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         "github.com/sirupsen/logrus"
  32         log "github.com/sirupsen/logrus"
  33         "golang.org/x/crypto/blake2b"
  34 )
  35
  36 type sliceNumpy struct {
  37         filter                filter
  38         threads               int
  39         chi2CaseControlColumn string
  40         chi2CaseControlFile   string
  41         chi2Cases             []bool
  42         chi2PValue            float64
  43         minCoverage           int
  44         cgnames               []string
  45         includeVariant1       bool
  46         debugTag              tagID
  47 }
  48
  49 func (cmd *sliceNumpy) RunCommand(prog string, args []string, stdin io.Reader, stdout, stderr io.Writer) int {
  50         var err error
  51         defer func() {
  52                 if err != nil {
  53                         fmt.Fprintf(stderr, "%s\n", err)
  54                 }
  55         }()
  56         flags := flag.NewFlagSet("", flag.ContinueOnError)
  57         flags.SetOutput(stderr)
  58         pprof := flags.String("pprof", "", "serve Go profile data at http://`[addr]:port`")
  59         runlocal := flags.Bool("local", false, "run on local host (default: run in an arvados container)")
  60         projectUUID := flags.String("project", "", "project `UUID` for output data")
  61         priority := flags.Int("priority", 500, "container request priority")
  62         inputDir := flags.String("input-dir", "./in", "input `directory`")
  63         outputDir := flags.String("output-dir", "./out", "output `directory`")
  64         ref := flags.String("ref", "", "reference name (if blank, choose last one that appears in input)")
  65         regionsFilename := flags.String("regions", "", "only output columns/annotations that intersect regions in specified bed `file`")
  66         expandRegions := flags.Int("expand-regions", 0, "expand specified regions by `N` base pairs on each side`")
  67         mergeOutput := flags.Bool("merge-output", false, "merge output into one matrix.npy and one matrix.annotations.csv")
  68         hgvsSingle := flags.Bool("single-hgvs-matrix", false, "also generate hgvs-based matrix")
  69         hgvsChunked := flags.Bool("chunked-hgvs-matrix", false, "also generate hgvs-based matrix per chromosome")
  70         onehotSingle := flags.Bool("single-onehot", false, "generate one-hot tile-based matrix")
  71         onehotChunked := flags.Bool("chunked-onehot", false, "generate one-hot tile-based matrix per input chunk")
  72         debugTag := flags.Int("debug-tag", -1, "log debugging details about specified tag")
  73         flags.IntVar(&cmd.threads, "threads", 16, "number of memory-hungry assembly threads")
  74         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)")
  75         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)")
  76         flags.Float64Var(&cmd.chi2PValue, "chi2-p-value", 1, "do Χ² test and omit columns with p-value above this threshold")
  77         flags.BoolVar(&cmd.includeVariant1, "include-variant-1", false, "include most common variant when building one-hot matrix")
  78         cmd.filter.Flags(flags)
  79         err = flags.Parse(args)
  80         if err == flag.ErrHelp {
  81                 err = nil
  82                 return 0
  83         } else if err != nil {
  84                 return 2
  85         }
  86
  87         if *pprof != "" {
  88                 go func() {
  89                         log.Println(http.ListenAndServe(*pprof, nil))
  90                 }()
  91         }
  92
  93         if cmd.chi2PValue != 1 && (cmd.chi2CaseControlFile == "" || cmd.chi2CaseControlColumn == "") {
  94                 log.Errorf("cannot use provided -chi2-p-value=%f because -chi2-case-control-file= or -chi2-case-control-column= value is empty", cmd.chi2PValue)
  95                 return 2
  96         }
  97
  98         cmd.debugTag = tagID(*debugTag)
  99
 100         if !*runlocal {
 101                 runner := arvadosContainerRunner{
 102                         Name:        "lightning slice-numpy",
 103                         Client:      arvados.NewClientFromEnv(),
 104                         ProjectUUID: *projectUUID,
 105                         RAM:         750000000000,
 106                         VCPUs:       96,
 107                         Priority:    *priority,
 108                         KeepCache:   2,
 109                         APIAccess:   true,
 110                 }
 111                 err = runner.TranslatePaths(inputDir, regionsFilename, &cmd.chi2CaseControlFile)
 112                 if err != nil {
 113                         return 1
 114                 }
 115                 runner.Args = []string{"slice-numpy", "-local=true",
 116                         "-pprof=:6060",
 117                         "-input-dir=" + *inputDir,
 118                         "-output-dir=/mnt/output",
 119                         "-threads=" + fmt.Sprintf("%d", cmd.threads),
 120                         "-regions=" + *regionsFilename,
 121                         "-expand-regions=" + fmt.Sprintf("%d", *expandRegions),
 122                         "-merge-output=" + fmt.Sprintf("%v", *mergeOutput),
 123                         "-single-hgvs-matrix=" + fmt.Sprintf("%v", *hgvsSingle),
 124                         "-chunked-hgvs-matrix=" + fmt.Sprintf("%v", *hgvsChunked),
 125                         "-single-onehot=" + fmt.Sprintf("%v", *onehotSingle),
 126                         "-chunked-onehot=" + fmt.Sprintf("%v", *onehotChunked),
 127                         "-chi2-case-control-file=" + cmd.chi2CaseControlFile,
 128                         "-chi2-case-control-column=" + cmd.chi2CaseControlColumn,
 129                         "-chi2-p-value=" + fmt.Sprintf("%f", cmd.chi2PValue),
 130                         "-include-variant-1=" + fmt.Sprintf("%v", cmd.includeVariant1),
 131                         "-debug-tag=" + fmt.Sprintf("%d", cmd.debugTag),
 132                 }
 133                 runner.Args = append(runner.Args, cmd.filter.Args()...)
