Skip diffs on long ref seqs.
[lightning.git] / export.go
1 package lightning
2
3 import (
4         "bufio"
5         "bytes"
6         "context"
7         "errors"
8         "flag"
9         "fmt"
10         "io"
11         "net/http"
12         _ "net/http/pprof"
13         "os"
14         "path/filepath"
15         "runtime"
16         "sort"
17         "strconv"
18         "strings"
19         "sync"
20         "time"
21
22         "git.arvados.org/arvados.git/sdk/go/arvados"
23         "github.com/arvados/lightning/hgvs"
24         "github.com/klauspost/pgzip"
25         log "github.com/sirupsen/logrus"
26 )
27
28 type outputFormat struct {
29         Filename string
30         Head     func(out io.Writer, cgs []CompactGenome)
31         Print    func(out io.Writer, seqname string, varslice []hgvs.Variant)
32         PadLeft  bool
33 }
34
35 var (
36         outputFormats = map[string]outputFormat{
37                 "hgvs-onehot": outputFormatHGVSOneHot,
38                 "hgvs":        outputFormatHGVS,
39                 "pvcf":        outputFormatPVCF,
40                 "vcf":         outputFormatVCF,
41         }
42         outputFormatHGVS       = outputFormat{Filename: "out.csv", Head: headNone, Print: printHGVS}
43         outputFormatHGVSOneHot = outputFormat{Filename: "out.csv", Head: headNone, Print: printHGVSOneHot}
44         outputFormatPVCF       = outputFormat{Filename: "out.vcf", Head: headPVCF, Print: printPVCF, PadLeft: true}
45         outputFormatVCF        = outputFormat{Filename: "out.vcf", Head: headVCF, Print: printVCF, PadLeft: true}
46         headNone               = func(io.Writer, []CompactGenome) {}
47 )
48
49 type exporter struct {
50         outputFormat   outputFormat
51         outputPerChrom bool
52         compress       bool
53         maxTileSize    int
54 }
55
56 func (cmd *exporter) RunCommand(prog string, args []string, stdin io.Reader, stdout, stderr io.Writer) int {
57         var err error
58         defer func() {
59                 if err != nil {
60                         fmt.Fprintf(stderr, "%s\n", err)
61                 }
62         }()
63         flags := flag.NewFlagSet("", flag.ContinueOnError)
64         flags.SetOutput(stderr)
65         pprof := flags.String("pprof", "", "serve Go profile data at http://`[addr]:port`")
66         pprofdir := flags.String("pprof-dir", "", "write Go profile data to `directory` periodically")
67         runlocal := flags.Bool("local", false, "run on local host (default: run in an arvados container)")
68         projectUUID := flags.String("project", "", "project `UUID` for output data")
69         priority := flags.Int("priority", 500, "container request priority")
70         refname := flags.String("ref", "", "reference genome `name`")
71         inputDir := flags.String("input-dir", ".", "input `directory`")
72         outputDir := flags.String("output-dir", ".", "output `directory`")
73         outputFormatStr := flags.String("output-format", "hgvs", "output `format`: hgvs, pvcf, or vcf")
74         outputBed := flags.String("output-bed", "", "also output bed `file`")
75         flags.BoolVar(&cmd.outputPerChrom, "output-per-chromosome", true, "output one file per chromosome")
76         flags.BoolVar(&cmd.compress, "z", false, "write gzip-compressed output files")
77         labelsFilename := flags.String("output-labels", "", "also output genome labels csv `file`")
78         flags.IntVar(&cmd.maxTileSize, "max-tile-size", 50000, "don't try to make annotations for tiles bigger than given `size`")
79         err = flags.Parse(args)
80         if err == flag.ErrHelp {
81                 err = nil
82                 return 0
83         } else if err != nil {
84                 return 2
85         }
86         if flag.NArg() > 0 {
87                 err = fmt.Errorf("extra unparsed command line arguments: %q", flag.Args())
88                 return 2
89         }
90
91         if f, ok := outputFormats[*outputFormatStr]; !ok {
92                 err = fmt.Errorf("invalid output format %q", *outputFormatStr)
93                 return 2
94         } else {
95                 cmd.outputFormat = f
96         }
97
98         if *pprof != "" {
99                 go func() {
100                         log.Println(http.ListenAndServe(*pprof, nil))
101                 }()
102         }
103         if *pprofdir != "" {
104                 go writeProfilesPeriodically(*pprofdir)
105         }
106
107         if !*runlocal {
108                 if *outputDir != "." {
109                         err = errors.New("cannot specify output directory in container mode: not implemented")
110                         return 1
111                 }
112                 runner := arvadosContainerRunner{
113                         Name:        "lightning export",
114                         Client:      arvados.NewClientFromEnv(),
115                         ProjectUUID: *projectUUID,
116                         RAM:         700000000000,
117                         VCPUs:       96,
118                         Priority:    *priority,
