1 // Copyright (C) The Lightning Authors. All rights reserved.
3 // SPDX-License-Identifier: AGPL-3.0
28 "git.arvados.org/arvados.git/sdk/go/arvados"
29 "github.com/arvados/lightning/hgvs"
30 "github.com/kshedden/gonpy"
31 log "github.com/sirupsen/logrus"
32 "golang.org/x/crypto/blake2b"
35 type sliceNumpy struct {
38 chi2CaseControlColumn string
39 chi2CaseControlFile string
46 func (cmd *sliceNumpy) RunCommand(prog string, args []string, stdin io.Reader, stdout, stderr io.Writer) int {
50 fmt.Fprintf(stderr, "%s\n", err)
53 flags := flag.NewFlagSet("", flag.ContinueOnError)
54 flags.SetOutput(stderr)
55 pprof := flags.String("pprof", "", "serve Go profile data at http://`[addr]:port`")
56 runlocal := flags.Bool("local", false, "run on local host (default: run in an arvados container)")
57 projectUUID := flags.String("project", "", "project `UUID` for output data")
58 priority := flags.Int("priority", 500, "container request priority")
59 inputDir := flags.String("input-dir", "./in", "input `directory`")
60 outputDir := flags.String("output-dir", "./out", "output `directory`")
61 ref := flags.String("ref", "", "reference name (if blank, choose last one that appears in input)")
62 regionsFilename := flags.String("regions", "", "only output columns/annotations that intersect regions in specified bed `file`")
63 expandRegions := flags.Int("expand-regions", 0, "expand specified regions by `N` base pairs on each side`")
64 mergeOutput := flags.Bool("merge-output", false, "merge output into one matrix.npy and one matrix.annotations.csv")
65 hgvsSingle := flags.Bool("single-hgvs-matrix", false, "also generate hgvs-based matrix")
66 hgvsChunked := flags.Bool("chunked-hgvs-matrix", false, "also generate hgvs-based matrix per chromosome")
67 onehotSingle := flags.Bool("single-onehot", false, "generate one-hot tile-based matrix")
68 onehotChunked := flags.Bool("chunked-onehot", false, "generate one-hot tile-based matrix per input chunk")
69 flags.IntVar(&cmd.threads, "threads", 16, "number of memory-hungry assembly threads")
70 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)")
71 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)")
72 flags.Float64Var(&cmd.chi2PValue, "chi2-p-value", 1, "do Χ² test and omit columns with p-value above this threshold")
73 cmd.filter.Flags(flags)
74 err = flags.Parse(args)
75 if err == flag.ErrHelp {
78 } else if err != nil {
84 log.Println(http.ListenAndServe(*pprof, nil))
88 if cmd.chi2PValue != 1 && (cmd.chi2CaseControlFile == "" || cmd.chi2CaseControlColumn == "") {
89 log.Errorf("cannot use provided -chi2-p-value=%f because -chi2-case-control-file= or -chi2-case-control-column= value is empty", cmd.chi2PValue)
94 runner := arvadosContainerRunner{
95 Name: "lightning slice-numpy",
96 Client: arvados.NewClientFromEnv(),
97 ProjectUUID: *projectUUID,
104 err = runner.TranslatePaths(inputDir, regionsFilename, &cmd.chi2CaseControlFile)
108 runner.Args = []string{"slice-numpy", "-local=true",
110 "-input-dir=" + *inputDir,
111 "-output-dir=/mnt/output",
112 "-threads=" + fmt.Sprintf("%d", cmd.threads),
113 "-regions=" + *regionsFilename,
114 "-expand-regions=" + fmt.Sprintf("%d", *expandRegions),
115 "-merge-output=" + fmt.Sprintf("%v", *mergeOutput),
116 "-single-hgvs-matrix=" + fmt.Sprintf("%v", *hgvsSingle),
117 "-chunked-hgvs-matrix=" + fmt.Sprintf("%v", *hgvsChunked),
118 "-single-onehot=" + fmt.Sprintf("%v", *onehotSingle),
119 "-chunked-onehot=" + fmt.Sprintf("%v", *onehotChunked),
120 "-chi2-case-control-file=" + cmd.chi2CaseControlFile,
121 "-chi2-case-control-column=" + cmd.chi2CaseControlColumn,
122 "-chi2-p-value=" + fmt.Sprintf("%f", cmd.chi2PValue),
124 runner.Args = append(runner.Args, cmd.filter.Args()...)