 134                 var output string
 135                 output, err = runner.Run()
 136                 if err != nil {
 137                         return 1
 138                 }
 139                 fmt.Fprintln(stdout, output)
 140                 return 0
 141         }
 142
 143         infiles, err := allFiles(*inputDir, matchGobFile)
 144         if err != nil {
 145                 return 1
 146         }
 147         if len(infiles) == 0 {
 148                 err = fmt.Errorf("no input files found in %s", *inputDir)
 149                 return 1
 150         }
 151         sort.Strings(infiles)
 152
 153         var refseq map[string][]tileLibRef
 154         var reftiledata = make(map[tileLibRef][]byte, 11000000)
 155         in0, err := open(infiles[0])
 156         if err != nil {
 157                 return 1
 158         }
 159
 160         matchGenome, err := regexp.Compile(cmd.filter.MatchGenome)
 161         if err != nil {
 162                 err = fmt.Errorf("-match-genome: invalid regexp: %q", cmd.filter.MatchGenome)
 163                 return 1
 164         }
 165
 166         cmd.cgnames = nil
 167         var tagset [][]byte
 168         DecodeLibrary(in0, strings.HasSuffix(infiles[0], ".gz"), func(ent *LibraryEntry) error {
 169                 if len(ent.TagSet) > 0 {
 170                         tagset = ent.TagSet
 171                 }
 172                 for _, cseq := range ent.CompactSequences {
 173                         if cseq.Name == *ref || *ref == "" {
 174                                 refseq = cseq.TileSequences
 175                         }
 176                 }
 177                 for _, cg := range ent.CompactGenomes {
 178                         if matchGenome.MatchString(cg.Name) {
 179                                 cmd.cgnames = append(cmd.cgnames, cg.Name)
 180                         }
 181                 }
 182                 for _, tv := range ent.TileVariants {
 183                         if tv.Ref {
 184                                 reftiledata[tileLibRef{tv.Tag, tv.Variant}] = tv.Sequence
 185                         }
 186                 }
 187                 return nil
 188         })
 189         if err != nil {
 190                 return 1
 191         }
 192         in0.Close()
 193         if refseq == nil {
 194                 err = fmt.Errorf("%s: reference sequence not found", infiles[0])
 195                 return 1
 196         }
 197         if len(tagset) == 0 {
 198                 err = fmt.Errorf("tagset not found")
 199                 return 1
 200         }
 201
 202         taglib := &tagLibrary{}
 203         err = taglib.setTags(tagset)
 204         if err != nil {
 205                 return 1
 206         }
 207         taglen := taglib.TagLen()
 208
 209         if len(cmd.cgnames) == 0 {
 210                 err = fmt.Errorf("no genomes found matching regexp %q", cmd.filter.MatchGenome)
 211                 return 1
 212         }
 213         sort.Strings(cmd.cgnames)
 214         err = cmd.useCaseControlFiles()
 215         if err != nil {
 216                 return 1
 217         }
 218         cmd.minCoverage = int(math.Ceil(cmd.filter.MinCoverage * float64(len(cmd.cgnames))))
 219
 220         {
 221                 labelsFilename := *outputDir + "/samples.csv"
 222                 log.Infof("writing labels to %s", labelsFilename)
 223                 var f *os.File
 224                 f, err = os.Create(labelsFilename)
 225                 if err != nil {
 226                         return 1
 227                 }
 228                 defer f.Close()
 229                 for i, name := range cmd.cgnames {
 230                         cc := 0
 231                         if cmd.chi2Cases != nil && cmd.chi2Cases[i] {
 232                                 cc = 1
 233                         }
 234                         _, err = fmt.Fprintf(f, "%d,%q,%d\n", i, trimFilenameForLabel(name), cc)
 235                         if err != nil {
 236                                 err = fmt.Errorf("write %s: %w", labelsFilename, err)
 237                                 return 1
 238                         }
 239                 }
 240                 err = f.Close()
 241                 if err != nil {
 242                         err = fmt.Errorf("close %s: %w", labelsFilename, err)
 243                         return 1
 244                 }
 245         }
 246
 247         log.Info("indexing reference tiles")
 248         type reftileinfo struct {
 249                 variant  tileVariantID
 250                 seqname  string // chr1
 251                 pos      int    // distance from start of chromosome to starttag
 252                 tiledata []byte // acgtggcaa...
 253         }
 254         isdup := map[tagID]bool{}
 255         reftile := map[tagID]*reftileinfo{}
 256         for seqname, cseq := range refseq {
 257                 pos := 0
 258                 for _, libref := range cseq {
 259                         if cmd.filter.MaxTag >= 0 && libref.Tag > tagID(cmd.filter.MaxTag) {
 260                                 continue
 261                         }
 262                         tiledata := reftiledata[libref]
 263                         if len(tiledata) == 0 {
 264                                 err = fmt.Errorf("missing tiledata for tag %d variant %d in %s in ref", libref.Tag, libref.Variant, seqname)
 265                                 return 1
 266                         }
 267                         foundthistag := false
 268                         taglib.FindAll(tiledata[:len(tiledata)-1], func(tagid tagID, offset, _ int) {
 269                                 if !foundthistag && tagid == libref.Tag {
 270                                         foundthistag = true
 271                                         return
 272                                 }
 273                                 if dupref, ok := reftile[tagid]; ok {
 274                                         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)
 275                                         delete(reftile, tagid)
 276                                 } else {
 277                                         log.Printf("found tag %d at offset %d inside tile variant %+v on %s @ %d", tagid, offset, libref, seqname, pos+offset+1)
 278                                 }
 279                                 isdup[tagid] = true
 280                         })
 281                         if isdup[libref.Tag] {
 282                                 log.Printf("dropping reference tile %+v from %s @ %d, tag not unique", libref, seqname, pos)
 283                         } else if reftile[libref.Tag] != nil {
 284                                 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)
 285                                 delete(reftile, libref.Tag)
 286                                 log.Printf("dropping reference tile %+v from %s @ %d, tag not unique", libref, seqname, pos)
 287                                 isdup[libref.Tag] = true
 288                         } else {
 289                                 reftile[libref.Tag] = &reftileinfo{
 290                                         seqname:  seqname,
 291                                         variant:  libref.Variant,
 292                                         tiledata: tiledata,
 293                                         pos:      pos,
 294                                 }
 295                         }
 296                         pos += len(tiledata) - taglen
 297                 }
 298                 log.Printf("... %s done, len %d", seqname, pos+taglen)
 299         }
 300
 301         var mask *mask
 302         if *regionsFilename != "" {
 303                 log.Printf("loading regions from %s", *regionsFilename)
 304                 mask, err = makeMask(*regionsFilename, *expandRegions)
 305                 if err != nil {
 306                         return 1
 307                 }
 308                 log.Printf("before applying mask, len(reftile) == %d", len(reftile))
 309                 log.Printf("deleting reftile entries for regions outside %d intervals", mask.Len())
 310                 for tag, rt := range reftile {
 311                         if !mask.Check(strings.TrimPrefix(rt.seqname, "chr"), rt.pos, rt.pos+len(rt.tiledata)) {
 312                                 delete(reftile, tag)
 313                         }
 314                 }
 315                 log.Printf("after applying mask, len(reftile) == %d", len(reftile))
 316         }
 317
 318         type hgvsColSet map[hgvs.Variant][2][]int8
 319         encodeHGVS := throttle{Max: len(refseq)}
 320         encodeHGVSTodo := map[string]chan hgvsColSet{}
 321         tmpHGVSCols := map[string]*os.File{}
 322         if *hgvsChunked {
 323                 for seqname := range refseq {
 324                         var f *os.File
 325                         f, err = os.Create(*outputDir + "/tmp." + seqname + ".gob")
 326                         if err != nil {
 327                                 return 1
 328                         }
 329                         defer os.Remove(f.Name())
 330                         bufw := bufio.NewWriterSize(f, 1<<24)
 331                         enc := gob.NewEncoder(bufw)
 332                         tmpHGVSCols[seqname] = f
 333                         todo := make(chan hgvsColSet, 128)
 334                         encodeHGVSTodo[seqname] = todo
 335                         encodeHGVS.Go(func() error {
 336                                 for colset := range todo {
 337                                         err := enc.Encode(colset)
 338                                         if err != nil {
 339                                                 encodeHGVS.Report(err)
 340                                                 for range todo {
 341                                                 }
 342                                                 return err
 343                                         }
 344                                 }
 345                                 return bufw.Flush()
 346                         })
 347                 }
 348         }
 349
 350         var toMerge [][]int16
 351         if *mergeOutput || *hgvsSingle {
 352                 toMerge = make([][]int16, len(infiles))
 353         }
 354         var onehotIndirect [][2][]uint32 // [chunkIndex][axis][index]
 355         var onehotChunkSize []uint32
 356         var onehotXrefs [][]onehotXref
 357         if *onehotSingle {
 358                 onehotIndirect = make([][2][]uint32, len(infiles))
 359                 onehotChunkSize = make([]uint32, len(infiles))
 360                 onehotXrefs = make([][]onehotXref, len(infiles))
 361         }
 362
 363         throttleMem := throttle{Max: cmd.threads} // TODO: estimate using mem and data size
 364         throttleNumpyMem := throttle{Max: cmd.threads/2 + 1}
 365         log.Info("generating annotations and numpy matrix for each slice")
 366         var done int64
 367         for infileIdx, infile := range infiles {
 368                 infileIdx, infile := infileIdx, infile
 369                 throttleMem.Go(func() error {
 370                         seq := make(map[tagID][]TileVariant, 50000)
 371                         cgs := make(map[string]CompactGenome, len(cmd.cgnames))
 372                         f, err := open(infile)
 373                         if err != nil {
 374                                 return err
 375                         }
 376                         defer f.Close()
 377                         log.Infof("%04d: reading %s", infileIdx, infile)
 378                         err = DecodeLibrary(f, strings.HasSuffix(infile, ".gz"), func(ent *LibraryEntry) error {
 379                                 for _, tv := range ent.TileVariants {
 380                                         if tv.Ref {
 381                                                 continue
 382                                         }
 383                                         if mask != nil && reftile[tv.Tag] == nil {
 384                                                 // Don't waste
 385                                                 // time/memory on
 386                                                 // masked-out tiles.
