import (
"bufio"
"bytes"
+ "encoding/gob"
"flag"
"fmt"
"io"
+ "io/ioutil"
+ "math"
"net/http"
_ "net/http/pprof"
"os"
+ "regexp"
"runtime"
+ "runtime/debug"
"sort"
+ "strconv"
"strings"
"sync/atomic"
+ "unsafe"
"git.arvados.org/arvados.git/sdk/go/arvados"
"github.com/arvados/lightning/hgvs"
"github.com/kshedden/gonpy"
- "github.com/sirupsen/logrus"
log "github.com/sirupsen/logrus"
"golang.org/x/crypto/blake2b"
)
type sliceNumpy struct {
- filter filter
- threads int
+ filter filter
+ threads int
+ chi2CaseControlColumn string
+ chi2CaseControlFile string
+ chi2Cases []bool
+ chi2PValue float64
+ minCoverage int
+ cgnames []string
}
func (cmd *sliceNumpy) RunCommand(prog string, args []string, stdin io.Reader, stdout, stderr io.Writer) int {
ref := flags.String("ref", "", "reference name (if blank, choose last one that appears in input)")
regionsFilename := flags.String("regions", "", "only output columns/annotations that intersect regions in specified bed `file`")
expandRegions := flags.Int("expand-regions", 0, "expand specified regions by `N` base pairs on each side`")
+ mergeOutput := flags.Bool("merge-output", false, "merge output into one matrix.npy and one matrix.annotations.csv")
+ hgvsSingle := flags.Bool("single-hgvs-matrix", false, "also generate hgvs-based matrix")
+ hgvsChunked := flags.Bool("chunked-hgvs-matrix", false, "also generate hgvs-based matrix per chromosome")
+ onehotSingle := flags.Bool("single-onehot", false, "generate one-hot tile-based matrix")
+ onehotChunked := flags.Bool("chunked-onehot", false, "generate one-hot tile-based matrix per input chunk")
flags.IntVar(&cmd.threads, "threads", 16, "number of memory-hungry assembly threads")
+ 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)")
+ 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)")
+ flags.Float64Var(&cmd.chi2PValue, "chi2-p-value", 1, "do Χ² test and omit columns with p-value above this threshold")
cmd.filter.Flags(flags)
err = flags.Parse(args)
if err == flag.ErrHelp {
}()
}
+ if cmd.chi2PValue != 1 && (cmd.chi2CaseControlFile == "" || cmd.chi2CaseControlColumn == "") {
+ log.Errorf("cannot use provided -chi2-p-value=%f because -chi2-case-control-file= or -chi2-case-control-column= value is empty", cmd.chi2PValue)
+ return 2
+ }
+
if !*runlocal {
runner := arvadosContainerRunner{
Name: "lightning slice-numpy",
Client: arvados.NewClientFromEnv(),
ProjectUUID: *projectUUID,
- RAM: 240000000000,
- VCPUs: 64,
+ RAM: 750000000000,
+ VCPUs: 96,
Priority: *priority,
KeepCache: 2,
APIAccess: true,
}
- err = runner.TranslatePaths(inputDir, regionsFilename)
+ err = runner.TranslatePaths(inputDir, regionsFilename, &cmd.chi2CaseControlFile)
if err != nil {
return 1
}
runner.Args = []string{"slice-numpy", "-local=true",
- "-pprof", ":6060",
- "-input-dir", *inputDir,
- "-output-dir", "/mnt/output",
- "-threads", fmt.Sprintf("%d", cmd.threads),
- "-regions", *regionsFilename,
- "-expand-regions", fmt.Sprintf("%d", *expandRegions),
+ "-pprof=:6060",
+ "-input-dir=" + *inputDir,
+ "-output-dir=/mnt/output",
+ "-threads=" + fmt.Sprintf("%d", cmd.threads),
+ "-regions=" + *regionsFilename,
+ "-expand-regions=" + fmt.Sprintf("%d", *expandRegions),
+ "-merge-output=" + fmt.Sprintf("%v", *mergeOutput),
+ "-single-hgvs-matrix=" + fmt.Sprintf("%v", *hgvsSingle),
+ "-chunked-hgvs-matrix=" + fmt.Sprintf("%v", *hgvsChunked),
+ "-single-onehot=" + fmt.Sprintf("%v", *onehotSingle),
+ "-chunked-onehot=" + fmt.Sprintf("%v", *onehotChunked),
+ "-chi2-case-control-file=" + cmd.chi2CaseControlFile,
+ "-chi2-case-control-column=" + cmd.chi2CaseControlColumn,
+ "-chi2-p-value=" + fmt.Sprintf("%f", cmd.chi2PValue),
}
runner.Args = append(runner.Args, cmd.filter.Args()...)
