1 // Copyright (C) The Lightning Authors. All rights reserved.
3 // SPDX-License-Identifier: AGPL-3.0
27 "git.arvados.org/arvados.git/sdk/go/arvados"
28 "github.com/arvados/lightning/hgvs"
29 "github.com/kshedden/gonpy"
30 log "github.com/sirupsen/logrus"
31 "golang.org/x/crypto/blake2b"
34 type sliceNumpy struct {
37 chi2CaseControlColumn string
38 chi2CaseControlFile string
45 func (cmd *sliceNumpy) RunCommand(prog string, args []string, stdin io.Reader, stdout, stderr io.Writer) int {
49 fmt.Fprintf(stderr, "%s\n", err)
52 flags := flag.NewFlagSet("", flag.ContinueOnError)
53 flags.SetOutput(stderr)
54 pprof := flags.String("pprof", "", "serve Go profile data at http://`[addr]:port`")
55 runlocal := flags.Bool("local", false, "run on local host (default: run in an arvados container)")
56 projectUUID := flags.String("project", "", "project `UUID` for output data")
57 priority := flags.Int("priority", 500, "container request priority")
58 inputDir := flags.String("input-dir", "./in", "input `directory`")
59 outputDir := flags.String("output-dir", "./out", "output `directory`")
60 ref := flags.String("ref", "", "reference name (if blank, choose last one that appears in input)")
61 regionsFilename := flags.String("regions", "", "only output columns/annotations that intersect regions in specified bed `file`")
62 expandRegions := flags.Int("expand-regions", 0, "expand specified regions by `N` base pairs on each side`")
63 mergeOutput := flags.Bool("merge-output", false, "merge output into one matrix.npy and one matrix.annotations.csv")
64 hgvsSingle := flags.Bool("single-hgvs-matrix", false, "also generate hgvs-based matrix")
65 hgvsChunked := flags.Bool("chunked-hgvs-matrix", false, "also generate hgvs-based matrix per chromosome")
66 onehotSingle := flags.Bool("single-onehot", false, "generate one-hot tile-based matrix")
67 onehotChunked := flags.Bool("chunked-onehot", false, "generate one-hot tile-based matrix per input chunk")
68 flags.IntVar(&cmd.threads, "threads", 16, "number of memory-hungry assembly threads")
69 flags.StringVar(&cmd.chi2CaseControlFile, "chi2-case-control-file", "", "tsv file or directory indicating cases and controls for Χ² test (if directory, all .tsv files will be read)")
70 flags.StringVar(&cmd.chi2CaseControlColumn, "chi2-case-control-column", "", "name of case/control column in case-control files for Χ² test (value must be 0 for control, 1 for case)")
71 flags.Float64Var(&cmd.chi2PValue, "chi2-p-value", 1, "do Χ² test and omit columns with p-value above this threshold")
72 cmd.filter.Flags(flags)
73 err = flags.Parse(args)
74 if err == flag.ErrHelp {
77 } else if err != nil {
83 log.Println(http.ListenAndServe(*pprof, nil))
87 if cmd.chi2PValue != 1 && (cmd.chi2CaseControlFile == "" || cmd.chi2CaseControlColumn == "") {
88 log.Errorf("cannot use provided -chi2-p-value=%f because -chi2-case-control-file= or -chi2-case-control-column= value is empty", cmd.chi2PValue)
93 runner := arvadosContainerRunner{
94 Name: "lightning slice-numpy",
95 Client: arvados.NewClientFromEnv(),
96 ProjectUUID: *projectUUID,
103 err = runner.TranslatePaths(inputDir, regionsFilename, &cmd.chi2CaseControlFile)
107 runner.Args = []string{"slice-numpy", "-local=true",
109 "-input-dir=" + *inputDir,
110 "-output-dir=/mnt/output",
111 "-threads=" + fmt.Sprintf("%d", cmd.threads),
112 "-regions=" + *regionsFilename,
113 "-expand-regions=" + fmt.Sprintf("%d", *expandRegions),
114 "-merge-output=" + fmt.Sprintf("%v", *mergeOutput),
115 "-single-hgvs-matrix=" + fmt.Sprintf("%v", *hgvsSingle),
116 "-chunked-hgvs-matrix=" + fmt.Sprintf("%v", *hgvsChunked),
117 "-single-onehot=" + fmt.Sprintf("%v", *onehotSingle),
118 "-chunked-onehot=" + fmt.Sprintf("%v", *onehotChunked),
119 "-chi2-case-control-file=" + cmd.chi2CaseControlFile,
120 "-chi2-case-control-column=" + cmd.chi2CaseControlColumn,
121 "-chi2-p-value=" + fmt.Sprintf("%f", cmd.chi2PValue),
123 runner.Args = append(runner.Args, cmd.filter.Args()...)
