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
47 func (cmd *sliceNumpy) RunCommand(prog string, args []string, stdin io.Reader, stdout, stderr io.Writer) int {
51 fmt.Fprintf(stderr, "%s\n", err)
54 flags := flag.NewFlagSet("", flag.ContinueOnError)
55 flags.SetOutput(stderr)
56 pprof := flags.String("pprof", "", "serve Go profile data at http://`[addr]:port`")
57 runlocal := flags.Bool("local", false, "run on local host (default: run in an arvados container)")
58 projectUUID := flags.String("project", "", "project `UUID` for output data")
59 priority := flags.Int("priority", 500, "container request priority")
60 inputDir := flags.String("input-dir", "./in", "input `directory`")
61 outputDir := flags.String("output-dir", "./out", "output `directory`")
62 ref := flags.String("ref", "", "reference name (if blank, choose last one that appears in input)")
63 regionsFilename := flags.String("regions", "", "only output columns/annotations that intersect regions in specified bed `file`")
64 expandRegions := flags.Int("expand-regions", 0, "expand specified regions by `N` base pairs on each side`")
65 mergeOutput := flags.Bool("merge-output", false, "merge output into one matrix.npy and one matrix.annotations.csv")
66 hgvsSingle := flags.Bool("single-hgvs-matrix", false, "also generate hgvs-based matrix")
67 hgvsChunked := flags.Bool("chunked-hgvs-matrix", false, "also generate hgvs-based matrix per chromosome")
68 onehotSingle := flags.Bool("single-onehot", false, "generate one-hot tile-based matrix")
69 onehotChunked := flags.Bool("chunked-onehot", false, "generate one-hot tile-based matrix per input chunk")
70 flags.IntVar(&cmd.threads, "threads", 16, "number of memory-hungry assembly threads")
71 flags.StringVar(&cmd.chi2CaseControlFile, "chi2-case-control-file", "", "tsv file or directory indicating cases and controls for Χ² test (if directory, all .tsv files will be read)")
72 flags.StringVar(&cmd.chi2CaseControlColumn, "chi2-case-control-column", "", "name of case/control column in case-control files for Χ² test (value must be 0 for control, 1 for case)")
73 flags.Float64Var(&cmd.chi2PValue, "chi2-p-value", 1, "do Χ² test and omit columns with p-value above this threshold")
74 flags.BoolVar(&cmd.includeVariant1, "include-variant-1", false, "include most common variant when building one-hot matrix")
75 cmd.filter.Flags(flags)
76 err = flags.Parse(args)
77 if err == flag.ErrHelp {
80 } else if err != nil {
86 log.Println(http.ListenAndServe(*pprof, nil))
90 if cmd.chi2PValue != 1 && (cmd.chi2CaseControlFile == "" || cmd.chi2CaseControlColumn == "") {
91 log.Errorf("cannot use provided -chi2-p-value=%f because -chi2-case-control-file= or -chi2-case-control-column= value is empty", cmd.chi2PValue)
96 runner := arvadosContainerRunner{
97 Name: "lightning slice-numpy",
98 Client: arvados.NewClientFromEnv(),
99 ProjectUUID: *projectUUID,
106 err = runner.TranslatePaths(inputDir, regionsFilename, &cmd.chi2CaseControlFile)
110 runner.Args = []string{"slice-numpy", "-local=true",
112 "-input-dir=" + *inputDir,
113 "-output-dir=/mnt/output",
114 "-threads=" + fmt.Sprintf("%d", cmd.threads),
115 "-regions=" + *regionsFilename,
116 "-expand-regions=" + fmt.Sprintf("%d", *expandRegions),
117 "-merge-output=" + fmt.Sprintf("%v", *mergeOutput),
118 "-single-hgvs-matrix=" + fmt.Sprintf("%v", *hgvsSingle),
119 "-chunked-hgvs-matrix=" + fmt.Sprintf("%v", *hgvsChunked),
120 "-single-onehot=" + fmt.Sprintf("%v", *onehotSingle),
121 "-chunked-onehot=" + fmt.Sprintf("%v", *onehotChunked),
122 "-chi2-case-control-file=" + cmd.chi2CaseControlFile,
123 "-chi2-case-control-column=" + cmd.chi2CaseControlColumn,
124 "-chi2-p-value=" + fmt.Sprintf("%f", cmd.chi2PValue),
125 "-include-variant-1=" + fmt.Sprintf("%v", cmd.includeVariant1),
127 runner.Args = append(runner.Args, cmd.filter.Args()...)
