants {
 374                                         if tv.Ref {
 375                                                 continue
 376                                         }
 377                                         if mask != nil && reftile[tv.Tag] == nil {
 378                                                 // Don't waste
 379                                                 // time/memory on
 380                                                 // masked-out tiles.
 381                                                 continue
 382                                         }
 383                                         variants := seq[tv.Tag]
 384                                         if len(variants) == 0 {
 385                                                 variants = make([]TileVariant, 100)
 386                                         }
 387                                         for len(variants) <= int(tv.Variant) {
 388                                                 variants = append(variants, TileVariant{})
 389                                         }
 390                                         variants[int(tv.Variant)] = tv
 391                                         seq[tv.Tag] = variants
 392                                 }
 393                                 for _, cg := range ent.CompactGenomes {
 394                                         if !matchGenome.MatchString(cg.Name) {
 395                                                 continue
 396                                         }
 397                                         // pad to full slice size
 398                                         // to avoid out-of-bounds
 399                                         // checks later
 400                                         if sliceSize := 2 * int(cg.EndTag-cg.StartTag); len(cg.Variants) < sliceSize {
 401                                                 cg.Variants = append(cg.Variants, make([]tileVariantID, sliceSize-len(cg.Variants))...)
 402                                         }
 403                                         cgs[cg.Name] = cg
 404                                 }
 405                                 return nil
 406                         })
 407                         if err != nil {
 408                                 return err
 409                         }
 410                         tagstart := cgs[cmd.cgnames[0]].StartTag
 411                         tagend := cgs[cmd.cgnames[0]].EndTag
 412
 413                         // TODO: filters
 414
 415                         log.Infof("%04d: renumber/dedup variants for tags %d-%d", infileIdx, tagstart, tagend)
 416                         variantRemap := make([][]tileVariantID, tagend-tagstart)
 417                         throttleCPU := throttle{Max: runtime.GOMAXPROCS(0)}
 418                         for tag, variants := range seq {
 419                                 tag, variants := tag, variants
 420                                 throttleCPU.Acquire()
 421                                 go func() {
 422                                         defer throttleCPU.Release()
 423                                         count := make(map[[blake2b.Size256]byte]int, len(variants))
 424
 425                                         rt := reftile[tag]
 426                                         if rt != nil {
 427                                                 count[blake2b.Sum256(rt.tiledata)] = 0
 428                                         }
 429
 430                                         for _, cg := range cgs {
 431                                                 idx := int(tag-tagstart) * 2
 432                                                 for allele := 0; allele < 2; allele++ {
 433                                                         v := cg.Variants[idx+allele]
 434                                                         if v > 0 && len(variants[v].Sequence) > 0 {
 435                                                                 count[variants[v].Blake2b]++
 436                                                         }
 437                                                 }
 438                                         }
 439                                         // hash[i] will be the hash of
 440                                         // the variant(s) that should
 441                                         // be at rank i (0-based).
 442                                         hash := make([][blake2b.Size256]byte, 0, len(count))
 443                                         for b := range count {
 444                                                 hash = append(hash, b)
 445                                         }
 446                                         sort.Slice(hash, func(i, j int) bool {
 447                                                 bi, bj := &hash[i], &hash[j]
 448                                                 if ci, cj := count[*bi], count[*bj]; ci != cj {
 449                                                         return ci > cj
 450                                                 } else {
 451                                                         return bytes.Compare((*bi)[:], (*bj)[:]) < 0
 452                                                 }
 453                                         })
 454                                         // rank[b] will be the 1-based
 455                                         // new variant number for
 456                                         // variants whose hash is b.
 457                                         rank := make(map[[blake2b.Size256]byte]tileVariantID, len(hash))
 458                                         for i, h := range hash {
 459                                                 rank[h] = tileVariantID(i + 1)
 460                                         }
 461                                         // remap[v] will be the new
 462                                         // variant number for original
 463                                         // variant number v.
 464                                         remap := make([]tileVariantID, len(variants))
 465                                         for i, tv := range variants {
 466                                                 remap[i] = rank[tv.Blake2b]
 467                                         }
 468                                         variantRemap[tag-tagstart] = remap
 469                                         if rt != nil {
 470                                                 rt.variant = rank[blake2b.Sum256(rt.tiledata)]
 471                                         }
 472                                 }()
 473                         }
 474                         throttleCPU.Wait()
 475
 476                         var onehotChunk [][]int8
 477                         var onehotXref []onehotXref
 478
 479                         annotationsFilename := fmt.Sprintf("%s/matrix.%04d.annotations.csv", *outputDir, infileIdx)
 480                         log.Infof("%04d: writing %s", infileIdx, annotationsFilename)
 481                         annof, err := os.Create(annotationsFilename)
 482                         if err != nil {
 483                                 return err
 484                         }
 485                         annow := bufio.NewWriterSize(annof, 1<<20)
 486                         outcol := 0
 487                         for tag := tagstart; tag < tagend; tag++ {
 488                                 rt := reftile[tag]
 489                                 if rt == nil && mask != nil {
 490                                         // Excluded by specified regions
 491                                         continue
 492                                 }
 493                                 if cmd.filter.MaxTag >= 0 && tag > tagID(cmd.filter.MaxTag) {
 494                                         continue
 495                                 }
 496                                 remap := variantRemap[tag-tagstart]
 497                                 maxv := tileVariantID(0)
 498                                 for _, v := range remap {
 499                                         if maxv < v {
 500                                                 maxv = v
 501                                         }
 502                                 }
 503                                 if *onehotChunked || *onehotSingle {
 504                                         onehot, xrefs := cmd.tv2homhet(cgs, maxv, remap, tag, tagstart)
 505                                         onehotChunk = append(onehotChunk, onehot...)
