-// Copyright (C) The Lightning Authors. All rights reserved.
-//
-// SPDX-License-Identifier: AGPL-3.0
-
-package lightning
-
-import (
- "bufio"
- "bytes"
- "encoding/gob"
- "encoding/json"
- "errors"
- "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/james-bowman/nlp"
- "github.com/kshedden/gonpy"
- "github.com/sirupsen/logrus"
- log "github.com/sirupsen/logrus"
- "golang.org/x/crypto/blake2b"
- "gonum.org/v1/gonum/mat"
-)
-
-const annotationMaxTileSpan = 100
-
-type sliceNumpy struct {
- filter filter
- threads int
- chi2Cases []bool
- chi2PValue float64
- pcaComponents int
- minCoverage int
- includeVariant1 bool
- debugTag tagID
-
- cgnames []string
- samples []sampleInfo
- trainingSet []int // samples index => training set index, or -1 if not in training set
- trainingSetSize int
- pvalue func(onehot []bool) float64
- pvalueCallCount int64
-}
-
-func (cmd *sliceNumpy) RunCommand(prog string, args []string, stdin io.Reader, stdout, stderr io.Writer) int {
- err := cmd.run(prog, args, stdin, stdout, stderr)
- if err != nil {
- fmt.Fprintf(stderr, "%s\n", err)
- return 1
- }
- return 0
-}
-
-func (cmd *sliceNumpy) run(prog string, args []string, stdin io.Reader, stdout, stderr io.Writer) error {
- flags := flag.NewFlagSet("", flag.ContinueOnError)
- flags.SetOutput(stderr)
- pprof := flags.String("pprof", "", "serve Go profile data at http://`[addr]:port`")
- runlocal := flags.Bool("local", false, "run on local host (default: run in an arvados container)")
- arvadosRAM := flags.Int("arvados-ram", 750000000000, "amount of memory to request for arvados container (`bytes`)")
- arvadosVCPUs := flags.Int("arvados-vcpus", 96, "number of VCPUs to request for arvados container")
- projectUUID := flags.String("project", "", "project `UUID` for output data")
- priority := flags.Int("priority", 500, "container request priority")
- preemptible := flags.Bool("preemptible", true, "request preemptible instance")
- inputDir := flags.String("input-dir", "./in", "input `directory`")
- outputDir := flags.String("output-dir", "./out", "output `directory`")
- 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")
- samplesFilename := flags.String("samples", "", "`samples.csv` file with training/validation and case/control groups (see 'lightning choose-samples')")
- caseControlOnly := flags.Bool("case-control-only", false, "drop samples that are not in case/control groups")
- onlyPCA := flags.Bool("pca", false, "run principal component analysis, write components to pca.npy and samples.csv")
- flags.IntVar(&cmd.pcaComponents, "pca-components", 4, "number of PCA components to compute / use in logistic regression")
- maxPCATiles := flags.Int("max-pca-tiles", 0, "maximum tiles to use as PCA input (filter, then drop every 2nd colum pair until below max)")
- debugTag := flags.Int("debug-tag", -1, "log debugging details about specified tag")
- flags.IntVar(&cmd.threads, "threads", 16, "number of memory-hungry assembly threads, and number of VCPUs to request for arvados container")
- flags.Float64Var(&cmd.chi2PValue, "chi2-p-value", 1, "do Χ² test (or logistic regression if -samples file has PCA components) 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 {
- return nil
- } else if err != nil {
- return err
- } else if flags.NArg() > 0 {
- return fmt.Errorf("errant command line arguments after parsed flags: %v", flags.Args())
- }
-
- if *pprof != "" {
- go func() {
- log.Println(http.ListenAndServe(*pprof, nil))