119                         APIAccess:   true,
120                 }
121                 err = runner.TranslatePaths(inputDir)
122                 if err != nil {
123                         return 1
124                 }
125                 if *outputBed != "" {
126                         if strings.Contains(*outputBed, "/") {
127                                 err = fmt.Errorf("cannot use -output-bed filename %q containing '/' char", *outputBed)
128                                 return 1
129                         }
130                         *outputBed = "/mnt/output/" + *outputBed
131                 }
132                 runner.Args = []string{"export", "-local=true",
133                         "-pprof", ":6000",
134                         "-pprof-dir", "/mnt/output",
135                         "-ref", *refname,
136                         "-output-format", *outputFormatStr,
137                         "-output-bed", *outputBed,
138                         "-output-labels", "/mnt/output/labels.csv",
139                         "-output-per-chromosome=" + fmt.Sprintf("%v", cmd.outputPerChrom),
140                         "-max-tile-size", fmt.Sprintf("%d", cmd.maxTileSize),
141                         "-input-dir", *inputDir,
142                         "-output-dir", "/mnt/output",
143                         "-z=" + fmt.Sprintf("%v", cmd.compress),
144                 }
145                 var output string
146                 output, err = runner.Run()
147                 if err != nil {
148                         return 1
149                 }
150                 fmt.Fprintln(stdout, output)
151                 return 0
152         }
153
154         var cgs []CompactGenome
155         tilelib := &tileLibrary{
156                 retainNoCalls:       true,
157                 retainTileSequences: true,
158                 compactGenomes:      map[string][]tileVariantID{},
159         }
160         err = tilelib.LoadDir(context.Background(), *inputDir, nil)
161         if err != nil {
162                 return 1
163         }
164
165         refseq, ok := tilelib.refseqs[*refname]
166         if !ok {
167                 err = fmt.Errorf("reference name %q not found in input; have %v", *refname, func() (names []string) {
168                         for name := range tilelib.refseqs {
169                                 names = append(names, name)
170                         }
171                         return
172                 }())
173                 return 1
174         }
175
176         names := cgnames(tilelib)
177         for _, name := range names {
178                 cgs = append(cgs, CompactGenome{Name: name, Variants: tilelib.compactGenomes[name]})
179         }
180         if *labelsFilename != "" {
181                 log.Infof("writing labels to %s", *labelsFilename)
182                 var f *os.File
183                 f, err = os.OpenFile(*labelsFilename, os.O_CREATE|os.O_WRONLY, 0777)
184                 if err != nil {
185                         return 1
186                 }
187                 defer f.Close()
188                 for i, name := range names {
189                         _, err = fmt.Fprintf(f, "%d,%q,%q\n", i, trimFilenameForLabel(name), cmd.outputFormat.Filename)
190                         if err != nil {
191                                 err = fmt.Errorf("write %s: %w", *labelsFilename, err)
192                                 return 1
193                         }
194                 }
195                 err = f.Close()
196                 if err != nil {
197                         err = fmt.Errorf("close %s: %w", *labelsFilename, err)
198                         return 1
199                 }
200         }
201
202         var bedout io.Writer
203         var bedfile *os.File
204         var bedbufw *bufio.Writer
205         if *outputBed != "" {
206                 bedfile, err = os.OpenFile(*outputBed, os.O_CREATE|os.O_WRONLY, 0666)
207                 if err != nil {
208                         return 1
209                 }
210                 defer bedfile.Close()
211                 bedbufw = bufio.NewWriterSize(bedfile, 16*1024*1024)
212                 bedout = bedbufw
213         }
214
215         err = cmd.export(*outputDir, bedout, tilelib, refseq, cgs)
216         if err != nil {
217                 return 1
218         }
219         if bedout != nil {
220                 err = bedbufw.Flush()
221                 if err != nil {
222                         return 1
223                 }
224                 err = bedfile.Close()
225                 if err != nil {
226                         return 1
227                 }
228         }
229         return 0
230 }
231
232 func (cmd *exporter) export(outdir string, bedout io.Writer, tilelib *tileLibrary, refseq map[string][]tileLibRef, cgs []CompactGenome) error {
233         var seqnames []string
234         var missing []tileLibRef
235         for seqname, librefs := range refseq {
236                 seqnames = append(seqnames, seqname)
237                 for _, libref := range librefs {