var output string
return 0
}
- infiles, err := allGobFiles(*inputDir)
+ infiles, err := allFiles(*inputDir, matchGobFile)
if err != nil {
return 1
}
}
sort.Strings(infiles)
- var cgnames []string
var refseq map[string][]tileLibRef
+ var reftiledata = make(map[tileLibRef][]byte, 11000000)
in0, err := open(infiles[0])
if err != nil {
return 1
}
+
+ matchGenome, err := regexp.Compile(cmd.filter.MatchGenome)
+ if err != nil {
+ err = fmt.Errorf("-match-genome: invalid regexp: %q", cmd.filter.MatchGenome)
+ return 1
+ }
+
+ cmd.cgnames = nil
taglen := -1
DecodeLibrary(in0, strings.HasSuffix(infiles[0], ".gz"), func(ent *LibraryEntry) error {
if len(ent.TagSet) > 0 {
}
}
for _, cg := range ent.CompactGenomes {
- cgnames = append(cgnames, cg.Name)
+ if matchGenome.MatchString(cg.Name) {
+ cmd.cgnames = append(cmd.cgnames, cg.Name)
+ }
+ }
+ for _, tv := range ent.TileVariants {
+ if tv.Ref {
+ reftiledata[tileLibRef{tv.Tag, tv.Variant}] = tv.Sequence
+ }
}
return nil
})
err = fmt.Errorf("tagset not found")
return 1
}
- sort.Strings(cgnames)
+ if len(cmd.cgnames) == 0 {
+ err = fmt.Errorf("no genomes found matching regexp %q", cmd.filter.MatchGenome)
+ return 1
+ }
+ sort.Strings(cmd.cgnames)
+ err = cmd.useCaseControlFiles()
+ if err != nil {
+ return 1
+ }
+ cmd.minCoverage = int(math.Ceil(cmd.filter.MinCoverage * float64(len(cmd.cgnames))))
{
- labelsFilename := *outputDir + "/labels.csv"
+ labelsFilename := *outputDir + "/samples.csv"
log.Infof("writing labels to %s", labelsFilename)
var f *os.File
f, err = os.Create(labelsFilename)
return 1
}
defer f.Close()
- for i, name := range cgnames {
- _, err = fmt.Fprintf(f, "%d,%q\n", i, trimFilenameForLabel(name))
+ for i, name := range cmd.cgnames {
+ cc := 0
+ if cmd.chi2Cases != nil && cmd.chi2Cases[i] {
+ cc = 1
+ }
+ _, err = fmt.Fprintf(f, "%d,%q,%d\n", i, trimFilenameForLabel(name), cc)
if err != nil {
err = fmt.Errorf("write %s: %w", labelsFilename, err)
return 1
}
}
- log.Info("building list of reference tiles to load") // TODO: more efficient if we had saved all ref tiles in slice0
+ log.Info("indexing reference tiles")
type reftileinfo struct {
variant tileVariantID
seqname string // chr1
- pos int // distance from start of chr1 to start of tile
+ pos int // distance from start of chromosome to starttag
tiledata []byte // acgtggcaa...
}
+ isdup := map[tagID]bool{}
reftile := map[tagID]*reftileinfo{}
for seqname, cseq := range refseq {
+ pos := 0
for _, libref := range cseq {
- reftile[libref.Tag] = &reftileinfo{seqname: seqname, variant: libref.Variant}
+ tiledata := reftiledata[libref]
+ if len(tiledata) == 0 {
+ err = fmt.Errorf("missing tiledata for tag %d variant %d in %s in ref", libref.Tag, libref.Variant, seqname)
+ return 1
+ }
+ if isdup[libref.Tag] {
+ log.Printf("dropping reference tile %+v from %s @ %d, tag not unique", libref, seqname, pos)
+ } else if reftile[libref.Tag] != nil {
+ 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)
+ delete(reftile, libref.Tag)
+ log.Printf("dropping reference tile %+v from %s @ %d, tag not unique", libref, seqname, pos)
+ isdup[libref.Tag] = true
+ } else {
+ reftile[libref.Tag] = &reftileinfo{
+ seqname: seqname,
+ variant: libref.Variant,
+ tiledata: tiledata,
+ pos: pos,
+ }
+ }
+ pos += len(tiledata) - taglen
}
+ log.Printf("... %s done, len %d", seqname, pos+taglen)
}
- log.Info("loading reference tiles from all slices")
- throttleCPU := throttle{Max: runtime.GOMAXPROCS(0)}
- for _, infile := range infiles {
- infile := infile
- throttleCPU.Go(func() error {
- defer log.Infof("%s: done", infile)
- f, err := open(infile)
+
+ var mask *mask
+ if *regionsFilename != "" {
+ log.Printf("loading regions from %s", *regionsFilename)
+ mask, err = makeMask(*regionsFilename, *expandRegions)
+ if err != nil {
+ return 1
+ }
+ log.Printf("before applying mask, len(reftile) == %d", len(reftile))
+ log.Printf("deleting reftile entries for regions outside %d intervals", mask.Len())
+ for tag, rt := range reftile {
+ if !mask.Check(strings.TrimPrefix(rt.seqname, "chr"), rt.pos, rt.pos+len(rt.tiledata)) {
+ delete(reftile, tag)
+ }
+ }
+ log.Printf("after applying mask, len(reftile) == %d", len(reftile))
+ }
+
+ type hgvsColSet map[hgvs.Variant][2][]int8
+ encodeHGVS := throttle{Max: len(refseq)}
+ encodeHGVSTodo := map[string]chan hgvsColSet{}
+ tmpHGVSCols := map[string]*os.File{}
+ if *hgvsChunked {
+ for seqname := range refseq {
+ var f *os.File
+ f, err = os.Create(*outputDir + "/tmp." + seqname + ".gob")
if err != nil {
- return err
+ return 1
}
- defer f.Close()
- return DecodeLibrary(f, strings.HasSuffix(infile, ".gz"), func(ent *LibraryEntry) error {
- for _, tv := range ent.TileVariants {
- if dst, ok := reftile[tv.Tag]; ok && dst.variant == tv.Variant {
- dst.tiledata = tv.Sequence
+ defer os.Remove(f.Name())
+ bufw := bufio.NewWriterSize(f, 1<<24)
+ enc := gob.NewEncoder(bufw)
+ tmpHGVSCols[seqname] = f
+ todo := make(chan hgvsColSet, 128)
+ encodeHGVSTodo[seqname] = todo
+ encodeHGVS.Go(func() error {
+ for colset := range todo {
+ err := enc.Encode(colset)
+ if err != nil {
+ encodeHGVS.Report(err)
+ for range todo {
+ }
+ return err
}
}
- return nil
+ return bufw.Flush()
})
- })
- }
- if err = throttleCPU.Wait(); err != nil {
- return 1
+ }
}
- log.Info("reconstructing reference sequences")
- for seqname, cseq := range refseq {
- seqname, cseq := seqname, cseq
- throttleCPU.Go(func() error {
- defer log.Printf("... %s done", seqname)
- pos := 0
- for _, libref := range cseq {
- rt := reftile[libref.Tag]
- rt.pos = pos
- pos += len(rt.tiledata) - taglen
- }
- return nil
- })
+ var toMerge [][]int16
+ if *mergeOutput || *hgvsSingle {
+ toMerge = make([][]int16, len(infiles))
+ }
+ var onehotIndirect [][2][]uint32 // [chunkIndex][axis][index]
+ var onehotXrefs [][]onehotXref
+ if *onehotSingle {
+ onehotIndirect = make([][2][]uint32, len(infiles))
+ onehotXrefs = make([][]onehotXref, len(infiles))
}
- throttleCPU.Wait()
-
- log.Info("TODO: determining which tiles intersect given regions")
throttleMem := throttle{Max: cmd.threads} // TODO: estimate using mem and data size
throttleNumpyMem := throttle{Max: cmd.threads/2 + 1}
infileIdx, infile := infileIdx, infile
throttleMem.Go(func() error {
seq := make(map[tagID][]TileVariant, 50000)
- cgs := make(map[string]CompactGenome, len(cgnames))
+ cgs := make(map[string]CompactGenome, len(cmd.cgnames))
f, err := open(infile)
if err != nil {
return err
}
defer f.Close()
- log.Infof("reading %s", infile)
+ log.Infof("%04d: reading %s", infileIdx, infile)
err = DecodeLibrary(f, strings.HasSuffix(infile, ".gz"), func(ent *LibraryEntry) error {
for _, tv := range ent.TileVariants {
+ if tv.Ref {
+ continue
+ }
+ if mask != nil && reftile[tv.Tag] == nil {
+ // Don't waste
+ // time/memory on
+ // masked-out tiles.