 506                                         onehotXref = append(onehotXref, xrefs...)
 507                                 }
 508                                 if rt == nil {
 509                                         // Reference does not use any
 510                                         // variant of this tile
 511                                         outcol++
 512                                         continue
 513                                 }
 514                                 fmt.Fprintf(annow, "%d,%d,%d,=,%s,%d,,,\n", tag, outcol, rt.variant, rt.seqname, rt.pos)
 515                                 variants := seq[tag]
 516                                 reftilestr := strings.ToUpper(string(rt.tiledata))
 517
 518                                 done := make([]bool, maxv+1)
 519                                 variantDiffs := make([][]hgvs.Variant, maxv+1)
 520                                 for v, tv := range variants {
 521                                         v := remap[v]
 522                                         if v == rt.variant || done[v] {
 523                                                 continue
 524                                         } else {
 525                                                 done[v] = true
 526                                         }
 527                                         if len(tv.Sequence) < taglen || !bytes.HasSuffix(rt.tiledata, tv.Sequence[len(tv.Sequence)-taglen:]) {
 528                                                 fmt.Fprintf(annow, "%d,%d,%d,,%s,%d,,,\n", tag, outcol, v, rt.seqname, rt.pos)
 529                                                 continue
 530                                         }
 531                                         if lendiff := len(rt.tiledata) - len(tv.Sequence); lendiff < -1000 || lendiff > 1000 {
 532                                                 fmt.Fprintf(annow, "%d,%d,%d,,%s,%d,,,\n", tag, outcol, v, rt.seqname, rt.pos)
 533                                                 continue
 534                                         }
 535                                         diffs, _ := hgvs.Diff(reftilestr, strings.ToUpper(string(tv.Sequence)), 0)
 536                                         for i := range diffs {
 537                                                 diffs[i].Position += rt.pos
 538                                         }
 539                                         for _, diff := range diffs {
 540                                                 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)
 541                                         }
 542                                         if *hgvsChunked {
 543                                                 variantDiffs[v] = diffs
 544                                         }
 545                                 }
 546                                 if *hgvsChunked {
 547                                         // We can now determine, for each HGVS
 548                                         // variant (diff) in this reftile
 549                                         // region, whether a given genome
 550                                         // phase/allele (1) has the variant, (0) has
 551                                         // =ref or a different variant in that
 552                                         // position, or (-1) is lacking
 553                                         // coverage / couldn't be diffed.
 554                                         hgvsCol := hgvsColSet{}
 555                                         for _, diffs := range variantDiffs {
 556                                                 for _, diff := range diffs {
 557                                                         if _, ok := hgvsCol[diff]; ok {
 558                                                                 continue
 559                                                         }
 560                                                         hgvsCol[diff] = [2][]int8{
 561                                                                 make([]int8, len(cmd.cgnames)),
 562                                                                 make([]int8, len(cmd.cgnames)),
 563                                                         }
 564                                                 }
 565                                         }
 566                                         for row, name := range cmd.cgnames {
 567                                                 variants := cgs[name].Variants[(tag-tagstart)*2:]
 568                                                 for ph := 0; ph < 2; ph++ {
 569                                                         v := variants[ph]
 570                                                         if int(v) >= len(remap) {
 571                                                                 v = 0
 572                                                         } else {
 573                                                                 v = remap[v]
 574                                                         }
 575                                                         if v == rt.variant {
 576                                                                 // hgvsCol[*][ph][row] is already 0
 577                                                         } else if len(variantDiffs[v]) == 0 {
 578                                                                 // lacking coverage / couldn't be diffed
 579                                                                 for _, col := range hgvsCol {
 580                                                                         col[ph][row] = -1
 581                                                                 }
 582                                                         } else {
 583                                                                 for _, diff := range variantDiffs[v] {
 584                                                                         hgvsCol[diff][ph][row] = 1
 585                                                                 }
 586                                                         }
 587                                                 }
 588                                         }
 589                                         for diff, colpair := range hgvsCol {
 590                                                 allele2homhet(colpair)
 591                                                 if !cmd.filterHGVScolpair(colpair) {
 592                                                         delete(hgvsCol, diff)
 593                                                 }
 594                                         }
 595                                         if len(hgvsCol) > 0 {
