annotation.py

import sys

from collections import defaultdict
import numpy as np
from math import isnan

from pysam import VariantFile

from svrunner_utils import eprint, warn, vcf_to_pybed
from svreader.vcfwrapper import VCFRecord, SVReader, SVWriter

HOM_REF = (0, 0)
HET_VAR = (0, 1)
HOM_VAR = (1, 1)

SVTYPER_GENO_LIKELI_TAG = "GL"
GENOMESTRIP_GENO_LIKELI_TAG = "GP"

Geno_likeli_tag = SVTYPER_GENO_LIKELI_TAG


def Variant(sample):
    if sample.get('GT') in [HET_VAR, HOM_VAR]:
        return True
    else:
        return False


class VariantRecord(VCFRecord):
    """
    A lightweight object to annotated the final records
    """
    def __init__(self, record):
        """
        A pysam VariantRecord wrapper
        """
        super(VariantRecord, self).__init__(record)

    @property
    def start(self):
        return self.record.pos

    @property
    def end(self):
        return self.record.stop

    @property
    def svtype(self):
        return self._sv_type

    @property
    def svlen(self):
        return abs(self.stop - self.start)

    @property
    def passed(self):
        if "PASS" in self.record.filter:
            return True
        else:
            return False

    def setNewId(self, identifier):
        try:
            self.record.info['SOURCEID'] = self.id
        except KeyError:
            eprint("SOURCEID absent from record info keys,")
            sys.exit(1)
        self.id = identifier

    def num_variant_samples(self):
        return sum([Variant(s) for s in self.samples.values()])

    def variant_read_support(self):
        return max([s.get('AO')[0] for s in self.samples.values()])

    def qual(self):
        return sum([s.get('SQ') for s in self.samples.values()])

    def GQ_sum_score(self):
        return sum([s.get('SQ') for s in self.samples.values()])

    def setQual(self):
        self.record.qual = self.qual()

    def AddSupportInfos(self):
        supp_reads = self.variant_read_support()
        num_supp_samples = self.num_variant_samples()
        try:
            self.record.info['MAX_SUPP_READS'] = supp_reads
            self.record.info['NUM_SUPP_SAMPLES'] = num_supp_samples
        except KeyError:
            eprint("SUPP_READS or NUM_SUPP_SAMPLES absent from record info keys")
            sys.exit(1)

    def UnifiedPass(self):
        """
           All records passing the filters (PASS, .) ar now labelled PASS
        """
        record = self.record
        filters = [f for f in record.filter]
        # We make the assumption when a "." is present no other filter
        # are present
        if len(filters) == 0 or "." in filters:
            record.filter.clear()
            record.filter.add("PASS")


class VariantRecordSample(object):
    """
    A lightweight object to VariantRecordSample
    """
    def __init__(self, variantsample):
        self.variantsample = variantsample

    def genotype(self):
        return self.variantsample.get('GT')

    def SQ_score(self):
        # Phred-scaled probability that this site is variant
        # (non-reference in this sample)
        return self.variantsample.get('SQ')

    def GQ_score(self):
        # Genotype quality
        return self.variantsample.get('GQ')

    def GL_score(self):
        # Genotype Likelihood, log10-scaled likelihoods of the data given the
        # called genotype for each possible genotype generated from the
        # reference and alternate alleles given the sample ploidy
        return self.variantsample.get('GL')

    def AltSupport(self):
        return self.variantsample.get('AO')[0]

    @property
    def isVariant(self):
        if self.genotype() in [HET_VAR, HOM_VAR]:
            return True
        else:
            return False


class VCFReader(SVReader):

    def __init__(self, file_name, sv_to_report=None):
        super(VCFReader, self).__init__(file_name)
        self.filename = file_name
        self.sv_to_report = sv_to_report
        self.vcf_reader = VariantFile(file_name)

        self.add_metadata()

    def __iter__(self):
        return self

    def __next__(self):
        while True:
            raw_record = next(self.vcf_reader)
            record = VariantRecord(raw_record)
            return record

    def getHeader(self):
        return self.vcf_reader.header

    def addInfo(self, name, number, type, description):
        self.vcf_reader.header.info.add(id=name,
                                        number=number,
                                        type=type,
                                        description=description)

    def addFilter(self, name, description):
        self.vcf_reader.header.filters.add(id=name,
                                           number=None,
                                           type=None,
                                           description=description)

    def add_metadata(self):
        self.addInfo("SOURCEID", 1, "String",
                     "The source sv identifier")
        self.addInfo("MAX_SUPP_READS", 1, "Integer",
                     "Max number of supporting reads")
        self.addInfo("NUM_SUPP_SAMPLES", 1, "Integer",
                     "Number of supporting samples")
        self.addFilter("LOWSUPPORT",
                       "total supp reads < 5 or supp samples < 2")

    def getOrderedSamples(self):
        samples = self.vcf_reader.header.samples
        sample_names = [sample.rsplit('.')[0] for sample in samples]
        return sample_names

    def numSamples(self):
        return len(self.vcf_reader.header.samples)


class VCFWriter(SVWriter):

    def __init__(self, file_name,  template_reader, index=True):

        super(VCFWriter, self).__init__(file_name,
                                        template_reader.tool_name,
                                        template_reader)

    def _open(self):
        self.vcf_writer = VariantFile(self.filename, 'w',
                                      header=self.template_reader.getHeader())
        self._isopen = True

    def _write(self, record):
        self.vcf_writer.write(record.record)

