X-Git-Url: https://git.arvados.org/lightning.git/blobdiff_plain/0139f5a4367b378cb0031a1ac7558d3d76b44f5b..ceee3803f9b1ad3eef8b7abd45dc1327c062738c:/export.go diff --git a/export.go b/export.go index ac7f5292be..1ea08fe757 100644 --- a/export.go +++ b/export.go @@ -1,3 +1,7 @@ +// Copyright (C) The Lightning Authors. All rights reserved. +// +// SPDX-License-Identifier: AGPL-3.0 + package lightning import ( @@ -14,36 +18,51 @@ import ( "path/filepath" "runtime" "sort" + "strconv" "strings" "sync" "time" "git.arvados.org/arvados.git/sdk/go/arvados" "github.com/arvados/lightning/hgvs" + "github.com/klauspost/pgzip" + "github.com/kshedden/gonpy" + "github.com/sirupsen/logrus" log "github.com/sirupsen/logrus" ) -type outputFormat struct { - Filename string - Print func(out io.Writer, seqname string, varslice []hgvs.Variant) - PadLeft bool +type tvVariant struct { + hgvs.Variant + librefs map[tileLibRef]bool } -var ( - outputFormats = map[string]outputFormat{ - "hgvs-onehot": outputFormatHGVSOneHot, - "hgvs": outputFormatHGVS, - "vcf": outputFormatVCF, - } - outputFormatHGVS = outputFormat{Filename: "out.csv", Print: printHGVS} - outputFormatHGVSOneHot = outputFormat{Filename: "out.csv", Print: printHGVSOneHot} - outputFormatVCF = outputFormat{Filename: "out.vcf", Print: printVCF, PadLeft: true} -) +type outputFormat interface { + Filename() string + PadLeft() bool + Head(out io.Writer, cgs []CompactGenome, cases []bool, p float64) error + Print(out io.Writer, seqname string, varslice []tvVariant) error + Finish(outdir string, out io.Writer, seqname string) error + MaxGoroutines() int +} + +var outputFormats = map[string]func() outputFormat{ + "hgvs-numpy": func() outputFormat { + return &formatHGVSNumpy{alleles: map[string][][]int8{}} + }, + "hgvs-onehot": func() outputFormat { return formatHGVSOneHot{} }, + "hgvs": func() outputFormat { return formatHGVS{} }, + "pvcf": func() outputFormat { return formatPVCF{} }, + "vcf": func() outputFormat { return formatVCF{} }, +} type exporter struct { outputFormat outputFormat outputPerChrom bool + compress bool maxTileSize int + filter filter + maxPValue float64 + cases []bool } func (cmd *exporter) RunCommand(prog string, args []string, stdin io.Reader, stdout, stderr io.Writer) int { @@ -62,12 +81,16 @@ func (cmd *exporter) RunCommand(prog string, args []string, stdin io.Reader, std priority := flags.Int("priority", 500, "container request priority") refname := flags.String("ref", "", "reference genome `name`") inputDir := flags.String("input-dir", ".", "input `directory`") + cases := flags.String("cases", "", "file indicating which genomes are positive cases (for computing p-values)") + flags.Float64Var(&cmd.maxPValue, "p-value", 1, "do chi square test and omit columns with p-value above this threshold") outputDir := flags.String("output-dir", ".", "output `directory`") - outputFormatStr := flags.String("output-format", "hgvs", "output `format`: hgvs or vcf") + outputFormatStr := flags.String("output-format", "hgvs", "output `format`: hgvs, pvcf, or vcf") outputBed := flags.String("output-bed", "", "also output bed `file`") flags.BoolVar(&cmd.outputPerChrom, "output-per-chromosome", true, "output one file per