125 output, err = runner.Run()
129 fmt.Fprintln(stdout, output)
133 infiles, err := allFiles(*inputDir, matchGobFile)
137 if len(infiles) == 0 {
138 err = fmt.Errorf("no input files found in %s", *inputDir)
141 sort.Strings(infiles)
143 var refseq map[string][]tileLibRef
144 var reftiledata = make(map[tileLibRef][]byte, 11000000)
145 in0, err := open(infiles[0])
150 matchGenome, err := regexp.Compile(cmd.filter.MatchGenome)
152 err = fmt.Errorf("-match-genome: invalid regexp: %q", cmd.filter.MatchGenome)
158 DecodeLibrary(in0, strings.HasSuffix(infiles[0], ".gz"), func(ent *LibraryEntry) error {
159 if len(ent.TagSet) > 0 {
160 taglen = len(ent.TagSet[0])
162 for _, cseq := range ent.CompactSequences {
163 if cseq.Name == *ref || *ref == "" {
164 refseq = cseq.TileSequences
167 for _, cg := range ent.CompactGenomes {
168 if matchGenome.MatchString(cg.Name) {
169 cmd.cgnames = append(cmd.cgnames, cg.Name)
172 for _, tv := range ent.TileVariants {
174 reftiledata[tileLibRef{tv.Tag, tv.Variant}] = tv.Sequence
184 err = fmt.Errorf("%s: reference sequence not found", infiles[0])
188 err = fmt.Errorf("tagset not found")
191 if len(cmd.cgnames) == 0 {
192 err = fmt.Errorf("no genomes found matching regexp %q", cmd.filter.MatchGenome)
195 sort.Strings(cmd.cgnames)
196 err = cmd.useCaseControlFiles()
200 cmd.minCoverage = int(math.Ceil(cmd.filter.MinCoverage * float64(len(cmd.cgnames))))
203 labelsFilename := *outputDir + "/samples.csv"
204 log.Infof("writing labels to %s", labelsFilename)
206 f, err = os.Create(labelsFilename)
211 for i, name := range cmd.cgnames {
213 if cmd.chi2Cases != nil && cmd.chi2Cases[i] {
216 _, err = fmt.Fprintf(f, "%d,%q,%d\n", i, trimFilenameForLabel(name), cc)
218 err = fmt.Errorf("write %s: %w", labelsFilename, err)
224 err = fmt.Errorf("close %s: %w", labelsFilename, err)
229 log.Info("indexing reference tiles")
230 type reftileinfo struct {
231 variant tileVariantID
232 seqname string // chr1
233 pos int // distance from start of chromosome to starttag
234 tiledata []byte // acgtggcaa...
236 isdup := map[tagID]bool{}
237 reftile := map[tagID]*reftileinfo{}
238 for seqname, cseq := range refseq {
240 for _, libref := range cseq {
241 tiledata := reftiledata[libref]
242 if len(tiledata) == 0 {
243 err = fmt.Errorf("missing tiledata for tag %d variant %d in %s in ref", libref.Tag, libref.Variant, seqname)
246 if isdup[libref.Tag] {
247 log.Printf("dropping reference tile %+v from %s @ %d, tag not unique", libref, seqname, pos)
248 } else if reftile[libref.Tag] != nil {
249 log.Printf("dropping reference tile %+v from %s @ %d, tag not unique", tileLibRef{Tag: libref.Tag, Variant: reftile[libref.Tag].variant}, reftile[libref.Tag].seqname, reftile[libref.Tag].pos)
250 delete(reftile, libref.Tag)
251 log.Printf("dropping reference tile %+v from %s @ %d, tag not unique", libref, seqname, pos)
252 isdup[libref.Tag] = true
254 reftile[libref.Tag] = &reftileinfo{
256 variant: libref.Variant,
261 pos += len(tiledata) - taglen
263 log.Printf("... %s done, len %d", seqname, pos+taglen)
267 if *regionsFilename != "" {
268 log.Printf("loading regions from %s", *regionsFilename)
269 mask, err = makeMask(*regionsFilename, *expandRegions)
273 log.Printf("before applying mask, len(reftile) == %d", len(reftile))
274 log.Printf("deleting reftile entries for regions outside %d intervals", mask.Len())
275 for tag, rt := range reftile {
276 if !mask.Check(strings.TrimPrefix(rt.seqname, "chr"), rt.pos, rt.pos+len(rt.tiledata)) {