238                         if libref.Variant != 0 && tilelib.TileVariantSequence(libref) == nil {
239                                 missing = append(missing, libref)
240                         }
241                 }
242         }
243         sort.Strings(seqnames)
244
245         if len(missing) > 0 {
246                 if limit := 100; len(missing) > limit {
247                         log.Warnf("first %d missing tiles: %v", limit, missing[:limit])
248                 } else {
249                         log.Warnf("missing tiles: %v", missing)
250                 }
251                 return fmt.Errorf("%d needed tiles are missing from library", len(missing))
252         }
253
254         outw := make([]io.WriteCloser, len(seqnames))
255         bedw := make([]io.WriteCloser, len(seqnames))
256
257         var merges sync.WaitGroup
258         merge := func(dst io.Writer, src []io.WriteCloser, label string) {
259                 var mtx sync.Mutex
260                 for i, seqname := range seqnames {
261                         pr, pw := io.Pipe()
262                         src[i] = pw
263                         merges.Add(1)
264                         seqname := seqname
265                         go func() {
266                                 defer merges.Done()
267                                 log.Infof("writing %s %s", seqname, label)
268                                 scanner := bufio.NewScanner(pr)
269                                 for scanner.Scan() {
270                                         mtx.Lock()
271                                         dst.Write(scanner.Bytes())
272                                         dst.Write([]byte{'\n'})
273                                         mtx.Unlock()
274                                 }
275                                 log.Infof("writing %s %s done", seqname, label)
276                         }()
277                 }
278         }
279         if cmd.outputPerChrom {
280                 for i, seqname := range seqnames {
281                         fnm := filepath.Join(outdir, strings.Replace(cmd.outputFormat.Filename, ".", "."+seqname+".", 1))
282                         if cmd.compress {
283                                 fnm += ".gz"
284                         }
285                         f, err := os.OpenFile(fnm, os.O_CREATE|os.O_WRONLY|os.O_TRUNC, 0666)
286                         if err != nil {
287                                 return err
288                         }
289                         defer f.Close()
290                         log.Infof("writing %q", f.Name())
291                         outw[i] = f
292                         if cmd.compress {
293                                 z := pgzip.NewWriter(f)
294                                 defer z.Close()
295                                 outw[i] = z
296                         }
297                         cmd.outputFormat.Head(outw[i], cgs)
298                 }
299         } else {
300                 fnm := filepath.Join(outdir, cmd.outputFormat.Filename)
301                 if cmd.compress {
302                         fnm += ".gz"
303                 }
304                 f, err := os.OpenFile(fnm, os.O_CREATE|os.O_WRONLY|os.O_TRUNC, 0666)
305                 if err != nil {
306                         return err
307                 }
308                 defer f.Close()
309                 log.Infof("writing %q", fnm)
310                 var out io.Writer = f
311                 if cmd.compress {
312                         z := pgzip.NewWriter(out)
313                         defer z.Close()
314                         out = z
315                 }
316                 cmd.outputFormat.Head(out, cgs)
317                 merge(out, outw, "output")
318         }
319         if bedout != nil {
320                 merge(bedout, bedw, "bed")
321         }
322
323         throttle := throttle{Max: runtime.NumCPU()}
324         log.Infof("assembling %d sequences in %d goroutines", len(seqnames), throttle.Max)
325         for seqidx, seqname := range seqnames {
326                 seqidx, seqname := seqidx, seqname
327                 outw := outw[seqidx]
328                 bedw := bedw[seqidx]
329                 throttle.Acquire()
330                 go func() {
331                         defer throttle.Release()
332                         if bedw != nil {
333                                 defer bedw.Close()
334                         }
335                         outwb := bufio.NewWriterSize(outw, 8*1024*1024)
336                         cmd.exportSeq(outwb, bedw, tilelib.taglib.keylen, seqname, refseq[seqname], tilelib, cgs)
337                         err := outwb.Flush()
338                         throttle.Report(err)
339                         err = outw.Close()
340                         throttle.Report(err)
341                 }()
342         }
343
344         merges.Wait()
345         throttle.Wait()
346         return throttle.Err()
347 }
348
349 // Align genome tiles to reference tiles, write diffs to outw, and (if
350 // bedw is not nil) write tile coverage to bedw.