 596                                                 encodeHGVSTodo[rt.seqname] <- hgvsCol
 597                                         }
 598                                 }
 599                                 outcol++
 600                         }
 601                         err = annow.Flush()
 602                         if err != nil {
 603                                 return err
 604                         }
 605                         err = annof.Close()
 606                         if err != nil {
 607                                 return err
 608                         }
 609
 610                         if *onehotChunked {
 611                                 // transpose onehotChunk[col][row] to numpy[row*ncols+col]
 612                                 rows := len(cmd.cgnames)
 613                                 cols := len(onehotChunk)
 614                                 log.Infof("%04d: preparing onehot numpy (rows=%d, cols=%d, mem=%d)", infileIdx, len(cmd.cgnames), len(onehotChunk), len(cmd.cgnames)*len(onehotChunk))
 615                                 throttleNumpyMem.Acquire()
 616                                 out := onehotcols2int8(onehotChunk)
 617                                 fnm := fmt.Sprintf("%s/onehot.%04d.npy", *outputDir, infileIdx)
 618                                 err = writeNumpyInt8(fnm, out, rows, cols)
 619                                 if err != nil {
 620                                         return err
 621                                 }
 622                                 fnm = fmt.Sprintf("%s/onehot-columns.%04d.npy", *outputDir, infileIdx)
 623                                 err = writeNumpyInt32(fnm, onehotXref2int32(onehotXref), 4, len(onehotXref))
 624                                 if err != nil {
 625                                         return err
 626                                 }
 627                                 debug.FreeOSMemory()
 628                                 throttleNumpyMem.Release()
 629                         }
 630                         if *onehotSingle {
 631                                 onehotIndirect[infileIdx] = onehotChunk2Indirect(onehotChunk)
 632                                 onehotChunkSize[infileIdx] = uint32(len(onehotChunk))
 633                                 onehotXrefs[infileIdx] = onehotXref
 634                                 n := len(onehotIndirect[infileIdx][0])
 635                                 log.Infof("%04d: keeping onehot coordinates in memory (n=%d, mem=%d)", infileIdx, n, n*8*2)
 636                         }
 637                         if !(*onehotSingle || *onehotChunked) || *mergeOutput || *hgvsSingle {
 638                                 log.Infof("%04d: preparing numpy (rows=%d, cols=%d)", infileIdx, len(cmd.cgnames), 2*outcol)
 639                                 throttleNumpyMem.Acquire()
 640                                 rows := len(cmd.cgnames)
 641                                 cols := 2 * outcol
 642                                 out := make([]int16, rows*cols)
 643                                 for row, name := range cmd.cgnames {
 644                                         out := out[row*cols:]
 645                                         outcol := 0
 646                                         for col, v := range cgs[name].Variants {
 647                                                 tag := tagstart + tagID(col/2)
 648                                                 if mask != nil && reftile[tag] == nil || (cmd.filter.MaxTag >= 0 && tag > tagID(cmd.filter.MaxTag)) {
 649                                                         continue
 650                                                 }
 651                                                 if variants, ok := seq[tag]; ok && len(variants) > int(v) && len(variants[v].Sequence) > 0 {
 652                                                         out[outcol] = int16(variantRemap[tag-tagstart][v])
 653                                                 } else {
 654                                                         out[outcol] = -1
 655                                                 }
 656                                                 outcol++
 657                                         }
 658                                 }
 659                                 seq = nil
 660                                 cgs = nil
 661                                 debug.FreeOSMemory()
 662                                 throttleNumpyMem.Release()
 663                                 if *mergeOutput || *hgvsSingle {
 664                                         log.Infof("%04d: matrix fragment %d rows x %d cols", infileIdx, rows, cols)
 665                                         toMerge[infileIdx] = out
 666                                 }
 667                                 if !*mergeOutput && !*onehotChunked && !*onehotSingle {
 668                                         fnm := fmt.Sprintf("%s/matrix.%04d.npy", *outputDir, infileIdx)
 669                                         err = writeNumpyInt16(fnm, out, rows, cols)
 670                                         if err != nil {
 671                                                 return err
 672                                         }
 673                                 }
 674                         }
 675                         debug.FreeOSMemory()
 676                         log.Infof("%s: done (%d/%d)", infile, int(atomic.AddInt64(&done, 1)), len(infiles))
 677                         return nil
 678                 })
 679         }
 680         if err = throttleMem.Wait(); err != nil {
 681                 return 1
 682         }
 683
 684         if *hgvsChunked {
 685                 log.Info("flushing hgvsCols temp files")
 686                 for seqname := range refseq {
 687                         close(encodeHGVSTodo[seqname])
 688                 }
 689                 err = encodeHGVS.Wait()
 690                 if err != nil {
 691                         return 1
 692                 }
 693                 for seqname := range refseq {
 694                         log.Infof("%s: reading hgvsCols from temp file", seqname)
 695                         f := tmpHGVSCols[seqname]
 696                         _, err = f.Seek(0, io.SeekStart)
 697                         if err != nil {
 698                                 return 1
 699                         }
 700                         var hgvsCols hgvsColSet
 701                         dec := gob.NewDecoder(bufio.NewReaderSize(f, 1<<24))
 702                         for err == nil {
 703                                 err = dec.Decode(&hgvsCols)
 704                         }
 705                         if err != io.EOF {
 706                                 return 1
 707                         }
