Add -log10(pvalue) row to onehot-columns.npy output from slicenumpy.
[lightning.git] / slicenumpy.go
index c6859f3653f506b4b4b3d2d76b205b1bdccf0bf3..db4b0d367b6210ca6ec1f802b7889693f5d45047 100644 (file)
@@ -8,6 +8,7 @@ import (
        "bufio"
        "bytes"
        "encoding/gob"
+       "errors"
        "flag"
        "fmt"
        "io"
@@ -28,6 +29,7 @@ import (
        "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"
 )
@@ -41,6 +43,8 @@ type sliceNumpy struct {
        chi2PValue            float64
        minCoverage           int
        cgnames               []string
+       includeVariant1       bool
+       debugTag              tagID
 }
 
 func (cmd *sliceNumpy) RunCommand(prog string, args []string, stdin io.Reader, stdout, stderr io.Writer) int {
@@ -66,10 +70,12 @@ func (cmd *sliceNumpy) RunCommand(prog string, args []string, stdin io.Reader, s
        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")
+       debugTag := flags.Int("debug-tag", -1, "log debugging details about specified tag")
        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")
+       flags.BoolVar(&cmd.includeVariant1, "include-variant-1", false, "include most common variant when building one-hot matrix")
        cmd.filter.Flags(flags)
        err = flags.Parse(args)
        if err == flag.ErrHelp {
@@ -90,6 +96,8 @@ func (cmd *sliceNumpy) RunCommand(prog string, args []string, stdin io.Reader, s
                return 2
        }
 
+       cmd.debugTag = tagID(*debugTag)
+
        if !*runlocal {
                runner := arvadosContainerRunner{
                        Name:        "lightning slice-numpy",
@@ -120,6 +128,8 @@ func (cmd *sliceNumpy) RunCommand(prog string, args []string, stdin io.Reader, s
                        "-chi2-case-control-file=" + cmd.chi2CaseControlFile,
                        "-chi2-case-control-column=" + cmd.chi2CaseControlColumn,
                        "-chi2-p-value=" + fmt.Sprintf("%f", cmd.chi2PValue),
+                       "-include-variant-1=" + fmt.Sprintf("%v", cmd.includeVariant1),
+                       "-debug-tag=" + fmt.Sprintf("%d", cmd.debugTag),
                }
                runner.Args = append(runner.Args, cmd.filter.Args()...)
                var output string
@@ -156,7 +166,7 @@ func (cmd *sliceNumpy) RunCommand(prog string, args []string, stdin io.Reader, s
 
        cmd.cgnames = nil
        var tagset [][]byte
-       DecodeLibrary(in0, strings.HasSuffix(infiles[0], ".gz"), func(ent *LibraryEntry) error {
+       err = DecodeLibrary(in0, strings.HasSuffix(infiles[0], ".gz"), func(ent *LibraryEntry) error {
                if len(ent.TagSet) > 0 {
                        tagset = ent.TagSet
                }
@@ -247,7 +257,7 @@ func (cmd *sliceNumpy) RunCommand(prog string, args []string, stdin io.Reader, s
        for seqname, cseq := range refseq {
                pos := 0
                for _, libref := range cseq {
-                       if libref.Tag > tagID(cmd.filter.MaxTag) {
+                       if cmd.filter.MaxTag >= 0 && libref.Tag > tagID(cmd.filter.MaxTag) {
                                continue
                        }
                        tiledata := reftiledata[libref]
@@ -343,15 +353,19 @@ func (cmd *sliceNumpy) RunCommand(prog string, args []string, stdin io.Reader, s
                toMerge = make([][]int16, len(infiles))
        }
        var onehotIndirect [][2][]uint32 // [chunkIndex][axis][index]
+       var onehotChunkSize []uint32
        var onehotXrefs [][]onehotXref
        if *onehotSingle {
                onehotIndirect = make([][2][]uint32, len(infiles))
+               onehotChunkSize = make([]uint32, len(infiles))
                onehotXrefs = make([][]onehotXref, len(infiles))
        }
+       chunkStartTag := make([]tagID, len(infiles))
 