351 func (cmd *exporter) exportSeq(outw, bedw io.Writer, taglen int, seqname string, reftiles []tileLibRef, tilelib *tileLibrary, cgs []CompactGenome) {
352         t0 := time.Now()
353         progressbar := time.NewTicker(time.Minute)
354         defer progressbar.Stop()
355         var outmtx sync.Mutex
356         defer outmtx.Lock()
357         refpos := 0
358         variantAt := map[int][]hgvs.Variant{} // variantAt[chromOffset][genomeIndex*2+phase]
359         for refstep, libref := range reftiles {
360                 select {
361                 case <-progressbar.C:
362                         var eta interface{}
363                         if refstep > 0 {
364                                 fin := t0.Add(time.Duration(float64(time.Now().Sub(t0)) * float64(len(reftiles)) / float64(refstep)))
365                                 eta = fmt.Sprintf("%v (%v)", fin.Format(time.RFC3339), fin.Sub(time.Now()))
366                         } else {
367                                 eta = "N/A"
368                         }
369                         log.Printf("exportSeq: %s: refstep %d of %d, %.0f/s, ETA %v", seqname, refstep, len(reftiles), float64(refstep)/time.Now().Sub(t0).Seconds(), eta)
370                 default:
371                 }
372                 diffs := map[tileLibRef][]hgvs.Variant{}
373                 refseq := tilelib.TileVariantSequence(libref)
374                 tagcoverage := 0 // number of times the start tag was found in genomes -- max is len(cgs)*2
375                 for cgidx, cg := range cgs {
376                         for phase := 0; phase < 2; phase++ {
377                                 if len(cg.Variants) <= int(libref.Tag)*2+phase {
378                                         continue
379                                 }
380                                 variant := cg.Variants[int(libref.Tag)*2+phase]
381                                 if variant == 0 {
382                                         continue
383                                 }
384                                 tagcoverage++
385                                 if variant == libref.Variant {
386                                         continue
387                                 }
388                                 glibref := tileLibRef{Tag: libref.Tag, Variant: variant}
389                                 vars, ok := diffs[glibref]
390                                 if !ok {
391                                         genomeseq := tilelib.TileVariantSequence(glibref)
392                                         if len(genomeseq) == 0 {
393                                                 // Hash is known but sequence
394                                                 // is not, e.g., retainNoCalls
395                                                 // was false during import
396                                                 continue
397                                         }
398                                         if len(genomeseq) > cmd.maxTileSize {
399                                                 continue
400                                         }
401                                         refSequence := refseq
402                                         // If needed, extend the
403                                         // reference sequence up to
404                                         // the tag at the end of the
405                                         // genomeseq sequence.