129 output, err = runner.Run()
133 fmt.Fprintln(stdout, output)
137 infiles, err := allFiles(*inputDir, matchGobFile)
141 if len(infiles) == 0 {
142 err = fmt.Errorf("no input files found in %s", *inputDir)
145 sort.Strings(infiles)
147 var refseq map[string][]tileLibRef
148 var reftiledata = make(map[tileLibRef][]byte, 11000000)
149 in0, err := open(infiles[0])
154 matchGenome, err := regexp.Compile(cmd.filter.MatchGenome)
156 err = fmt.Errorf("-match-genome: invalid regexp: %q", cmd.filter.MatchGenome)
162 DecodeLibrary(in0, strings.HasSuffix(infiles[0], ".gz"), func(ent *LibraryEntry) error {
163 if len(ent.TagSet) > 0 {
166 for _, cseq := range ent.CompactSequences {
167 if cseq.Name == *ref || *ref == "" {
168 refseq = cseq.TileSequences
171 for _, cg := range ent.CompactGenomes {
172 if matchGenome.MatchString(cg.Name) {
173 cmd.cgnames = append(cmd.cgnames, cg.Name)
176 for _, tv := range ent.TileVariants {
178 reftiledata[tileLibRef{tv.Tag, tv.Variant}] = tv.Sequence
188 err = fmt.Errorf("%s: reference sequence not found", infiles[0])
191 if len(tagset) == 0 {
192 err = fmt.Errorf("tagset not found")
196 taglib := &tagLibrary{}
197 err = taglib.setTags(tagset)
201 taglen := taglib.TagLen()
203 if len(cmd.cgnames) == 0 {
204 err = fmt.Errorf("no genomes found matching regexp %q", cmd.filter.MatchGenome)
207 sort.Strings(cmd.cgnames)
208 err = cmd.useCaseControlFiles()
212 cmd.minCoverage = int(math.Ceil(cmd.filter.MinCoverage * float64(len(cmd.cgnames))))
215 labelsFilename := *outputDir + "/samples.csv"
216 log.Infof("writing labels to %s", labelsFilename)
218 f, err = os.Create(labelsFilename)
223 for i, name := range cmd.cgnames {
225 if cmd.chi2Cases != nil && cmd.chi2Cases[i] {
228 _, err = fmt.Fprintf(f, "%d,%q,%d\n", i, trimFilenameForLabel(name), cc)
230 err = fmt.Errorf("write %s: %w", labelsFilename, err)
236 err = fmt.Errorf("close %s: %w", labelsFilename, err)
241 log.Info("indexing reference tiles")
242 type reftileinfo struct {
243 variant tileVariantID
244 seqname string // chr1
245 pos int // distance from start of chromosome to starttag
246 tiledata []byte // acgtggcaa...
248 isdup := map[tagID]bool{}
249 reftile := map[tagID]*reftileinfo{}
250 for seqname, cseq := range refseq {
252 for _, libref := range cseq {
253 if cmd.filter.MaxTag >= 0 && libref.Tag > tagID(cmd.filter.MaxTag) {
256 tiledata := reftiledata[libref]
257 if len(tiledata) == 0 {
258 err = fmt.Errorf("missing tiledata for tag %d variant %d in %s in ref", libref.Tag, libref.Variant, seqname)
261 foundthistag := false
262 taglib.FindAll(tiledata[:len(tiledata)-1], func(tagid tagID, offset, _ int) {
263 if !foundthistag && tagid == libref.Tag {
267 if dupref, ok := reftile[tagid]; ok {
268 log.Printf("dropping reference tile %+v from %s @ %d, tag not unique, also found inside %+v from %s @ %d", tileLibRef{Tag: tagid, Variant: dupref.variant}, dupref.seqname, dupref.pos, libref, seqname, pos+offset+1)
269 delete(reftile, tagid)
271 log.Printf("found tag %d at offset %d inside tile variant %+v on %s @ %d", tagid, offset, libref, seqname, pos+offset+1)
275 if isdup[libref.Tag] {
276 log.Printf("dropping reference tile %+v from %s @ %d, tag not unique", libref, seqname, pos)
277 } else if reftile[libref.Tag] != nil {
278 log.Printf("dropping reference tile %+v from %s @ %d, tag not unique", tileLibRef{Tag: libref.Tag, Variant: reftile[libref.Tag].variant}, reftile[libref.Tag].seqname, reftile[libref.Tag].pos)
279 delete(reftile, libref.Tag)
280 log.Printf("dropping reference tile %+v from %s @ %d, tag not unique", libref, seqname, pos)
281 isdup[libref.Tag] = true
283 reftile[libref.Tag] = &reftileinfo{
285 variant: libref.Variant,
290 pos += len(tiledata) - taglen
292 log.Printf("... %s done, len %d", seqname, pos+taglen)
296 if *regionsFilename != "" {
297 log.Printf("loading regions from %s", *regionsFilename)
298 mask, err = makeMask(*regionsFilename, *expandRegions)