        throttleMem := throttle{Max: cmd.threads} // TODO: estimate using mem and data size
        throttleNumpyMem := throttle{Max: cmd.threads/2 + 1}
        log.Info("generating annotations and numpy matrix for each slice")
+       var errSkip = errors.New("skip infile")
        var done int64
        for infileIdx, infile := range infiles {
                infileIdx, infile := infileIdx, infile
@@ -375,6 +389,9 @@ func (cmd *sliceNumpy) RunCommand(prog string, args []string, stdin io.Reader, s
                                                // masked-out tiles.
                                                continue
                                        }
+                                       if tv.Tag == cmd.debugTag {
+                                               log.Printf("infile %d %s tag %d variant %d hash %x", infileIdx, infile, tv.Tag, tv.Variant, tv.Blake2b[:3])
+                                       }
                                        variants := seq[tv.Tag]
                                        if len(variants) == 0 {
                                                variants = make([]TileVariant, 100)
@@ -386,6 +403,9 @@ func (cmd *sliceNumpy) RunCommand(prog string, args []string, stdin io.Reader, s
                                        seq[tv.Tag] = variants
                                }
                                for _, cg := range ent.CompactGenomes {
+                                       if cmd.filter.MaxTag >= 0 && cg.StartTag > tagID(cmd.filter.MaxTag) {
+                                               return errSkip
+                                       }
                                        if !matchGenome.MatchString(cg.Name) {
                                                continue
                                        }
@@ -399,11 +419,14 @@ func (cmd *sliceNumpy) RunCommand(prog string, args []string, stdin io.Reader, s
                                }
                                return nil
                        })
-                       if err != nil {
+                       if err == errSkip {
+                               return nil
+                       } else if err != nil {
                                return err
                        }
                        tagstart := cgs[cmd.cgnames[0]].StartTag
                        tagend := cgs[cmd.cgnames[0]].EndTag
+                       chunkStartTag[infileIdx] = tagstart
 
                        // TODO: filters
 
@@ -412,9 +435,7 @@ func (cmd *sliceNumpy) RunCommand(prog string, args []string, stdin io.Reader, s
                        throttleCPU := throttle{Max: runtime.GOMAXPROCS(0)}
                        for tag, variants := range seq {
                                tag, variants := tag, variants
-                               throttleCPU.Acquire()
-                               go func() {
-                                       defer throttleCPU.Release()
+                               throttleCPU.Go(func() error {
                                        count := make(map[[blake2b.Size256]byte]int, len(variants))
 
                                        rt := reftile[tag]
@@ -422,13 +443,16 @@ func (cmd *sliceNumpy) RunCommand(prog string, args []string, stdin io.Reader, s
                                                count[blake2b.Sum256(rt.tiledata)] = 0
                                        }
 
-                                       for _, cg := range cgs {
+                                       for cgname, cg := range cgs {
                                                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]++
                                                        }
+                                                       if v > 0 && tag == cmd.debugTag {
+                                                               log.Printf("tag %d cg %s allele %d tv %d hash %x count is now %d", tag, cgname, allele, v, variants[v].Blake2b[:3], count[variants[v].Blake2b])
+                                                       }
                                                }
                                        }
                                        // hash[i] will be the hash of
@@ -453,6 +477,11 @@ func (cmd *sliceNumpy) RunCommand(prog string, args []string, stdin io.Reader, s
                                        for i, h := range hash {
                                                rank[h] = tileVariantID(i + 1)
                                        }
+                                       if tag == cmd.debugTag {
+                                               for h, r := range rank {
+                                                       log.Printf("tag %d rank(%x) = %v", tag, h[:3], r)
+                                               }
+                                       }
                                        // remap[v] will be the new
                                        // variant number for original
                                        // variant number v.
@@ -460,11 +489,23 @@ func (cmd *sliceNumpy) RunCommand(prog string, args []string, stdin io.Reader, s
                                        for i, tv := range variants {
                                                remap[i] = rank[tv.Blake2b]
                                        }
+                                       if tag == cmd.debugTag {
+                                               for in, out := range remap {
+                                                       if out > 0 {
+                                                               log.Printf("tag %d remap %d => %d", tag, in, out)
+                                                       }
+                                               }
+                                       }
                                        variantRemap[tag-tagstart] = remap
                                        if rt != nil {
-                                               rt.variant = rank[blake2b.Sum256(rt.tiledata)]
+                                               refrank := rank[blake2b.Sum256(rt.tiledata)]
+                                               if tag == cmd.debugTag {
+                                                       log.Printf("tag %d reftile variant %d => %d", tag, rt.variant, refrank)
+                                               }
+                                               rt.variant = refrank
                                        }
-                               }()
+                                       return nil
+                               })
                        }
                        throttleCPU.Wait()
 