 387                                                 continue
 388                                         }
 389                                         if tv.Tag == cmd.debugTag {
 390                                                 log.Printf("infile %d %s tag %d variant %d hash %x", infileIdx, infile, tv.Tag, tv.Variant, tv.Blake2b[:3])
 391                                         }
 392                                         variants := seq[tv.Tag]
 393                                         if len(variants) == 0 {
 394                                                 variants = make([]TileVariant, 100)
 395                                         }
 396                                         for len(variants) <= int(tv.Variant) {
 397                                                 variants = append(variants, TileVariant{})
 398                                         }
 399                                         variants[int(tv.Variant)] = tv
 400                                         seq[tv.Tag] = variants
 401                                 }
 402                                 for _, cg := range ent.CompactGenomes {
 403                                         if !matchGenome.MatchString(cg.Name) {
 404                                                 continue
 405                                         }
 406                                         // pad to full slice size
 407                                         // to avoid out-of-bounds
 408                                         // checks later
 409                                         if sliceSize := 2 * int(cg.EndTag-cg.StartTag); len(cg.Variants) < sliceSize {
 410                                                 cg.Variants = append(cg.Variants, make([]tileVariantID, sliceSize-len(cg.Variants))...)
 411                                         }
 412                                         cgs[cg.Name] = cg
 413                                 }
 414                                 return nil
 415                         })
 416                         if err != nil {
 417                                 return err
 418                         }
 419                         tagstart := cgs[cmd.cgnames[0]].StartTag
 420                         tagend := cgs[cmd.cgnames[0]].EndTag
 421
 422                         // TODO: filters
 423
 424                         log.Infof("%04d: renumber/dedup variants for tags %d-%d", infileIdx, tagstart, tagend)
 425                         variantRemap := make([][]tileVariantID, tagend-tagstart)
 426                         throttleCPU := throttle{Max: runtime.GOMAXPROCS(0)}
 427                         for tag, variants := range seq {
 428                                 tag, variants := tag, variants
 429                                 throttleCPU.Acquire()
 430                                 go func() {
 431                                         defer throttleCPU.Release()
 432                                         count := make(map[[blake2b.Size256]byte]int, len(variants))
 433
 434                                         rt := reftile[tag]
 435                                         if rt != nil {
 436                                                 count[blake2b.Sum256(rt.tiledata)] = 0
 437                                         }
 438
 439                                         for cgname, cg := range cgs {
 440                                                 idx := int(tag-tagstart) * 2
 441                                                 for allele := 0; allele < 2; allele++ {
 442                                                         v := cg.Variants[idx+allele]
 443                                                         if v > 0 && len(variants[v].Sequence) > 0 {
 444                                                                 count[variants[v].Blake2b]++
 445                                                                 if tag == cmd.debugTag {
 446                                                                         log.Printf("tag %d cg %s allele %d tv %d hash %x count is now %d", tag, cgname, allele, v, variants[v].Blake2b[:3], count[variants[v].Blake2b])
 447                                                                 }
 448                                                         }
 449                                                 }
 450                                         }
 451                                         // hash[i] will be the hash of
 452                                         // the variant(s) that should
 453                                         // be at rank i (0-based).
 454                                         hash := make([][blake2b.Size256]byte, 0, len(count))
 455                                         for b := range count {
 456                                                 hash = append(hash, b)
 457                                         }
 458                                         sort.Slice(hash, func(i, j int) bool {
 459                                                 bi, bj := &hash[i], &hash[j]
 460                                                 if ci, cj := count[*bi], count[*bj]; ci != cj {
 461                                                         return ci > cj
 462                                                 } else {
 463                                                         return bytes.Compare((*bi)[:], (*bj)[:]) < 0
 464                                                 }
 465                                         })
 466                                         // rank[b] will be the 1-based
 467                                         // new variant number for
 468                                         // variants whose hash is b.
 469                                         rank := make(map[[blake2b.Size256]byte]tileVariantID, len(hash))
 470                                         for i, h := range hash {
 471                                                 rank[h] = tileVariantID(i + 1)
 472                                         }
 473                                         if tag == cmd.debugTag {
 474                                                 for h, r := range rank {
 475                                                         log.Printf("tag %d rank(%x) = %v", tag, h[:3], r)
 476                                                 }
 477                                         }
 478                                         // remap[v] will be the new
 479                                         // variant number for original
 480                                         // variant number v.