+ continue
+ }
variants := seq[tv.Tag]
if len(variants) == 0 {
variants = make([]TileVariant, 100)
seq[tv.Tag] = variants
}
for _, cg := range ent.CompactGenomes {
+ if !matchGenome.MatchString(cg.Name) {
+ continue
+ }
+ // pad to full slice size
+ // to avoid out-of-bounds
+ // checks later
+ if sliceSize := 2 * int(cg.EndTag-cg.StartTag); len(cg.Variants) < sliceSize {
+ cg.Variants = append(cg.Variants, make([]tileVariantID, sliceSize-len(cg.Variants))...)
+ }
cgs[cg.Name] = cg
}
return nil
if err != nil {
return err
}
- tagstart := cgs[cgnames[0]].StartTag
- tagend := cgs[cgnames[0]].EndTag
+ tagstart := cgs[cmd.cgnames[0]].StartTag
+ tagend := cgs[cmd.cgnames[0]].EndTag
// TODO: filters
- log.Infof("renumber/dedup variants for tags %d-%d", tagstart, tagend)
+ log.Infof("%04d: renumber/dedup variants for tags %d-%d", infileIdx, tagstart, tagend)
variantRemap := make([][]tileVariantID, tagend-tagstart)
throttleCPU := throttle{Max: runtime.GOMAXPROCS(0)}
for tag, variants := range seq {
go func() {
defer throttleCPU.Release()
count := make(map[[blake2b.Size256]byte]int, len(variants))
+
+ rt := reftile[tag]
+ if rt != nil {
+ count[blake2b.Sum256(rt.tiledata)] = 0
+ }
+
for _, cg := range cgs {
- idx := (tag - tagstart) * 2
- if int(idx) < len(cg.Variants) {
- count[variants[cg.Variants[idx]].Blake2b]++
- count[variants[cg.Variants[idx+1]].Blake2b]++
+ idx := int(tag-tagstart) * 2
+ for allele := 0; allele < 2; allele++ {
+ v := cg.Variants[idx+allele]
+ if v > 0 && len(variants[v].Sequence) > 0 {
+ count[variants[v].Blake2b]++
+ }
}
}
// hash[i] will be the hash of
remap[i] = rank[tv.Blake2b]
}
variantRemap[tag-tagstart] = remap
+ if rt != nil {
+ rt.variant = rank[blake2b.Sum256(rt.tiledata)]
+ }
}()
}
throttleCPU.Wait()
+ var onehotChunk [][]int8
+ var onehotXref []onehotXref
+
annotationsFilename := fmt.Sprintf("%s/matrix.%04d.annotations.csv", *outputDir, infileIdx)
- log.Infof("writing %s", annotationsFilename)
+ log.Infof("%04d: writing %s", infileIdx, annotationsFilename)
annof, err := os.Create(annotationsFilename)
if err != nil {
return err
}
annow := bufio.NewWriterSize(annof, 1<<20)
- for tag, variants := range seq {
+ outcol := 0
+ for tag := tagstart; tag < tagend; tag++ {
rt, ok := reftile[tag]
if !ok {
- // Reference does not use any
- // variant of this tile.
- // TODO: log this? mention it
- // in annotations?
+ if mask == nil {
+ outcol++
+ }
+ // Excluded by specified
+ // regions, or reference does
+ // not use any variant of this
+ // tile. (TODO: log this?
+ // mention it in annotations?)
continue
}
- outcol := tag - tagID(tagstart)
- reftilestr := strings.ToUpper(string(rt.tiledata))
remap := variantRemap[tag-tagstart]
+ maxv := tileVariantID(0)
+ for _, v := range remap {
+ if maxv < v {
+ maxv = v
+ }
+ }
+ if *onehotChunked || *onehotSingle {
+ onehot, xrefs := cmd.tv2homhet(cgs, maxv, remap, tag, tagstart)
+ onehotChunk = append(onehotChunk, onehot...)
+ onehotXref = append(onehotXref, xrefs...)