126 output, err = runner.Run()
130 fmt.Fprintln(stdout, output)
134 infiles, err := allFiles(*inputDir, matchGobFile)
138 if len(infiles) == 0 {
139 err = fmt.Errorf("no input files found in %s", *inputDir)
142 sort.Strings(infiles)
144 var refseq map[string][]tileLibRef
145 var reftiledata = make(map[tileLibRef][]byte, 11000000)
146 in0, err := open(infiles[0])
151 matchGenome, err := regexp.Compile(cmd.filter.MatchGenome)
153 err = fmt.Errorf("-match-genome: invalid regexp: %q", cmd.filter.MatchGenome)
159 DecodeLibrary(in0, strings.HasSuffix(infiles[0], ".gz"), func(ent *LibraryEntry) error {
160 if len(ent.TagSet) > 0 {
161 taglen = len(ent.TagSet[0])
163 for _, cseq := range ent.CompactSequences {
164 if cseq.Name == *ref || *ref == "" {
165 refseq = cseq.TileSequences
168 for _, cg := range ent.CompactGenomes {
169 if matchGenome.MatchString(cg.Name) {
170 cmd.cgnames = append(cmd.cgnames, cg.Name)
173 for _, tv := range ent.TileVariants {
175 reftiledata[tileLibRef{tv.Tag, tv.Variant}] = tv.Sequence
185 err = fmt.Errorf("%s: reference sequence not found", infiles[0])
189 err = fmt.Errorf("tagset not found")
192 if len(cmd.cgnames) == 0 {
193 err = fmt.Errorf("no genomes found matching regexp %q", cmd.filter.MatchGenome)
196 sort.Strings(cmd.cgnames)
197 err = cmd.useCaseControlFiles()
201 cmd.minCoverage = int(math.Ceil(cmd.filter.MinCoverage * float64(len(cmd.cgnames))))
204 labelsFilename := *outputDir + "/samples.csv"
205 log.Infof("writing labels to %s", labelsFilename)
207 f, err = os.Create(labelsFilename)
212 for i, name := range cmd.cgnames {
214 if cmd.chi2Cases != nil && cmd.chi2Cases[i] {
217 _, err = fmt.Fprintf(f, "%d,%q,%d\n", i, trimFilenameForLabel(name), cc)
219 err = fmt.Errorf("write %s: %w", labelsFilename, err)
225 err = fmt.Errorf("close %s: %w", labelsFilename, err)
230 log.Info("indexing reference tiles")
231 type reftileinfo struct {
232 variant tileVariantID
233 seqname string // chr1
234 pos int // distance from start of chromosome to starttag
235 tiledata []byte // acgtggcaa...
237 isdup := map[tagID]bool{}
238 reftile := map[tagID]*reftileinfo{}
239 for seqname, cseq := range refseq {
241 for _, libref := range cseq {
242 tiledata := reftiledata[libref]
243 if len(tiledata) == 0 {
244 err = fmt.Errorf("missing tiledata for tag %d variant %d in %s in ref", libref.Tag, libref.Variant, seqname)
247 if isdup[libref.Tag] {
248 log.Printf("dropping reference tile %+v from %s @ %d, tag not unique", libref, seqname, pos)
249 } else if reftile[libref.Tag] != nil {
250 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)
251 delete(reftile, libref.Tag)
252 log.Printf("dropping reference tile %+v from %s @ %d, tag not unique", libref, seqname, pos)
253 isdup[libref.Tag] = true
255 reftile[libref.Tag] = &reftileinfo{
257 variant: libref.Variant,
262 pos += len(tiledata) - taglen
264 log.Printf("... %s done, len %d", seqname, pos+taglen)
268 if *regionsFilename != "" {
269 log.Printf("loading regions from %s", *regionsFilename)
270 mask, err = makeMask(*regionsFilename, *expandRegions)
274 log.Printf("before applying mask, len(reftile) == %d", len(reftile))
275 log.Printf("deleting reftile entries for regions outside %d intervals", mask.Len())
276 for tag, rt := range reftile {
277 if !mask.Check(strings.TrimPrefix(rt.seqname, "chr"), rt.pos, rt.pos+len(rt.tiledata)) {
281 log.Printf("after applying mask, len(reftile) == %d", len(reftile))
284 type hgvsColSet map[hgvs.Variant][2][]int8
285 encodeHGVS := throttle{Max: len(refseq)}
286 encodeHGVSTodo := map[string]chan hgvsColSet{}
287 tmpHGVSCols := map[string]*os.File{}
289 for seqname := range refseq {
291 f, err = os.Create(*outputDir + "/tmp." + seqname + ".gob")
295 defer os.Remove(f.Name())
296 bufw := bufio.NewWriterSize(f, 1<<24)
297 enc := gob.NewEncoder(bufw)
298 tmpHGVSCols[seqname] = f
299 todo := make(chan hgvsColSet, 128)