 708                         log.Infof("%s: sorting %d hgvs variants", seqname, len(hgvsCols))
 709                         variants := make([]hgvs.Variant, 0, len(hgvsCols))
 710                         for v := range hgvsCols {
 711                                 variants = append(variants, v)
 712                         }
 713                         sort.Slice(variants, func(i, j int) bool {
 714                                 vi, vj := &variants[i], &variants[j]
 715                                 if vi.Position != vj.Position {
 716                                         return vi.Position < vj.Position
 717                                 } else if vi.Ref != vj.Ref {
 718                                         return vi.Ref < vj.Ref
 719                                 } else {
 720                                         return vi.New < vj.New
 721                                 }
 722                         })
 723                         rows := len(cmd.cgnames)
 724                         cols := len(variants) * 2
 725                         log.Infof("%s: building hgvs matrix (rows=%d, cols=%d, mem=%d)", seqname, rows, cols, rows*cols)
 726                         out := make([]int8, rows*cols)
 727                         for varIdx, variant := range variants {
 728                                 hgvsCols := hgvsCols[variant]
 729                                 for row := range cmd.cgnames {
 730                                         for ph := 0; ph < 2; ph++ {
 731                                                 out[row*cols+varIdx+ph] = hgvsCols[ph][row]
 732                                         }
 733                                 }
 734                         }
 735                         err = writeNumpyInt8(fmt.Sprintf("%s/hgvs.%s.npy", *outputDir, seqname), out, rows, cols)
 736                         if err != nil {
 737                                 return 1
 738                         }
 739                         out = nil
 740
 741                         fnm := fmt.Sprintf("%s/hgvs.%s.annotations.csv", *outputDir, seqname)
 742                         log.Infof("%s: writing hgvs column labels to %s", seqname, fnm)
 743                         var hgvsLabels bytes.Buffer
 744                         for varIdx, variant := range variants {
 745                                 fmt.Fprintf(&hgvsLabels, "%d,%s:g.%s\n", varIdx, seqname, variant.String())
 746                         }
 747                         err = ioutil.WriteFile(fnm, hgvsLabels.Bytes(), 0666)
 748                         if err != nil {
 749                                 return 1
 750                         }
 751                 }
 752         }
 753
 754         if *mergeOutput || *hgvsSingle {
 755                 var annow *bufio.Writer
 756                 var annof *os.File
 757                 if *mergeOutput {
 758                         annoFilename := fmt.Sprintf("%s/matrix.annotations.csv", *outputDir)
 759                         annof, err = os.Create(annoFilename)
 760                         if err != nil {
 761                                 return 1
 762                         }
 763                         annow = bufio.NewWriterSize(annof, 1<<20)
 764                 }
 765
 766                 rows := len(cmd.cgnames)
 767                 cols := 0
 768                 for _, chunk := range toMerge {
 769                         cols += len(chunk) / rows
 770                 }
 771                 log.Infof("merging output matrix (rows=%d, cols=%d, mem=%d) and annotations", rows, cols, rows*cols*2)
 772                 var out []int16
 773                 if *mergeOutput {
 774                         out = make([]int16, rows*cols)
 775                 }
 776                 hgvsCols := map[string][2][]int16{} // hgvs -> [[g0,g1,g2,...], [g0,g1,g2,...]] (slice of genomes for each phase)
 777                 startcol := 0
 778                 for outIdx, chunk := range toMerge {
 779                         chunkcols := len(chunk) / rows
 780                         if *mergeOutput {
 781                                 for row := 0; row < rows; row++ {
 782                                         copy(out[row*cols+startcol:], chunk[row*chunkcols:(row+1)*chunkcols])
 783                                 }
 784                         }
 785                         toMerge[outIdx] = nil
 786
 787                         annotationsFilename := fmt.Sprintf("%s/matrix.%04d.annotations.csv", *outputDir, outIdx)
 788                         log.Infof("reading %s", annotationsFilename)
 789                         buf, err := os.ReadFile(annotationsFilename)
 790                         if err != nil {
 791                                 return 1
 792                         }
 793                         if *mergeOutput {
 794                                 err = os.Remove(annotationsFilename)
 795                                 if err != nil {
 796                                         return 1
 797                                 }
 798                         }
 799                         for _, line := range bytes.Split(buf, []byte{'\n'}) {
 800                                 if len(line) == 0 {
 801                                         continue
 802                                 }
 803                                 fields := bytes.SplitN(line, []byte{','}, 9)
 804                                 tag, _ := strconv.Atoi(string(fields[0]))
 805                                 incol, _ := strconv.Atoi(string(fields[1]))
 806                                 tileVariant, _ := strconv.Atoi(string(fields[2]))
 807                                 hgvsID := string(fields[3])
 808                                 seqname := string(fields[4])
 809                                 pos, _ := strconv.Atoi(string(fields[5]))
 810                                 refseq := fields[6]
 811                                 if hgvsID == "" {
 812                                         // Null entry for un-diffable
 813                                         // tile variant
 814                                         continue
 815                                 }
 816                                 if hgvsID == "=" {
 817                                         // Null entry for ref tile
 818                                         continue
 819                                 }
 820                                 if mask != nil && !mask.Check(strings.TrimPrefix(seqname, "chr"), pos, pos+len(refseq)) {
 821                                         // The tile intersects one of
 822                                         // the selected regions, but
 823                                         // this particular HGVS
 824                                         // variant does not.