280 log.Printf("after applying mask, len(reftile) == %d", len(reftile))
283 type hgvsColSet map[hgvs.Variant][2][]int8
284 encodeHGVS := throttle{Max: len(refseq)}
285 encodeHGVSTodo := map[string]chan hgvsColSet{}
286 tmpHGVSCols := map[string]*os.File{}
288 for seqname := range refseq {
290 f, err = os.Create(*outputDir + "/tmp." + seqname + ".gob")
294 defer os.Remove(f.Name())
295 bufw := bufio.NewWriterSize(f, 1<<24)
296 enc := gob.NewEncoder(bufw)
297 tmpHGVSCols[seqname] = f
298 todo := make(chan hgvsColSet, 128)
299 encodeHGVSTodo[seqname] = todo
300 encodeHGVS.Go(func() error {
301 for colset := range todo {
302 err := enc.Encode(colset)
304 encodeHGVS.Report(err)
315 var toMerge [][]int16
316 if *mergeOutput || *hgvsSingle {
317 toMerge = make([][]int16, len(infiles))
319 var onehotChunks [][][]int8
320 var onehotXrefs [][]onehotXref
322 onehotChunks = make([][][]int8, len(infiles))
323 onehotXrefs = make([][]onehotXref, len(infiles))
326 throttleMem := throttle{Max: cmd.threads} // TODO: estimate using mem and data size
327 throttleNumpyMem := throttle{Max: cmd.threads/2 + 1}
328 log.Info("generating annotations and numpy matrix for each slice")
330 for infileIdx, infile := range infiles {
331 infileIdx, infile := infileIdx, infile
332 throttleMem.Go(func() error {
333 seq := make(map[tagID][]TileVariant, 50000)
334 cgs := make(map[string]CompactGenome, len(cmd.cgnames))
335 f, err := open(infile)
340 log.Infof("%04d: reading %s", infileIdx, infile)
341 err = DecodeLibrary(f, strings.HasSuffix(infile, ".gz"), func(ent *LibraryEntry) error {
342 for _, tv := range ent.TileVariants {
346 if mask != nil && reftile[tv.Tag] == nil {
352 variants := seq[tv.Tag]
353 if len(variants) == 0 {
354 variants = make([]TileVariant, 100)
356 for len(variants) <= int(tv.Variant) {
357 variants = append(variants, TileVariant{})
359 variants[int(tv.Variant)] = tv
360 seq[tv.Tag] = variants
362 for _, cg := range ent.CompactGenomes {
363 if !matchGenome.MatchString(cg.Name) {
366 // pad to full slice size
367 // to avoid out-of-bounds
369 if sliceSize := 2 * int(cg.EndTag-cg.StartTag); len(cg.Variants) < sliceSize {
370 cg.Variants = append(cg.Variants, make([]tileVariantID, sliceSize-len(cg.Variants))...)
379 tagstart := cgs[cmd.cgnames[0]].StartTag
380 tagend := cgs[cmd.cgnames[0]].EndTag
384 log.Infof("%04d: renumber/dedup variants for tags %d-%d", infileIdx, tagstart, tagend)
385 variantRemap := make([][]tileVariantID, tagend-tagstart)
386 throttleCPU := throttle{Max: runtime.GOMAXPROCS(0)}
387 for tag, variants := range seq {
388 tag, variants := tag, variants
389 throttleCPU.Acquire()
391 defer throttleCPU.Release()
392 count := make(map[[blake2b.Size256]byte]int, len(variants))
396 count[blake2b.Sum256(rt.tiledata)] = 0
399 for _, cg := range cgs {
400 idx := int(tag-tagstart) * 2
401 for allele := 0; allele < 2; allele++ {
402 v := cg.Variants[idx+allele]
403 if v > 0 && len(variants[v].Sequence) > 0 {
404 count[variants[v].Blake2b]++
408 // hash[i] will be the hash of
409 // the variant(s) that should
410 // be at rank i (0-based).
411 hash := make([][blake2b.Size256]byte, 0, len(count))
412 for b := range count {
413 hash = append(hash, b)
415 sort.Slice(hash, func(i, j int) bool {
416 bi, bj := &hash[i], &hash[j]
417 if ci, cj := count[*bi], count[*bj]; ci != cj {
420 return bytes.Compare((*bi)[:], (*bj)[:]) < 0
423 // rank[b] will be the 1-based
424 // new variant number for
425 // variants whose hash is b.