300 encodeHGVSTodo[seqname] = todo
301 encodeHGVS.Go(func() error {
302 for colset := range todo {
303 err := enc.Encode(colset)
305 encodeHGVS.Report(err)
316 var toMerge [][]int16
317 if *mergeOutput || *hgvsSingle {
318 toMerge = make([][]int16, len(infiles))
320 var onehotIndirect [][2][]uint32 // [chunkIndex][axis][index]
321 var onehotXrefs [][]onehotXref
323 onehotIndirect = make([][2][]uint32, len(infiles))
324 onehotXrefs = make([][]onehotXref, len(infiles))
327 throttleMem := throttle{Max: cmd.threads} // TODO: estimate using mem and data size
328 throttleNumpyMem := throttle{Max: cmd.threads/2 + 1}
329 log.Info("generating annotations and numpy matrix for each slice")
331 for infileIdx, infile := range infiles {
332 infileIdx, infile := infileIdx, infile
333 throttleMem.Go(func() error {
334 seq := make(map[tagID][]TileVariant, 50000)
335 cgs := make(map[string]CompactGenome, len(cmd.cgnames))
336 f, err := open(infile)
341 log.Infof("%04d: reading %s", infileIdx, infile)
342 err = DecodeLibrary(f, strings.HasSuffix(infile, ".gz"), func(ent *LibraryEntry) error {
343 for _, tv := range ent.TileVariants {
347 if mask != nil && reftile[tv.Tag] == nil {
353 variants := seq[tv.Tag]
354 if len(variants) == 0 {
355 variants = make([]TileVariant, 100)
357 for len(variants) <= int(tv.Variant) {
358 variants = append(variants, TileVariant{})
360 variants[int(tv.Variant)] = tv
361 seq[tv.Tag] = variants
363 for _, cg := range ent.CompactGenomes {
364 if !matchGenome.MatchString(cg.Name) {
367 // pad to full slice size
368 // to avoid out-of-bounds
370 if sliceSize := 2 * int(cg.EndTag-cg.StartTag); len(cg.Variants) < sliceSize {
371 cg.Variants = append(cg.Variants, make([]tileVariantID, sliceSize-len(cg.Variants))...)
380 tagstart := cgs[cmd.cgnames[0]].StartTag
381 tagend := cgs[cmd.cgnames[0]].EndTag
385 log.Infof("%04d: renumber/dedup variants for tags %d-%d", infileIdx, tagstart, tagend)
386 variantRemap := make([][]tileVariantID, tagend-tagstart)
387 throttleCPU := throttle{Max: runtime.GOMAXPROCS(0)}
388 for tag, variants := range seq {
389 tag, variants := tag, variants
390 throttleCPU.Acquire()
392 defer throttleCPU.Release()
393 count := make(map[[blake2b.Size256]byte]int, len(variants))
397 count[blake2b.Sum256(rt.tiledata)] = 0
400 for _, cg := range cgs {
401 idx := int(tag-tagstart) * 2
402 for allele := 0; allele < 2; allele++ {
403 v := cg.Variants[idx+allele]
404 if v > 0 && len(variants[v].Sequence) > 0 {
405 count[variants[v].Blake2b]++
409 // hash[i] will be the hash of
410 // the variant(s) that should
411 // be at rank i (0-based).
412 hash := make([][blake2b.Size256]byte, 0, len(count))
413 for b := range count {
414 hash = append(hash, b)
416 sort.Slice(hash, func(i, j int) bool {
417 bi, bj := &hash[i], &hash[j]
418 if ci, cj := count[*bi], count[*bj]; ci != cj {
421 return bytes.Compare((*bi)[:], (*bj)[:]) < 0
424 // rank[b] will be the 1-based
425 // new variant number for
426 // variants whose hash is b.
427 rank := make(map[[blake2b.Size256]byte]tileVariantID, len(hash))
428 for i, h := range hash {
429 rank[h] = tileVariantID(i + 1)
431 // remap[v] will be the new
432 // variant number for original
434 remap := make([]tileVariantID, len(variants))
435 for i, tv := range variants {
436 remap[i] = rank[tv.Blake2b]
438 variantRemap[tag-tagstart] = remap
440 rt.variant = rank[blake2b.Sum256(rt.tiledata)]
446 var onehotChunk [][]int8
447 var onehotXref []onehotXref
449 annotationsFilename := fmt.Sprintf("%s/matrix.%04d.annotations.csv", *outputDir, infileIdx)
450 log.Infof("%04d: writing %s", infileIdx, annotationsFilename)
451 annof, err := os.Create(annotationsFilename)
455 annow := bufio.NewWriterSize(annof, 1<<20)
457 for tag := tagstart; tag < tagend; tag++ {
458 rt, ok := reftile[tag]
463 // Excluded by specified
464 // regions, or reference does
465 // not use any variant of this
466 // tile. (TODO: log this?