 481                                         remap := make([]tileVariantID, len(variants))
 482                                         for i, tv := range variants {
 483                                                 remap[i] = rank[tv.Blake2b]
 484                                         }
 485                                         if tag == cmd.debugTag {
 486                                                 log.Printf("tag %d remap %+v", tag, remap)
 487                                         }
 488                                         variantRemap[tag-tagstart] = remap
 489                                         if rt != nil {
 490                                                 refrank := rank[blake2b.Sum256(rt.tiledata)]
 491                                                 if tag == cmd.debugTag {
 492                                                         log.Printf("tag %d reftile variant %d => %d", tag, rt.variant, refrank)
 493                                                 }
 494                                                 rt.variant = refrank
 495                                         }
 496                                 }()
 497                         }
 498                         throttleCPU.Wait()
 499
 500                         var onehotChunk [][]int8
 501                         var onehotXref []onehotXref
 502
 503                         annotationsFilename := fmt.Sprintf("%s/matrix.%04d.annotations.csv", *outputDir, infileIdx)
 504                         log.Infof("%04d: writing %s", infileIdx, annotationsFilename)
 505                         annof, err := os.Create(annotationsFilename)
 506                         if err != nil {
 507                                 return err
 508                         }
 509                         annow := bufio.NewWriterSize(annof, 1<<20)
 510                         outcol := 0
 511                         for tag := tagstart; tag < tagend; tag++ {
 512                                 rt := reftile[tag]
 513                                 if rt == nil && mask != nil {
 514                                         // Excluded by specified regions
 515                                         continue
 516                                 }
 517                                 if cmd.filter.MaxTag >= 0 && tag > tagID(cmd.filter.MaxTag) {
 518                                         continue
 519                                 }
 520                                 remap := variantRemap[tag-tagstart]
 521                                 maxv := tileVariantID(0)
 522                                 for _, v := range remap {
 523                                         if maxv < v {
 524                                                 maxv = v
 525                                         }
 526                                 }
 527                                 if *onehotChunked || *onehotSingle {
 528                                         if tag == cmd.debugTag {
 529                                                 log.WithFields(logrus.Fields{
 530                                                         "cgs[2].Variants[tag*2:(tag+1)*2]": cgs[cmd.cgnames[2]].Variants[(tag-tagstart)*2 : (tag-tagstart+1)*2],
 531                                                 }).Info("before tv2homhet")
 532                                         }
 533                                         onehot, xrefs := cmd.tv2homhet(cgs, maxv, remap, tag, tagstart)
 534                                         if tag == cmd.debugTag {
 535                                                 log.WithFields(logrus.Fields{
 536                                                         "onehot": onehot,
 537                                                         "xrefs":  xrefs,
 538                                                 }).Info("tv2homhet()")
 539                                         }
 540                                         onehotChunk = append(onehotChunk, onehot...)
 541                                         onehotXref = append(onehotXref, xrefs...)
 542                                 }
 543                                 if rt == nil {
 544                                         // Reference does not use any
 545                                         // variant of this tile
 546                                         outcol++
 547                                         continue
 548                                 }
 549                                 fmt.Fprintf(annow, "%d,%d,%d,=,%s,%d,,,\n", tag, outcol, rt.variant, rt.seqname, rt.pos)
 550                                 variants := seq[tag]
 551                                 reftilestr := strings.ToUpper(string(rt.tiledata))
 552
 553                                 done := make([]bool, maxv+1)
 554                                 variantDiffs := make([][]hgvs.Variant, maxv+1)
 555                                 for v, tv := range variants {
 556                                         v := remap[v]
 557                                         if v == rt.variant || done[v] {
 558                                                 continue
 559                                         } else {
 560                                                 done[v] = true
 561                                         }
 562                                         if len(tv.Sequence) < taglen || !bytes.HasSuffix(rt.tiledata, tv.Sequence[len(tv.Sequence)-taglen:]) {
 563                                                 fmt.Fprintf(annow, "%d,%d,%d,,%s,%d,,,\n", tag, outcol, v, rt.seqname, rt.pos)
 564                                                 continue
 565                                         }
 566                                         if lendiff := len(rt.tiledata) - len(tv.Sequence); lendiff < -1000 || lendiff > 1000 {
 567                                                 fmt.Fprintf(annow, "%d,%d,%d,,%s,%d,,,\n", tag, outcol, v, rt.seqname, rt.pos)
 568                                                 continue
 569                                         }
 570                                         diffs, _ := hgvs.Diff(reftilestr, strings.ToUpper(string(tv.Sequence)), 0)
 571                                         for i := range diffs {
 572                                                 diffs[i].Position += rt.pos
 573                                         }
 574                                         for _, diff := range diffs {
 575                                                 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)
 576                                         }
 577                                         if *hgvsChunked {
 578                                                 variantDiffs[v] = diffs
 579                                         }
 580                                 }
 581                                 if *hgvsChunked {
 582                                         // We can now determine, for each HGVS
 583                                         // variant (diff) in this reftile
 584                                         // region, whether a given genome
 585                                         // phase/allele (1) has the variant, (0) has
 586                                         // =ref or a different variant in that
 587                                         // position, or (-1) is lacking
 588                                         // coverage / couldn't be diffed.
 589                                         hgvsCol := hgvsColSet{}
 590                                         for _, diffs := range variantDiffs {
 591                                                 for _, diff := range diffs {
 592                                                         if _, ok := hgvsCol[diff]; ok {
 593                                                                 continue
 594                                                         }
 595                                                         hgvsCol[diff] = [2][]int8{
 596                                                                 make([]int8, len(cmd.cgnames)),
 597                                                                 make([]int8, len(cmd.cgnames)),
 598                                                         }
 599                                                 }
 600                                         }
 601                                         for row, name := range cmd.cgnames {
 602                                                 variants := cgs[name].Variants[(tag-tagstart)*2:]
 603                                                 for ph := 0; ph < 2; ph++ {
 604                                                         v := variants[ph]
 605                                                         if int(v) >= len(remap) {
 606                                                                 v = 0
 607                                                         } else {
 608                                                                 v = remap[v]
 609                                                         }
 610                                                         if v == rt.variant {
 611                                                                 // hgvsCol[*][ph][row] is already 0
 612                                                         } else if len(variantDiffs[v]) == 0 {
 613                                                                 // lacking coverage / couldn't be diffed
 614                                                                 for _, col := range hgvsCol {
 615                                                                         col[ph][row] = -1
 616                                                                 }
 617                                                         } else {
 618                                                                 for _, diff := range variantDiffs[v] {
 619                                                                         hgvsCol[diff][ph][row] = 1
 620                                                                 }
 621                                                         }
 622                                                 }
 623                                         }
 624                                         for diff, colpair := range hgvsCol {
 625                                                 allele2homhet(colpair)
 626                                                 if !cmd.filterHGVScolpair(colpair) {
 627                                                         delete(hgvsCol, diff)
 628                                                 }
 629                                         }
 630                                         if len(hgvsCol) > 0 {
 631                                                 encodeHGVSTodo[rt.seqname] <- hgvsCol
 632                                         }
 633                                 }
 634                                 outcol++
 635                         }
 636                         err = annow.Flush()
 637                         if err != nil {
 638                                 return err
 639                         }
 640                         err = annof.Close()
 641                         if err != nil {
 642                                 return err
 643                         }
 644
 645                         if *onehotChunked {
 646                                 // transpose onehotChunk[col][row] to numpy[row*ncols+col]
 647                                 rows := len(cmd.cgnames)
 648                                 cols := len(onehotChunk)
 649                                 log.Infof("%04d: preparing onehot numpy (rows=%d, cols=%d, mem=%d)", infileIdx, rows, cols, rows*cols)
 650                                 throttleNumpyMem.Acquire()
 651                                 out := onehotcols2int8(onehotChunk)
 652                                 fnm := fmt.Sprintf("%s/onehot.%04d.npy", *outputDir, infileIdx)
 653                                 err = writeNumpyInt8(fnm, out, rows, cols)
 654                                 if err != nil {
 655                                         return err