302 log.Printf("before applying mask, len(reftile) == %d", len(reftile))
303 log.Printf("deleting reftile entries for regions outside %d intervals", mask.Len())
304 for tag, rt := range reftile {
305 if !mask.Check(strings.TrimPrefix(rt.seqname, "chr"), rt.pos, rt.pos+len(rt.tiledata)) {
309 log.Printf("after applying mask, len(reftile) == %d", len(reftile))
312 type hgvsColSet map[hgvs.Variant][2][]int8
313 encodeHGVS := throttle{Max: len(refseq)}
314 encodeHGVSTodo := map[string]chan hgvsColSet{}
315 tmpHGVSCols := map[string]*os.File{}
317 for seqname := range refseq {
319 f, err = os.Create(*outputDir + "/tmp." + seqname + ".gob")
323 defer os.Remove(f.Name())
324 bufw := bufio.NewWriterSize(f, 1<<24)
325 enc := gob.NewEncoder(bufw)
326 tmpHGVSCols[seqname] = f
327 todo := make(chan hgvsColSet, 128)
328 encodeHGVSTodo[seqname] = todo
329 encodeHGVS.Go(func() error {
330 for colset := range todo {
331 err := enc.Encode(colset)
333 encodeHGVS.Report(err)
344 var toMerge [][]int16
345 if *mergeOutput || *hgvsSingle {
346 toMerge = make([][]int16, len(infiles))
348 var onehotIndirect [][2][]uint32 // [chunkIndex][axis][index]
349 var onehotChunkSize []uint32
350 var onehotXrefs [][]onehotXref
352 onehotIndirect = make([][2][]uint32, len(infiles))
353 onehotChunkSize = make([]uint32, len(infiles))
354 onehotXrefs = make([][]onehotXref, len(infiles))
357 throttleMem := throttle{Max: cmd.threads} // TODO: estimate using mem and data size
358 throttleNumpyMem := throttle{Max: cmd.threads/2 + 1}
359 log.Info("generating annotations and numpy matrix for each slice")
361 for infileIdx, infile := range infiles {
362 infileIdx, infile := infileIdx, infile
363 throttleMem.Go(func() error {
364 seq := make(map[tagID][]TileVariant, 50000)
365 cgs := make(map[string]CompactGenome, len(cmd.cgnames))
366 f, err := open(infile)
371 log.Infof("%04d: reading %s", infileIdx, infile)
372 err = DecodeLibrary(f, strings.HasSuffix(infile, ".gz"), func(ent *LibraryEntry) error {
373 for _, tv := range ent.TileVariants {
377 if mask != nil && reftile[tv.Tag] == nil {
383 variants := seq[tv.Tag]
384 if len(variants) == 0 {
385 variants = make([]TileVariant, 100)
387 for len(variants) <= int(tv.Variant) {
388 variants = append(variants, TileVariant{})
390 variants[int(tv.Variant)] = tv
391 seq[tv.Tag] = variants
393 for _, cg := range ent.CompactGenomes {
394 if !matchGenome.MatchString(cg.Name) {
397 // pad to full slice size
398 // to avoid out-of-bounds
400 if sliceSize := 2 * int(cg.EndTag-cg.StartTag); len(cg.Variants) < sliceSize {
401 cg.Variants = append(cg.Variants, make([]tileVariantID, sliceSize-len(cg.Variants))...)
410 tagstart := cgs[cmd.cgnames[0]].StartTag
411 tagend := cgs[cmd.cgnames[0]].EndTag
415 log.Infof("%04d: renumber/dedup variants for tags %d-%d", infileIdx, tagstart, tagend)
416 variantRemap := make([][]tileVariantID, tagend-tagstart)
417 throttleCPU := throttle{Max: runtime.GOMAXPROCS(0)}
418 for tag, variants := range seq {
419 tag, variants := tag, variants
420 throttleCPU.Acquire()
422 defer throttleCPU.Release()
423 count := make(map[[blake2b.Size256]byte]int, len(variants))
427 count[blake2b.Sum256(rt.tiledata)] = 0
430 for _, cg := range cgs {
431 idx := int(tag-tagstart) * 2
432 for allele := 0; allele < 2; allele++ {
433 v := cg.Variants[idx+allele]
434 if v > 0 && len(variants[v].Sequence) > 0 {
435 count[variants[v].Blake2b]++
439 // hash[i] will be the hash of
440 // the variant(s) that should
441 // be at rank i (0-based).
442 hash := make([][blake2b.Size256]byte, 0, len(count))
443 for b := range count {
444 hash = append(hash, b)
446 sort.Slice(hash, func(i, j int) bool {
447 bi, bj := &hash[i], &hash[j]
448 if ci, cj := count[*bi], count[*bj]; ci != cj {
451 return bytes.Compare((*bi)[:], (*bj)[:]) < 0
454 // rank[b] will be the 1-based
455 // new variant number for
456 // variants whose hash is b.