467 // mention it in annotations?)
470 remap := variantRemap[tag-tagstart]
471 maxv := tileVariantID(0)
472 for _, v := range remap {
477 if *onehotChunked || *onehotSingle {
478 onehot, xrefs := cmd.tv2homhet(cgs, maxv, remap, tag, tagstart)
479 onehotChunk = append(onehotChunk, onehot...)
480 onehotXref = append(onehotXref, xrefs...)
482 fmt.Fprintf(annow, "%d,%d,%d,=,%s,%d,,,\n", tag, outcol, rt.variant, rt.seqname, rt.pos)
484 reftilestr := strings.ToUpper(string(rt.tiledata))
486 done := make([]bool, maxv+1)
487 variantDiffs := make([][]hgvs.Variant, maxv+1)
488 for v, tv := range variants {
490 if v == rt.variant || done[v] {
495 if len(tv.Sequence) < taglen || !bytes.HasSuffix(rt.tiledata, tv.Sequence[len(tv.Sequence)-taglen:]) {
496 fmt.Fprintf(annow, "%d,%d,%d,,%s,%d,,,\n", tag, outcol, v, rt.seqname, rt.pos)
499 if lendiff := len(rt.tiledata) - len(tv.Sequence); lendiff < -1000 || lendiff > 1000 {
500 fmt.Fprintf(annow, "%d,%d,%d,,%s,%d,,,\n", tag, outcol, v, rt.seqname, rt.pos)
503 diffs, _ := hgvs.Diff(reftilestr, strings.ToUpper(string(tv.Sequence)), 0)
504 for i := range diffs {
505 diffs[i].Position += rt.pos
507 for _, diff := range diffs {
508 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)
511 variantDiffs[v] = diffs
515 // We can now determine, for each HGVS
516 // variant (diff) in this reftile
517 // region, whether a given genome
518 // phase/allele (1) has the variant, (0) has
519 // =ref or a different variant in that
520 // position, or (-1) is lacking
521 // coverage / couldn't be diffed.
522 hgvsCol := hgvsColSet{}
523 for _, diffs := range variantDiffs {
524 for _, diff := range diffs {
525 if _, ok := hgvsCol[diff]; ok {
528 hgvsCol[diff] = [2][]int8{
529 make([]int8, len(cmd.cgnames)),
530 make([]int8, len(cmd.cgnames)),
534 for row, name := range cmd.cgnames {
535 variants := cgs[name].Variants[(tag-tagstart)*2:]
536 for ph := 0; ph < 2; ph++ {
538 if int(v) >= len(remap) {
544 // hgvsCol[*][ph][row] is already 0
545 } else if len(variantDiffs[v]) == 0 {
546 // lacking coverage / couldn't be diffed
547 for _, col := range hgvsCol {
551 for _, diff := range variantDiffs[v] {
552 hgvsCol[diff][ph][row] = 1
557 for diff, colpair := range hgvsCol {
558 allele2homhet(colpair)
559 if !cmd.filterHGVScolpair(colpair) {
560 delete(hgvsCol, diff)
563 if len(hgvsCol) > 0 {
564 encodeHGVSTodo[rt.seqname] <- hgvsCol
579 // transpose onehotChunk[col][row] to numpy[row*ncols+col]
580 rows := len(cmd.cgnames)
581 cols := len(onehotChunk)
582 log.Infof("%04d: preparing onehot numpy (rows=%d, cols=%d, mem=%d)", infileIdx, len(cmd.cgnames), len(onehotChunk), len(cmd.cgnames)*len(onehotChunk))
583 throttleNumpyMem.Acquire()
584 out := onehotcols2int8(onehotChunk)
585 fnm := fmt.Sprintf("%s/onehot.%04d.npy", *outputDir, infileIdx)
586 err = writeNumpyInt8(fnm, out, rows, cols)
590 fnm = fmt.Sprintf("%s/onehot-columns.%04d.npy", *outputDir, infileIdx)
591 err = writeNumpyInt32(fnm, onehotXref2int32(onehotXref), 4, len(onehotXref))
596 throttleNumpyMem.Release()
599 onehotIndirect[infileIdx] = onehotChunk2Indirect(onehotChunk)
600 onehotXrefs[infileIdx] = onehotXref
601 n := len(onehotIndirect[infileIdx][0])
602 log.Infof("%04d: keeping onehot coordinates in memory (n=%d, mem=%d)", infileIdx, n, n*8)
604 if !(*onehotSingle || *onehotChunked) || *mergeOutput || *hgvsSingle {