406                                         refstepend := refstep + 1
407                                         for refstepend < len(reftiles) && len(refSequence) >= taglen && !bytes.EqualFold(refSequence[len(refSequence)-taglen:], genomeseq[len(genomeseq)-taglen:]) && len(refSequence) <= cmd.maxTileSize {
408                                                 if &refSequence[0] == &refseq[0] {
409                                                         refSequence = append([]byte(nil), refSequence...)
410                                                 }
411                                                 refSequence = append(refSequence, tilelib.TileVariantSequence(reftiles[refstepend])...)
412                                                 refstepend++
413                                         }
414                                         // (TODO: handle no-calls)
415                                         if len(refSequence) <= cmd.maxTileSize {
416                                                 refstr := strings.ToUpper(string(refSequence))
417                                                 genomestr := strings.ToUpper(string(genomeseq))
418                                                 vars, _ = hgvs.Diff(refstr, genomestr, time.Second)
419                                         }
420                                         diffs[glibref] = vars
421                                 }
422                                 for _, v := range vars {
423                                         if cmd.outputFormat.PadLeft {
424                                                 v = v.PadLeft()
425                                         }
426                                         v.Position += refpos
427                                         varslice := variantAt[v.Position]
428                                         if varslice == nil {
429                                                 varslice = make([]hgvs.Variant, len(cgs)*2)
430                                                 variantAt[v.Position] = varslice
431                                         }
432                                         varslice[cgidx*2+phase] = v
433                                 }
434                         }
435                 }
436                 refpos += len(refseq) - taglen
437
438                 // Flush entries from variantAt that are behind
439                 // refpos. Flush all entries if this is the last
440                 // reftile of the path/chromosome.
441                 flushpos := make([]int, 0, len(variantAt))
442                 lastrefstep := refstep == len(reftiles)-1
443                 for pos := range variantAt {
444                         if lastrefstep || pos <= refpos {
445                                 flushpos = append(flushpos, pos)
446                         }
447                 }
448                 sort.Slice(flushpos, func(i, j int) bool { return flushpos[i] < flushpos[j] })
449                 flushvariants := make([][]hgvs.Variant, len(flushpos))
450                 for i, pos := range flushpos {
451                         varslice := variantAt[pos]
452                         delete(variantAt, pos)
453                         for i := range varslice {
454                                 if varslice[i].Position == 0 {
455                                         varslice[i].Position = pos
456                                 }
457                         }
458                         flushvariants[i] = varslice
459                 }
460                 outmtx.Lock()
461                 go func() {
462                         defer outmtx.Unlock()
463                         for _, varslice := range flushvariants {
464                                 cmd.outputFormat.Print(outw, seqname, varslice)
465                         }
466                 }()
467                 if bedw != nil && len(refseq) > 0 {
468                         tilestart := refpos - len(refseq) + taglen
469                         tileend := refpos
470                         if !lastrefstep {
471                                 tileend += taglen
472                         }
473                         thickstart := tilestart + taglen
474                         if refstep == 0 {
475                                 thickstart = 0
476                         }
477                         thickend := refpos
478
479                         // coverage score, 0 to 1000
480                         score := 1000
481                         if len(cgs) > 0 {
482                                 score = 1000 * tagcoverage / len(cgs) / 2
483                         }
484
485                         fmt.Fprintf(bedw, "%s %d %d %d %d . %d %d\n",
486                                 seqname, tilestart, tileend,
487                                 libref.Tag,
488                                 score,
489                                 thickstart, thickend)
490                 }
491         }
492 }
493
494 func bucketVarsliceByRef(varslice []hgvs.Variant) map[string]map[string]int {
495         byref := map[string]map[string]int{}