 825                                         continue
 826                                 }
 827                                 hgvsColPair := hgvsCols[hgvsID]
 828                                 if hgvsColPair[0] == nil {
 829                                         // values in new columns start
 830                                         // out as -1 ("no data yet")
 831                                         // or 0 ("=ref") here, may
 832                                         // change to 1 ("hgvs variant
 833                                         // present") below, either on
 834                                         // this line or a future line.
 835                                         hgvsColPair = [2][]int16{make([]int16, len(cmd.cgnames)), make([]int16, len(cmd.cgnames))}
 836                                         rt, ok := reftile[tagID(tag)]
 837                                         if !ok {
 838                                                 err = fmt.Errorf("bug: seeing annotations for tag %d, but it has no reftile entry", tag)
 839                                                 return 1
 840                                         }
 841                                         for ph := 0; ph < 2; ph++ {
 842                                                 for row := 0; row < rows; row++ {
 843                                                         v := chunk[row*chunkcols+incol*2+ph]
 844                                                         if tileVariantID(v) == rt.variant {
 845                                                                 hgvsColPair[ph][row] = 0
 846                                                         } else {
 847                                                                 hgvsColPair[ph][row] = -1
 848                                                         }
 849                                                 }
 850                                         }
 851                                         hgvsCols[hgvsID] = hgvsColPair
 852                                         if annow != nil {
 853                                                 hgvsref := hgvs.Variant{
 854                                                         Position: pos,
 855                                                         Ref:      string(refseq),
 856                                                         New:      string(refseq),
 857                                                 }
 858                                                 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])
 859                                         }
 860                                 }
 861                                 if annow != nil {
 862                                         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])
 863                                 }
 864                                 for ph := 0; ph < 2; ph++ {
 865                                         for row := 0; row < rows; row++ {
 866                                                 v := chunk[row*chunkcols+incol*2+ph]
 867                                                 if int(v) == tileVariant {
 868                                                         hgvsColPair[ph][row] = 1
 869                                                 }
 870                                         }
 871                                 }
 872                         }
 873
 874                         startcol += chunkcols
 875                 }
 876                 if *mergeOutput {
 877                         err = annow.Flush()
 878                         if err != nil {
 879                                 return 1
 880                         }
 881                         err = annof.Close()
 882                         if err != nil {
 883                                 return 1
 884                         }
 885                         err = writeNumpyInt16(fmt.Sprintf("%s/matrix.npy", *outputDir), out, rows, cols)
 886                         if err != nil {
 887                                 return 1
 888                         }
 889                 }
 890                 out = nil
 891
 892                 if *hgvsSingle {
 893                         cols = len(hgvsCols) * 2
 894                         log.Printf("building hgvs-based matrix: %d rows x %d cols", rows, cols)
 895                         out = make([]int16, rows*cols)
 896                         hgvsIDs := make([]string, 0, cols/2)
 897                         for hgvsID := range hgvsCols {
 898                                 hgvsIDs = append(hgvsIDs, hgvsID)
 899                         }
 900                         sort.Strings(hgvsIDs)
 901                         var hgvsLabels bytes.Buffer
 902                         for idx, hgvsID := range hgvsIDs {
 903                                 fmt.Fprintf(&hgvsLabels, "%d,%s\n", idx, hgvsID)
 904                                 for ph := 0; ph < 2; ph++ {
 905                                         hgvscol := hgvsCols[hgvsID][ph]
 906                                         for row, val := range hgvscol {
 907                                                 out[row*cols+idx*2+ph] = val
 908                                         }
 909                                 }
 910                         }
 911                         err = writeNumpyInt16(fmt.Sprintf("%s/hgvs.npy", *outputDir), out, rows, cols)
 912                         if err != nil {
 913                                 return 1
 914                         }
 915
 916                         fnm := fmt.Sprintf("%s/hgvs.annotations.csv", *outputDir)
 917                         log.Printf("writing hgvs labels: %s", fnm)
 918                         err = ioutil.WriteFile(fnm, hgvsLabels.Bytes(), 0777)
 919                         if err != nil {
 920                                 return 1
 921                         }
 922                 }
 923         }
 924         if *onehotSingle {
 925                 nzCount := 0
 926                 for _, part := range onehotIndirect {
 927                         nzCount += len(part[0])
 928                 }
 929                 onehot := make([]uint32, nzCount*2) // [r,r,r,...,c,c,c,...]