605 log.Infof("%04d: preparing numpy", infileIdx)
606 throttleNumpyMem.Acquire()
607 rows := len(cmd.cgnames)
609 out := make([]int16, rows*cols)
610 for row, name := range cmd.cgnames {
611 out := out[row*cols:]
613 for col, v := range cgs[name].Variants {
614 tag := tagstart + tagID(col/2)
615 if mask != nil && reftile[tag] == nil {
618 if variants, ok := seq[tag]; ok && len(variants) > int(v) && len(variants[v].Sequence) > 0 {
619 out[outcol] = int16(variantRemap[tag-tagstart][v])
629 throttleNumpyMem.Release()
630 if *mergeOutput || *hgvsSingle {
631 log.Infof("%04d: matrix fragment %d rows x %d cols", infileIdx, rows, cols)
632 toMerge[infileIdx] = out
634 if !*mergeOutput && !*onehotChunked && !*onehotSingle {
635 fnm := fmt.Sprintf("%s/matrix.%04d.npy", *outputDir, infileIdx)
636 err = writeNumpyInt16(fnm, out, rows, cols)
643 log.Infof("%s: done (%d/%d)", infile, int(atomic.AddInt64(&done, 1)), len(infiles))
647 if err = throttleMem.Wait(); err != nil {
652 log.Info("flushing hgvsCols temp files")
653 for seqname := range refseq {
654 close(encodeHGVSTodo[seqname])
656 err = encodeHGVS.Wait()
660 for seqname := range refseq {
661 log.Infof("%s: reading hgvsCols from temp file", seqname)
662 f := tmpHGVSCols[seqname]
663 _, err = f.Seek(0, io.SeekStart)
667 var hgvsCols hgvsColSet
668 dec := gob.NewDecoder(bufio.NewReaderSize(f, 1<<24))
670 err = dec.Decode(&hgvsCols)
675 log.Infof("%s: sorting %d hgvs variants", seqname, len(hgvsCols))
676 variants := make([]hgvs.Variant, 0, len(hgvsCols))
677 for v := range hgvsCols {
678 variants = append(variants, v)
680 sort.Slice(variants, func(i, j int) bool {
681 vi, vj := &variants[i], &variants[j]
682 if vi.Position != vj.Position {
683 return vi.Position < vj.Position
684 } else if vi.Ref != vj.Ref {
685 return vi.Ref < vj.Ref
687 return vi.New < vj.New
690 rows := len(cmd.cgnames)
691 cols := len(variants) * 2
692 log.Infof("%s: building hgvs matrix (rows=%d, cols=%d, mem=%d)", seqname, rows, cols, rows*cols)
693 out := make([]int8, rows*cols)
694 for varIdx, variant := range variants {
695 hgvsCols := hgvsCols[variant]
696 for row := range cmd.cgnames {
697 for ph := 0; ph < 2; ph++ {
698 out[row*cols+varIdx+ph] = hgvsCols[ph][row]
702 err = writeNumpyInt8(fmt.Sprintf("%s/hgvs.%s.npy", *outputDir, seqname), out, rows, cols)
708 fnm := fmt.Sprintf("%s/hgvs.%s.annotations.csv", *outputDir, seqname)
709 log.Infof("%s: writing hgvs column labels to %s", seqname, fnm)
710 var hgvsLabels bytes.Buffer
711 for varIdx, variant := range variants {
712 fmt.Fprintf(&hgvsLabels, "%d,%s:g.%s\n", varIdx, seqname, variant.String())
714 err = ioutil.WriteFile(fnm, hgvsLabels.Bytes(), 0666)
721 if *mergeOutput || *hgvsSingle {
722 var annow *bufio.Writer
725 annoFilename := fmt.Sprintf("%s/matrix.annotations.csv", *outputDir)
726 annof, err = os.Create(annoFilename)
730 annow = bufio.NewWriterSize(annof, 1<<20)
733 rows := len(cmd.cgnames)
735 for _, chunk := range toMerge {
736 cols += len(chunk) / rows
738 log.Infof("merging output matrix (rows=%d, cols=%d, mem=%d) and annotations", rows, cols, rows*cols*2)
741 out = make([]int16, rows*cols)
743 hgvsCols := map[string][2][]int16{} // hgvs -> [[g0,g1,g2,...], [g0,g1,g2,...]] (slice of genomes for each phase)
745 for outIdx, chunk := range toMerge {
746 chunkcols := len(chunk) / rows