496         for _, v := range varslice {
497                 if v.Ref == "" && v.New == "" {
498                         continue
499                 }
500                 alts := byref[v.Ref]
501                 if alts == nil {
502                         alts = map[string]int{}
503                         byref[v.Ref] = alts
504                 }
505                 alts[v.New]++
506         }
507         return byref
508 }
509
510 func headVCF(out io.Writer, cgs []CompactGenome) {
511         fmt.Fprint(out, "#CHROM\tPOS\tID\tREF\tALT\tQUAL\tFILTER\tINFO\n")
512 }
513
514 func printVCF(out io.Writer, seqname string, varslice []hgvs.Variant) {
515         for ref, alts := range bucketVarsliceByRef(varslice) {
516                 altslice := make([]string, 0, len(alts))
517                 for alt := range alts {
518                         altslice = append(altslice, alt)
519                 }
520                 sort.Strings(altslice)
521
522                 info := "AC="
523                 for i, a := range altslice {
524                         if i > 0 {
525                                 info += ","
526                         }
527                         info += strconv.Itoa(alts[a])
528                 }
529                 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)
530         }
531 }
532
533 func headPVCF(out io.Writer, cgs []CompactGenome) {
534         fmt.Fprintln(out, `##FORMAT=<ID=GT,Number=1,Type=String,Description="Genotype">`)
535         fmt.Fprintf(out, "#CHROM\tPOS\tID\tREF\tALT\tQUAL\tFILTER\tINFO\tFORMAT")
536         for _, cg := range cgs {
537                 fmt.Fprintf(out, "\t%s", cg.Name)
538         }
539         fmt.Fprintf(out, "\n")
540 }
541
542 func printPVCF(out io.Writer, seqname string, varslice []hgvs.Variant) {
543         for ref, alts := range bucketVarsliceByRef(varslice) {
544                 altslice := make([]string, 0, len(alts))
545                 for alt := range alts {
546                         altslice = append(altslice, alt)
547                 }
548                 sort.Strings(altslice)
549                 for i, a := range altslice {
550                         alts[a] = i + 1
551                 }
552                 fmt.Fprintf(out, "%s\t%d\t.\t%s\t%s\t.\t.\t.\tGT", seqname, varslice[0].Position, ref, strings.Join(altslice, ","))
553                 for i := 0; i < len(varslice); i += 2 {
554                         v1, v2 := varslice[i], varslice[i+1]
555                         a1, a2 := alts[v1.New], alts[v2.New]
556                         if v1.Ref != ref {
557                                 // variant on allele 0 belongs on a
558                                 // different output line -- same
559                                 // chr,pos but different "ref" length
560                                 a1 = 0
561                         }
562                         if v2.Ref != ref {
563                                 a2 = 0
564                         }
565                         fmt.Fprintf(out, "\t%d/%d", a1, a2)
566                 }
567                 out.Write([]byte{'\n'})
568         }
569 }
570
571 func printHGVS(out io.Writer, seqname string, varslice []hgvs.Variant) {
572         for i := 0; i < len(varslice)/2; i++ {
573                 if i > 0 {
574                         out.Write([]byte{'\t'})
575                 }
576                 var1, var2 := varslice[i*2], varslice[i*2+1]
577                 if var1 == var2 {
578                         if var1.Ref == var1.New {
579                                 out.Write([]byte{'.'})
580                         } else {
581                                 fmt.Fprintf(out, "%s:g.%s", seqname, var1.String())
582                         }
583                 } else {
584                         fmt.Fprintf(out, "%s:g.[%s];[%s]", seqname, var1.String(), var2.String())
585                 }
586         }
587         out.Write([]byte{'\n'})
588 }
589
590 func printHGVSOneHot(out io.Writer, seqname string, varslice []hgvs.Variant) {
591         vars := map[hgvs.Variant]bool{}
592         for _, v := range varslice {
593                 if v.Ref != v.New {
594                         vars[v] = true
595                 }
596         }
597
598         // sort variants to ensure output is deterministic
599         sorted := make([]hgvs.Variant, 0, len(vars))
600         for v := range vars {
601                 sorted = append(sorted, v)
602         }
603         sort.Slice(sorted, func(a, b int) bool { return hgvs.Less(sorted[a], sorted[b]) })
604
605         for _, v := range sorted {
606                 fmt.Fprintf(out, "%s.%s", seqname, v.String())
607                 for i := 0; i < len(varslice); i += 2 {
608                         if varslice[i] == v || varslice[i+1] == v {
609                                 out.Write([]byte("\t1"))
610                         } else {
611                                 out.Write([]byte("\t0"))
612                         }
613                 }
614                 out.Write([]byte{'\n'})
615         }
616 }