 930                 var xrefs []onehotXref
 931                 chunkOffset := uint32(0)
 932                 outcol := 0
 933                 for i, part := range onehotIndirect {
 934                         for i := range part[1] {
 935                                 part[1][i] += chunkOffset
 936                         }
 937                         copy(onehot[outcol:], part[0])
 938                         copy(onehot[outcol+nzCount:], part[1])
 939                         xrefs = append(xrefs, onehotXrefs[i]...)
 940
 941                         outcol += len(part[0])
 942                         chunkOffset += onehotChunkSize[i]
 943
 944                         part[0] = nil
 945                         part[1] = nil
 946                         onehotXrefs[i] = nil
 947                         debug.FreeOSMemory()
 948                 }
 949                 fnm := fmt.Sprintf("%s/onehot.npy", *outputDir)
 950                 err = writeNumpyUint32(fnm, onehot, 2, nzCount)
 951                 if err != nil {
 952                         return 1
 953                 }
 954                 fnm = fmt.Sprintf("%s/onehot-columns.npy", *outputDir)
 955                 err = writeNumpyInt32(fnm, onehotXref2int32(xrefs), 4, len(xrefs))
 956                 if err != nil {
 957                         return 1
 958                 }
 959         }
 960         return 0
 961 }
 962
 963 // Read case/control files, remove non-case/control entries from
 964 // cmd.cgnames, and build cmd.chi2Cases.
 965 func (cmd *sliceNumpy) useCaseControlFiles() error {
 966         if cmd.chi2CaseControlFile == "" {
 967                 return nil
 968         }
 969         infiles, err := allFiles(cmd.chi2CaseControlFile, nil)
 970         if err != nil {
 971                 return err
 972         }
 973         // index in cmd.cgnames => case(true) / control(false)
 974         cc := map[int]bool{}
 975         for _, infile := range infiles {
 976                 f, err := open(infile)
 977                 if err != nil {
 978                         return err
 979                 }
 980                 buf, err := io.ReadAll(f)
 981                 f.Close()
 982                 if err != nil {
 983                         return err
 984                 }
 985                 ccCol := -1
 986                 for _, tsv := range bytes.Split(buf, []byte{'\n'}) {
 987                         if len(tsv) == 0 {
 988                                 continue
 989                         }
 990                         split := strings.Split(string(tsv), "\t")
 991                         if ccCol < 0 {
 992                                 // header row
 993                                 for col, name := range split {
 994                                         if name == cmd.chi2CaseControlColumn {
 995                                                 ccCol = col
 996                                                 break
 997                                         }
 998                                 }
 999                                 if ccCol < 0 {
1000                                         return fmt.Errorf("%s: no column named %q in header row %q", infile, cmd.chi2CaseControlColumn, tsv)
1001                                 }
1002                                 continue
1003                         }
1004                         if len(split) <= ccCol {
1005                                 continue
1006                         }
1007                         pattern := split[0]
1008                         found := -1
1009                         for i, name := range cmd.cgnames {
1010                                 if strings.Contains(name, pattern) {
1011                                         if found >= 0 {
1012                                                 log.Warnf("pattern %q in %s matches multiple genome IDs (%qs, %q)", pattern, infile, cmd.cgnames[found], name)
1013                                         }
1014                                         found = i
1015                                 }
1016                         }
1017                         if found < 0 {
1018                                 log.Warnf("pattern %q in %s does not match any genome IDs", pattern, infile)
1019                                 continue
1020                         }
1021                         if split[ccCol] == "0" {
1022                                 cc[found] = false
1023                         }
1024                         if split[ccCol] == "1" {
1025                                 cc[found] = true
1026                         }
1027                 }
1028         }
1029         allnames := cmd.cgnames
1030         cmd.cgnames = nil
1031         cmd.chi2Cases = nil
1032         ncases := 0
1033         for i, name := range allnames {
1034                 if cc, ok := cc[i]; ok {
1035                         cmd.cgnames = append(cmd.cgnames, name)
1036                         cmd.chi2Cases = append(cmd.chi2Cases, cc)
1037                         if cc {
1038                                 ncases++
1039                         }
1040                 }
1041         }