+ }
+ fmt.Fprintf(annow, "%d,%d,%d,=,%s,%d,,,\n", tag, outcol, rt.variant, rt.seqname, rt.pos)
+ variants := seq[tag]
+ reftilestr := strings.ToUpper(string(rt.tiledata))
+
+ done := make([]bool, maxv+1)
+ variantDiffs := make([][]hgvs.Variant, maxv+1)
for v, tv := range variants {
+ v := remap[v]
+ if v == rt.variant || done[v] {
+ continue
+ } else {
+ done[v] = true
+ }
if len(tv.Sequence) < taglen || !bytes.HasSuffix(rt.tiledata, tv.Sequence[len(tv.Sequence)-taglen:]) {
+ fmt.Fprintf(annow, "%d,%d,%d,,%s,%d,,,\n", tag, outcol, v, rt.seqname, rt.pos)
continue
}
if lendiff := len(rt.tiledata) - len(tv.Sequence); lendiff < -1000 || lendiff > 1000 {
+ fmt.Fprintf(annow, "%d,%d,%d,,%s,%d,,,\n", tag, outcol, v, rt.seqname, rt.pos)
continue
}
diffs, _ := hgvs.Diff(reftilestr, strings.ToUpper(string(tv.Sequence)), 0)
+ for i := range diffs {
+ diffs[i].Position += rt.pos
+ }
for _, diff := range diffs {
- diff.Position += rt.pos
- fmt.Fprintf(annow, "%d,%d,%d,%s:g.%s\n", tag, outcol, remap[v], rt.seqname, diff.String())
+ 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)
+ }
+ if *hgvsChunked {
+ variantDiffs[v] = diffs
}
}
+ if *hgvsChunked {
+ // We can now determine, for each HGVS
+ // variant (diff) in this reftile
+ // region, whether a given genome
+ // phase/allele (1) has the variant, (0) has
+ // =ref or a different variant in that
+ // position, or (-1) is lacking
+ // coverage / couldn't be diffed.
+ hgvsCol := hgvsColSet{}
+ for _, diffs := range variantDiffs {
+ for _, diff := range diffs {
+ if _, ok := hgvsCol[diff]; ok {
+ continue
+ }
+ hgvsCol[diff] = [2][]int8{
+ make([]int8, len(cmd.cgnames)),
+ make([]int8, len(cmd.cgnames)),
+ }
+ }
+ }
+ for row, name := range cmd.cgnames {
+ variants := cgs[name].Variants[(tag-tagstart)*2:]
+ for ph := 0; ph < 2; ph++ {
+ v := variants[ph]
+ if int(v) >= len(remap) {
+ v = 0
+ } else {
+ v = remap[v]
+ }
+ if v == rt.variant {
+ // hgvsCol[*][ph][row] is already 0
+ } else if len(variantDiffs[v]) == 0 {
+ // lacking coverage / couldn't be diffed
+ for _, col := range hgvsCol {
+ col[ph][row] = -1
+ }
+ } else {
+ for _, diff := range variantDiffs[v] {
+ hgvsCol[diff][ph][row] = 1
+ }
+ }
+ }
+ }
+ for diff, colpair := range hgvsCol {
+ allele2homhet(colpair)
+ if !cmd.filterHGVScolpair(colpair) {
+ delete(hgvsCol, diff)
+ }
+ }
+ if len(hgvsCol) > 0 {
+ encodeHGVSTodo[rt.seqname] <- hgvsCol
+ }
+ }
+ outcol++
}
err = annow.Flush()
if err != nil {
return err
}
- throttleNumpyMem.Acquire()
- log.Infof("%s: preparing numpy", infile)
- rows := len(cgnames)
- cols := 2 * int(tagend-tagstart)
- out := make([]int16, rows*cols)
- for row, name := range cgnames {
- out := out[row*cols:]
- for col, v := range cgs[name].Variants {
- if variants, ok := seq[tagstart+tagID(col/2)]; ok && len(variants) > int(v) && len(variants[v].Sequence) > 0 {
- out[col] = int16(variantRemap[col/2][v])
- } else {
- out[col] = -1
+ if *onehotChunked {
+ // transpose onehotChunk[col][row] to numpy[row*ncols+col]
+ rows := len(cmd.cgnames)
+ cols := len(onehotChunk)
+ log.Infof("%04d: preparing onehot numpy (rows=%d, cols=%d, mem=%d)", infileIdx, len(cmd.cgnames), len(onehotChunk), len(cmd.cgnames)*len(onehotChunk))
+ throttleNumpyMem.Acquire()
+ out := onehotcols2int8(onehotChunk)
+ fnm := fmt.Sprintf("%s/onehot.%04d.npy", *outputDir, infileIdx)
+ err = writeNumpyInt8(fnm, out, rows, cols)
+ if err != nil {
+ return err
+ }
+ fnm = fmt.Sprintf("%s/onehot-columns.%04d.npy", *outputDir, infileIdx)
+ err = writeNumpyInt32(fnm, onehotXref2int32(onehotXref), 4, len(onehotXref))
+ if err != nil {
+ return err
+ }
+ debug.FreeOSMemory()
+ throttleNumpyMem.Release()
+ }
+ if *onehotSingle {
+ onehotIndirect[infileIdx] = onehotChunk2Indirect(onehotChunk)
+ onehotXrefs[infileIdx] = onehotXref
+ n := len(onehotIndirect[infileIdx][0])
+ log.Infof("%04d: keeping onehot coordinates in memory (n=%d, mem=%d)", infileIdx, n, n*8)
+ }
+ if !(*onehotSingle || *onehotChunked) || *mergeOutput || *hgvsSingle {
+ log.Infof("%04d: preparing numpy", infileIdx)
+ throttleNumpyMem.Acquire()
+ rows := len(cmd.cgnames)
+ cols := 2 * outcol
+ out := make([]int16, rows*cols)
+ for row, name := range cmd.cgnames {
+ out := out[row*cols:]
+ outcol := 0
+ for col, v := range cgs[name].Variants {
+ tag := tagstart + tagID(col/2)
+ if mask != nil && reftile[tag] == nil {
+ continue
+ }
+ if variants, ok := seq[tag]; ok && len(variants) > int(v) && len(variants[v].Sequence) > 0 {
+ out[outcol] = int16(variantRemap[tag-tagstart][v])
+ } else {
+ out[outcol] = -1
+ }
+ outcol++
+ }
+ }
+ seq = nil
+ cgs = nil
+ debug.FreeOSMemory()
+ throttleNumpyMem.Release()
+ if *mergeOutput || *hgvsSingle {
+ log.Infof("%04d: matrix fragment %d rows x %d cols", infileIdx, rows, cols)
+ toMerge[infileIdx] = out
+ }
+ if !*mergeOutput && !*onehotChunked && !*onehotSingle {