chromosome") + flags.BoolVar(&cmd.compress, "z", false, "write gzip-compressed output files") labelsFilename := flags.String("output-labels", "", "also output genome labels csv `file`") flags.IntVar(&cmd.maxTileSize, "max-tile-size", 50000, "don't try to make annotations for tiles bigger than given `size`") + cmd.filter.Flags(flags) err = flags.Parse(args) if err == flag.ErrHelp { err = nil @@ -84,7 +107,7 @@ func (cmd *exporter) RunCommand(prog string, args []string, stdin io.Reader, std err = fmt.Errorf("invalid output format %q", *outputFormatStr) return 2 } else { - cmd.outputFormat = f + cmd.outputFormat = f() } if *pprof != "" { @@ -105,12 +128,12 @@ func (cmd *exporter) RunCommand(prog string, args []string, stdin io.Reader, std Name: "lightning export", Client: arvados.NewClientFromEnv(), ProjectUUID: *projectUUID, - RAM: 700000000000, + RAM: 750000000000, VCPUs: 96, Priority: *priority, APIAccess: true, } - err = runner.TranslatePaths(inputDir) + err = runner.TranslatePaths(inputDir, cases) if err != nil { return 1 } @@ -125,6 +148,8 @@ func (cmd *exporter) RunCommand(prog string, args []string, stdin io.Reader, std "-pprof", ":6000", "-pprof-dir", "/mnt/output", "-ref", *refname, + "-cases", *cases, + "-p-value", fmt.Sprintf("%f", cmd.maxPValue), "-output-format", *outputFormatStr, "-output-bed", *outputBed, "-output-labels", "/mnt/output/labels.csv", @@ -132,7 +157,9 @@ func (cmd *exporter) RunCommand(prog string, args []string, stdin io.Reader, std "-max-tile-size", fmt.Sprintf("%d", cmd.maxTileSize), "-input-dir", *inputDir, "-output-dir", "/mnt/output", + "-z=" + fmt.Sprintf("%v", cmd.compress), } + runner.Args = append(runner.Args, cmd.filter.Args()...) var output string output, err = runner.Run() if err != nil { @@ -148,7 +175,7 @@ func (cmd *exporter) RunCommand(prog string, args []string, stdin io.Reader, std retainTileSequences: true, compactGenomes: map[string][]tileVariantID{}, } - err = tilelib.LoadDir(context.Background(), *inputDir, nil) + err = tilelib.LoadDir(context.Background(), *inputDir) if err != nil { return 1 } @@ -164,6 +191,9 @@ func (cmd *exporter) RunCommand(prog string, args []string, stdin io.Reader, std return 1 } + log.Infof("filtering: %+v", cmd.filter) + cmd.filter.Apply(tilelib) + names := cgnames(tilelib) for _, name := range names { cgs = append(cgs, CompactGenome{Name: name, Variants: tilelib.compactGenomes[name]}) @@ -177,7 +207,7 @@ func (cmd *exporter) RunCommand(prog string, args []string, stdin io.Reader, std } defer f.Close() for i, name := range names { - _, err = fmt.Fprintf(f, "%d,%q,%q\n", i, trimFilenameForLabel(name), cmd.outputFormat.Filename) + _, err = fmt.Fprintf(f, "%d,%q,%q\n", i, trimFilenameForLabel(name), cmd.outputFormat.Filename()) if err != nil { err = fmt.Errorf("write %s: %w", *labelsFilename, err) return 1 @@ -190,6 +220,44 @@ func (cmd *exporter) RunCommand(prog string, args []string, stdin io.Reader, std } } + cmd.cases = make([]bool, len(names)) + if *cases != "" { + log.Infof("reading cases file: %s", *cases) + var f io.ReadCloser + f, err = open(*cases) + if err != nil { + return 1 + } + defer f.Close() + var buf []byte + buf, err = io.ReadAll(f) + if err != nil { + return 1 + } + for _, pattern := range bytes.Split(buf, []byte("\n")) { + if len(pattern) == 0 { + continue + } + pattern := string(pattern) + idx := -1 + for i, name := range names { + if !strings.Contains(name, pattern) { + continue + } else if idx >= 0 { + err = fmt.Errorf("pattern %q in cases file matches multiple genome IDs: %q, %q", pattern, names[idx], name) + return 1 + } else { + idx = i + } + } + if idx < 0 { + log.Warnf("pattern %q in cases file does not match any genome IDs", pattern) + continue + } + cmd.cases[idx] = true + } + } + var bedout io.Writer var bedfile *os.File var bedbufw *bufio.Writer @@ -269,22 +337,45 @@ func (cmd *exporter) export(outdir string, bedout io.Writer, tilelib *tileLibrar } if cmd.outputPerChrom { for i, seqname := range seqnames { - f, err := os.OpenFile(filepath.Join(outdir, strings.Replace(cmd.outputFormat.Filename, ".", "."+seqname+".", 1)), os.O_CREATE|os.O_WRONLY, 0666) + fnm := filepath.Join(outdir, strings.Replace(cmd.outputFormat.Filename(), ".", "."+seqname+".", 1)) + if cmd.compress { + fnm += ".gz" + } + f, err := os.OpenFile(fnm, os.O_CREATE|os.O_WRONLY|os.O_TRUNC, 0666) if err != nil { return err } defer f.Close() log.Infof("writing %q", f.Name()) outw[i] = f + if cmd.compress { + z := pgzip.NewWriter(f) + defer z.Close() + outw[i] = z + } + err = cmd.outputFormat.Head(outw[i], cgs, cmd.cases, cmd.maxPValue) + if err != nil { + return err + } } } else { - fnm := filepath.Join(outdir, cmd.outputFormat.Filename) - log.Infof("writing %q", fnm) - out, err := os.OpenFile(fnm, os.O_CREATE|os.O_WRONLY, 0666) + fnm := filepath.Join(outdir, cmd.outputFormat.Filename()) + if cmd.compress { + fnm += ".gz" + } + f, err := os.OpenFile(fnm, os.O_CREATE|os.O_WRONLY|os.O_TRUNC, 0666) if err != nil { return err } - defer out.Close() + defer f.Close() + log.Infof("writing %q", fnm) + var out io.Writer = f + if cmd.compress { + z := pgzip.NewWriter(out) + defer z.Close() + out = z + } + cmd.outputFormat.Head(out, cgs, cmd.cases, cmd.maxPValue) merge(out, outw, "output") } if bedout != nil { @@ -292,6 +383,9 @@ func (cmd *exporter) export(outdir string, bedout io.Writer, tilelib *tileLibrar } throttle := throttle{Max: runtime.NumCPU()} + if max := cmd.outputFormat.MaxGoroutines(); max > 0 { + throttle.Max = max + } log.Infof("assembling %d sequences in %d goroutines", len(seqnames), throttle.Max) for seqidx, seqname := range seqnames { seqidx, seqname := seqidx, seqname @@ -303,34 +397,41 @@ func (cmd *exporter) export(outdir string, bedout io.Writer, tilelib *tileLibrar if bedw != nil { defer bedw.Close() } - defer outw.Close() outwb := bufio.NewWriterSize(outw, 8*1024*1024) - defer outwb.Flush() - cmd.exportSeq(outwb, bedw, tilelib.taglib.keylen, seqname, refseq[seqname], tilelib, cgs) + eachVariant(bedw, tilelib.taglib.keylen, seqname, refseq[seqname], tilelib, cgs, cmd.outputFormat.PadLeft(), cmd.maxTileSize, func(varslice []tvVariant) { + err := cmd.outputFormat.Print(outwb, seqname, varslice) + throttle.Report(err) + }) + err := cmd.outputFormat.Finish(outdir, outwb, seqname) + throttle.Report(err) + err = outwb.Flush() + throttle.Report(err) + err = outw.Close() + throttle.Report(err) }() } merges.Wait() throttle.Wait() - return nil + return