@@ -485,8 +526,8 @@ func (cmd *sliceNumpy) RunCommand(prog string, args []string, stdin io.Reader, s
                                        // Excluded by specified regions
                                        continue
                                }
-                               if tag > tagID(cmd.filter.MaxTag) {
-                                       continue
+                               if cmd.filter.MaxTag >= 0 && tag > tagID(cmd.filter.MaxTag) {
+                                       break
                                }
                                remap := variantRemap[tag-tagstart]
                                maxv := tileVariantID(0)
@@ -497,6 +538,12 @@ func (cmd *sliceNumpy) RunCommand(prog string, args []string, stdin io.Reader, s
                                }
                                if *onehotChunked || *onehotSingle {
                                        onehot, xrefs := cmd.tv2homhet(cgs, maxv, remap, tag, tagstart)
+                                       if tag == cmd.debugTag {
+                                               log.WithFields(logrus.Fields{
+                                                       "onehot": onehot,
+                                                       "xrefs":  xrefs,
+                                               }).Info("tv2homhet()")
+                                       }
                                        onehotChunk = append(onehotChunk, onehot...)
                                        onehotXref = append(onehotXref, xrefs...)
                                }
@@ -606,7 +653,7 @@ func (cmd *sliceNumpy) RunCommand(prog string, args []string, stdin io.Reader, s
                                // 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))
+                               log.Infof("%04d: preparing onehot numpy (rows=%d, cols=%d, mem=%d)", infileIdx, rows, cols, rows*cols)
                                throttleNumpyMem.Acquire()
                                out := onehotcols2int8(onehotChunk)
                                fnm := fmt.Sprintf("%s/onehot.%04d.npy", *outputDir, infileIdx)
@@ -624,30 +671,38 @@ func (cmd *sliceNumpy) RunCommand(prog string, args []string, stdin io.Reader, s
                        }
                        if *onehotSingle {
                                onehotIndirect[infileIdx] = onehotChunk2Indirect(onehotChunk)
+                               onehotChunkSize[infileIdx] = uint32(len(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)
+                               log.Infof("%04d: keeping onehot coordinates in memory (n=%d, mem=%d)", infileIdx, n, n*8*2)
                        }
                        if !(*onehotSingle || *onehotChunked) || *mergeOutput || *hgvsSingle {
-                               log.Infof("%04d: preparing numpy", infileIdx)
+                               log.Infof("%04d: preparing numpy (rows=%d, cols=%d)", infileIdx, len(cmd.cgnames), 2*outcol)
                                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
+                                       outidx := row * cols
                                        for col, v := range cgs[name].Variants {
                                                tag := tagstart + tagID(col/2)
+                                               if cmd.filter.MaxTag >= 0 && tag > tagID(cmd.filter.MaxTag) {
+                                                       break
+                                               }
                                                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])
+                                               if v == 0 {
+                                                       out[outidx] = 0 // tag not found / spanning tile
+                                               } else if variants, ok := seq[tag]; ok && int(v) < len(variants) && len(variants[v].Sequence) > 0 {
+                                                       out[outidx] = int16(variantRemap[tag-tagstart][v])
                                                } else {
-                                                       out[outcol] = -1
+                                                       out[outidx] = -1 // low quality tile variant
+                                               }
+                                               if tag == cmd.debugTag {
+                                                       log.Printf("tag %d row %d col %d outidx %d v %d out %d", tag, row, col, outidx, v, out[outidx])
                                                }
-                                               outcol++
+                                               outidx++
                                        }
                                }
                                seq = nil
@@ -922,16 +977,19 @@ func (cmd *sliceNumpy) RunCommand(prog string, args []string, stdin io.Reader, s
                }
                onehot := make([]uint32, nzCount*2) // [r,r,r,...,c,c,c,...]
                var xrefs []onehotXref
+               chunkOffset := uint32(0)
                outcol := 0
                for i, part := range onehotIndirect {
                        for i := range part[1] {
-                               part[1][i] += uint32(outcol)
+                               part[1][i] += chunkOffset
                        }
                        copy(onehot[outcol:], part[0])
                        copy(onehot[outcol+nzCount:], part[1])
-                       outcol += len(part[0])
                        xrefs = append(xrefs, onehotXrefs[i]...)
 
+                       outcol += len(part[0])
+                       chunkOffset += onehotChunkSize[i]
+
                        part[0] = nil
                        part[1] = nil
                        onehotXrefs[i] = nil
@@ -943,11 +1001,33 @@ func (cmd *sliceNumpy) RunCommand(prog string, args []string, stdin io.Reader, s
                        return 1
                }
                fnm = fmt.Sprintf("%s/onehot-columns.npy", *outputDir)
-               err = writeNumpyInt32(fnm, onehotXref2int32(xrefs), 4, len(xrefs))
+               err = writeNumpyInt32(fnm, onehotXref2int32(xrefs), 5, len(xrefs))
                if err != nil {
                        return 1
                }
        }
+       if !*mergeOutput && !*onehotChunked && !*onehotSingle {
+               tagoffsetFilename := *outputDir + "/chunk-tag-offset.csv"
+               log.Infof("writing tag offsets to %s", tagoffsetFilename)
+               var f *os.File
+               f, err = os.Create(tagoffsetFilename)
+               if err != nil {
+                       return 1
+               }
+               defer f.Close()
+               for idx, offset := range chunkStartTag {
+                       _, err = fmt.Fprintf(f, "%q,%d\n", fmt.Sprintf("matrix.%04d.npy", idx), offset)
+                       if err != nil {
+                               err = fmt.Errorf("write %s: %w", tagoffsetFilename, err)
+                               return 1
+                       }
+               }
+               err = f.Close()
+               if err != nil {
+                       err = fmt.Errorf("close %s: %w", tagoffsetFilename, err)
+                       return 1
+               }
+       }
        return 0
 }
 