- }()
- }
-
- if cmd.chi2PValue != 1 && *samplesFilename == "" {
- return fmt.Errorf("cannot use provided -chi2-p-value=%f because -samples= value is empty", cmd.chi2PValue)
- }
-
- cmd.debugTag = tagID(*debugTag)
-
- if !*runlocal {
- runner := arvadosContainerRunner{
- Name: "lightning slice-numpy",
- Client: arvados.NewClientFromEnv(),
- ProjectUUID: *projectUUID,
- RAM: int64(*arvadosRAM),
- VCPUs: *arvadosVCPUs,
- Priority: *priority,
- KeepCache: 2,
- APIAccess: true,
- Preemptible: *preemptible,
- }
- err = runner.TranslatePaths(inputDir, regionsFilename, samplesFilename)
- if err != nil {
- return err
- }
- 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),
- "-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),
- "-samples=" + *samplesFilename,
- "-case-control-only=" + fmt.Sprintf("%v", *caseControlOnly),
- "-pca=" + fmt.Sprintf("%v", *onlyPCA),
- "-pca-components=" + fmt.Sprintf("%d", cmd.pcaComponents),
- "-max-pca-tiles=" + fmt.Sprintf("%d", *maxPCATiles),
- "-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
- output, err = runner.Run()
- if err != nil {
- return err
- }
- fmt.Fprintln(stdout, output)
- return nil
- }
-
- infiles, err := allFiles(*inputDir, matchGobFile)
- if err != nil {
- return err
- }
- if len(infiles) == 0 {
- err = fmt.Errorf("no input files found in %s", *inputDir)
- return err
- }
- sort.Strings(infiles)
-
- var refseq map[string][]tileLibRef
- var reftiledata = make(map[tileLibRef][]byte, 11000000)
- in0, err := open(infiles[0])
- if err != nil {
- return err
- }
-
- matchGenome, err := regexp.Compile(cmd.filter.MatchGenome)
- if err != nil {
- err = fmt.Errorf("-match-genome: invalid regexp: %q", cmd.filter.MatchGenome)
- return err
- }
-
- if *samplesFilename != "" {
- cmd.samples, err = loadSampleInfo(*samplesFilename)
- if err != nil {
- return err
- }
- } else if *caseControlOnly {
- return fmt.Errorf("-case-control-only does not make sense without -samples")
- }
-
- cmd.cgnames = nil
- var tagset [][]byte
- err = DecodeLibrary(in0, strings.HasSuffix(infiles[0], ".gz"), func(ent *LibraryEntry) error {
- if len(ent.TagSet) > 0 {
- tagset = ent.TagSet
- }
- for _, cseq := range ent.CompactSequences {
- if cseq.Name == *ref || *ref == "" {
- refseq = cseq.TileSequences
- }
- }
- for _, cg := range ent.CompactGenomes {
- 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
- })
- if err != nil {
- return err
- }
- in0.Close()
- if refseq == nil {
- err = fmt.Errorf("%s: reference sequence not found", infiles[0])
- return err
- }
- if len(tagset) == 0 {
- err = fmt.Errorf("tagset not found")
- return err
- }
-
- taglib := &tagLibrary{}
- err = taglib.setTags(tagset)
- if err != nil {
- return err
- }
- taglen := taglib.TagLen()
- sort.Strings(cmd.cgnames)
-
- if len(cmd.cgnames) == 0 {
- return fmt.Errorf("fatal: 0 matching samples in library, nothing to do")
- }
- cmd.trainingSet = make([]int, len(cmd.cgnames))
- if *samplesFilename == "" {
- cmd.trainingSetSize = len(cmd.cgnames)
- for i, name := range cmd.cgnames {
- cmd.samples = append(cmd.samples, sampleInfo{
- id: trimFilenameForLabel(name),
- isTraining: true,
- })
- cmd.trainingSet[i] = i
- }
- } else if len(cmd.cgnames) != len(cmd.samples) {
- return fmt.Errorf("mismatched sample list: %d samples in library, %d in %s", len(cmd.cgnames), len(cmd.samples), *samplesFilename)
- } else {
- for i, name := range cmd.cgnames {
- if s := trimFilenameForLabel(name); s != cmd.samples[i].id {