1042         log.Printf("%d cases, %d controls, %d neither (dropped)", ncases, len(cmd.cgnames)-ncases, len(allnames)-len(cmd.cgnames))
1043         return nil
1044 }
1045
1046 func (cmd *sliceNumpy) filterHGVScolpair(colpair [2][]int8) bool {
1047         if cmd.chi2PValue >= 1 {
1048                 return true
1049         }
1050         col0 := make([]bool, 0, len(cmd.chi2Cases))
1051         col1 := make([]bool, 0, len(cmd.chi2Cases))
1052         cases := make([]bool, 0, len(cmd.chi2Cases))
1053         for i, c := range cmd.chi2Cases {
1054                 if colpair[0][i] < 0 {
1055                         continue
1056                 }
1057                 col0 = append(col0, colpair[0][i] != 0)
1058                 col1 = append(col1, colpair[1][i] != 0)
1059                 cases = append(cases, c)
1060         }
1061         return len(cases) >= cmd.minCoverage &&
1062                 (pvalue(col0, cases) <= cmd.chi2PValue || pvalue(col1, cases) <= cmd.chi2PValue)
1063 }
1064
1065 func writeNumpyUint32(fnm string, out []uint32, 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 * 4,
1081         }).Infof("writing numpy: %s", fnm)
1082         npw.Shape = []int{rows, cols}
1083         npw.WriteUint32(out)
1084         err = bufw.Flush()
1085         if err != nil {
1086                 return err
1087         }
1088         return output.Close()
1089 }
1090
1091 func writeNumpyInt32(fnm string, out []int32, rows, cols int) error {
1092         output, err := os.Create(fnm)
1093         if err != nil {
1094                 return err
1095         }
1096         defer output.Close()
1097         bufw := bufio.NewWriterSize(output, 1<<26)
1098         npw, err := gonpy.NewWriter(nopCloser{bufw})
1099         if err != nil {
1100                 return err
1101         }
1102         log.WithFields(log.Fields{
1103                 "filename": fnm,
1104                 "rows":     rows,
1105                 "cols":     cols,
1106                 "bytes":    rows * cols * 4,
1107         }).Infof("writing numpy: %s", fnm)
1108         npw.Shape = []int{rows, cols}
1109         npw.WriteInt32(out)
1110         err = bufw.Flush()
1111         if err != nil {
1112                 return err
1113         }
1114         return output.Close()
1115 }
1116
1117 func writeNumpyInt16(fnm string, out []int16, rows, cols int) error {
1118         output, err := os.Create(fnm)
1119         if err != nil {
1120                 return err
1121         }
1122         defer output.Close()
1123         bufw := bufio.NewWriterSize(output, 1<<26)
1124         npw, err := gonpy.NewWriter(nopCloser{bufw})
1125         if err != nil {
1126                 return err
1127         }
1128         log.WithFields(log.Fields{
1129                 "filename": fnm,
1130                 "rows":     rows,
1131                 "cols":     cols,
1132                 "bytes":    rows * cols * 2,
1133         }).Infof("writing numpy: %s", fnm)
1134         npw.Shape = []int{rows, cols}
1135         npw.WriteInt16(out)
1136         err = bufw.Flush()
1137         if err != nil {
1138                 return err
1139         }
1140         return output.Close()
1141 }
1142
1143 func writeNumpyInt8(fnm string, out []int8, rows, cols int) error {
1144         output, err := os.Create(fnm)
1145         if err != nil {
1146                 return err
1147         }
1148         defer output.Close()
1149         bufw := bufio.NewWriterSize(output, 1<<26)
1150         npw, err := gonpy.NewWriter(nopCloser{bufw})
1151         if err != nil {
1152                 return err
1153         }
1154         log.WithFields(log.Fields{
1155                 "filename": fnm,
1156                 "rows":     rows,
1157                 "cols":     cols,
1158                 "bytes":    rows * cols,
1159         }).Infof("writing numpy: %s", fnm)
1160         npw.Shape = []int{rows, cols}
1161         npw.WriteInt8(out)
1162         err = bufw.Flush()
1163         if err != nil {
1164                 return err
1165         }
1166         return output.Close()
1167 }
1168
1169 func allele2homhet(colpair [2][]int8) {
1170         a, b := colpair[0], colpair[1]
1171         for i, av := range a {
1172                 bv := b[i]
1173                 if av < 0 || bv < 0 {
1174                         // no-call
1175                         a[i], b[i] = -1, -1
1176                 } else if av > 0 && bv > 0 {
1177                         // hom
1178                         a[i], b[i] = 1, 0
1179                 } else if av > 0 || bv > 0 {
1180                         // het
1181                         a[i], b[i] = 0, 1
1182                 } else {
1183                         // ref (or a different variant in same position)
1184                         // (this is a no-op) a[i], b[i] = 0, 0
1185                 }
1186         }
1187 }
1188
1189 type onehotXref struct {
1190         tag     tagID
1191         variant tileVariantID
1192         het     bool
1193         pvalue  float64
1194 }
1195
1196 const onehotXrefSize = unsafe.Sizeof(onehotXref{})
1197
1198 // Build onehot matrix (m[tileVariantIndex][genome] == 0 or 1) for all
1199 // variants of a single tile/tag#.