457 rank := make(map[[blake2b.Size256]byte]tileVariantID, len(hash))
458 for i, h := range hash {
459 rank[h] = tileVariantID(i + 1)
461 // remap[v] will be the new
462 // variant number for original
464 remap := make([]tileVariantID, len(variants))
465 for i, tv := range variants {
466 remap[i] = rank[tv.Blake2b]
468 variantRemap[tag-tagstart] = remap
470 rt.variant = rank[blake2b.Sum256(rt.tiledata)]
476 var onehotChunk [][]int8
477 var onehotXref []onehotXref
479 annotationsFilename := fmt.Sprintf("%s/matrix.%04d.annotations.csv", *outputDir, infileIdx)
480 log.Infof("%04d: writing %s", infileIdx, annotationsFilename)
481 annof, err := os.Create(annotationsFilename)
485 annow := bufio.NewWriterSize(annof, 1<<20)
487 for tag := tagstart; tag < tagend; tag++ {
489 if rt == nil && mask != nil {
490 // Excluded by specified regions
493 if cmd.filter.MaxTag >= 0 && tag > tagID(cmd.filter.MaxTag) {
496 remap := variantRemap[tag-tagstart]
497 maxv := tileVariantID(0)
498 for _, v := range remap {
503 if *onehotChunked || *onehotSingle {
504 onehot, xrefs := cmd.tv2homhet(cgs, maxv, remap, tag, tagstart)
505 onehotChunk = append(onehotChunk, onehot...)
506 onehotXref = append(onehotXref, xrefs...)
509 // Reference does not use any
510 // variant of this tile
514 fmt.Fprintf(annow, "%d,%d,%d,=,%s,%d,,,\n", tag, outcol, rt.variant, rt.seqname, rt.pos)
516 reftilestr := strings.ToUpper(string(rt.tiledata))
518 done := make([]bool, maxv+1)
519 variantDiffs := make([][]hgvs.Variant, maxv+1)
520 for v, tv := range variants {
522 if v == rt.variant || done[v] {
527 if len(tv.Sequence) < taglen || !bytes.HasSuffix(rt.tiledata, tv.Sequence[len(tv.Sequence)-taglen:]) {
528 fmt.Fprintf(annow, "%d,%d,%d,,%s,%d,,,\n", tag, outcol, v, rt.seqname, rt.pos)
531 if lendiff := len(rt.tiledata) - len(tv.Sequence); lendiff < -1000 || lendiff > 1000 {
532 fmt.Fprintf(annow, "%d,%d,%d,,%s,%d,,,\n", tag, outcol, v, rt.seqname, rt.pos)
535 diffs, _ := hgvs.Diff(reftilestr, strings.ToUpper(string(tv.Sequence)), 0)
536 for i := range diffs {
537 diffs[i].Position += rt.pos
539 for _, diff := range diffs {
540 fmt.Fprintf(annow, "%d,%d,%d,%s:g.%s,%s,%d,%s,%s,%s\n", tag, outcol, v, rt.seqname, diff.String(), rt.seqname, diff.Position, diff.Ref, diff.New, diff.Left)
543 variantDiffs[v] = diffs
547 // We can now determine, for each HGVS
548 // variant (diff) in this reftile
549 // region, whether a given genome
550 // phase/allele (1) has the variant, (0) has
551 // =ref or a different variant in that
552 // position, or (-1) is lacking
553 // coverage / couldn't be diffed.
554 hgvsCol := hgvsColSet{}
555 for _, diffs := range variantDiffs {
556 for _, diff := range diffs {
557 if _, ok := hgvsCol[diff]; ok {
560 hgvsCol[diff] = [2][]int8{
561 make([]int8, len(cmd.cgnames)),
562 make([]int8, len(cmd.cgnames)),
566 for row, name := range cmd.cgnames {
567 variants := cgs[name].Variants[(tag-tagstart)*2:]
568 for ph := 0; ph < 2; ph++ {
570 if int(v) >= len(remap) {
576 // hgvsCol[*][ph][row] is already 0
577 } else if len(variantDiffs[v]) == 0 {
578 // lacking coverage / couldn't be diffed
579 for _, col := range hgvsCol {
583 for _, diff := range variantDiffs[v] {
584 hgvsCol[diff][ph][row] = 1
589 for diff, colpair := range hgvsCol {
590 allele2homhet(colpair)
591 if !cmd.filterHGVScolpair(colpair) {
592 delete(hgvsCol, diff)
595 if len(hgvsCol) > 0 {
596 encodeHGVSTodo[rt.seqname] <- hgvsCol
611 // transpose onehotChunk[col][row] to numpy[row*ncols+col]
612 rows := len(cmd.cgnames)
613 cols := len(onehotChunk)
614 log.Infof("%04d: preparing onehot numpy (rows=%d, cols=%d, mem=%d)", infileIdx, len(cmd.cgnames), len(onehotChunk), len(cmd.cgnames)*len(onehotChunk))
615 throttleNumpyMem.Acquire()