 656                                 }
 657                                 fnm = fmt.Sprintf("%s/onehot-columns.%04d.npy", *outputDir, infileIdx)
 658                                 err = writeNumpyInt32(fnm, onehotXref2int32(onehotXref), 4, len(onehotXref))
 659                                 if err != nil {
 660                                         return err
 661                                 }
 662                                 debug.FreeOSMemory()
 663                                 throttleNumpyMem.Release()
 664                         }
 665                         if *onehotSingle {
 666                                 onehotIndirect[infileIdx] = onehotChunk2Indirect(onehotChunk)
 667                                 onehotChunkSize[infileIdx] = uint32(len(onehotChunk))
 668                                 onehotXrefs[infileIdx] = onehotXref
 669                                 n := len(onehotIndirect[infileIdx][0])
 670                                 log.Infof("%04d: keeping onehot coordinates in memory (n=%d, mem=%d)", infileIdx, n, n*8*2)
 671                         }
 672                         if !(*onehotSingle || *onehotChunked) || *mergeOutput || *hgvsSingle {
 673                                 log.Infof("%04d: preparing numpy (rows=%d, cols=%d)", infileIdx, len(cmd.cgnames), 2*outcol)
 674                                 throttleNumpyMem.Acquire()
 675                                 rows := len(cmd.cgnames)
 676                                 cols := 2 * outcol
 677                                 out := make([]int16, rows*cols)
 678                                 for row, name := range cmd.cgnames {
 679                                         out := out[row*cols:]
 680                                         outcol := 0
 681                                         for col, v := range cgs[name].Variants {
 682                                                 tag := tagstart + tagID(col/2)
 683                                                 if mask != nil && reftile[tag] == nil || (cmd.filter.MaxTag >= 0 && tag > tagID(cmd.filter.MaxTag)) {
 684                                                         continue
 685                                                 }
 686                                                 if variants, ok := seq[tag]; ok && len(variants) > int(v) && len(variants[v].Sequence) > 0 {
 687                                                         out[outcol] = int16(variantRemap[tag-tagstart][v])
 688                                                 } else {
 689                                                         out[outcol] = -1
 690                                                 }
 691                                                 outcol++
 692                                         }
 693                                 }
 694                                 seq = nil
 695                                 cgs = nil
 696                                 debug.FreeOSMemory()
 697                                 throttleNumpyMem.Release()
 698                                 if *mergeOutput || *hgvsSingle {
 699                                         log.Infof("%04d: matrix fragment %d rows x %d cols", infileIdx, rows, cols)
 700                                         toMerge[infileIdx] = out
 701                                 }
 702                                 if !*mergeOutput && !*onehotChunked && !*onehotSingle {
 703                                         fnm := fmt.Sprintf("%s/matrix.%04d.npy", *outputDir, infileIdx)
 704                                         err = writeNumpyInt16(fnm, out, rows, cols)
 705                                         if err != nil {
 706                                                 return err
 707                                         }
 708                                 }
 709                         }
 710                         debug.FreeOSMemory()
 711                         log.Infof("%s: done (%d/%d)", infile, int(atomic.AddInt64(&done, 1)), len(infiles))
 712                         return nil
 713                 })
 714         }
 715         if err = throttleMem.Wait(); err != nil {
 716                 return 1
 717         }
 718
 719         if *hgvsChunked {
 720                 log.Info("flushing hgvsCols temp files")
 721                 for seqname := range refseq {
 722                         close(encodeHGVSTodo[seqname])
 723                 }
 724                 err = encodeHGVS.Wait()
 725                 if err != nil {
 726                         return 1
 727                 }
 728                 for seqname := range refseq {
 729                         log.Infof("%s: reading hgvsCols from temp file", seqname)
 730                         f := tmpHGVSCols[seqname]
 731                         _, err = f.Seek(0, io.SeekStart)
 732                         if err != nil {
 733                                 return 1
 734                         }
 735                         var hgvsCols hgvsColSet
 736                         dec := gob.NewDecoder(bufio.NewReaderSize(f, 1<<24))
 737                         for err == nil {
 738                                 err = dec.Decode(&hgvsCols)
 739                         }
 740                         if err != io.EOF {
 741                                 return 1
 742                         }
 743                         log.Infof("%s: sorting %d hgvs variants", seqname, len(hgvsCols))
 744                         variants := make([]hgvs.Variant, 0, len(hgvsCols))
 745                         for v := range hgvsCols {
 746                                 variants = append(variants, v)
 747                         }
 748                         sort.Slice(variants, func(i, j int) bool {
 749                                 vi, vj := &variants[i], &variants[j]
 750                                 if vi.Position != vj.Position {
 751                                         return vi.Position < vj.Position
 752                                 } else if vi.Ref != vj.Ref {
 753                                         return vi.Ref < vj.Ref
 754                                 } else {
 755                                         return vi.New < vj.New
 756                                 }
 757                         })
 758                         rows := len(cmd.cgnames)
 759                         cols := len(variants) * 2
 760                         log.Infof("%s: building hgvs matrix (rows=%d, cols=%d, mem=%d)", seqname, rows, cols, rows*cols)
 761                         out := make([]int8, rows*cols)
 762                         for varIdx, variant := range variants {
 763                                 hgvsCols := hgvsCols[variant]
 764                                 for row := range cmd.cgnames {
 765                                         for ph := 0; ph < 2; ph++ {
 766                                                 out[row*cols+varIdx+ph] = hgvsCols[ph][row]
 767                                         }
 768                                 }
 769                         }
 770                         err = writeNumpyInt8(fmt.Sprintf("%s/hgvs.%s.npy", *outputDir, seqname), out, rows, cols)
 771                         if err != nil {
 772                                 return 1
 773                         }
 774                         out = nil
 775
 776                         fnm := fmt.Sprintf("%s/hgvs.%s.annotations.csv", *outputDir, seqname)
 777                         log.Infof("%s: writing hgvs column labels to %s", seqname, fnm)
 778                         var hgvsLabels bytes.Buffer
 779                         for varIdx, variant := range variants {
 780                                 fmt.Fprintf(&hgvsLabels, "%d,%s:g.%s\n", varIdx, seqname, variant.String())
 781                         }
 782                         err = ioutil.WriteFile(fnm, hgvsLabels.Bytes(), 0666)
 783                         if err != nil {
 784                                 return 1
 785                         }
 786                 }
 787         }
 788
 789         if *mergeOutput || *hgvsSingle {
 790                 var annow *bufio.Writer
 791                 var annof *os.File
 792                 if *mergeOutput {
 793                         annoFilename := fmt.Sprintf("%s/matrix.annotations.csv", *outputDir)
 794                         annof, err = os.Create(annoFilename)
 795                         if err != nil {
 796                                 return 1
 797                         }
 798                         annow = bufio.NewWriterSize(annof, 1<<20)
 799                 }
 800
 801                 rows := len(cmd.cgnames)
 802                 cols := 0
 803                 for _, chunk := range toMerge {
 804                         cols += len(chunk) / rows
 805                 }
 806                 log.Infof("merging output matrix (rows=%d, cols=%d, mem=%d) and annotations", rows, cols, rows*cols*2)
 807                 var out []int16
 808                 if *mergeOutput {
 809                         out = make([]int16, rows*cols)
 810                 }
 811                 hgvsCols := map[string][2][]int16{} // hgvs -> [[g0,g1,g2,...], [g0,g1,g2,...]] (slice of genomes for each phase)
 812                 startcol := 0
 813                 for outIdx, chunk := range toMerge {
 814                         chunkcols := len(chunk) / rows
 815                         if *mergeOutput {
 816                                 for row := 0; row < rows; row++ {
 817                                         copy(out[row*cols+startcol:], chunk[row*chunkcols:(row+1)*chunkcols])
 818                                 }
 819                         }
 820                         toMerge[outIdx] = nil
 821
 822                         annotationsFilename := fmt.Sprintf("%s/matrix.%04d.annotations.csv", *outputDir, outIdx)
 823                         log.Infof("reading %s", annotationsFilename)
 824                         buf, err := os.ReadFile(annotationsFilename)
 825                         if err != nil {
 826                                 return 1
 827                         }
 828                         if *mergeOutput {
 829                                 err = os.Remove(annotationsFilename)
 830                                 if err != nil {
 831                                         return 1
 832                                 }
 833                         }
 834                         for _, line := range bytes.Split(buf, []byte{'\n'}) {
 835                                 if len(line) == 0 {
 836                                         continue
 837                                 }
 838                                 fields := bytes.SplitN(line, []byte{','}, 9)
 839                                 tag, _ := strconv.Atoi(string(fields[0]))
 840                                 incol, _ := strconv.Atoi(string(fields[1]))
 841                                 tileVariant, _ := strconv.Atoi(string(fields[2]))
 842                                 hgvsID := string(fields[3])
 843                                 seqname := string(fields[4])
 844                                 pos, _ := strconv.Atoi(string(fields[5]))
 845                                 refseq := fields[6]
 846                                 if hgvsID == "" {
 847                                         // Null entry for un-diffable
 848                                         // tile variant
 849                                         continue
 850                                 }
 851                                 if hgvsID == "=" {
 852                                         // Null entry for ref tile
 853                                         continue
 854                                 }
 855                                 if mask != nil && !mask.Check(strings.TrimPrefix(seqname, "chr"), pos, pos+len(refseq)) {
 856                                         // The tile intersects one of
 857                                         // the selected regions, but
 858                                         // this particular HGVS
 859                                         // variant does not.