1200 //
1201 // Return nil if no tile variant passes Χ² filter.
1202 func (cmd *sliceNumpy) tv2homhet(cgs map[string]CompactGenome, maxv tileVariantID, remap []tileVariantID, tag, chunkstarttag tagID) ([][]int8, []onehotXref) {
1203         if maxv < 1 || (maxv < 2 && !cmd.includeVariant1) {
1204                 // everyone has the most common variant (of the variants we don't drop)
1205                 return nil, nil
1206         }
1207         tagoffset := tag - chunkstarttag
1208         coverage := 0
1209         for _, cg := range cgs {
1210                 if cg.Variants[tagoffset*2] > 0 && cg.Variants[tagoffset*2+1] > 0 {
1211                         coverage++
1212                 }
1213         }
1214         if coverage < cmd.minCoverage {
1215                 return nil, nil
1216         }
1217         obs := make([][]bool, (maxv+1)*2) // 2 slices (hom + het) for each variant#
1218         for i := range obs {
1219                 obs[i] = make([]bool, len(cmd.cgnames))
1220         }
1221         for cgid, name := range cmd.cgnames {
1222                 cgvars := cgs[name].Variants[tagoffset*2:]
1223                 tv0, tv1 := remap[cgvars[0]], remap[cgvars[1]]
1224                 for v := tileVariantID(1); v <= maxv; v++ {
1225                         if tv0 == v && tv1 == v {
1226                                 obs[v*2][cgid] = true
1227                         } else if tv0 == v || tv1 == v {
1228                                 obs[v*2+1][cgid] = true
1229                         }
1230                 }
1231         }
1232         var onehot [][]int8
1233         var xref []onehotXref
1234         for col := 2; col < len(obs); col++ {
1235                 // col 0,1 correspond to tile variant 0, i.e.,
1236                 // no-call; col 2,3 correspond to the most common
1237                 // variant; so we (normally) start at col 4.
1238                 if col < 4 && !cmd.includeVariant1 {
1239                         continue
1240                 }
1241                 p := pvalue(obs[col], cmd.chi2Cases)
1242                 if cmd.chi2PValue < 1 && !(p < cmd.chi2PValue) {
1243                         continue
1244                 }
1245                 onehot = append(onehot, bool2int8(obs[col]))
1246                 xref = append(xref, onehotXref{
1247                         tag:     tag,
1248                         variant: tileVariantID(col >> 1),
1249                         het:     col&1 == 1,
1250                         pvalue:  p,
1251                 })
1252         }
1253         return onehot, xref
1254 }
1255
1256 func bool2int8(in []bool) []int8 {
1257         out := make([]int8, len(in))
1258         for i, v := range in {
1259                 if v {
1260                         out[i] = 1
1261                 }
1262         }
1263         return out
1264 }
1265
1266 // convert a []onehotXref with length N to a numpy-style []int32
1267 // matrix with N columns, one row per field of onehotXref struct.
1268 //
1269 // Hom/het row contains hom=0, het=1.
1270 //
1271 // P-value row contains 1000000x actual p-value.
1272 func onehotXref2int32(xrefs []onehotXref) []int32 {
1273         xcols := len(xrefs)
1274         xdata := make([]int32, 4*xcols)
1275         for i, xref := range xrefs {
1276                 xdata[i] = int32(xref.tag)
1277                 xdata[xcols+i] = int32(xref.variant)
1278                 if xref.het {
1279                         xdata[xcols*2+i] = 1
1280                 }
1281                 xdata[xcols*3+i] = int32(xref.pvalue * 1000000)
1282         }
1283         return xdata
1284 }
1285
1286 // transpose onehot data from in[col][row] to numpy-style
1287 // out[row*cols+col].
1288 func onehotcols2int8(in [][]int8) []int8 {
1289         if len(in) == 0 {
1290                 return nil
1291         }
1292         cols := len(in)
1293         rows := len(in[0])
1294         out := make([]int8, rows*cols)
1295         for row := 0; row < rows; row++ {
1296                 outrow := out[row*cols:]
1297                 for col, incol := range in {
1298                         outrow[col] = incol[row]
1299                 }
1300         }
1301         return out
1302 }
1303
1304 // Return [2][]uint32{rowIndices, colIndices} indicating which
1305 // elements of matrixT[c][r] have non-zero values.
1306 func onehotChunk2Indirect(matrixT [][]int8) [2][]uint32 {
1307         var nz [2][]uint32
1308         for c, col := range matrixT {
1309                 for r, val := range col {
1310                         if val != 0 {
1311                                 nz[0] = append(nz[0], uint32(r))
1312                                 nz[1] = append(nz[1], uint32(c))
1313                         }
1314                 }
1315         }
1316         return nz
1317 }