616 out := onehotcols2int8(onehotChunk)
617 fnm := fmt.Sprintf("%s/onehot.%04d.npy", *outputDir, infileIdx)
618 err = writeNumpyInt8(fnm, out, rows, cols)
622 fnm = fmt.Sprintf("%s/onehot-columns.%04d.npy", *outputDir, infileIdx)
623 err = writeNumpyInt32(fnm, onehotXref2int32(onehotXref), 4, len(onehotXref))
628 throttleNumpyMem.Release()
631 onehotIndirect[infileIdx] = onehotChunk2Indirect(onehotChunk)
632 onehotChunkSize[infileIdx] = uint32(len(onehotChunk))
633 onehotXrefs[infileIdx] = onehotXref
634 n := len(onehotIndirect[infileIdx][0])
635 log.Infof("%04d: keeping onehot coordinates in memory (n=%d, mem=%d)", infileIdx, n, n*8*2)
637 if !(*onehotSingle || *onehotChunked) || *mergeOutput || *hgvsSingle {
638 log.Infof("%04d: preparing numpy (rows=%d, cols=%d)", infileIdx, len(cmd.cgnames), 2*outcol)
639 throttleNumpyMem.Acquire()
640 rows := len(cmd.cgnames)
642 out := make([]int16, rows*cols)
643 for row, name := range cmd.cgnames {
644 out := out[row*cols:]
646 for col, v := range cgs[name].Variants {
647 tag := tagstart + tagID(col/2)
648 if mask != nil && reftile[tag] == nil || (cmd.filter.MaxTag >= 0 && tag > tagID(cmd.filter.MaxTag)) {
651 if variants, ok := seq[tag]; ok && len(variants) > int(v) && len(variants[v].Sequence) > 0 {
652 out[outcol] = int16(variantRemap[tag-tagstart][v])
662 throttleNumpyMem.Release()
663 if *mergeOutput || *hgvsSingle {
664 log.Infof("%04d: matrix fragment %d rows x %d cols", infileIdx, rows, cols)
665 toMerge[infileIdx] = out
667 if !*mergeOutput && !*onehotChunked && !*onehotSingle {
668 fnm := fmt.Sprintf("%s/matrix.%04d.npy", *outputDir, infileIdx)
669 err = writeNumpyInt16(fnm, out, rows, cols)
676 log.Infof("%s: done (%d/%d)", infile, int(atomic.AddInt64(&done, 1)), len(infiles))
680 if err = throttleMem.Wait(); err != nil {
685 log.Info("flushing hgvsCols temp files")
686 for seqname := range refseq {
687 close(encodeHGVSTodo[seqname])
689 err = encodeHGVS.Wait()
693 for seqname := range refseq {
694 log.Infof("%s: reading hgvsCols from temp file", seqname)
695 f := tmpHGVSCols[seqname]
696 _, err = f.Seek(0, io.SeekStart)
700 var hgvsCols hgvsColSet
701 dec := gob.NewDecoder(bufio.NewReaderSize(f, 1<<24))
703 err = dec.Decode(&hgvsCols)
708 log.Infof("%s: sorting %d hgvs variants", seqname, len(hgvsCols))
709 variants := make([]hgvs.Variant, 0, len(hgvsCols))
710 for v := range hgvsCols {
711 variants = append(variants, v)
713 sort.Slice(variants, func(i, j int) bool {
714 vi, vj := &variants[i], &variants[j]
715 if vi.Position != vj.Position {
716 return vi.Position < vj.Position
717 } else if vi.Ref != vj.Ref {
718 return vi.Ref < vj.Ref
720 return vi.New < vj.New
723 rows := len(cmd.cgnames)
724 cols := len(variants) * 2
725 log.Infof("%s: building hgvs matrix (rows=%d, cols=%d, mem=%d)", seqname, rows, cols, rows*cols)
726 out := make([]int8, rows*cols)
727 for varIdx, variant := range variants {
728 hgvsCols := hgvsCols[variant]
729 for row := range cmd.cgnames {
730 for ph := 0; ph < 2; ph++ {
731 out[row*cols+varIdx+ph] = hgvsCols[ph][row]
735 err = writeNumpyInt8(fmt.Sprintf("%s/hgvs.%s.npy", *outputDir, seqname), out, rows, cols)
741 fnm := fmt.Sprintf("%s/hgvs.%s.annotations.csv", *outputDir, seqname)
742 log.Infof("%s: writing hgvs column labels to %s", seqname, fnm)
743 var hgvsLabels bytes.Buffer
744 for varIdx, variant := range variants {
745 fmt.Fprintf(&hgvsLabels, "%d,%s:g.%s\n", varIdx, seqname, variant.String())
747 err = ioutil.WriteFile(fnm, hgvsLabels.Bytes(), 0666)
754 if *mergeOutput || *hgvsSingle {
755 var annow *bufio.Writer
758 annoFilename := fmt.Sprintf("%s/matrix.annotations.csv", *outputDir)
759 annof, err = os.Create(annoFilename)
763 annow = bufio.NewWriterSize(annof, 1<<20)