- return fmt.Errorf("mismatched sample list: sample %d is %q in library, %q in %s", i, s, cmd.samples[i].id, *samplesFilename)
- }
- }
- if *caseControlOnly {
- for i := 0; i < len(cmd.samples); i++ {
- if !cmd.samples[i].isTraining && !cmd.samples[i].isValidation {
- if i+1 < len(cmd.samples) {
- copy(cmd.samples[i:], cmd.samples[i+1:])
- copy(cmd.cgnames[i:], cmd.cgnames[i+1:])
- }
- cmd.samples = cmd.samples[:len(cmd.samples)-1]
- cmd.cgnames = cmd.cgnames[:len(cmd.cgnames)-1]
- i--
- }
- }
- }
- cmd.chi2Cases = nil
- cmd.trainingSetSize = 0
- for i := range cmd.cgnames {
- if cmd.samples[i].isTraining {
- cmd.trainingSet[i] = cmd.trainingSetSize
- cmd.trainingSetSize++
- cmd.chi2Cases = append(cmd.chi2Cases, cmd.samples[i].isCase)
- } else {
- cmd.trainingSet[i] = -1
- }
- }
- if cmd.pvalue == nil {
- cmd.pvalue = func(onehot []bool) float64 {
- return pvalue(onehot, cmd.chi2Cases)
- }
- }
- }
- if cmd.filter.MinCoverage == 1 {
- // In the generic formula below, floating point
- // arithmetic can effectively push the coverage
- // threshold above 1.0, which is impossible/useless.
- // 1.0 needs to mean exactly 100% coverage.
- cmd.minCoverage = len(cmd.cgnames)
- } else {
- cmd.minCoverage = int(math.Ceil(cmd.filter.MinCoverage * float64(len(cmd.cgnames))))
- }
-
- if len(cmd.samples[0].pcaComponents) > 0 {
- cmd.pvalue = glmPvalueFunc(cmd.samples, cmd.pcaComponents)
- // Unfortunately, statsmodel/glm lib logs stuff to
- // os.Stdout when it panics on an unsolvable
- // problem. We recover() from the panic in glm.go, but
- // we also need to commandeer os.Stdout to avoid
- // producing large quantities of logs.
- stdoutWas := os.Stdout
- defer func() { os.Stdout = stdoutWas }()
- os.Stdout, err = os.Open(os.DevNull)
- if err != nil {
- return err
- }
- }
-
- // cgnamemap[name]==true for samples that we are including in
- // output
- cgnamemap := map[string]bool{}
- for _, name := range cmd.cgnames {
- cgnamemap[name] = true
- }
-
- err = writeSampleInfo(cmd.samples, *outputDir)
- if err != nil {
- return err
- }
-
- log.Info("indexing reference tiles")
- type reftileinfo struct {
- variant tileVariantID
- seqname string // chr1
- pos int // distance from start of chromosome to starttag
- tiledata []byte // acgtggcaa...
- excluded bool // true if excluded by regions file
- nexttag tagID // tagID of following tile (-1 for last tag of chromosome)
- }
- isdup := map[tagID]bool{}
- reftile := map[tagID]*reftileinfo{}
- for seqname, cseq := range refseq {
- pos := 0
- lastreftag := tagID(-1)
- for _, libref := range cseq {
- if cmd.filter.MaxTag >= 0 && libref.Tag > tagID(cmd.filter.MaxTag) {
- continue
- }
- 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 err
- }
- foundthistag := false
- taglib.FindAll(tiledata[:len(tiledata)-1], func(tagid tagID, offset, _ int) {
- if !foundthistag && tagid == libref.Tag {
- foundthistag = true
- return
- }
- if dupref, ok := reftile[tagid]; ok {
- log.Printf("dropping reference tile %+v from %s @ %d, tag not unique, also found inside %+v from %s @ %d", tileLibRef{Tag: tagid, Variant: dupref.variant}, dupref.seqname, dupref.pos, libref, seqname, pos+offset+1)
- delete(reftile, tagid)
- } else {
- log.Printf("found tag %d at offset %d inside tile variant %+v on %s @ %d", tagid, offset, libref, seqname, pos+offset+1)
- }
- isdup[tagid] = true
- })
- 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,
- nexttag: -1,
- }
- if lastreftag >= 0 {