throttle.Err() } -// Align genome tiles to reference tiles, write diffs to outw, and (if -// bedw is not nil) write tile coverage to bedw. -func (cmd *exporter) exportSeq(outw, bedw io.Writer, taglen int, seqname string, reftiles []tileLibRef, tilelib *tileLibrary, cgs []CompactGenome) { +// Align genome tiles to reference tiles, call callback func on each +// variant, and (if bedw is not nil) write tile coverage to bedw. +func eachVariant(bedw io.Writer, taglen int, seqname string, reftiles []tileLibRef, tilelib *tileLibrary, cgs []CompactGenome, padLeft bool, maxTileSize int, callback func(varslice []tvVariant)) { t0 := time.Now() progressbar := time.NewTicker(time.Minute) defer progressbar.Stop() var outmtx sync.Mutex defer outmtx.Lock() refpos := 0 - variantAt := map[int][]hgvs.Variant{} // variantAt[chromOffset][genomeIndex*2+phase] + variantAt := map[int][]tvVariant{} // variantAt[chromOffset][genomeIndex*2+phase] for refstep, libref := range reftiles { select { case <-progressbar.C: var eta interface{} if refstep > 0 { - fin := t0.Add(time.Now().Sub(t0) * time.Duration(len(reftiles)) / time.Duration(refstep)) + fin := t0.Add(time.Duration(float64(time.Now().Sub(t0)) * float64(len(reftiles)) / float64(refstep))) eta = fmt.Sprintf("%v (%v)", fin.Format(time.RFC3339), fin.Sub(time.Now())) } else { eta = "N/A" @@ -338,56 +439,71 @@ func (cmd *exporter) exportSeq(outw, bedw io.Writer, taglen int, seqname string, log.Printf("exportSeq: %s: refstep %d of %d, %.0f/s, ETA %v", seqname, refstep, len(reftiles), float64(refstep)/time.Now().Sub(t0).Seconds(), eta) default: } + diffs := map[tileLibRef][]hgvs.Variant{} refseq := tilelib.TileVariantSequence(libref) tagcoverage := 0 // number of times the start tag was found in genomes -- max is len(cgs)*2 for cgidx, cg := range cgs { for phase := 0; phase < 2; phase++ { - if len(cg.Variants) <= int(libref.Tag)*2+phase { - continue - } - variant := cg.Variants[int(libref.Tag)*2+phase] - if variant == 0 { - continue + var variant tileVariantID + if i := int(libref.Tag)*2 + phase; len(cg.Variants) > i { + variant = cg.Variants[i] } - tagcoverage++ - if variant == libref.Variant { - continue + if variant > 0 { + tagcoverage++ } - genomeseq := tilelib.TileVariantSequence(tileLibRef{Tag: libref.Tag, Variant: variant}) - if len(genomeseq) == 0 { - // Hash is known but sequence - // is not, e.g., retainNoCalls - // was false during import + if variant == libref.Variant || variant == 0 { continue } - if len(genomeseq) > cmd.maxTileSize { - continue - } - refSequence := refseq - // If needed, extend the reference - // sequence up to the tag at the end - // of the genomeseq sequence. - refstepend := refstep + 1 - for refstepend < len(reftiles) && len(refSequence) >= taglen && !bytes.EqualFold(refSequence[len(refSequence)-taglen:], genomeseq[len(genomeseq)-taglen:]) && len(refSequence) <= cmd.maxTileSize { - if &refSequence[0] == &refseq[0] { - refSequence = append([]byte(nil), refSequence...) + glibref := tileLibRef{Tag: libref.Tag, Variant: variant} + vars, ok := diffs[glibref] + if !ok { + genomeseq := tilelib.TileVariantSequence(glibref) + if len(genomeseq) == 0 { + // Hash is known but sequence + // is not, e.g., retainNoCalls + // was false during import + continue + } + if len(genomeseq) > maxTileSize { + continue } - refSequence = append(refSequence, tilelib.TileVariantSequence(reftiles[refstepend])...) - refstepend++ + refSequence := refseq + // If needed, extend the + // reference sequence up to + // the tag at the end of the + // genomeseq sequence. + refstepend := refstep + 1 + for refstepend < len(reftiles) && len(refSequence) >= taglen && !bytes.EqualFold(refSequence[len(refSequence)-taglen:], genomeseq[len(genomeseq)-taglen:]) && len(refSequence) <= maxTileSize { + if &refSequence[0] == &refseq[0] { + refSequence = append([]byte(nil), refSequence...) + } + refSequence = append(refSequence, tilelib.TileVariantSequence(reftiles[refstepend])...) + refstepend++ + } + // (TODO: handle no-calls) + if len(refSequence) <= maxTileSize { + refstr := strings.ToUpper(string(refSequence)) + genomestr := strings.ToUpper(string(genomeseq)) + vars, _ = hgvs.Diff(refstr, genomestr, time.Second) + } + diffs[glibref] = vars } - // (TODO: handle no-calls) - vars, _ := hgvs.Diff(strings.ToUpper(string(refSequence)), strings.ToUpper(string(genomeseq)), time.Second) for _, v := range vars { - if cmd.outputFormat.PadLeft { + if padLeft { v = v.PadLeft() } v.Position += refpos varslice := variantAt[v.Position] if varslice == nil { - varslice = make([]hgvs.Variant, len(cgs)*2) + varslice = make([]tvVariant, len(cgs)*2) variantAt[v.Position] = varslice } - varslice[cgidx*2+phase] = v + varslice[cgidx*2+phase].Variant = v + if varslice[cgidx*2+phase].librefs == nil { + varslice[cgidx*2+phase].librefs = map[tileLibRef]bool{glibref: true} + } else { + varslice[cgidx*2+phase].librefs[glibref] = true + } } } } @@ -404,13 +520,33 @@ func (cmd *exporter) exportSeq(outw, bedw io.Writer, taglen int, seqname string, } } sort.Slice(flushpos, func(i, j int) bool { return flushpos[i] < flushpos[j] }) - flushvariants := make([][]hgvs.Variant, len(flushpos)) + flushvariants := make([][]tvVariant, len(flushpos)) for i, pos := range flushpos { varslice := variantAt[pos] delete(variantAt, pos) + // Check for uninitialized (zero-value) + // elements in varslice for i := range varslice { - if varslice[i].Position == 0 { - varslice[i].Position = pos + if varslice[i].Position != 0 { + // Not a zero-value element + continue + } + // Set the position so + // varslice[*].Position are all equal + varslice[i].Position = pos + // This could be either =ref or a + // missing/low-quality tile. Figure + // out which. + vidx := int(libref.Tag)*2 + i%2 + if vidx >= len(cgs[i/2].Variants) { + // Missing tile. + varslice[i].New = "-" + continue + } + v := cgs[i/2].Variants[vidx] + if v < 1 || len(tilelib.TileVariantSequence(tileLibRef{Tag: libref.Tag, Variant: v})) == 0 { + // Missing/low-quality tile. + varslice[i].New = "-" // fasta "gap of indeterminate length" } } flushvariants[i] = varslice @@ -419,7 +555,7 @@ func (cmd *exporter) exportSeq(outw, bedw io.Writer, taglen int, seqname string, go func() { defer outmtx.Unlock() for _, varslice := range flushvariants { - cmd.outputFormat.Print(outw, seqname, varslice) + callback(varslice) } }() if bedw != nil && len(refseq) > 0 { @@ -449,21 +585,79 @@ func (cmd *exporter) exportSeq(outw, bedw