+ fnm := fmt.Sprintf("%s/matrix.%04d.npy", *outputDir, infileIdx)
+ err = writeNumpyInt16(fnm, out, rows, cols)
+ if err != nil {
+ return err
}
}
}
- seq = nil
- throttleNumpyMem.Release()
+ debug.FreeOSMemory()
+ log.Infof("%s: done (%d/%d)", infile, int(atomic.AddInt64(&done, 1)), len(infiles))
+ return nil
+ })
+ }
+ if err = throttleMem.Wait(); err != nil {
+ return 1
+ }
- fnm := fmt.Sprintf("%s/matrix.%04d.npy", *outputDir, infileIdx)
- output, err := os.Create(fnm)
+ if *hgvsChunked {
+ log.Info("flushing hgvsCols temp files")
+ for seqname := range refseq {
+ close(encodeHGVSTodo[seqname])
+ }
+ err = encodeHGVS.Wait()
+ if err != nil {
+ return 1
+ }
+ for seqname := range refseq {
+ log.Infof("%s: reading hgvsCols from temp file", seqname)
+ f := tmpHGVSCols[seqname]
+ _, err = f.Seek(0, io.SeekStart)
if err != nil {
- return err
+ return 1
}
- defer output.Close()
- bufw := bufio.NewWriterSize(output, 1<<26)
- npw, err := gonpy.NewWriter(nopCloser{bufw})
+ var hgvsCols hgvsColSet
+ dec := gob.NewDecoder(bufio.NewReaderSize(f, 1<<24))
+ for err == nil {
+ err = dec.Decode(&hgvsCols)
+ }
+ if err != io.EOF {
+ return 1
+ }
+ log.Infof("%s: sorting %d hgvs variants", seqname, len(hgvsCols))
+ variants := make([]hgvs.Variant, 0, len(hgvsCols))
+ for v := range hgvsCols {
+ variants = append(variants, v)
+ }
+ sort.Slice(variants, func(i, j int) bool {
+ vi, vj := &variants[i], &variants[j]
+ if vi.Position != vj.Position {
+ return vi.Position < vj.Position
+ } else if vi.Ref != vj.Ref {
+ return vi.Ref < vj.Ref
+ } else {
+ return vi.New < vj.New
+ }
+ })
+ rows := len(cmd.cgnames)
+ cols := len(variants) * 2
+ log.Infof("%s: building hgvs matrix (rows=%d, cols=%d, mem=%d)", seqname, rows, cols, rows*cols)
+ out := make([]int8, rows*cols)
+ for varIdx, variant := range variants {
+ hgvsCols := hgvsCols[variant]
+ for row := range cmd.cgnames {
+ for ph := 0; ph < 2; ph++ {
+ out[row*cols+varIdx+ph] = hgvsCols[ph][row]
+ }
+ }
+ }
+ err = writeNumpyInt8(fmt.Sprintf("%s/hgvs.%s.npy", *outputDir, seqname), out, rows, cols)
if err != nil {
- return err
+ return 1
}
- log.WithFields(logrus.Fields{
- "filename": fnm,
- "rows": rows,
- "cols": cols,
- }).Info("writing numpy")
- npw.Shape = []int{rows, cols}
- npw.WriteInt16(out)
- err = bufw.Flush()
+ out = nil
+
+ fnm := fmt.Sprintf("%s/hgvs.%s.annotations.csv", *outputDir, seqname)
+ log.Infof("%s: writing hgvs column labels to %s", seqname, fnm)
+ var hgvsLabels bytes.Buffer
+ for varIdx, variant := range variants {
+ fmt.Fprintf(&hgvsLabels, "%d,%s:g.%s\n", varIdx, seqname, variant.String())
+ }
+ err = ioutil.WriteFile(fnm, hgvsLabels.Bytes(), 0666)
if err != nil {
- return err
+ return 1
}
- err = output.Close()
+ }
+ }
+
+ if *mergeOutput || *hgvsSingle {
+ var annow *bufio.Writer
+ var annof *os.File
+ if *mergeOutput {
+ annoFilename := fmt.Sprintf("%s/matrix.annotations.csv", *outputDir)
+ annof, err = os.Create(annoFilename)
if err != nil {
- return err
+ return 1
}
- log.Infof("%s: done (%d/%d)", infile, int(atomic.AddInt64(&done, 1)), len(infiles))
- return nil
- })
+ annow = bufio.NewWriterSize(annof, 1<<20)
+ }
+
+ rows := len(cmd.cgnames)
+ cols := 0
+ for _, chunk := range toMerge {
+ cols += len(chunk) / rows
+ }
+ log.Infof("merging output matrix (rows=%d, cols=%d, mem=%d) and annotations", rows, cols, rows*cols*2)
+ var out []int16
+ if *mergeOutput {
+ out = make([]int16, rows*cols)
+ }
+ hgvsCols := map[string][2][]int16{} // hgvs -> [[g0,g1,g2,...], [g0,g1,g2,...]] (slice of genomes for each phase)
+ startcol := 0
+ for outIdx, chunk := range toMerge {
+ chunkcols := len(chunk) / rows
+ if *mergeOutput {
+ for row := 0; row < rows; row++ {
+ copy(out[row*cols+startcol:], chunk[row*chunkcols:(row+1)*chunkcols])
+ }
+ }
+ toMerge[outIdx] = nil
+
+ annotationsFilename := fmt.Sprintf("%s/matrix.%04d.annotations.csv", *outputDir, outIdx)
+ log.Infof("reading %s", annotationsFilename)
+ buf, err := os.ReadFile(annotationsFilename)
+ if err != nil {
+ return 1
+ }
+ if *mergeOutput {
+ err = os.Remove(annotationsFilename)
+ if err != nil {
+ return 1
+ }
+ }
+ for _, line := range bytes.Split(buf, []byte{'\n'}) {
+ if len(line) == 0 {
+ continue
+ }
+ fields := bytes.SplitN(line, []byte{','}, 9)
+ tag, _ := strconv.Atoi(string(fields[0]))
+ incol, _ := strconv.Atoi(string(fields[1]))
+ tileVariant, _ := strconv.Atoi(string(fields[2]))
+ hgvsID := string(fields[3])
+ seqname := string(fields[4])
+ pos, _ := strconv.Atoi(string(fields[5]))
+ refseq := fields[6]
+ if hgvsID == "" {
+ // Null entry for un-diffable
+ // tile variant
+ continue
+ }
+ if hgvsID == "=" {
+ // Null entry for ref tile
+ continue
+ }
+ if mask != nil && !mask.Check(strings.TrimPrefix(seqname, "chr"), pos, pos+len(refseq)) {
+ // The tile intersects one of
+ // the selected regions, but
+ // this particular HGVS
+ // variant does not.