- reftile[lastreftag].nexttag = libref.Tag
- }
- lastreftag = libref.Tag
- }
- pos += len(tiledata) - taglen
- }
- log.Printf("... %s done, len %d", seqname, pos+taglen)
- }
-
- var mask *mask
- if *regionsFilename != "" {
- log.Printf("loading regions from %s", *regionsFilename)
- mask, err = makeMask(*regionsFilename, *expandRegions)
- if err != nil {
- return err
- }
- log.Printf("before applying mask, len(reftile) == %d", len(reftile))
- log.Printf("deleting reftile entries for regions outside %d intervals", mask.Len())
- for _, rt := range reftile {
- if !mask.Check(strings.TrimPrefix(rt.seqname, "chr"), rt.pos, rt.pos+len(rt.tiledata)) {
- rt.excluded = true
- }
- }
- 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
- }
- 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 bufw.Flush()
- })
- }
- }
-
- var toMerge [][]int16
- if *mergeOutput || *hgvsSingle {
- toMerge = make([][]int16, len(infiles))
- }
- var onehotIndirect [][2][]uint32 // [chunkIndex][axis][index]
- var onehotChunkSize []uint32
- var onehotXrefs [][]onehotXref
- if *onehotSingle || *onlyPCA {
- 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
- throttleMem.Go(func() error {
- seq := make(map[tagID][]TileVariant, 50000)
- cgs := make(map[string]CompactGenome, len(cmd.cgnames))
- f, err := open(infile)
- if err != nil {
- return err
- }
- defer f.Close()
- 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
- }
- // Skip tile with no
- // corresponding ref tile, if
- // mask is in play (we can't
- // determine coordinates for
- // these)
- if mask != nil && reftile[tv.Tag] == nil {
- continue
- }
- // Skip tile whose
- // corresponding ref tile is
- // outside target regions --
- // unless it's a potential
- // spanning tile.
- if mask != nil && reftile[tv.Tag].excluded &&
- (int(tv.Tag+1) >= len(tagset) ||
- (bytes.HasSuffix(tv.Sequence, tagset[tv.Tag+1]) && reftile[tv.Tag+1] != nil && !reftile[tv.Tag+1].excluded)) {
- 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)
- }
- for len(variants) <= int(tv.Variant) {
- variants = append(variants, TileVariant{})
- }
- variants[int(tv.Variant)] = tv
- seq[tv.Tag] = variants
- }
- for _, cg := range ent.CompactGenomes {
- if cmd.filter.MaxTag >= 0 && cg.StartTag > tagID(cmd.filter.MaxTag) {
- return errSkip
- }
- if !cgnamemap[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 == errSkip {
- return nil
- } else if err != nil {
- return fmt.Errorf("%04d: DecodeLibrary(%s): err", infileIdx, infile)
- }
- tagstart := cgs[cmd.cgnames[0]].StartTag
- tagend := cgs[cmd.cgnames[0]].EndTag
- chunkStartTag[infileIdx] = tagstart
-
- // TODO: filters
-
- 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 {
- tag, variants := tag, variants
- throttleCPU.Go(func() error {
- alleleCoverage := 0
- count := make(map[[blake2b.Size256]byte]int, len(variants))
-
- rt := reftile[tag]
- if rt != nil {
- count[blake2b.Sum256(rt.tiledata)] = 0
- }
-
- 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]++
- alleleCoverage++
- }
- 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])
- }
- }
- }
- if alleleCoverage < cmd.minCoverage*2 {
- idx := int(tag-tagstart) * 2
- for _, cg := range cgs {
- cg.Variants[idx] = 0
- cg.Variants[idx+1] = 0
- }
- if tag == cmd.debugTag {
- log.Printf("tag %d alleleCoverage %d < min %d, sample data wiped", tag, alleleCoverage, cmd.minCoverage*2)
- }
- return nil
- }
-
- // hash[i] will be the hash of
- // the variant(s) that should
- // be at rank i (0-based).