io.Writer, taglen int, seqname string, } } -func printVCF(out io.Writer, seqname string, varslice []hgvs.Variant) { - refs := map[string]map[string]int{} +func bucketVarsliceByRef(varslice []tvVariant) map[string]map[string]int { + byref := map[string]map[string]int{} for _, v := range varslice { if v.Ref == "" && v.New == "" { + // =ref + continue + } + if v.New == "-" { + // no-call continue } - alts := refs[v.Ref] + alts := byref[v.Ref] if alts == nil { alts = map[string]int{} - refs[v.Ref] = alts + byref[v.Ref] = alts + } + alts[v.New]++ + } + return byref +} + +type formatVCF struct{} + +func (formatVCF) MaxGoroutines() int { return 0 } +func (formatVCF) Filename() string { return "out.vcf" } +func (formatVCF) PadLeft() bool { return true } +func (formatVCF) Finish(string, io.Writer, string) error { return nil } +func (formatVCF) Head(out io.Writer, cgs []CompactGenome, cases []bool, p float64) error { + _, err := fmt.Fprint(out, "#CHROM\tPOS\tID\tREF\tALT\tQUAL\tFILTER\tINFO\n") + return err +} +func (formatVCF) Print(out io.Writer, seqname string, varslice []tvVariant) error { + for ref, alts := range bucketVarsliceByRef(varslice) { + altslice := make([]string, 0, len(alts)) + for alt := range alts { + altslice = append(altslice, alt) + } + sort.Strings(altslice) + + info := "AC=" + for i, a := range altslice { + if i > 0 { + info += "," + } + info += strconv.Itoa(alts[a]) + } + _, err := fmt.Fprintf(out, "%s\t%d\t.\t%s\t%s\t.\t.\t%s\n", seqname, varslice[0].Position, ref, strings.Join(altslice, ","), info) + if err != nil { + return err } - alts[v.New] = 0 } - for ref, alts := range refs { - var altslice []string + return nil +} + +type formatPVCF struct{} + +func (formatPVCF) MaxGoroutines() int { return 0 } +func (formatPVCF) Filename() string { return "out.vcf" } +func (formatPVCF) PadLeft() bool { return true } +func (formatPVCF) Finish(string, io.Writer, string) error { return nil } +func (formatPVCF) Head(out io.Writer, cgs []CompactGenome, cases []bool, p float64) error { + fmt.Fprintln(out, `##FORMAT=`) + fmt.Fprintf(out, "#CHROM\tPOS\tID\tREF\tALT\tQUAL\tFILTER\tINFO\tFORMAT") + for _, cg := range cgs { + fmt.Fprintf(out, "\t%s", cg.Name) + } + _, err := fmt.Fprintf(out, "\n") + return err +} + +func (formatPVCF) Print(out io.Writer, seqname string, varslice []tvVariant) error { + for ref, alts := range bucketVarsliceByRef(varslice) { + altslice := make([]string, 0, len(alts)) for alt := range alts { altslice = append(altslice, alt) } @@ -471,46 +665,92 @@ func printVCF(out io.Writer, seqname string, varslice []hgvs.Variant) { for i, a := range altslice { alts[a] = i + 1 } - fmt.Fprintf(out, "%s\t%d\t%s\t%s", seqname, varslice[0].Position, ref, strings.Join(altslice, ",")) + _, err := fmt.Fprintf(out, "%s\t%d\t.\t%s\t%s\t.\t.\t.