766 rows := len(cmd.cgnames)
768 for _, chunk := range toMerge {
769 cols += len(chunk) / rows
771 log.Infof("merging output matrix (rows=%d, cols=%d, mem=%d) and annotations", rows, cols, rows*cols*2)
774 out = make([]int16, rows*cols)
776 hgvsCols := map[string][2][]int16{} // hgvs -> [[g0,g1,g2,...], [g0,g1,g2,...]] (slice of genomes for each phase)
778 for outIdx, chunk := range toMerge {
779 chunkcols := len(chunk) / rows
781 for row := 0; row < rows; row++ {
782 copy(out[row*cols+startcol:], chunk[row*chunkcols:(row+1)*chunkcols])
785 toMerge[outIdx] = nil
787 annotationsFilename := fmt.Sprintf("%s/matrix.%04d.annotations.csv", *outputDir, outIdx)
788 log.Infof("reading %s", annotationsFilename)
789 buf, err := os.ReadFile(annotationsFilename)
794 err = os.Remove(annotationsFilename)
799 for _, line := range bytes.Split(buf, []byte{'\n'}) {
803 fields := bytes.SplitN(line, []byte{','}, 9)
804 tag, _ := strconv.Atoi(string(fields[0]))
805 incol, _ := strconv.Atoi(string(fields[1]))
806 tileVariant, _ := strconv.Atoi(string(fields[2]))
807 hgvsID := string(fields[3])
808 seqname := string(fields[4])
809 pos, _ := strconv.Atoi(string(fields[5]))
812 // Null entry for un-diffable
817 // Null entry for ref tile
820 if mask != nil && !mask.Check(strings.TrimPrefix(seqname, "chr"), pos, pos+len(refseq)) {
821 // The tile intersects one of
822 // the selected regions, but
823 // this particular HGVS
827 hgvsColPair := hgvsCols[hgvsID]
828 if hgvsColPair[0] == nil {
829 // values in new columns start
830 // out as -1 ("no data yet")
831 // or 0 ("=ref") here, may
832 // change to 1 ("hgvs variant
833 // present") below, either on
834 // this line or a future line.
835 hgvsColPair = [2][]int16{make([]int16, len(cmd.cgnames)), make([]int16, len(cmd.cgnames))}
836 rt, ok := reftile[tagID(tag)]
838 err = fmt.Errorf("bug: seeing annotations for tag %d, but it has no reftile entry", tag)
841 for ph := 0; ph < 2; ph++ {
842 for row := 0; row < rows; row++ {
843 v := chunk[row*chunkcols+incol*2+ph]
844 if tileVariantID(v) == rt.variant {
845 hgvsColPair[ph][row] = 0
847 hgvsColPair[ph][row] = -1
851 hgvsCols[hgvsID] = hgvsColPair
853 hgvsref := hgvs.Variant{
858 fmt.Fprintf(annow, "%d,%d,%d,%s:g.%s,%s,%d,%s,%s,%s\n", tag, incol+startcol/2, rt.variant, seqname, hgvsref.String(), seqname, pos, refseq, refseq, fields[8])
862 fmt.Fprintf(annow, "%d,%d,%d,%s,%s,%d,%s,%s,%s\n", tag, incol+startcol/2, tileVariant, hgvsID, seqname, pos, refseq, fields[7], fields[8])
864 for ph := 0; ph < 2; ph++ {
865 for row := 0; row < rows; row++ {
866 v := chunk[row*chunkcols+incol*2+ph]
867 if int(v) == tileVariant {
868 hgvsColPair[ph][row] = 1
874 startcol += chunkcols
885 err = writeNumpyInt16(fmt.Sprintf("%s/matrix.npy", *outputDir), out, rows, cols)
893 cols = len(hgvsCols) * 2
894 log.Printf("building hgvs-based matrix: %d rows x %d cols", rows, cols)
895 out = make([]int16, rows*cols)
896 hgvsIDs := make([]string, 0, cols/2)
897 for hgvsID := range hgvsCols {
898 hgvsIDs = append(hgvsIDs, hgvsID)
900 sort.Strings(hgvsIDs)
901 var hgvsLabels bytes.Buffer
902 for idx, hgvsID := range hgvsIDs {
903 fmt.Fprintf(&hgvsLabels, "%d,%s\n", idx, hgvsID)
904 for ph := 0; ph < 2; ph++ {
905 hgvscol := hgvsCols[hgvsID][ph]
906 for row, val := range hgvscol {
907 out[row*cols+idx*2+ph] = val
911 err = writeNumpyInt16(fmt.Sprintf("%s/hgvs.npy", *outputDir), out, rows, cols)
916 fnm := fmt.Sprintf("%s/hgvs.annotations.csv", *outputDir)
917 log.Printf("writing hgvs labels: %s", fnm)
918 err = ioutil.WriteFile(fnm, hgvsLabels.Bytes(), 0777)
926 for _, part := range onehotIndirect {
927 nzCount += len(part[0])
929 onehot := make([]uint32, nzCount*2) // [r,r,r,...,c,c,c,...]