 860                                         continue
 861                                 }
 862                                 hgvsColPair := hgvsCols[hgvsID]
 863                                 if hgvsColPair[0] == nil {
 864                                         // values in new columns start
 865                                         // out as -1 ("no data yet")
 866                                         // or 0 ("=ref") here, may
 867                                         // change to 1 ("hgvs variant
 868                                         // present") below, either on
 869                                         // this line or a future line.
 870                                         hgvsColPair = [2][]int16{make([]int16, len(cmd.cgnames)), make([]int16, len(cmd.cgnames))}
 871                                         rt, ok := reftile[tagID(tag)]
 872                                         if !ok {
 873                                                 err = fmt.Errorf("bug: seeing annotations for tag %d, but it has no reftile entry", tag)
 874                                                 return 1
 875                                         }
 876                                         for ph := 0; ph < 2; ph++ {
 877                                                 for row := 0; row < rows; row++ {
 878                                                         v := chunk[row*chunkcols+incol*2+ph]
 879                                                         if tileVariantID(v) == rt.variant {
 880                                                                 hgvsColPair[ph][row] = 0
 881                                                         } else {
 882                                                                 hgvsColPair[ph][row] = -1
 883                                                         }
 884                                                 }
 885                                         }
 886                                         hgvsCols[hgvsID] = hgvsColPair
 887                                         if annow != nil {
 888                                                 hgvsref := hgvs.Variant{
 889                                                         Position: pos,
 890                                                         Ref:      string(refseq),
 891                                                         New:      string(refseq),
 892                                                 }
 893                                                 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])
 894                                         }
 895                                 }
 896                                 if annow != nil {
 897                                         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])
 898                                 }
 899                                 for ph := 0; ph < 2; ph++ {
 900                                         for row := 0; row < rows; row++ {
 901                                                 v := chunk[row*chunkcols+incol*2+ph]
 902                                                 if int(v) == tileVariant {
 903                                                         hgvsColPair[ph][row] = 1
 904                                                 }
 905                                         }
 906                                 }
 907                         }
 908
 909                         startcol += chunkcols
 910                 }
 911                 if *mergeOutput {
 912                         err = annow.Flush()
 913                         if err != nil {
 914                                 return 1
 915                         }
 916                         err = annof.Close()
 917                         if err != nil {
 918                                 return 1
 919                         }
 920                         err = writeNumpyInt16(fmt.Sprintf("%s/matrix.npy", *outputDir), out, rows, cols)
 921                         if err != nil {
 922                                 return 1
 923                         }
 924                 }
 925                 out = nil
 926
 927                 if *hgvsSingle {
 928                         cols = len(hgvsCols) * 2
 929                         log.Printf("building hgvs-based matrix: %d rows x %d cols", rows, cols)
 930                         out = make([]int16, rows*cols)
 931                         hgvsIDs := make([]string, 0, cols/2)
 932                         for hgvsID := range hgvsCols {
 933                                 hgvsIDs = append(hgvsIDs, hgvsID)
 934                         }
 935                         sort.Strings(hgvsIDs)
 936                         var hgvsLabels bytes.Buffer
 937                         for idx, hgvsID := range hgvsIDs {
 938                                 fmt.Fprintf(&hgvsLabels, "%d,%s\n", idx, hgvsID)
 939                                 for ph := 0; ph < 2; ph++ {
 940                                         hgvscol := hgvsCols[hgvsID][ph]
 941                                         for row, val := range hgvscol {
 942                                                 out[row*cols+idx*2+ph] = val
 943                                         }
 944                                 }
 945                         }
 946                         err = writeNumpyInt16(fmt.Sprintf("%s/hgvs.npy", *outputDir), out, rows, cols)
 947                         if err != nil {
 948                                 return 1
 949                         }
 950
 951                         fnm := fmt.Sprintf("%s/hgvs.annotations.csv", *outputDir)
 952                         log.Printf("writing hgvs labels: %s", fnm)
 953                         err = ioutil.WriteFile(fnm, hgvsLabels.Bytes(), 0777)
 954                         if err != nil {
 955                                 return 1
 956                         }
 957                 }
 958         }
 959         if *onehotSingle {
 960                 nzCount := 0
 961                 for _, part := range onehotIndirect {
 962                         nzCount += len(part[0])
 963                 }
 964                 onehot := make([]uint32, nzCount*2) // [r,r,r,...,c,c,c,...]
 965                 var xrefs []onehotXref
 966                 chunkOffset := uint32(0)
 967                 outcol := 0
 968                 for i, part := range onehotIndirect {
 969                         for i := range part[1] {
 970                                 part[1][i] += chunkOffset
 971                         }
 972                         copy(onehot[outcol:], part[0])
 973                         copy(onehot[outcol+nzCount:], part[1])
 974                         xrefs = append(xrefs, onehotXrefs[i]...)