- hash := make([][blake2b.Size256]byte, 0, len(count))
- for b := range count {
- hash = append(hash, b)
- }
- sort.Slice(hash, func(i, j int) bool {
- bi, bj := &hash[i], &hash[j]
- if ci, cj := count[*bi], count[*bj]; ci != cj {
- return ci > cj
- } else {
- return bytes.Compare((*bi)[:], (*bj)[:]) < 0
- }
- })
- // rank[b] will be the 1-based
- // new variant number for
- // variants whose hash is b.
- rank := make(map[[blake2b.Size256]byte]tileVariantID, len(hash))
- 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.
- remap := make([]tileVariantID, len(variants))
- 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 {
- 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()
-
- var onehotChunk [][]int8
- var onehotXref []onehotXref
-
- var annotationsFilename string
- if *onlyPCA {
- annotationsFilename = "/dev/null"
- } else {
- annotationsFilename = fmt.Sprintf("%s/matrix.%04d.annotations.csv", *outputDir, infileIdx)
- log.Infof("%04d: writing %s", infileIdx, annotationsFilename)
- }
- annof, err := os.Create(annotationsFilename)
- if err != nil {
- return err
- }
- annow := bufio.NewWriterSize(annof, 1<<20)
- outcol := 0
- for tag := tagstart; tag < tagend; tag++ {
- rt := reftile[tag]
- if rt == nil && mask != nil {
- // With no ref tile, we don't
- // have coordinates to say
- // this is in the desired
- // regions -- so it's not.
- // TODO: handle ref spanning
- // tile case.
- continue
- }
- if rt != nil && rt.excluded {
- // TODO: don't skip yet --
- // first check for spanning
- // tile variants that
- // intersect non-excluded ref
- // tiles.
- continue
- }
- if cmd.filter.MaxTag >= 0 && tag > tagID(cmd.filter.MaxTag) {
- break
- }
- remap := variantRemap[tag-tagstart]
- if remap == nil {
- // was not assigned above,
- // because minCoverage
- outcol++
- continue
- }
- maxv := tileVariantID(0)
- for _, v := range remap {
- if maxv < v {
- maxv = v
- }
- }
- if *onehotChunked || *onehotSingle || *onlyPCA {
- onehot, xrefs := cmd.tv2homhet(cgs, maxv, remap, tag, tagstart, seq)
- if tag == cmd.debugTag {
- log.WithFields(logrus.Fields{
- "onehot": onehot,
- "xrefs": xrefs,
- }).Info("tv2homhet()")
- }
- onehotChunk = append(onehotChunk, onehot...)
- onehotXref = append(onehotXref, xrefs...)
- }
- if *onlyPCA {
- outcol++
- continue
- }
- if rt == nil {
- // Reference does not use any
- // variant of this tile
- //
- // TODO: diff against the
- // relevant portion of the
- // ref's spanning tile
- outcol++
- continue
- }
- 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 == 0 || v == rt.variant || done[v] {
- continue
- } else {
- done[v] = true
- }
- if len(tv.Sequence) < taglen {
- continue
- }
- // if reftilestr doesn't end
- // in the same tag as tv,
- // extend reftilestr with
- // following ref tiles until
- // it does (up to an arbitrary
- // sanity-check limit)
- reftilestr := reftilestr
- endtagstr := strings.ToUpper(string(tv.Sequence[len(tv.Sequence)-taglen:]))
- for i, rt := 0, rt; i < annotationMaxTileSpan && !strings.HasSuffix(reftilestr, endtagstr) && rt.nexttag >= 0; i++ {
- rt = reftile[rt.nexttag]
- if rt == nil {
- break
- }
- reftilestr += strings.ToUpper(string(rt.tiledata[taglen:]))
- }
- if mask != nil && !mask.Check(strings.TrimPrefix(rt.seqname, "chr"), rt.pos, rt.pos+len(reftilestr)) {
- continue
- }
- if !strings.HasSuffix(reftilestr, endtagstr) {
- fmt.Fprintf(annow, "%d,%d,%d,,%s,%d,,,\n", tag, outcol, v, rt.seqname, rt.pos)
- continue
- }
- if lendiff := len(reftilestr) - 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 {