\tGT", seqname, varslice[0].Position, ref, strings.Join(altslice, ",")) + if err != nil { + return err + } for i := 0; i < len(varslice); i += 2 { v1, v2 := varslice[i], varslice[i+1] a1, a2 := alts[v1.New], alts[v2.New] if v1.Ref != ref { + // variant on allele 0 belongs on a + // different output line -- same + // chr,pos but different "ref" length a1 = 0 } if v2.Ref != ref { a2 = 0 } - fmt.Fprintf(out, "\t%d/%d", a1, a2) + _, err := fmt.Fprintf(out, "\t%d/%d", a1, a2) + if err != nil { + return err + } + } + _, err = out.Write([]byte{'\n'}) + if err != nil { + return err } - out.Write([]byte{'\n'}) } + return nil } -func printHGVS(out io.Writer, seqname string, varslice []hgvs.Variant) { +type formatHGVS struct{} + +func (formatHGVS) MaxGoroutines() int { return 0 } +func (formatHGVS) Filename() string { return "out.tsv" } +func (formatHGVS) PadLeft() bool { return false } +func (formatHGVS) Head(out io.Writer, cgs []CompactGenome, cases []bool, p float64) error { return nil } +func (formatHGVS) Finish(string, io.Writer, string) error { return nil } +func (formatHGVS) Print(out io.Writer, seqname string, varslice []tvVariant) error { for i := 0; i < len(varslice)/2; i++ { if i > 0 { out.Write([]byte{'\t'}) } var1, var2 := varslice[i*2], varslice[i*2+1] - if var1 == var2 { + if var1.New == "-" || var2.New == "-" { + _, err := out.Write([]byte{'N'}) + if err != nil { + return err + } + continue + } + if var1.Variant == var2.Variant { if var1.Ref == var1.New { - out.Write([]byte{'.'}) + _, err := out.Write([]byte{'.'}) + if err != nil { + return err + } } else { - fmt.Fprintf(out, "%s:g.%s", seqname, var1.String()) + _, err := fmt.Fprintf(out, "%s:g.%s", seqname, var1.String()) + if err != nil { + return err + } } } else { - fmt.Fprintf(out, "%s:g.[%s];[%s]", seqname, var1.String(), var2.String()) + _, err := fmt.Fprintf(out, "%s:g.[%s];[%s]", seqname, var1.String(), var2.String()) + if err != nil { + return err + } } } - out.Write([]byte{'\n'}) + _, err := out.Write([]byte{'\n'}) + return err } -func printHGVSOneHot(out io.Writer, seqname string, varslice []hgvs.Variant) { +type formatHGVSOneHot struct{} + +func (formatHGVSOneHot) MaxGoroutines() int { return 0 } +func (formatHGVSOneHot) Filename() string { return "out.tsv" } +func (formatHGVSOneHot) PadLeft() bool { return false } +func (formatHGVSOneHot) Head(out io.Writer, cgs []CompactGenome, cases []bool, p float64) error { + return nil +} +func (formatHGVSOneHot) Finish(string, io.Writer, string) error { return nil } +func (formatHGVSOneHot) Print(out io.Writer, seqname string, varslice []tvVariant) error { vars := map[hgvs.Variant]bool{} for _, v := range varslice { if v.Ref != v.New { - vars[v] = true + vars[v.Variant] = true } } @@ -522,14 +762,150 @@ func printHGVSOneHot(out io.Writer, seqname string, varslice []hgvs.Variant) { sort.Slice(sorted, func(a, b int) bool { return hgvs.Less(sorted[a], sorted[b]) }) for _, v := range sorted { + if v.New == "-" { + continue + } fmt.Fprintf(out, "%s.%s", seqname, v.String()) for i := 0; i < len(varslice); i += 2 { - if varslice[i] == v || varslice[i+1] == v { + if varslice[i].Variant == v || varslice[i+1].Variant == v { out.Write([]byte("\t1")) } else { out.Write([]byte("\t0")) } } - out.Write([]byte{'\n'}) + _, err := out.Write([]byte{'\n'}) + if err != nil { + return err + } + } + return nil +} + +type formatHGVSNumpy struct { + sync.Mutex + writelock sync.Mutex + alleles map[string][][]int8 // alleles[seqname][variantidx][genomeidx*2+phase] + cases []bool + maxPValue float64 +} + +func (*formatHGVSNumpy) MaxGoroutines() int { return 4 } +func (*formatHGVSNumpy) Filename() string { return "annotations.csv" } +func (*formatHGVSNumpy) PadLeft() bool { return false } +func (f *formatHGVSNumpy) Head(out io.Writer, cgs []CompactGenome, cases []bool, p float64) error { + f.cases = cases + f.maxPValue = p + return nil +} +func (f *formatHGVSNumpy) Print(outw io.Writer, seqname string, varslice []tvVariant) error { + // sort variants to ensure output is deterministic + sorted := make([]hgvs.Variant, 0, len(varslice)) + for _, v := range varslice { + sorted = append(sorted, v.Variant) + } + sort.Slice(sorted, func(a, b int) bool { return hgvs.Less(sorted[a], sorted[b]) }) + + f.Lock() + seqalleles := f.alleles[seqname] + f.Unlock() + + chi2x := make([]bool, 0, len(varslice)) + chi2y := make([]bool, 0, len(varslice)) + + // append a row to seqalleles for each unique non-ref variant + // in varslice. + var previous hgvs.Variant + for _, v := range sorted { + if previous == v || v.Ref == v.New || v.New == "-" { + continue + } + previous = v + chi2x, chi2y := chi2x, chi2y + newrow := make([]int8, len(varslice)) + for i, allele := range varslice { + if allele.Variant == v { + newrow[i] = 1 + chi2x = append(chi2x, true) + chi2y = append(chi2y, f.cases[i/2]) + } else if allele.Variant.New == "-" { + newrow[i] = -1 + } else { + chi2x = append(chi2x, false) + chi2y = append(chi2y, f.cases[i/2]) + } + } + if f.maxPValue < 1 && pvalue(chi2x, chi2y) > f.maxPValue { + continue + } + seqalleles = append(seqalleles, newrow) + _, err := fmt.Fprintf(outw, "%d,%q\n", len(seqalleles)-1, seqname+"."+v.String()) + if err != nil { + return err + } + } + + f.Lock() + f.alleles[seqname] = seqalleles + f.Unlock() + return nil +} +func (f *formatHGVSNumpy) Finish(outdir string, _ io.Writer, seqname string) error { + // Write seqname's data to a .npy matrix with one row per + // genome and 2 columns per variant. + f.Lock() + seqalleles := f.alleles[seqname] + delete(f.alleles, seqname) + f.Unlock() + if len(seqalleles) == 0 { + return nil + } + out := make([]int8, len(seqalleles)*len(seqalleles[0])) + rows := len(seqalleles[0]) / 2 + cols := len(seqalleles) * 2 + // copy seqalleles[varidx][genome*2+phase] to + // out[genome*nvars*2 + varidx*2 + phase] + for varidx, alleles := range seqalleles { + for g := 0; g < len(alleles)/2; g++ { + aa, ab := alleles[g*2], alleles[g*2+1] + if aa < 0 || ab < 0 { + // no-call + out[g*cols+varidx*2] = -1 + out[g*cols+varidx*2+1] = -1 + } else if aa > 0 && ab > 0 { + // hom + out[g*cols+varidx*2] = 1 + } else if aa > 0 || ab > 0 { + // het + out[g*cols+varidx*2+1] = 1 + } + } } + outf, err := os.OpenFile(outdir+"/matrix."+seqname+".npy", os.O_CREATE|os.O_EXCL|os.O_WRONLY, 0777) + if err != nil { + return err + } + defer outf.Close() + bufw := bufio.NewWriter(outf) + npw, err := gonpy.NewWriter(nopCloser{bufw}) + if err != nil { + return err + } + log.WithFields(logrus.Fields{ + "seqname": seqname, + "rows": rows, + "cols": cols, + }).Info("writing numpy") + npw.Shape = []int{rows, cols} + f.writelock.Lock() // serialize because WriteInt8 uses lots of memory + npw.WriteInt8(out) + f.writelock.Unlock() + err = bufw.Flush() + if err != nil { + return err + } + err = outf.Close() + if err != nil { + return err + } + return nil }