426 rank := make(map[[blake2b.Size256]byte]tileVariantID, len(hash))
427 for i, h := range hash {
428 rank[h] = tileVariantID(i + 1)
430 // remap[v] will be the new
431 // variant number for original
433 remap := make([]tileVariantID, len(variants))
434 for i, tv := range variants {
435 remap[i] = rank[tv.Blake2b]
437 variantRemap[tag-tagstart] = remap
439 rt.variant = rank[blake2b.Sum256(rt.tiledata)]
445 var onehotChunk [][]int8
446 var onehotXref []onehotXref
448 annotationsFilename := fmt.Sprintf("%s/matrix.%04d.annotations.csv", *outputDir, infileIdx)
449 log.Infof("%04d: writing %s", infileIdx, annotationsFilename)
450 annof, err := os.Create(annotationsFilename)
454 annow := bufio.NewWriterSize(annof, 1<<20)
456 for tag := tagstart; tag < tagend; tag++ {
457 rt, ok := reftile[tag]
462 // Excluded by specified
463 // regions, or reference does
464 // not use any variant of this
465 // tile. (TODO: log this?
466 // mention it in annotations?)
469 remap := variantRemap[tag-tagstart]
470 maxv := tileVariantID(0)
471 for _, v := range remap {
476 if *onehotChunked || *onehotSingle {
477 onehot, xrefs := cmd.tv2homhet(cgs, maxv, remap, tag, tagstart)
478 onehotChunk = append(onehotChunk, onehot...)
479 onehotXref = append(onehotXref, xrefs...)
481 fmt.Fprintf(annow, "%d,%d,%d,=,%s,%d,,,\n", tag, outcol, rt.variant, rt.seqname, rt.pos)
483 reftilestr := strings.ToUpper(string(rt.tiledata))
485 done := make([]bool, maxv+1)
486 variantDiffs := make([][]hgvs.Variant, maxv+1)
487 for v, tv := range variants {
489 if v == rt.variant || done[v] {
494 if len(tv.Sequence) < taglen || !bytes.HasSuffix(rt.tiledata, tv.Sequence[len(tv.Sequence)-taglen:]) {
495 fmt.Fprintf(annow, "%d,%d,%d,,%s,%d,,,\n", tag, outcol, v, rt.seqname, rt.pos)
498 if lendiff := len(rt.tiledata) - len(tv.Sequence); lendiff < -1000 || lendiff > 1000 {
499 fmt.Fprintf(annow, "%d,%d,%d,,%s,%d,,,\n", tag, outcol, v, rt.seqname, rt.pos)
502 diffs, _ := hgvs.Diff(reftilestr, strings.ToUpper(string(tv.Sequence)), 0)
503 for i := range diffs {
504 diffs[i].Position += rt.pos
506 for _, diff := range diffs {
507 fmt.Fprintf(annow, "%d,%d,%d,%s:g.%s,%s,%d,%s,%s,%s\n", tag, outcol, v, rt.seqname, diff.String(), rt.seqname, diff.Position, diff.Ref, diff.New, diff.Left)
510 variantDiffs[v] = diffs
514 // We can now determine, for each HGVS
515 // variant (diff) in this reftile
516 // region, whether a given genome
517 // phase/allele (1) has the variant, (0) has
518 // =ref or a different variant in that
519 // position, or (-1) is lacking
520 // coverage / couldn't be diffed.