748 for row := 0; row < rows; row++ {
749 copy(out[row*cols+startcol:], chunk[row*chunkcols:(row+1)*chunkcols])
752 toMerge[outIdx] = nil
754 annotationsFilename := fmt.Sprintf("%s/matrix.%04d.annotations.csv", *outputDir, outIdx)
755 log.Infof("reading %s", annotationsFilename)
756 buf, err := os.ReadFile(annotationsFilename)
761 err = os.Remove(annotationsFilename)
766 for _, line := range bytes.Split(buf, []byte{'\n'}) {
770 fields := bytes.SplitN(line, []byte{','}, 9)
771 tag, _ := strconv.Atoi(string(fields[0]))
772 incol, _ := strconv.Atoi(string(fields[1]))
773 tileVariant, _ := strconv.Atoi(string(fields[2]))
774 hgvsID := string(fields[3])
775 seqname := string(fields[4])
776 pos, _ := strconv.Atoi(string(fields[5]))
779 // Null entry for un-diffable
784 // Null entry for ref tile
787 if mask != nil && !mask.Check(strings.TrimPrefix(seqname, "chr"), pos, pos+len(refseq)) {
788 // The tile intersects one of
789 // the selected regions, but
790 // this particular HGVS
794 hgvsColPair := hgvsCols[hgvsID]
795 if hgvsColPair[0] == nil {
796 // values in new columns start
797 // out as -1 ("no data yet")
798 // or 0 ("=ref") here, may
799 // change to 1 ("hgvs variant
800 // present") below, either on
801 // this line or a future line.
802 hgvsColPair = [2][]int16{make([]int16, len(cmd.cgnames)), make([]int16, len(cmd.cgnames))}
803 rt, ok := reftile[tagID(tag)]
805 err = fmt.Errorf("bug: seeing annotations for tag %d, but it has no reftile entry", tag)
808 for ph := 0; ph < 2; ph++ {
809 for row := 0; row < rows; row++ {
810 v := chunk[row*chunkcols+incol*2+ph]
811 if tileVariantID(v) == rt.variant {
812 hgvsColPair[ph][row] = 0
814 hgvsColPair[ph][row] = -1
818 hgvsCols[hgvsID] = hgvsColPair
820 hgvsref := hgvs.Variant{
825 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])
829 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])
831 for ph := 0; ph < 2; ph++ {
832 for row := 0; row < rows; row++ {
833 v := chunk[row*chunkcols+incol*2+ph]
834 if int(v) == tileVariant {
835 hgvsColPair[ph][row] = 1
841 startcol += chunkcols
852 err = writeNumpyInt16(fmt.Sprintf("%s/matrix.npy", *outputDir), out, rows, cols)
860 cols = len(hgvsCols) * 2
861 log.Printf("building hgvs-based matrix: %d rows x %d cols", rows, cols)
862 out = make([]int16, rows*cols)
863 hgvsIDs := make([]string, 0, cols/2)
864 for hgvsID := range hgvsCols {
865 hgvsIDs = append(hgvsIDs, hgvsID)
867 sort.Strings(hgvsIDs)
868 var hgvsLabels bytes.Buffer
869 for idx, hgvsID := range hgvsIDs {
870 fmt.Fprintf(&hgvsLabels, "%d,%s\n", idx, hgvsID)
871 for ph := 0; ph < 2; ph++ {
872 hgvscol := hgvsCols[hgvsID][ph]
873 for row, val := range hgvscol {
874 out[row*cols+idx*2+ph] = val
878 err = writeNumpyInt16(fmt.Sprintf("%s/hgvs.npy", *outputDir), out, rows, cols)
883 fnm := fmt.Sprintf("%s/hgvs.annotations.csv", *outputDir)
884 log.Printf("writing hgvs labels: %s", fnm)
885 err = ioutil.WriteFile(fnm, hgvsLabels.Bytes(), 0777)
893 for _, part := range onehotIndirect {
894 nzCount += len(part[0])
896 onehot := make([]uint32, nzCount*2) // [r,r,r,...,c,c,c,...]
897 var xrefs []onehotXref
899 for i, part := range onehotIndirect {
900 for i := range part[1] {
901 part[1][i] += uint32(outcol)
903 copy(onehot[outcol:], part[0])
904 copy(onehot[outcol+nzCount:], part[1])
905 outcol += len(part[0])
906 xrefs = append(xrefs, onehotXrefs[i]...)
