// Copyright (C) The Lightning Authors. All rights reserved.
//
// SPDX-License-Identifier: AGPL-3.0
package lightning
import (
"bufio"
"bytes"
"encoding/gob"
"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
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
}
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")
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, "generate pca matrix")
pcaComponents := flags.Int("pca-components", 4, "number of PCA components")
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 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,
}
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", *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 = cmd.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.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))))
}
{
samplesOutFilename := *outputDir + "/samples.csv"
log.Infof("writing sample metadata to %s", samplesOutFilename)
var f *os.File
f, err = os.Create(samplesOutFilename)
if err != nil {
return err
}
defer f.Close()
for i, si := range cmd.samples {
var cc, tv string
if si.isCase {
cc = "1"
} else if si.isControl {
cc = "0"
}
if si.isTraining {
tv = "1"
} else {
tv = "0"
}
_, err = fmt.Fprintf(f, "%d,%s,%s,%s\n", i, si.id, cc, tv)
if err != nil {
err = fmt.Errorf("write %s: %w", samplesOutFilename, err)
return err
}
}
err = f.Close()
if err != nil {
err = fmt.Errorf("close %s: %w", samplesOutFilename, err)
return err
}
log.Print("done")
}
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 !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 == 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
}
}
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(*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")
samplesOutFilename := *outputDir + "/samples.csv"
log.Infof("writing sample metadata to %s", samplesOutFilename)
var f *os.File
f, err = os.Create(samplesOutFilename)
if err != nil {
return err
}
defer f.Close()
for i, si := range cmd.samples {
var cc, tv string
if si.isCase {
cc = "1"
} else if si.isControl {
cc = "0"
}
if si.isTraining {
tv = "1"
} else {
tv = "0"
}
var pcavals string
for c := 0; c < outcols; c++ {
pcavals += fmt.Sprintf(",%f", pca.At(i, c))
}
_, err = fmt.Fprintf(f, "%d,%s,%s,%s%s\n", i, si.id, cc, tv, pcavals)
if err != nil {
err = fmt.Errorf("write %s: %w", samplesOutFilename, err)
return err
}
}
err = f.Close()
if err != nil {
err = fmt.Errorf("close %s: %w", samplesOutFilename, err)
return err
}
log.Print("done")
}
}
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 (cmd *sliceNumpy) 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)
}
si = append(si, sampleInfo{
id: split[1],
isCase: split[2] == "1",
isControl: split[2] == "0",
isTraining: split[3] == "1",
isValidation: split[3] == "0",
})
}
return si, 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
}
p := pvalue(obs[col], cmd.chi2Cases)
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
}