 975
 976                         outcol += len(part[0])
 977                         chunkOffset += onehotChunkSize[i]
 978
 979                         part[0] = nil
 980                         part[1] = nil
 981                         onehotXrefs[i] = nil
 982                         debug.FreeOSMemory()
 983                 }
 984                 fnm := fmt.Sprintf("%s/onehot.npy", *outputDir)
 985                 err = writeNumpyUint32(fnm, onehot, 2, nzCount)
 986                 if err != nil {
 987                         return 1
 988                 }
 989                 fnm = fmt.Sprintf("%s/onehot-columns.npy", *outputDir)
 990                 err = writeNumpyInt32(fnm, onehotXref2int32(xrefs), 4, len(xrefs))
 991                 if err != nil {
 992                         return 1
 993                 }
 994         }
 995         return 0
 996 }
 997
 998 // Read case/control files, remove non-case/control entries from
 999 // cmd.cgnames, and build cmd.chi2Cases.
1000 func (cmd *sliceNumpy) useCaseControlFiles() error {
1001         if cmd.chi2CaseControlFile == "" {
1002                 return nil
1003         }
1004         infiles, err := allFiles(cmd.chi2CaseControlFile, nil)
1005         if err != nil {
1006                 return err
1007         }
1008         // index in cmd.cgnames => case(true) / control(false)
1009         cc := map[int]bool{}
1010         for _, infile := range infiles {
1011                 f, err := open(infile)
1012                 if err != nil {
1013                         return err
1014                 }
1015                 buf, err := io.ReadAll(f)
1016                 f.Close()
1017                 if err != nil {
1018                         return err
1019                 }
1020                 ccCol := -1
1021                 for _, tsv := range bytes.Split(buf, []byte{'\n'}) {
1022                         if len(tsv) == 0 {
1023                                 continue
1024                         }
1025                         split := strings.Split(string(tsv), "\t")
1026                         if ccCol < 0 {
1027                                 // header row
1028                                 for col, name := range split {
1029                                         if name == cmd.chi2CaseControlColumn {
1030                                                 ccCol = col
1031                                                 break
1032                                         }
1033                                 }
1034                                 if ccCol < 0 {
1035                                         return fmt.Errorf("%s: no column named %q in header row %q", infile, cmd.chi2CaseControlColumn, tsv)
1036                                 }
1037                                 continue
1038                         }
1039                         if len(split) <= ccCol {
1040                                 continue
1041                         }
1042                         pattern := split[0]
1043                         found := -1
1044                         for i, name := range cmd.cgnames {
1045                                 if strings.Contains(name, pattern) {
1046                                         if found >= 0 {
1047                                                 log.Warnf("pattern %q in %s matches multiple genome IDs (%qs, %q)", pattern, infile, cmd.cgnames[found], name)
1048                                         }
1049                                         found = i
1050                                 }
1051                         }
1052                         if found < 0 {
1053                                 log.Warnf("pattern %q in %s does not match any genome IDs", pattern, infile)
1054                                 continue
1055                         }
1056                         if split[ccCol] == "0" {
1057                                 cc[found] = false
1058                         }
1059                         if split[ccCol] == "1" {
1060                                 cc[found] = true
1061                         }
1062                 }
1063         }
1064         allnames := cmd.cgnames
1065         cmd.cgnames = nil
1066         cmd.chi2Cases = nil
1067         ncases := 0
1068         for i, name := range allnames {
1069                 if cc, ok := cc[i]; ok {
1070                         cmd.cgnames = append(cmd.cgnames, name)
1071                         cmd.chi2Cases = append(cmd.chi2Cases, cc)
1072                         if cc {
1073                                 ncases++
1074                         }
1075                 }
1076         }
1077         log.Printf("%d cases, %d controls, %d neither (dropped)", ncases, len(cmd.cgnames)-ncases, len(allnames)-len(cmd.cgnames))
1078         return nil
1079 }
1080
1081 func (cmd *sliceNumpy) filterHGVScolpair(colpair [2][]int8) bool {
1082         if cmd.chi2PValue >= 1 {
1083                 return true
1084         }
1085         col0 := make([]bool, 0, len(cmd.chi2Cases))
1086         col1 := make([]bool, 0, len(cmd.chi2Cases))
1087         cases := make([]bool, 0, len(cmd.chi2Cases))
1088         for i, c := range cmd.chi2Cases {
1089                 if colpair[0][i] < 0 {
1090                         continue
1091                 }
1092                 col0 = append(col0, colpair[0][i] != 0)
1093                 col1 = append(col1, colpair[1][i] != 0)
1094                 cases = append(cases, c)
1095         }
1096         return len(cases) >= cmd.minCoverage &&
1097                 (pvalue(col0, cases) <= cmd.chi2PValue || pvalue(col1, cases) <= cmd.chi2PValue)
1098 }
1099
1100 func writeNumpyUint32(fnm string, out []uint32, rows, cols int) error {
1101         output, err := os.Create(fnm)
1102         if err != nil {
1103                 return err
1104         }
1105         defer output.Close()
1106         bufw := bufio.NewWriterSize(output, 1<<26)
1107         npw, err := gonpy.NewWriter(nopCloser{bufw})
1108         if err != nil {
1109                 return err
1110         }
1111         log.WithFields(log.Fields{
1112                 "filename": fnm,
1113                 "rows":     rows,
1114                 "cols":     cols,
1115                 "bytes":    rows * cols * 4,
1116         }).Infof("writing numpy: %s", fnm)
1117         npw.Shape = []int{rows, cols}
1118         npw.WriteUint32(out)
1119         err = bufw.Flush()
1120         if err != nil {
1121                 return err
1122         }
1123         return output.Close()
1124 }
1125
1126 func writeNumpyInt32(fnm string, out []int32, rows, cols int) error {
1127         output, err := os.Create(fnm)
1128         if err != nil {
1129                 return err
1130         }
1131         defer output.Close()
1132         bufw := bufio.NewWriterSize(output, 1<<26)
1133         npw, err := gonpy.NewWriter(nopCloser{bufw})
1134         if err != nil {
1135                 return err
1136         }
1137         log.WithFields(log.Fields{
1138                 "filename": fnm,
1139                 "rows":     rows,
1140                 "cols":     cols,
1141                 "bytes":    rows * cols * 4,
1142         }).Infof("writing numpy: %s", fnm)
1143         npw.Shape = []int{rows, cols}
1144         npw.WriteInt32(out)
1145         err = bufw.Flush()
1146         if err != nil {
1147                 return err
1148         }
1149         return output.Close()
1150 }
1151
1152 func writeNumpyInt16(fnm string, out []int16, rows, cols int) error {
1153         output, err := os.Create(fnm)
1154         if err != nil {
1155                 return err
1156         }
1157         defer output.Close()
1158         bufw := bufio.NewWriterSize(output, 1<<26)
1159         npw, err := gonpy.NewWriter(nopCloser{bufw})
1160         if err != nil {
1161                 return err
1162         }
1163         log.WithFields(log.Fields{
1164                 "filename": fnm,
1165                 "rows":     rows,
1166                 "cols":     cols,
1167                 "bytes":    rows * cols * 2,
1168         }).Infof("writing numpy: %s", fnm)
1169         npw.Shape = []int{rows, cols}
1170         npw.WriteInt16(out)
1171         err = bufw.Flush()
1172         if err != nil {
1173                 return err
1174         }
1175         return output.Close()
1176 }
1177
1178 func writeNumpyInt8(fnm string, out []int8, rows, cols int) error {
1179         output, err := os.Create(fnm)
1180         if err != nil {
1181                 return err
1182         }
1183         defer output.Close()
1184         bufw := bufio.NewWriterSize(output, 1<<26)
1185         npw, err := gonpy.NewWriter(nopCloser{bufw})
1186         if err != nil {
1187                 return err
1188         }
1189         log.WithFields(log.Fields{
1190                 "filename": fnm,
1191                 "rows":     rows,
1192                 "cols":     cols,
1193                 "bytes":    rows * cols,
1194         }).Infof("writing numpy: %s", fnm)
1195         npw.Shape = []int{rows, cols}
1196         npw.WriteInt8(out)
1197         err = bufw.Flush()
1198         if err != nil {
1199                 return err
1200         }
1201         return output.Close()
1202 }
1203
1204 func allele2homhet(colpair [2][]int8) {
1205         a, b := colpair[0], colpair[1]
1206         for i, av := range a {
1207                 bv := b[i]
1208                 if av < 0 || bv < 0 {
1209                         // no-call
1210                         a[i], b[i] = -1, -1
1211                 } else if av > 0 && bv > 0 {
1212                         // hom
1213                         a[i], b[i] = 1, 0
1214                 } else if av > 0 || bv > 0 {
1215                         // het
1216                         a[i], b[i] = 0, 1
1217                 } else {
1218                         // ref (or a different variant in same position)
1219                         // (this is a no-op) a[i], b[i] = 0, 0
1220                 }
1221         }
1222 }
1223
1224 type onehotXref struct {
1225         tag     tagID
1226         variant tileVariantID
1227         het     bool
1228         pvalue  float64
1229 }
1230
1231 const onehotXrefSize = unsafe.Sizeof(onehotXref{})
1232
1233 // Build onehot matrix (m[tileVariantIndex][genome] == 0 or 1) for all
1234 // variants of a single tile/tag#.