913 fnm := fmt.Sprintf("%s/onehot.npy", *outputDir)
914 err = writeNumpyUint32(fnm, onehot, 2, nzCount)
918 fnm = fmt.Sprintf("%s/onehot-columns.npy", *outputDir)
919 err = writeNumpyInt32(fnm, onehotXref2int32(xrefs), 4, len(xrefs))
927 // Read case/control files, remove non-case/control entries from
928 // cmd.cgnames, and build cmd.chi2Cases.
929 func (cmd *sliceNumpy) useCaseControlFiles() error {
930 if cmd.chi2CaseControlFile == "" {
933 infiles, err := allFiles(cmd.chi2CaseControlFile, nil)
937 // index in cmd.cgnames => case(true) / control(false)
939 for _, infile := range infiles {
940 f, err := open(infile)
944 buf, err := io.ReadAll(f)
950 for _, tsv := range bytes.Split(buf, []byte{'\n'}) {
954 split := strings.Split(string(tsv), "\t")
957 for col, name := range split {
958 if name == cmd.chi2CaseControlColumn {
964 return fmt.Errorf("%s: no column named %q in header row %q", infile, cmd.chi2CaseControlColumn, tsv)
968 if len(split) <= ccCol {
973 for i, name := range cmd.cgnames {
974 if strings.Contains(name, pattern) {
976 log.Warnf("pattern %q in %s matches multiple genome IDs (%qs, %q)", pattern, infile, cmd.cgnames[found], name)
982 log.Warnf("pattern %q in %s does not match any genome IDs", pattern, infile)
985 if split[ccCol] == "0" {
988 if split[ccCol] == "1" {
993 allnames := cmd.cgnames
997 for i, name := range allnames {
998 if cc, ok := cc[i]; ok {
999 cmd.cgnames = append(cmd.cgnames, name)
1000 cmd.chi2Cases = append(cmd.chi2Cases, cc)
1006 log.Printf("%d cases, %d controls, %d neither (dropped)", ncases, len(cmd.cgnames)-ncases, len(allnames)-len(cmd.cgnames))
1010 func (cmd *sliceNumpy) filterHGVScolpair(colpair [2][]int8) bool {
1011 if cmd.chi2PValue >= 1 {
1014 col0 := make([]bool, 0, len(cmd.chi2Cases))
1015 col1 := make([]bool, 0, len(cmd.chi2Cases))
1016 cases := make([]bool, 0, len(cmd.chi2Cases))
1017 for i, c := range cmd.chi2Cases {
1018 if colpair[0][i] < 0 {
1021 col0 = append(col0, colpair[0][i] != 0)
1022 col1 = append(col1, colpair[1][i] != 0)
1023 cases = append(cases, c)
1025 return len(cases) >= cmd.minCoverage &&
1026 (pvalue(col0, cases) <= cmd.chi2PValue || pvalue(col1, cases) <= cmd.chi2PValue)
1029 func writeNumpyUint32(fnm string, out []uint32, rows, cols int) error {
1030 output, err := os.Create(fnm)
1034 defer output.Close()
1035 bufw := bufio.NewWriterSize(output, 1<<26)
1036 npw, err := gonpy.NewWriter(nopCloser{bufw})
1040 log.WithFields(log.Fields{
1044 "bytes": rows * cols * 4,
1045 }).Infof("writing numpy: %s", fnm)
1046 npw.Shape = []int{rows, cols}
1047 npw.WriteUint32(out)
1052 return output.Close()
1055 func writeNumpyInt32(fnm string, out []int32, rows, cols int) error {
1056 output, err := os.Create(fnm)
1060 defer output.Close()
1061 bufw := bufio.NewWriterSize(output, 1<<26)
1062 npw, err := gonpy.NewWriter(nopCloser{bufw})
1066 log.WithFields(log.Fields{
1070 "bytes": rows * cols * 4,
1071 }).Infof("writing numpy: %s", fnm)
1072 npw.Shape = []int{rows, cols}
1078 return output.Close()
1081 func writeNumpyInt16(fnm string, out []int16, rows, cols int) error {
1082 output, err := os.Create(fnm)
1086 defer output.Close()
1087 bufw := bufio.NewWriterSize(output, 1<<26)
1088 npw, err := gonpy.NewWriter(nopCloser{bufw})
1092 log.WithFields(log.Fields{
1096 "bytes": rows * cols * 2,
1097 }).Infof("writing numpy: %s", fnm)
1098 npw.Shape = []int{rows, cols}
1104 return output.Close()
1107 func writeNumpyInt8(fnm string, out []int8, rows, cols int) error {
1108 output, err := os.Create(fnm)
1112 defer output.Close()
1113 bufw := bufio.NewWriterSize(output, 1<<26)
1114 npw, err := gonpy.NewWriter(nopCloser{bufw})
1118 log.WithFields(log.Fields{
1122 "bytes": rows * cols,
1123 }).Infof("writing numpy: %s", fnm)
1124 npw.Shape = []int{rows, cols}
1130 return output.Close()
1133 func allele2homhet(colpair [2][]int8) {
1134 a, b := colpair[0], colpair[1]
1135 for i, av := range a {
1137 if av < 0 || bv < 0 {
1140 } else if av > 0 && bv > 0 {
1143 } else if av > 0 || bv > 0 {
1147 // ref (or a different variant in same position)
1148 // (this is a no-op) a[i], b[i] = 0, 0
1153 type onehotXref struct {
1155 variant tileVariantID
1160 const onehotXrefSize = unsafe.Sizeof(onehotXref{})
1162 // Build onehot matrix (m[variant*2+isHet][genome] == 0 or 1) for all
1163 // variants of a single tile/tag#.