+ continue
+ }
+ hgvsColPair := hgvsCols[hgvsID]
+ if hgvsColPair[0] == nil {
+ // values in new columns start
+ // out as -1 ("no data yet")
+ // or 0 ("=ref") here, may
+ // change to 1 ("hgvs variant
+ // present") below, either on
+ // this line or a future line.
+ hgvsColPair = [2][]int16{make([]int16, len(cmd.cgnames)), make([]int16, len(cmd.cgnames))}
+ rt, ok := reftile[tagID(tag)]
+ if !ok {
+ err = fmt.Errorf("bug: seeing annotations for tag %d, but it has no reftile entry", tag)
+ return 1
+ }
+ for ph := 0; ph < 2; ph++ {
+ for row := 0; row < rows; row++ {
+ v := chunk[row*chunkcols+incol*2+ph]
+ if tileVariantID(v) == rt.variant {
+ hgvsColPair[ph][row] = 0
+ } else {
+ hgvsColPair[ph][row] = -1
+ }
+ }
+ }
+ hgvsCols[hgvsID] = hgvsColPair
+ if annow != nil {
+ hgvsref := hgvs.Variant{
+ Position: pos,
+ Ref: string(refseq),
+ New: string(refseq),
+ }
+ 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])
+ }
+ }
+ if annow != nil {
+ 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])
+ }
+ for ph := 0; ph < 2; ph++ {
+ for row := 0; row < rows; row++ {
+ v := chunk[row*chunkcols+incol*2+ph]
+ if int(v) == tileVariant {
+ hgvsColPair[ph][row] = 1
+ }
+ }
+ }
+ }
+
+ startcol += chunkcols
+ }
+ if *mergeOutput {
+ err = annow.Flush()
+ if err != nil {
+ return 1
+ }
+ err = annof.Close()
+ if err != nil {
+ return 1
+ }
+ err = writeNumpyInt16(fmt.Sprintf("%s/matrix.npy", *outputDir), out, rows, cols)
+ if err != nil {
+ return 1
+ }
+ }
+ out = nil
+
+ if *hgvsSingle {
+ cols = len(hgvsCols) * 2
+ log.Printf("building hgvs-based matrix: %d rows x %d cols", rows, cols)
+ out = make([]int16, rows*cols)
+ hgvsIDs := make([]string, 0, cols/2)
+ for hgvsID := range hgvsCols {
+ hgvsIDs = append(hgvsIDs, hgvsID)
+ }
+ sort.Strings(hgvsIDs)
+ var hgvsLabels bytes.Buffer
+ for idx, hgvsID := range hgvsIDs {
+ fmt.Fprintf(&hgvsLabels, "%d,%s\n", idx, hgvsID)
+ for ph := 0; ph < 2; ph++ {
+ hgvscol := hgvsCols[hgvsID][ph]
+ for row, val := range hgvscol {
+ out[row*cols+idx*2+ph] = val
+ }
+ }
+ }
+ err = writeNumpyInt16(fmt.Sprintf("%s/hgvs.npy", *outputDir), out, rows, cols)
+ if err != nil {
+ return 1
+ }
+
+ fnm := fmt.Sprintf("%s/hgvs.annotations.csv", *outputDir)
+ log.Printf("writing hgvs labels: %s", fnm)
+ err = ioutil.WriteFile(fnm, hgvsLabels.Bytes(), 0777)
+ if err != nil {
+ return 1
+ }
+ }
}
- if err = throttleMem.Wait(); err != nil {
- return 1
+ if *onehotSingle {
+ nzCount := 0
+ for _, part := range onehotIndirect {
+ nzCount += len(part[0])
+ }
+ onehot := make([]uint32, nzCount*2) // [r,r,r,...,c,c,c,...]
+ var xrefs []onehotXref
+ outcol := 0
+ for i, part := range onehotIndirect {
+ for i := range part[1] {
+ part[1][i] += uint32(outcol)
+ }
+ copy(onehot[outcol:], part[0])
+ copy(onehot[outcol+nzCount:], part[1])
+ outcol += len(part[0])
+ xrefs = append(xrefs, onehotXrefs[i]...)
+
+ part[0] = nil
+ part[1] = nil
+ onehotXrefs[i] = nil
+ debug.FreeOSMemory()
+ }
+ fnm := fmt.Sprintf("%s/onehot.npy", *outputDir)
+ err = writeNumpyUint32(fnm, onehot, 2, nzCount)
+ if err != nil {
+ return 1
+ }
+ fnm = fmt.Sprintf("%s/onehot-columns.npy", *outputDir)
+ err = writeNumpyInt32(fnm, onehotXref2int32(xrefs), 4, len(xrefs))
+ if err != nil {
+ return 1
+ }
}
return 0
}
+
+// Read case/control files, remove non-case/control entries from
+// cmd.cgnames, and build cmd.chi2Cases.