@@ -1180,19 +1260,32 @@ func allele2homhet(colpair [2][]int8) {
 type onehotXref struct {
        tag     tagID
        variant tileVariantID
-       het     bool
+       hom     bool
        pvalue  float64
 }
 
 const onehotXrefSize = unsafe.Sizeof(onehotXref{})
 
-// Build onehot matrix (m[variant*2+isHet][genome] == 0 or 1) for all
+// Build onehot matrix (m[tileVariantIndex][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
+       if tag == cmd.debugTag {
+               tv := make([]tileVariantID, len(cmd.cgnames)*2)
+               for i, name := range cmd.cgnames {
+                       copy(tv[i*2:(i+1)*2], cgs[name].Variants[(tag-chunkstarttag)*2:])
+               }
+               log.WithFields(logrus.Fields{
+                       "cgs[i].Variants[tag*2+j]": tv,
+                       "maxv":                     maxv,
+                       "remap":                    remap,
+                       "tag":                      tag,
+                       "chunkstarttag":            chunkstarttag,
+               }).Info("tv2homhet()")
+       }
+       if maxv < 1 || (maxv < 2 && !cmd.includeVariant1) {
+               // everyone has the most common variant (of the variants we don't drop)
                return nil, nil
        }
        tagoffset := tag - chunkstarttag
@@ -1210,31 +1303,36 @@ func (cmd *sliceNumpy) tv2homhet(cgs map[string]CompactGenome, maxv tileVariantI
                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 {
+               cgvars := cgs[name].Variants[tagoffset*2:]
+               tv0, tv1 := remap[cgvars[0]], remap[cgvars[1]]
+               for v := tileVariantID(1); v <= maxv; v++ {
+                       if tv0 == v && tv1 == v {
                                obs[v*2][cgid] = true
-                       } else if remap[cgvars[tagoffset*2]] == v || remap[cgvars[tagoffset*2+1]] == v {
+                       } else if tv0 == v || tv1 == v {
                                obs[v*2+1][cgid] = true
                        }
                }
        }
        var onehot [][]int8
        var xref []onehotXref
-       for homcol := 4; homcol < len(obs); homcol += 2 {
-               for het := 0; het < 2; het++ {
-                       p := pvalue(obs[homcol+het], cmd.chi2Cases)
-                       if cmd.chi2PValue < 1 && !(p < cmd.chi2PValue) {
-                               continue
-                       }
-                       onehot = append(onehot, bool2int8(obs[homcol+het]))
-                       xref = append(xref, onehotXref{
-                               tag:     tag,
-                               variant: tileVariantID(homcol / 2),
-                               het:     het == 1,
-                               pvalue:  p,
-                       })
+       for col := 2; col < len(obs); col++ {
+               // col 0,1 correspond to tile variant 0, i.e.,
+               // no-call; col 2,3 correspond to the most common
+               // variant; so we (normally) start at col 4.
+               if col < 4 && !cmd.includeVariant1 {
+                       continue
                }
+               p := pvalue(obs[col], cmd.chi2Cases)
+               if cmd.chi2PValue < 1 && !(p < cmd.chi2PValue) {
+                       continue
+               }
+               onehot = append(onehot, bool2int8(obs[col]))
+               xref = append(xref, onehotXref{
+                       tag:     tag,
+                       variant: tileVariantID(col >> 1),
+                       hom:     col&1 == 0,
+                       pvalue:  p,
+               })
        }
        return onehot, xref
 }
@@ -1257,14 +1355,15 @@ func bool2int8(in []bool) []int8 {
 // P-value row contains 1000000x actual p-value.
 func onehotXref2int32(xrefs []onehotXref) []int32 {
        xcols := len(xrefs)
-       xdata := make([]int32, 4*xcols)
+       xdata := make([]int32, 5*xcols)
        for i, xref := range xrefs {
                xdata[i] = int32(xref.tag)
                xdata[xcols+i] = int32(xref.variant)
-               if xref.het {
+               if xref.hom {
                        xdata[xcols*2+i] = 1
                }
                xdata[xcols*3+i] = int32(xref.pvalue * 1000000)
+               xdata[xcols*4+i] = int32(-math.Log10(xref.pvalue) * 1000000)
        }
        return xdata
 }