- 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
- }
- err = annof.Close()
- if err != nil {
- return err
- }
-
- 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, rows, cols, rows*cols)
- 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 || *onlyPCA {
- 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*2)
- }
- if !(*onehotSingle || *onehotChunked || *onlyPCA) || *mergeOutput || *hgvsSingle {
- 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 {
- 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 rt := reftile[tag]; rt == nil || rt.excluded {
- continue
- }
- 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[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])
- }
- outidx++
- }
- }
- 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
- }
- }
- }
- 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 err
- }
-
- if *hgvsChunked {
- log.Info("flushing hgvsCols temp files")
- for seqname := range refseq {
- close(encodeHGVSTodo[seqname])
- }
- err = encodeHGVS.Wait()
- if err != nil {
- return err
- }
- 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
- }
- var hgvsCols hgvsColSet
- dec := gob.NewDecoder(bufio.NewReaderSize(f, 1<<24))
- for err == nil {
- err = dec.Decode(&hgvsCols)
- }
- if err != io.EOF {
- return err
- }
- 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
- }
- 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
- }
- }
- }
-
- 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
- }
- 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 err
- }
- if *mergeOutput {
- err = os.Remove(annotationsFilename)
- if err != nil {
- return err
- }
- }
- 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 err
- }
- 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 err
- }
- err = annof.Close()
- if err != nil {
- return err
- }
- err = writeNumpyInt16(fmt.Sprintf("%s/matrix.npy", *outputDir), out, rows, cols)
- if err != nil {
- return err
- }
- }
- 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 err
- }
-
- 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 err
- }
- }
- }
- if *onehotSingle || *onlyPCA {
- nzCount := 0
- for _, part := range onehotIndirect {
- nzCount += len(part[0])
- }
- 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] += chunkOffset
- }
- copy(onehot[outcol:], part[0])
- copy(onehot[outcol+nzCount:], part[1])
- xrefs = append(xrefs, onehotXrefs[i]...)
-
- outcol += len(part[0])
- chunkOffset += onehotChunkSize[i]
-
- part[0] = nil
- part[1] = nil
- onehotXrefs[i] = nil
- debug.FreeOSMemory()
- }
- if *onehotSingle {
- fnm := fmt.Sprintf("%s/onehot.npy", *outputDir)
- err = writeNumpyUint32(fnm, onehot, 2, nzCount)
- if err != nil {
- return err
- }
- fnm = fmt.Sprintf("%s/onehot-columns.npy", *outputDir)
- err = writeNumpyInt32(fnm, onehotXref2int32(xrefs), 5, len(xrefs))
- if err != nil {
- return err
- }
- fnm = fmt.Sprintf("%s/stats.json", *outputDir)
- j, err := json.Marshal(map[string]interface{}{
- "pvalueCallCount": cmd.pvalueCallCount,
- })
- if err != nil {
- return err
- }
- err = os.WriteFile(fnm, j, 0777)
- if err != nil {
- return err
- }
- }
- if *onlyPCA {
- cols := 0
- for _, c := range onehot[nzCount:] {
- if int(c) >= cols {
- cols = int(c) + 1
- }
- }
- if cols == 0 {
- return fmt.Errorf("cannot do PCA: one-hot matrix is empty")
- }
- log.Printf("have %d one-hot cols", cols)
- stride := 1
- for *maxPCATiles > 0 && cols > *maxPCATiles*2 {
- cols = (cols + 1) / 2
- stride = stride * 2
- }
- if cols%2 == 1 {
- // we work with pairs of columns
- cols++
- }