521 hgvsCol := hgvsColSet{}
522 for _, diffs := range variantDiffs {
523 for _, diff := range diffs {
524 if _, ok := hgvsCol[diff]; ok {
527 hgvsCol[diff] = [2][]int8{
528 make([]int8, len(cmd.cgnames)),
529 make([]int8, len(cmd.cgnames)),
533 for row, name := range cmd.cgnames {
534 variants := cgs[name].Variants[(tag-tagstart)*2:]
535 for ph := 0; ph < 2; ph++ {
537 if int(v) >= len(remap) {
543 // hgvsCol[*][ph][row] is already 0
544 } else if len(variantDiffs[v]) == 0 {
545 // lacking coverage / couldn't be diffed
546 for _, col := range hgvsCol {
550 for _, diff := range variantDiffs[v] {
551 hgvsCol[diff][ph][row] = 1
556 for diff, colpair := range hgvsCol {
557 allele2homhet(colpair)
558 if !cmd.filterHGVScolpair(colpair) {
559 delete(hgvsCol, diff)
562 if len(hgvsCol) > 0 {
563 encodeHGVSTodo[rt.seqname] <- hgvsCol
578 // transpose onehotChunk[col][row] to numpy[row*ncols+col]
579 rows := len(cmd.cgnames)
580 cols := len(onehotChunk)
581 log.Infof("%04d: preparing onehot numpy (rows=%d, cols=%d, mem=%d)", infileIdx, len(cmd.cgnames), len(onehotChunk), len(cmd.cgnames)*len(onehotChunk))
582 throttleNumpyMem.Acquire()
583 out := onehotcols2int8(onehotChunk)
584 fnm := fmt.Sprintf("%s/onehot.%04d.npy", *outputDir, infileIdx)
585 err = writeNumpyInt8(fnm, out, rows, cols)
589 fnm = fmt.Sprintf("%s/onehot-columns.%04d.npy", *outputDir, infileIdx)
590 err = writeNumpyInt32(fnm, onehotXref2int32(onehotXref), 4, len(onehotXref))
595 throttleNumpyMem.Release()
598 onehotChunks[infileIdx] = onehotChunk
599 onehotXrefs[infileIdx] = onehotXref
601 if !(*onehotSingle || *onehotChunked) || *mergeOutput || *hgvsSingle {
602 log.Infof("%04d: preparing numpy", infileIdx)
603 throttleNumpyMem.Acquire()
604 rows := len(cmd.cgnames)
606 out := make([]int16, rows*cols)
607 for row, name := range cmd.cgnames {
608 out := out[row*cols:]
610 for col, v := range cgs[name].Variants {
611 tag := tagstart + tagID(col/2)
612 if mask != nil && reftile[tag] == nil {
615 if variants, ok := seq[tag]; ok && len(variants) > int(v) && len(variants[v].Sequence) > 0 {
616 out[outcol] = int16(variantRemap[tag-tagstart][v])
626 throttleNumpyMem.Release()
627 if *mergeOutput || *hgvsSingle {
628 log.Infof("%04d: matrix fragment %d rows x %d cols", infileIdx, rows, cols)
629 toMerge[infileIdx] = out
631 if !*mergeOutput && !*onehotChunked && !*onehotSingle {
632 fnm := fmt.Sprintf("%s/matrix.%04d.npy", *outputDir, infileIdx)
633 err = writeNumpyInt16(fnm, out, rows, cols)
640 log.Infof("%s: done (%d/%d)", infile, int(atomic.AddInt64(&done, 1)), len(infiles))
644 if err = throttleMem.Wait(); err != nil {
649 log.Info("flushing hgvsCols temp files")
650 for seqname := range refseq {
651 close(encodeHGVSTodo[seqname])
653 err = encodeHGVS.Wait()
657 for seqname := range refseq {
658 log.Infof("%s: reading hgvsCols from temp file", seqname)
659 f := tmpHGVSCols[seqname]
660 _, err = f.Seek(0, io.SeekStart)
664 var hgvsCols hgvsColSet
665 dec := gob.NewDecoder(bufio.NewReaderSize(f, 1<<24))
667 err = dec.Decode(&hgvsCols)
672 log.Infof("%s: sorting %d hgvs variants", seqname, len(hgvsCols))
673 variants := make([]hgvs.Variant, 0, len(hgvsCols))
674 for v := range hgvsCols {
675 variants = append(variants, v)
677 sort.Slice(variants, func(i, j int) bool {
678 vi, vj := &variants[i], &variants[j]
679 if vi.Position != vj.Position {
680 return vi.Position < vj.Position
681 } else if vi.Ref != vj.Ref {
682 return vi.Ref < vj.Ref
684 return vi.New < vj.New
687 rows := len(cmd.cgnames)
688 cols := len(variants) * 2
689 log.Infof("%s: building hgvs matrix (rows=%d, cols=%d, mem=%d)", seqname, rows, cols, rows*cols)
690 out := make([]int8, rows*cols)
691 for varIdx, variant := range variants {
692 hgvsCols := hgvsCols[variant]
693 for row := range cmd.cgnames {
694 for ph := 0; ph < 2; ph++ {
695 out[row*cols+varIdx+ph] = hgvsCols[ph][row]
699 err = writeNumpyInt8(fmt.Sprintf("%s/hgvs.%s.npy", *outputDir, seqname), out, rows, cols)
705 fnm := fmt.Sprintf("%s/hgvs.%s.annotations.csv", *outputDir, seqname)
706 log.Infof("%s: writing hgvs column labels to %s", seqname, fnm)