930 var xrefs []onehotXref
931 chunkOffset := uint32(0)
933 for i, part := range onehotIndirect {
934 for i := range part[1] {
935 part[1][i] += chunkOffset
937 copy(onehot[outcol:], part[0])
938 copy(onehot[outcol+nzCount:], part[1])
939 xrefs = append(xrefs, onehotXrefs[i]...)
941 outcol += len(part[0])
942 chunkOffset += onehotChunkSize[i]
949 fnm := fmt.Sprintf("%s/onehot.npy", *outputDir)
950 err = writeNumpyUint32(fnm, onehot, 2, nzCount)
954 fnm = fmt.Sprintf("%s/onehot-columns.npy", *outputDir)
955 err = writeNumpyInt32(fnm, onehotXref2int32(xrefs), 4, len(xrefs))
963 // Read case/control files, remove non-case/control entries from
964 // cmd.cgnames, and build cmd.chi2Cases.
965 func (cmd *sliceNumpy) useCaseControlFiles() error {
966 if cmd.chi2CaseControlFile == "" {
969 infiles, err := allFiles(cmd.chi2CaseControlFile, nil)
973 // index in cmd.cgnames => case(true) / control(false)
975 for _, infile := range infiles {
976 f, err := open(infile)
980 buf, err := io.ReadAll(f)
986 for _, tsv := range bytes.Split(buf, []byte{'\n'}) {
990 split := strings.Split(string(tsv), "\t")
993 for col, name := range split {
994 if name == cmd.chi2CaseControlColumn {
1000 return fmt.Errorf("%s: no column named %q in header row %q", infile, cmd.chi2CaseControlColumn, tsv)
1004 if len(split) <= ccCol {
1009 for i, name := range cmd.cgnames {
1010 if strings.Contains(name, pattern) {
1012 log.Warnf("pattern %q in %s matches multiple genome IDs (%qs, %q)", pattern, infile, cmd.cgnames[found], name)
1018 log.Warnf("pattern %q in %s does not match any genome IDs", pattern, infile)
1021 if split[ccCol] == "0" {
1024 if split[ccCol] == "1" {
1029 allnames := cmd.cgnames
1033 for i, name := range allnames {
1034 if cc, ok := cc[i]; ok {
1035 cmd.cgnames = append(cmd.cgnames, name)
1036 cmd.chi2Cases = append(cmd.chi2Cases, cc)
1042 log.Printf("%d cases, %d controls, %d neither (dropped)", ncases, len(cmd.cgnames)-ncases, len(allnames)-len(cmd.cgnames))
1046 func (cmd *sliceNumpy) filterHGVScolpair(colpair [2][]int8) bool {
1047 if cmd.chi2PValue >= 1 {
1050 col0 := make([]bool, 0, len(cmd.chi2Cases))
1051 col1 := make([]bool, 0, len(cmd.chi2Cases))
1052 cases := make([]bool, 0, len(cmd.chi2Cases))
1053 for i, c := range cmd.chi2Cases {
1054 if colpair[0][i] < 0 {
1057 col0 = append(col0, colpair[0][i] != 0)
1058 col1 = append(col1, colpair[1][i] != 0)
1059 cases = append(cases, c)
1061 return len(cases) >= cmd.minCoverage &&
1062 (pvalue(col0, cases) <= cmd.chi2PValue || pvalue(col1, cases) <= cmd.chi2PValue)
1065 func writeNumpyUint32(fnm string, out []uint32, 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 * 4,
1081 }).Infof("writing numpy: %s", fnm)
1082 npw.Shape = []int{rows, cols}
1083 npw.WriteUint32(out)
1088 return output.Close()
1091 func writeNumpyInt32(fnm string, out []int32, rows, cols int) error {
1092 output, err := os.Create(fnm)
1096 defer output.Close()
1097 bufw := bufio.NewWriterSize(output, 1<<26)
1098 npw, err := gonpy.NewWriter(nopCloser{bufw})
1102 log.WithFields(log.Fields{
1106 "bytes": rows * cols * 4,
1107 }).Infof("writing numpy: %s", fnm)
1108 npw.Shape = []int{rows, cols}
1114 return output.Close()
1117 func writeNumpyInt16(fnm string, out []int16, rows, cols int) error {
1118 output, err := os.Create(fnm)
1122 defer output.Close()
1123 bufw := bufio.NewWriterSize(output, 1<<26)
1124 npw, err := gonpy.NewWriter(nopCloser{bufw})
1128 log.WithFields(log.Fields{
1132 "bytes": rows * cols * 2,
1133 }).Infof("writing numpy: %s", fnm)
1134 npw.Shape = []int{rows, cols}
1140 return output.Close()
1143 func writeNumpyInt8(fnm string, out []int8, rows, cols int) error {
1144 output, err := os.Create(fnm)
1148 defer output.Close()
1149 bufw := bufio.NewWriterSize(output, 1<<26)
1150 npw, err := gonpy.NewWriter(nopCloser{bufw})
1154 log.WithFields(log.Fields{
1158 "bytes": rows * cols,
1159 }).Infof("writing numpy: %s", fnm)
1160 npw.Shape = []int{rows, cols}
1166 return output.Close()
1169 func allele2homhet(colpair [2][]int8) {
1170 a, b := colpair[0], colpair[1]
1171 for i, av := range a {
1173 if av < 0 || bv < 0 {
1176 } else if av > 0 && bv > 0 {
1179 } else if av > 0 || bv > 0 {
1183 // ref (or a different variant in same position)
1184 // (this is a no-op) a[i], b[i] = 0, 0
1189 type onehotXref struct {
1191 variant tileVariantID
1196 const onehotXrefSize = unsafe.Sizeof(onehotXref{})
1198 // Build onehot matrix (m[tileVariantIndex][genome] == 0 or 1) for all
1199 // variants of a single tile/tag#.