- log.Printf("creating full matrix (%d rows) and training matrix (%d rows) with %d cols, stride %d", len(cmd.cgnames), cmd.trainingSetSize, cols, stride)
- mtxFull := mat.NewDense(len(cmd.cgnames), cols, nil)
- mtxTrain := mat.NewDense(cmd.trainingSetSize, cols, nil)
- for i, c := range onehot[nzCount:] {
- if int(c/2)%stride == 0 {
- outcol := int(c/2)/stride*2 + int(c)%2
- mtxFull.Set(int(onehot[i]), outcol, 1)
- if trainRow := cmd.trainingSet[int(onehot[i])]; trainRow >= 0 {
- mtxTrain.Set(trainRow, outcol, 1)
- }
- }
- }
- log.Print("fitting")
- transformer := nlp.NewPCA(cmd.pcaComponents)
- transformer.Fit(mtxTrain.T())
- log.Printf("transforming")
- pca, err := transformer.Transform(mtxFull.T())
- if err != nil {
- return err
- }
- pca = pca.T()
- outrows, outcols := pca.Dims()
- log.Printf("copying result to numpy output array: %d rows, %d cols", outrows, outcols)
- out := make([]float64, outrows*outcols)
- for i := 0; i < outrows; i++ {
- for j := 0; j < outcols; j++ {
- out[i*outcols+j] = pca.At(i, j)
- }
- }
- fnm := fmt.Sprintf("%s/pca.npy", *outputDir)
- log.Printf("writing numpy: %s", fnm)
- output, err := os.OpenFile(fnm, os.O_CREATE|os.O_TRUNC|os.O_WRONLY, 0777)
- if err != nil {
- return err
- }
- npw, err := gonpy.NewWriter(nopCloser{output})
- if err != nil {
- return fmt.Errorf("gonpy.NewWriter: %w", err)
- }
- npw.Shape = []int{outrows, outcols}
- err = npw.WriteFloat64(out)
- if err != nil {
- return fmt.Errorf("WriteFloat64: %w", err)
- }
- err = output.Close()
- if err != nil {
- return err
- }
- log.Print("done")
-
- log.Print("copying pca components to sampleInfo")
- for i := range cmd.samples {
- cmd.samples[i].pcaComponents = make([]float64, outcols)
- for c := 0; c < outcols; c++ {
- cmd.samples[i].pcaComponents[i] = pca.At(i, c)
- }
- }
- log.Print("done")
-
- err = writeSampleInfo(cmd.samples, *outputDir)
- if err != nil {
- return err
- }
- }
- }
- if !*mergeOutput && !*onehotChunked && !*onehotSingle && !*onlyPCA {
- 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 err
- }
- 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 err
- }
- }
- err = f.Close()
- if err != nil {
- err = fmt.Errorf("close %s: %w", tagoffsetFilename, err)
- return err
- }
- }
-
- return nil
-}
-
-type sampleInfo struct {
- id string
- isCase bool
- isControl bool
- isTraining bool
- isValidation bool
- pcaComponents []float64
-}
-
-// Read samples.csv file with case/control and training/validation
-// flags.
-func loadSampleInfo(samplesFilename string) ([]sampleInfo, error) {
- var si []sampleInfo
- f, err := open(samplesFilename)
- if err != nil {
- return nil, err
- }
- buf, err := io.ReadAll(f)
- f.Close()
- if err != nil {
- return nil, err
- }
- lineNum := 0
- for _, csv := range bytes.Split(buf, []byte{'\n'}) {
- lineNum++
- if len(csv) == 0 {
- continue
- }
- split := strings.Split(string(csv), ",")
- if len(split) < 4 {
- return nil, fmt.Errorf("%d fields < 4 in %s line %d: %q", len(split), samplesFilename, lineNum, csv)
- }
- if split[0] == "Index" && split[1] == "SampleID" && split[2] == "CaseControl" && split[3] == "TrainingValidation" {
- continue
- }
- idx, err := strconv.Atoi(split[0])
- if err != nil {
- if lineNum == 1 {
- return nil, fmt.Errorf("header does not look right: %q", csv)
- }
- return nil, fmt.Errorf("%s line %d: index: %s", samplesFilename, lineNum, err)
- }
- if idx != len(si) {
- return nil, fmt.Errorf("%s line %d: index %d out of order", samplesFilename, lineNum, idx)
- }
- var pcaComponents []float64
- if len(split) > 4 {
- for _, s := range split[4:] {