707 var hgvsLabels bytes.Buffer
708 for varIdx, variant := range variants {
709 fmt.Fprintf(&hgvsLabels, "%d,%s:g.%s\n", varIdx, seqname, variant.String())
711 err = ioutil.WriteFile(fnm, hgvsLabels.Bytes(), 0666)
718 if *mergeOutput || *hgvsSingle {
719 var annow *bufio.Writer
722 annoFilename := fmt.Sprintf("%s/matrix.annotations.csv", *outputDir)
723 annof, err = os.Create(annoFilename)
727 annow = bufio.NewWriterSize(annof, 1<<20)
730 rows := len(cmd.cgnames)
732 for _, chunk := range toMerge {
733 cols += len(chunk) / rows
735 log.Infof("merging output matrix (rows=%d, cols=%d, mem=%d) and annotations", rows, cols, rows*cols*2)
738 out = make([]int16, rows*cols)
740 hgvsCols := map[string][2][]int16{} // hgvs -> [[g0,g1,g2,...], [g0,g1,g2,...]] (slice of genomes for each phase)
742 for outIdx, chunk := range toMerge {
743 chunkcols := len(chunk) / rows
745 for row := 0; row < rows; row++ {
746 copy(out[row*cols+startcol:], chunk[row*chunkcols:(row+1)*chunkcols])
749 toMerge[outIdx] = nil
751 annotationsFilename := fmt.Sprintf("%s/matrix.%04d.annotations.csv", *outputDir, outIdx)
752 log.Infof("reading %s", annotationsFilename)
753 buf, err := os.ReadFile(annotationsFilename)
758 err = os.Remove(annotationsFilename)
763 for _, line := range bytes.Split(buf, []byte{'\n'}) {
767 fields := bytes.SplitN(line, []byte{','}, 9)
768 tag, _ := strconv.Atoi(string(fields[0]))
769 incol, _ := strconv.Atoi(string(fields[1]))
770 tileVariant, _ := strconv.Atoi(string(fields[2]))
771 hgvsID := string(fields[3])
772 seqname := string(fields[4])
773 pos, _ := strconv.Atoi(string(fields[5]))
776 // Null entry for un-diffable
781 // Null entry for ref tile
784 if mask != nil && !mask.Check(strings.TrimPrefix(seqname, "chr"), pos, pos+len(refseq)) {
785 // The tile intersects one of
786 // the selected regions, but
787 // this particular HGVS
791 hgvsColPair := hgvsCols[hgvsID]
792 if hgvsColPair[0] == nil {
793 // values in new columns start
794 // out as -1 ("no data yet")
795 // or 0 ("=ref") here, may
796 // change to 1 ("hgvs variant
797 // present") below, either on
798 // this line or a future line.
799 hgvsColPair = [2][]int16{make([]int16, len(cmd.cgnames)), make([]int16, len(cmd.cgnames))}
800 rt, ok := reftile[tagID(tag)]
802 err = fmt.Errorf("bug: seeing annotations for tag %d, but it has no reftile entry", tag)
805 for ph := 0; ph < 2; ph++ {
806 for row := 0; row < rows; row++ {
807 v := chunk[row*chunkcols+incol*2+ph]
808 if tileVariantID(v) == rt.variant {
809 hgvsColPair[ph][row] = 0
811 hgvsColPair[ph][row] = -1
815 hgvsCols[hgvsID] = hgvsColPair
817 hgvsref := hgvs.Variant{
822 fmt.Fprintf(annow, "%d,%d,%d,%s:g.%s,%s,%d,%s,%s,%s\n", tag, incol+startcol/2, rt.variant, seqname, hgvsref.String(), seqname, pos, refseq, refseq, fields[8])
826 fmt.Fprintf(annow, "%d,%d,%d,%s,%s,%d,%s,%s,%s\n", tag, incol+startcol/2, tileVariant, hgvsID, seqname, pos, refseq, fields[7], fields[8])
828 for ph := 0; ph < 2; ph++ {
829 for row := 0; row < rows; row++ {
830 v := chunk[row*chunkcols+incol*2+ph]
831 if int(v) == tileVariant {
832 hgvsColPair[ph][row] = 1
838 startcol += chunkcols
849 err = writeNumpyInt16(fmt.Sprintf("%s/matrix.npy", *outputDir), out, rows, cols)
857 cols = len(hgvsCols) * 2
858 log.Printf("building hgvs-based matrix: %d rows x %d cols", rows, cols)
859 out = make([]int16, rows*cols)
860 hgvsIDs := make([]string, 0, cols/2)
861 for hgvsID := range hgvsCols {
862 hgvsIDs = append(hgvsIDs, hgvsID)
864 sort.Strings(hgvsIDs)
865 var hgvsLabels bytes.Buffer
866 for idx, hgvsID := range hgvsIDs {
867 fmt.Fprintf(&hgvsLabels, "%d,%s\n", idx, hgvsID)
868 for ph := 0; ph < 2; ph++ {
869 hgvscol := hgvsCols[hgvsID][ph]
870 for row, val := range hgvscol {
871 out[row*cols+idx*2+ph] = val
875 err = writeNumpyInt16(fmt.Sprintf("%s/hgvs.npy", *outputDir), out, rows, cols)
880 fnm := fmt.Sprintf("%s/hgvs.annotations.csv", *outputDir)
881 log.Printf("writing hgvs labels: %s", fnm)
882 err = ioutil.WriteFile(fnm, hgvsLabels.Bytes(), 0777)
890 var xrefs []onehotXref
891 for i := range onehotChunks {
892 onehot = append(onehot, onehotChunks[i]...)