1201 // Return nil if no tile variant passes Χ² filter.
1202 func (cmd *sliceNumpy) tv2homhet(cgs map[string]CompactGenome, maxv tileVariantID, remap []tileVariantID, tag, chunkstarttag tagID) ([][]int8, []onehotXref) {
1203 if maxv < 1 || (maxv < 2 && !cmd.includeVariant1) {
1204 // everyone has the most common variant (of the variants we don't drop)
1207 tagoffset := tag - chunkstarttag
1209 for _, cg := range cgs {
1210 if cg.Variants[tagoffset*2] > 0 && cg.Variants[tagoffset*2+1] > 0 {
1214 if coverage < cmd.minCoverage {
1217 obs := make([][]bool, (maxv+1)*2) // 2 slices (hom + het) for each variant#
1218 for i := range obs {
1219 obs[i] = make([]bool, len(cmd.cgnames))
1221 for cgid, name := range cmd.cgnames {
1222 cgvars := cgs[name].Variants[tagoffset*2:]
1223 tv0, tv1 := remap[cgvars[0]], remap[cgvars[1]]
1224 for v := tileVariantID(1); v <= maxv; v++ {
1225 if tv0 == v && tv1 == v {
1226 obs[v*2][cgid] = true
1227 } else if tv0 == v || tv1 == v {
1228 obs[v*2+1][cgid] = true
1233 var xref []onehotXref
1234 for col := 2; col < len(obs); col++ {
1235 // col 0,1 correspond to tile variant 0, i.e.,
1236 // no-call; col 2,3 correspond to the most common
1237 // variant; so we (normally) start at col 4.
1238 if col < 4 && !cmd.includeVariant1 {
1241 p := pvalue(obs[col], cmd.chi2Cases)
1242 if cmd.chi2PValue < 1 && !(p < cmd.chi2PValue) {
1245 onehot = append(onehot, bool2int8(obs[col]))
1246 xref = append(xref, onehotXref{
1248 variant: tileVariantID(col >> 1),
1256 func bool2int8(in []bool) []int8 {
1257 out := make([]int8, len(in))
1258 for i, v := range in {
1266 // convert a []onehotXref with length N to a numpy-style []int32
1267 // matrix with N columns, one row per field of onehotXref struct.
1269 // Hom/het row contains hom=0, het=1.
1271 // P-value row contains 1000000x actual p-value.
1272 func onehotXref2int32(xrefs []onehotXref) []int32 {
1274 xdata := make([]int32, 4*xcols)
1275 for i, xref := range xrefs {
1276 xdata[i] = int32(xref.tag)
1277 xdata[xcols+i] = int32(xref.variant)
1279 xdata[xcols*2+i] = 1
1281 xdata[xcols*3+i] = int32(xref.pvalue * 1000000)
1286 // transpose onehot data from in[col][row] to numpy-style
1287 // out[row*cols+col].
1288 func onehotcols2int8(in [][]int8) []int8 {
1294 out := make([]int8, rows*cols)
1295 for row := 0; row < rows; row++ {
1296 outrow := out[row*cols:]
1297 for col, incol := range in {
1298 outrow[col] = incol[row]
1304 // Return [2][]uint32{rowIndices, colIndices} indicating which
1305 // elements of matrixT[c][r] have non-zero values.
1306 func onehotChunk2Indirect(matrixT [][]int8) [2][]uint32 {
1308 for c, col := range matrixT {
1309 for r, val := range col {
1311 nz[0] = append(nz[0], uint32(r))
1312 nz[1] = append(nz[1], uint32(c))