- f, err := strconv.ParseFloat(s, 64)
- if err != nil {
- return nil, fmt.Errorf("%s line %d: cannot parse float %q: %s", samplesFilename, lineNum, s, err)
- }
- pcaComponents = append(pcaComponents, f)
- }
- }
- si = append(si, sampleInfo{
- id: split[1],
- isCase: split[2] == "1",
- isControl: split[2] == "0",
- isTraining: split[3] == "1",
- isValidation: split[3] == "0" && len(split[2]) > 0, // fix errant 0s in input
- pcaComponents: pcaComponents,
- })
- }
- return si, nil
-}
-
-func writeSampleInfo(samples []sampleInfo, outputDir string) error {
- fnm := outputDir + "/samples.csv"
- log.Infof("writing sample metadata to %s", fnm)
- f, err := os.Create(fnm)
- if err != nil {
- return err
- }
- defer f.Close()
- pcaLabels := ""
- if len(samples) > 0 {
- for i := range samples[0].pcaComponents {
- pcaLabels += fmt.Sprintf(",PCA%d", i)
- }
- }
- _, err = fmt.Fprintf(f, "Index,SampleID,CaseControl,TrainingValidation%s\n", pcaLabels)
- if err != nil {
- return err
- }
- for i, si := range samples {
- var cc, tv string
- if si.isCase {
- cc = "1"
- } else if si.isControl {
- cc = "0"
- }
- if si.isTraining {
- tv = "1"
- } else if si.isValidation {
- tv = "0"
- }
- var pcavals string
- for _, pcaval := range si.pcaComponents {
- pcavals += fmt.Sprintf(",%f", pcaval)
- }
- _, err = fmt.Fprintf(f, "%d,%s,%s,%s%s\n", i, si.id, cc, tv, pcavals)
- if err != nil {
- return fmt.Errorf("write %s: %w", fnm, err)
- }
- }
- err = f.Close()
- if err != nil {
- return fmt.Errorf("close %s: %w", fnm, err)
- }
- log.Print("done")
- 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
- hom bool
- pvalue float64
-}
-
-const onehotXrefSize = unsafe.Sizeof(onehotXref{})
-
-// 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, seq map[tagID][]TileVariant) ([][]int8, []onehotXref) {
- 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
- coverage := 0
- for _, cg := range cgs {
- alleles := 0
- for _, v := range cg.Variants[tagoffset*2 : tagoffset*2+2] {
- if v > 0 && int(v) < len(seq[tag]) && len(seq[tag][v].Sequence) > 0 {
- alleles++
- }
- }
- if alleles == 2 {
- coverage++
- }
- }
- if coverage < cmd.minCoverage {
- return nil, nil
- }
- // "observed" array for p-value calculation (training set
- // only)
- obs := make([][]bool, (maxv+1)*2) // 2 slices (hom + het) for each variant#
- // one-hot output (all samples)
- outcols := make([][]int8, (maxv+1)*2)
- for i := range obs {
- obs[i] = make([]bool, cmd.trainingSetSize)
- outcols[i] = make([]int8, len(cmd.cgnames))
- }
- for cgid, name := range cmd.cgnames {
- tsid := cmd.trainingSet[cgid]
- 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 {
- if tsid >= 0 {
- obs[v*2][tsid] = true
- }
- outcols[v*2][cgid] = 1
- } else if tv0 == v || tv1 == v {
- if tsid >= 0 {
- obs[v*2+1][tsid] = true
- }
- outcols[v*2+1][cgid] = 1
- }
- }
- }
- var onehot [][]int8
- var xref []onehotXref
- 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
- }
- atomic.AddInt64(&cmd.pvalueCallCount, 1)
- p := cmd.pvalue(obs[col])
- if cmd.chi2PValue < 1 && !(p < cmd.chi2PValue) {
- continue
- }
- onehot = append(onehot, outcols[col])
- xref = append(xref, onehotXref{
- tag: tag,
- variant: tileVariantID(col >> 1),
- hom: col&1 == 0,
- pvalue: p,
- })
- }
- return onehot, xref
-}
-
-// 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, 5*xcols)
- for i, xref := range xrefs {
- xdata[i] = int32(xref.tag)
- xdata[xcols+i] = int32(xref.variant)
- 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
-}
-
-// 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