893 onehotChunks[i] = nil
894 xrefs = append(xrefs, onehotXrefs[i]...)
897 fnm := fmt.Sprintf("%s/onehot.npy", *outputDir)
898 err = writeNumpyInt8(fnm, onehotcols2int8(onehot), len(cmd.cgnames), len(onehot))
902 fnm = fmt.Sprintf("%s/onehot-columns.npy", *outputDir)
903 err = writeNumpyInt32(fnm, onehotXref2int32(xrefs), 4, len(xrefs))
911 // Read case/control files, remove non-case/control entries from
912 // cmd.cgnames, and build cmd.chi2Cases.
913 func (cmd *sliceNumpy) useCaseControlFiles() error {
914 if cmd.chi2CaseControlFile == "" {
917 infiles, err := allFiles(cmd.chi2CaseControlFile, nil)
921 // index in cmd.cgnames => case(true) / control(false)
923 for _, infile := range infiles {
924 f, err := open(infile)
928 buf, err := io.ReadAll(f)
934 for _, tsv := range bytes.Split(buf, []byte{'\n'}) {
938 split := strings.Split(string(tsv), "\t")
941 for col, name := range split {
942 if name == cmd.chi2CaseControlColumn {
948 return fmt.Errorf("%s: no column named %q in header row %q", infile, cmd.chi2CaseControlColumn, tsv)
952 if len(split) <= ccCol {
957 for i, name := range cmd.cgnames {
958 if strings.Contains(name, pattern) {
960 log.Warnf("pattern %q in %s matches multiple genome IDs (%qs, %q)", pattern, infile, cmd.cgnames[found], name)
966 log.Warnf("pattern %q in %s does not match any genome IDs", pattern, infile)
969 if split[ccCol] == "0" {
972 if split[ccCol] == "1" {
977 allnames := cmd.cgnames
981 for i, name := range allnames {
982 if cc, ok := cc[i]; ok {
983 cmd.cgnames = append(cmd.cgnames, name)
984 cmd.chi2Cases = append(cmd.chi2Cases, cc)
990 log.Printf("%d cases, %d controls, %d neither (dropped)", ncases, len(cmd.cgnames)-ncases, len(allnames)-len(cmd.cgnames))
994 func (cmd *sliceNumpy) filterHGVScolpair(colpair [2][]int8) bool {
995 if cmd.chi2PValue >= 1 {
998 col0 := make([]bool, 0, len(cmd.chi2Cases))
999 col1 := make([]bool, 0, len(cmd.chi2Cases))
1000 cases := make([]bool, 0, len(cmd.chi2Cases))
1001 for i, c := range cmd.chi2Cases {
1002 if colpair[0][i] < 0 {
1005 col0 = append(col0, colpair[0][i] != 0)
1006 col1 = append(col1, colpair[1][i] != 0)
1007 cases = append(cases, c)
1009 return len(cases) >= cmd.minCoverage &&
1010 (pvalue(col0, cases) <= cmd.chi2PValue || pvalue(col1, cases) <= cmd.chi2PValue)
1013 func writeNumpyInt32(fnm string, out []int32, rows, cols int) error {
1014 output, err := os.Create(fnm)
1018 defer output.Close()
1019 bufw := bufio.NewWriterSize(output, 1<<26)
1020 npw, err := gonpy.NewWriter(nopCloser{bufw})
1024 log.WithFields(log.Fields{
1028 "bytes": rows * cols * 4,
1029 }).Infof("writing numpy: %s", fnm)
1030 npw.Shape = []int{rows, cols}
1036 return output.Close()
1039 func writeNumpyInt16(fnm string, out []int16, rows, cols int) error {
1040 output, err := os.Create(fnm)
1044 defer output.Close()
1045 bufw := bufio.NewWriterSize(output, 1<<26)
1046 npw, err := gonpy.NewWriter(nopCloser{bufw})
1050 log.WithFields(log.Fields{
1054 "bytes": rows * cols * 2,
1055 }).Infof("writing numpy: %s", fnm)
1056 npw.Shape = []int{rows, cols}
1062 return output.Close()