+func (cmd *sliceNumpy) useCaseControlFiles() error {
+ if cmd.chi2CaseControlFile == "" {
+ return nil
+ }
+ infiles, err := allFiles(cmd.chi2CaseControlFile, nil)
+ if err != nil {
+ return err
+ }
+ // index in cmd.cgnames => case(true) / control(false)
+ cc := map[int]bool{}
+ for _, infile := range infiles {
+ f, err := open(infile)
+ if err != nil {
+ return err
+ }
+ buf, err := io.ReadAll(f)
+ f.Close()
+ if err != nil {
+ return err
+ }
+ ccCol := -1
+ for _, tsv := range bytes.Split(buf, []byte{'\n'}) {
+ if len(tsv) == 0 {
+ continue
+ }
+ split := strings.Split(string(tsv), "\t")
+ if ccCol < 0 {
+ // header row
+ for col, name := range split {
+ if name == cmd.chi2CaseControlColumn {
+ ccCol = col
+ break
+ }
+ }
+ if ccCol < 0 {
+ return fmt.Errorf("%s: no column named %q in header row %q", infile, cmd.chi2CaseControlColumn, tsv)
+ }
+ continue
+ }
+ if len(split) <= ccCol {
+ continue
+ }
+ pattern := split[0]
+ found := -1
+ for i, name := range cmd.cgnames {
+ if strings.Contains(name, pattern) {
+ if found >= 0 {
+ log.Warnf("pattern %q in %s matches multiple genome IDs (%qs, %q)", pattern, infile, cmd.cgnames[found], name)
+ }
+ found = i
+ }
+ }
+ if found < 0 {
+ log.Warnf("pattern %q in %s does not match any genome IDs", pattern, infile)
+ continue
+ }
+ if split[ccCol] == "0" {
+ cc[found] = false
+ }
+ if split[ccCol] == "1" {
+ cc[found] = true
+ }
+ }
+ }
+ allnames := cmd.cgnames
+ cmd.cgnames = nil
+ cmd.chi2Cases = nil
+ ncases := 0
+ for i, name := range allnames {
+ if cc, ok := cc[i]; ok {
+ cmd.cgnames = append(cmd.cgnames, name)
+ cmd.chi2Cases = append(cmd.chi2Cases, cc)
+ if cc {
+ ncases++
+ }
+ }
+ }
+ log.Printf("%d cases, %d controls, %d neither (dropped)", ncases, len(cmd.cgnames)-ncases, len(allnames)-len(cmd.cgnames))
+ return nil
+}
+
+func (cmd *sliceNumpy) filterHGVScolpair(colpair [2][]int8) bool {
+ if cmd.chi2PValue >= 1 {
+ return true
+ }
+ col0 := make([]bool, 0, len(cmd.chi2Cases))
+ col1 := make([]bool, 0, len(cmd.chi2Cases))
+ cases := make([]bool, 0, len(cmd.chi2Cases))
+ for i, c := range cmd.chi2Cases {
+ if colpair[0][i] < 0 {
+ continue
+ }
+ col0 = append(col0, colpair[0][i] != 0)
+ col1 = append(col1, colpair[1][i] != 0)
+ cases = append(cases, c)
+ }
+ return len(cases) >= cmd.minCoverage &&
+ (pvalue(col0, cases) <= cmd.chi2PValue || pvalue(col1, cases) <= cmd.chi2PValue)
+}
+
+func writeNumpyUint32(fnm string, out []uint32, rows, cols int) error {
+ output, err := os.Create(fnm)
+ if err != nil {
+ return err
+ }
+ defer output.Close()
+ bufw := bufio.NewWriterSize(output, 1<<26)
+ npw, err := gonpy.NewWriter(nopCloser{bufw})
+ if err != nil {
+ return err
+ }
+ log.WithFields(log.Fields{
+ "filename": fnm,
+ "rows": rows,
+ "cols": cols,
+ "bytes": rows * cols * 4,
+ }).Infof("writing numpy: %s", fnm)
+ npw.Shape = []int{rows, cols}
+ npw.WriteUint32(out)
+ err = bufw.Flush()
+ if err != nil {
+ return err
+ }
+ return output.Close()
+}
+
+func writeNumpyInt32(fnm string, out []int32, rows, cols int) error {
+ output, err := os.Create(fnm)
+ if err != nil {
+ return err
+ }
+ defer output.Close()
+ bufw := bufio.NewWriterSize(output, 1<<26)
+ npw, err := gonpy.NewWriter(nopCloser{bufw})
+ if err != nil {
+ return err
+ }
+ log.WithFields(log.Fields{
+ "filename": fnm,
+ "rows": rows,
+ "cols": cols,
+ "bytes": rows * cols * 4,
+ }).Infof("writing numpy: %s", fnm)
+ npw.Shape = []int{rows, cols}
+ npw.WriteInt32(out)
+ err = bufw.Flush()
+ if err != nil {
+ return err
+ }
+ return output.Close()
+}
+
+func writeNumpyInt16(fnm string, out []int16, rows, cols int) error {
+ output, err := os.Create(fnm)
+ if err != nil {
+ return err
+ }
+ defer output.Close()
+ bufw := bufio.NewWriterSize(output, 1<<26)
+ npw, err := gonpy.NewWriter(nopCloser{bufw})
+ if err != nil {
+ return err
+ }
+ log.WithFields(log.Fields{
+ "filename": fnm,
+ "rows": rows,
+ "cols": cols,
+ "bytes": rows * cols * 2,
+ }).Infof("writing numpy: %s", fnm)
+ npw.Shape = []int{rows, cols}
+ npw.WriteInt16(out)
+ err = bufw.Flush()
+ if err != nil {
+ return err
+ }
+ return output.Close()
+}
+
+func writeNumpyInt8(fnm string, out []int8, rows, cols int) error {
+ output, err := os.Create(fnm)
+ if err != nil {
+ return err
+ }
+ defer output.Close()
+ bufw := bufio.NewWriterSize(output, 1<<26)
+ npw, err := gonpy.NewWriter(nopCloser{bufw})
+ if err != nil {
+ return err
+ }
+ log.WithFields(log.Fields{
+ "filename": fnm,
+ "rows": rows,
+ "cols": cols,
+ "bytes": rows * cols,
+ }).Infof("writing numpy: %s", fnm)
+ npw.Shape = []int{rows, cols}
+ npw.WriteInt8(out)
+ err = bufw.Flush()
+ if err != nil {
+ return err
+ }
+ return output.Close()
+}
+
+func allele2homhet(colpair [2][]int8) {
+ a, b := colpair[0], colpair[1]
+ for i, av := range a {
+ bv := b[i]
+ if av < 0 || bv < 0 {
+ // no-call
+ a[i], b[i] = -1, -1
+ } else if av > 0 && bv > 0 {
+ // hom
+ a[i], b[i] = 1, 0
+ } else if av > 0 || bv > 0 {
+ // het
+ a[i], b[i] = 0, 1
+ } else {
+ // ref (or a different variant in same position)
+ // (this is a no-op) a[i], b[i] = 0, 0
+ }
+ }
+}
+
+type onehotXref struct {
+ tag tagID
+ variant tileVariantID
+ het bool
+ pvalue float64
+}
+
+const onehotXrefSize = unsafe.Sizeof(onehotXref{})
+
+// Build onehot matrix (m[variant*2+isHet][genome] == 0 or 1) for all
+// variants of a single tile/tag#.