1165 // Return nil if no tile variant passes Χ² filter.
1166 func (cmd *sliceNumpy) tv2homhet(cgs map[string]CompactGenome, maxv tileVariantID, remap []tileVariantID, tag, chunkstarttag tagID) ([][]int8, []onehotXref) {
1168 // everyone has the most common variant
1171 tagoffset := tag - chunkstarttag
1173 for _, cg := range cgs {
1174 if cg.Variants[tagoffset*2] > 0 && cg.Variants[tagoffset*2+1] > 0 {
1178 if coverage < cmd.minCoverage {
1181 obs := make([][]bool, (maxv+1)*2) // 2 slices (hom + het) for each variant#
1182 for i := range obs {
1183 obs[i] = make([]bool, len(cmd.cgnames))
1185 for cgid, name := range cmd.cgnames {
1186 cgvars := cgs[name].Variants
1187 for v := tileVariantID(2); v <= maxv; v++ {
1188 if remap[cgvars[tagoffset*2]] == v && remap[cgvars[tagoffset*2+1]] == v {
1189 obs[v*2][cgid] = true
1190 } else if remap[cgvars[tagoffset*2]] == v || remap[cgvars[tagoffset*2+1]] == v {
1191 obs[v*2+1][cgid] = true
1196 var xref []onehotXref
1197 for homcol := 4; homcol < len(obs); homcol += 2 {
1199 pvalue(obs[homcol], cmd.chi2Cases),
1200 pvalue(obs[homcol+1], cmd.chi2Cases),
1202 if cmd.chi2PValue < 1 && !(p[0] < cmd.chi2PValue || p[1] < cmd.chi2PValue) {
1205 for het := 0; het < 2; het++ {
1206 onehot = append(onehot, bool2int8(obs[homcol+het]))
1207 xref = append(xref, onehotXref{
1209 variant: tileVariantID(homcol / 2),
1218 func bool2int8(in []bool) []int8 {
1219 out := make([]int8, len(in))
1220 for i, v := range in {
1228 // convert a []onehotXref with length N to a numpy-style []int32
1229 // matrix with N columns, one row per field of onehotXref struct.
1231 // Hom/het row contains hom=0, het=1.
1233 // P-value row contains 1000000x actual p-value.
1234 func onehotXref2int32(xrefs []onehotXref) []int32 {
1236 xdata := make([]int32, 4*xcols)
1237 for i, xref := range xrefs {
1238 xdata[i] = int32(xref.tag)
1239 xdata[xcols+i] = int32(xref.variant)
1241 xdata[xcols*2+i] = 1
1243 xdata[xcols*3+i] = int32(xref.pvalue * 1000000)
1248 // transpose onehot data from in[col][row] to numpy-style
1249 // out[row*cols+col].
1250 func onehotcols2int8(in [][]int8) []int8 {
1256 out := make([]int8, rows*cols)
1257 for row := 0; row < rows; row++ {
1258 outrow := out[row*cols:]
1259 for col, incol := range in {
1260 outrow[col] = incol[row]
1266 // Return [2][]uint32{rowIndices, colIndices} indicating which
1267 // elements of matrixT[c][r] have non-zero values.
1268 func onehotChunk2Indirect(matrixT [][]int8) [2][]uint32 {
1270 for c, col := range matrixT {
1271 for r, val := range col {
1273 nz[0] = append(nz[0], uint32(r))
1274 nz[1] = append(nz[1], uint32(c))