1235 //
1236 // Return nil if no tile variant passes Χ² filter.
1237 func (cmd *sliceNumpy) tv2homhet(cgs map[string]CompactGenome, maxv tileVariantID, remap []tileVariantID, tag, chunkstarttag tagID) ([][]int8, []onehotXref) {
1238         if tag == cmd.debugTag {
1239                 tv := make([]tileVariantID, len(cmd.cgnames)*2)
1240                 for i, name := range cmd.cgnames {
1241                         copy(tv[i*2:(i+1)*2], cgs[name].Variants[(tag-chunkstarttag)*2:])
1242                 }
1243                 log.WithFields(logrus.Fields{
1244                         "cgs[i].Variants[tag*2+j]": tv,
1245                         "maxv":                     maxv,
1246                         "remap":                    remap,
1247                         "tag":                      tag,
1248                         "chunkstarttag":            chunkstarttag,
1249                 }).Info("tv2homhet()")
1250         }
1251         if maxv < 1 || (maxv < 2 && !cmd.includeVariant1) {
1252                 // everyone has the most common variant (of the variants we don't drop)
1253                 return nil, nil
1254         }
1255         tagoffset := tag - chunkstarttag
1256         coverage := 0
1257         for _, cg := range cgs {
1258                 if cg.Variants[tagoffset*2] > 0 && cg.Variants[tagoffset*2+1] > 0 {
1259                         coverage++
1260                 }
1261         }
1262         if coverage < cmd.minCoverage {
1263                 return nil, nil
1264         }
1265         obs := make([][]bool, (maxv+1)*2) // 2 slices (hom + het) for each variant#
1266         for i := range obs {
1267                 obs[i] = make([]bool, len(cmd.cgnames))
1268         }
1269         for cgid, name := range cmd.cgnames {
1270                 cgvars := cgs[name].Variants[tagoffset*2:]
1271                 tv0, tv1 := remap[cgvars[0]], remap[cgvars[1]]
1272                 for v := tileVariantID(1); v <= maxv; v++ {
1273                         if tv0 == v && tv1 == v {
1274                                 obs[v*2][cgid] = true
1275                         } else if tv0 == v || tv1 == v {
1276                                 obs[v*2+1][cgid] = true
1277                         }
1278                 }
1279         }
1280         var onehot [][]int8
1281         var xref []onehotXref
1282         for col := 2; col < len(obs); col++ {
1283                 // col 0,1 correspond to tile variant 0, i.e.,
1284                 // no-call; col 2,3 correspond to the most common
1285                 // variant; so we (normally) start at col 4.
1286                 if col < 4 && !cmd.includeVariant1 {
1287                         continue
1288                 }
1289                 p := pvalue(obs[col], cmd.chi2Cases)
1290                 if cmd.chi2PValue < 1 && !(p < cmd.chi2PValue) {
1291                         continue
1292                 }
1293                 onehot = append(onehot, bool2int8(obs[col]))
1294                 xref = append(xref, onehotXref{
1295                         tag:     tag,
1296                         variant: tileVariantID(col >> 1),
1297                         het:     col&1 == 1,
1298                         pvalue:  p,
1299                 })
1300         }
1301         return onehot, xref
1302 }
1303
1304 func bool2int8(in []bool) []int8 {
1305         out := make([]int8, len(in))
1306         for i, v := range in {
1307                 if v {
1308                         out[i] = 1
1309                 }
1310         }
1311         return out
1312 }
1313
1314 // convert a []onehotXref with length N to a numpy-style []int32
1315 // matrix with N columns, one row per field of onehotXref struct.
1316 //
1317 // Hom/het row contains hom=0, het=1.
1318 //
1319 // P-value row contains 1000000x actual p-value.
1320 func onehotXref2int32(xrefs []onehotXref) []int32 {
1321         xcols := len(xrefs)
1322         xdata := make([]int32, 4*xcols)
1323         for i, xref := range xrefs {
1324                 xdata[i] = int32(xref.tag)
1325                 xdata[xcols+i] = int32(xref.variant)
1326                 if xref.het {
1327                         xdata[xcols*2+i] = 1
1328                 }
1329                 xdata[xcols*3+i] = int32(xref.pvalue * 1000000)
1330         }
1331         return xdata
1332 }
1333
1334 // transpose onehot data from in[col][row] to numpy-style
1335 // out[row*cols+col].
1336 func onehotcols2int8(in [][]int8) []int8 {
1337         if len(in) == 0 {
1338                 return nil
1339         }
1340         cols := len(in)
1341         rows := len(in[0])
1342         out := make([]int8, rows*cols)
1343         for row := 0; row < rows; row++ {
1344                 outrow := out[row*cols:]
1345                 for col, incol := range in {
1346                         outrow[col] = incol[row]
1347                 }
1348         }
1349         return out
1350 }
1351
1352 // Return [2][]uint32{rowIndices, colIndices} indicating which
1353 // elements of matrixT[c][r] have non-zero values.
1354 func onehotChunk2Indirect(matrixT [][]int8) [2][]uint32 {
1355         var nz [2][]uint32
1356         for c, col := range matrixT {
1357                 for r, val := range col {
1358                         if val != 0 {
1359                                 nz[0] = append(nz[0], uint32(r))
1360                                 nz[1] = append(nz[1], uint32(c))
1361                         }
1362                 }
1363         }
1364         return nz
1365 }