1065 func writeNumpyInt8(fnm string, out []int8, rows, cols int) error {
1066 output, err := os.Create(fnm)
1070 defer output.Close()
1071 bufw := bufio.NewWriterSize(output, 1<<26)
1072 npw, err := gonpy.NewWriter(nopCloser{bufw})
1076 log.WithFields(log.Fields{
1080 "bytes": rows * cols,
1081 }).Infof("writing numpy: %s", fnm)
1082 npw.Shape = []int{rows, cols}
1088 return output.Close()
1091 func allele2homhet(colpair [2][]int8) {
1092 a, b := colpair[0], colpair[1]
1093 for i, av := range a {
1095 if av < 0 || bv < 0 {
1098 } else if av > 0 && bv > 0 {
1101 } else if av > 0 || bv > 0 {
1105 // ref (or a different variant in same position)
1106 // (this is a no-op) a[i], b[i] = 0, 0
1111 type onehotXref struct {
1113 variant tileVariantID
1118 // Build onehot matrix (m[variant*2+isHet][genome] == 0 or 1) for all
1119 // variants of a single tile/tag#.
1121 // Return nil if no tile variant passes Χ² filter.
1122 func (cmd *sliceNumpy) tv2homhet(cgs map[string]CompactGenome, maxv tileVariantID, remap []tileVariantID, tag, chunkstarttag tagID) ([][]int8, []onehotXref) {
1124 // everyone has the most common variant
1127 tagoffset := tag - chunkstarttag
1129 for _, cg := range cgs {
1130 if cg.Variants[tagoffset*2] > 0 && cg.Variants[tagoffset*2+1] > 0 {
1134 if coverage < cmd.minCoverage {
1137 obs := make([][]bool, (maxv+1)*2) // 2 slices (hom + het) for each variant#
1138 for i := range obs {
1139 obs[i] = make([]bool, len(cmd.cgnames))
1141 for cgid, name := range cmd.cgnames {
1142 cgvars := cgs[name].Variants
1143 for v := tileVariantID(2); v <= maxv; v++ {
1144 if remap[cgvars[tagoffset*2]] == v && remap[cgvars[tagoffset*2+1]] == v {
1145 obs[v*2][cgid] = true
1146 } else if remap[cgvars[tagoffset*2]] == v || remap[cgvars[tagoffset*2+1]] == v {
1147 obs[v*2+1][cgid] = true
1152 var xref []onehotXref
1153 for homcol := 4; homcol < len(obs); homcol += 2 {
1155 pvalue(obs[homcol], cmd.chi2Cases),
1156 pvalue(obs[homcol+1], cmd.chi2Cases),
1158 if cmd.chi2PValue < 1 && !(p[0] < cmd.chi2PValue || p[1] < cmd.chi2PValue) {
1161 for het := 0; het < 2; het++ {
1162 onehot = append(onehot, bool2int8(obs[homcol+het]))
1163 xref = append(xref, onehotXref{
1165 variant: tileVariantID(homcol / 2),
1174 func bool2int8(in []bool) []int8 {
1175 out := make([]int8, len(in))
1176 for i, v := range in {
1184 // convert a []onehotXref with length N to a numpy-style []int32
1185 // matrix with N columns, one row per field of onehotXref struct.
1187 // Hom/het row contains hom=0, het=1.
1189 // P-value row contains 1000000x actual p-value.
1190 func onehotXref2int32(xrefs []onehotXref) []int32 {
1192 xdata := make([]int32, 4*xcols)
1193 for i, xref := range xrefs {
1194 xdata[i] = int32(xref.tag)
1195 xdata[xcols+i] = int32(xref.variant)
1197 xdata[xcols*2+i] = 1
1199 xdata[xcols*3+i] = int32(xref.pvalue * 1000000)
1204 // transpose onehot data from in[col][row] to numpy-style
1205 // out[row*cols+col].
1206 func onehotcols2int8(in [][]int8) []int8 {
1212 out := make([]int8, rows*cols)
1213 for row := 0; row < rows; row++ {
1214 outrow := out[row*cols:]
1215 for col, incol := range in {
1216 outrow[col] = incol[row]