+//
+// Return nil if no tile variant passes Χ² filter.
+func (cmd *sliceNumpy) tv2homhet(cgs map[string]CompactGenome, maxv tileVariantID, remap []tileVariantID, tag, chunkstarttag tagID) ([][]int8, []onehotXref) {
+ if maxv < 2 {
+ // everyone has the most common variant
+ return nil, nil
+ }
+ tagoffset := tag - chunkstarttag
+ coverage := 0
+ for _, cg := range cgs {
+ if cg.Variants[tagoffset*2] > 0 && cg.Variants[tagoffset*2+1] > 0 {
+ coverage++
+ }
+ }
+ if coverage < cmd.minCoverage {
+ return nil, nil
+ }
+ obs := make([][]bool, (maxv+1)*2) // 2 slices (hom + het) for each variant#
+ for i := range obs {
+ obs[i] = make([]bool, len(cmd.cgnames))
+ }
+ for cgid, name := range cmd.cgnames {
+ cgvars := cgs[name].Variants
+ for v := tileVariantID(2); v <= maxv; v++ {
+ if remap[cgvars[tagoffset*2]] == v && remap[cgvars[tagoffset*2+1]] == v {
+ obs[v*2][cgid] = true
+ } else if remap[cgvars[tagoffset*2]] == v || remap[cgvars[tagoffset*2+1]] == v {
+ obs[v*2+1][cgid] = true
+ }
+ }
+ }
+ var onehot [][]int8
+ var xref []onehotXref
+ for homcol := 4; homcol < len(obs); homcol += 2 {
+ p := [2]float64{
+ pvalue(obs[homcol], cmd.chi2Cases),
+ pvalue(obs[homcol+1], cmd.chi2Cases),
+ }
+ if cmd.chi2PValue < 1 && !(p[0] < cmd.chi2PValue || p[1] < cmd.chi2PValue) {
+ continue
+ }
+ for het := 0; het < 2; het++ {
+ onehot = append(onehot, bool2int8(obs[homcol+het]))
+ xref = append(xref, onehotXref{
+ tag: tag,
+ variant: tileVariantID(homcol / 2),
+ het: het == 1,
+ pvalue: p[het],
+ })
+ }
+ }
+ return onehot, xref
+}
+
+func bool2int8(in []bool) []int8 {
+ out := make([]int8, len(in))
+ for i, v := range in {
+ if v {
+ out[i] = 1
+ }
+ }
+ return out
+}
+
+// convert a []onehotXref with length N to a numpy-style []int32
+// matrix with N columns, one row per field of onehotXref struct.
+//
+// Hom/het row contains hom=0, het=1.
+//
+// P-value row contains 1000000x actual p-value.
+func onehotXref2int32(xrefs []onehotXref) []int32 {
+ xcols := len(xrefs)
+ xdata := make([]int32, 4*xcols)
+ for i, xref := range xrefs {
+ xdata[i] = int32(xref.tag)
+ xdata[xcols+i] = int32(xref.variant)
+ if xref.het {
+ xdata[xcols*2+i] = 1
+ }
+ xdata[xcols*3+i] = int32(xref.pvalue * 1000000)
+ }
+ return xdata
+}
+
+// transpose onehot data from in[col][row] to numpy-style
+// out[row*cols+col].
+func onehotcols2int8(in [][]int8) []int8 {
+ if len(in) == 0 {
+ return nil
+ }
+ cols := len(in)
+ rows := len(in[0])
+ out := make([]int8, rows*cols)
+ for row := 0; row < rows; row++ {
+ outrow := out[row*cols:]
+ for col, incol := range in {
+ outrow[col] = incol[row]
+ }
+ }
+ return out
+}
+
+// Return [2][]uint32{rowIndices, colIndices} indicating which
+// elements of matrixT[c][r] have non-zero values.
+func onehotChunk2Indirect(matrixT [][]int8) [2][]uint32 {
+ var nz [2][]uint32
+ for c, col := range matrixT {
+ for r, val := range col {
+ if val != 0 {
+ nz[0] = append(nz[0], uint32(r))
+ nz[1] = append(nz[1], uint32(c))
+ }
+ }
+ }
+ return nz
+}
projects / lightning.git / blobdiff