    def _close(self):
        if self._isopen:
            self.vcf_writer.close()
        else:   # nothing was written
            self._dumpemptyvcf()


def ordered(a, b):
    # simply ordering the two string
    return (a, b) if a < b else (b, a)


def setLikeliTag(genotyper):
    global Geno_likeli_tag

    if genotyper == "svtyper":
        Geno_likeli_tag = SVTYPER_GENO_LIKELI_TAG
        warn("Assuming genotypes provided by svtyper software" +
             " hence tag is %s" % (Geno_likeli_tag))

    elif genotyper == "genomestrip":
        Geno_likeli_tag = GENOMESTRIP_GENO_LIKELI_TAG
        warn("Assuming genotypes provided by genomestrip software" +
             " hence tag is %s" % (Geno_likeli_tag))
    else:
        print("Unknown genotyping software")
        exit(1)


def getlikelihoods(sample):
    return sample.get('GL')


def probas(likelihoods):
    # transform log likelihoods into likelihoods
    return np.exp(np.array(likelihoods))


def getprobas(sample):
    # Transforming likelihods into probabilities
    return probas(getlikelihoods(sample))/np.sum(probas(getlikelihoods(sample)))


def ondiagonal(u_s, v_s):
    # Probability that, for that individual, the two SVs are identically
    # genotyped P1(0/0)*P2(0/0) + ... P1(1/1)*P2(1/1)
    # in the same way :
    p = getprobas(u_s)
    q = getprobas(v_s)
    proba = 0
    for a, b in zip(p, q):
        proba += a*b
    # print("Proba on %3.5f" %(proba))
    return proba


def offdiagonal(u_s, v_s):
    # Probability that, for that individual, the two SVs are not identically
    # in the same way, complement of the previous one
    p = getprobas(u_s)
    q = getprobas(v_s)
    proba = 0
    for i, a in enumerate(p):
        for j, b in enumerate(q):
            if i != j:
                proba += a*b
    # print("Proba off %3.2f" %(proba))
    return proba


def duplicatescore(u, v):
    # For the two SVs, max discordant genotype log-ratio proba
    # same genotypes against discordant against (worse individual)

    # u_s is the sample of id s of u (idem for v_s)
    # Valid samples
    valid_samples = []
    for s in u.samples:
        u_s = u.samples[s]
        v_s = v.samples[s]
        if (u_s.get('GQ') is not None
                and v_s.get('GQ') is not None):
            valid_samples.append(s)

    max_disc = 0
    computed = float('NaN')
    for s in valid_samples:
        # ondiago is not used, we keep it just for comprehension
        # ondiago = ondiagonal(s, u, v)
        u_s = u.samples[s]
        v_s = v.samples[s]
        offdiago = offdiagonal(u_s, v_s)
        if offdiago > max_disc:
            max_disc = offdiago
    if max_disc > 0 and max_disc < 1:
        ratio = (1-max_disc)/max_disc
        computed = np.log(ratio)
    return computed


def gstrength(u):
    # Sum of phred-like genotype qualities provides a measure of the
    # combined genotype quality of the site
    # np.sum([s['GQ'] if s['GQ'] is not None else 0 for s in u.samples.values()])
    return u.GQ_sum_score()


def variantstrength(u):
    # maximum SQ, where SQ stands for
    # Phred-scaled probability that this site is variant (non-reference)
    # in this sample)
    # QUAL = -10 * log(P(locus is reference in all samples)), which is
    # equal to the sum of the SQ scores.
    # see https://github.com/hall-lab/svtyper/issues/10
    # sum([s['SQ'] if s['SQ'] is not None else 0 for s in u.samples.values()])
    return u.qual()
    # max([s['SQ'] if s['SQ'] is not None else 0 for s in u.samples.values()])


def getduplicates_GQ(u, v):
    # select the prefered duplicate on the basis of the
    # Sum of phred-like genotype qualities
    # see gstrength
    # returns prefered, discarded, strength of both
    if gstrength(u) > gstrength(v):
        return (u, v, gstrength(u), gstrength(v))
    else:
        return (v, u, gstrength(v), gstrength(u))


def getduplicates_QUAL(u, v):
    # select the prefered duplicate on the basis of
    # Phred-scaled probability that this site is a variant
    # see variantstrength
    # returns prefered, discarded, strength of both
    if variantstrength(u) > variantstrength(v):
        return (u, v, variantstrength(u), variantstrength(v))
    else:
        return (v, u, variantstrength(v), variantstrength(u))


def getoverlap(u, osize):
    # percentage overlap given the size of the overlap
    return 100*osize/u.svlen


def add_redundancy_infos_header(reader):
    # Adding DUPLICATESCORE info (equivalent to GSDUPLICATESCORE)
    reader.addInfo("DUPLICATESCORE", 1, "Float",
                   "LOD score that the events are distinct based on the "
                   "genotypes of the most discordant sample")
    # Adding DUPLICATES info (equivalent to GSDUPLICATEOVERLAP)
    reader.addInfo("DUPLICATEOVERLAP", 1, "Float",
                   "Highest overlap with a duplicate event")
    # Adding DUPLICATEOVERLAP info (equivalent to GSDUPLICATEOVERLAP)
    reader.addInfo("DUPLICATES", ".", "String",
                   "List of duplicate events preferred to this one")
    # Adding NONDUPLICATEOVERLAP
    reader.addInfo("NONDUPLICATEOVERLAP", 1, "Float",
                   "Amount of overlap with a non-duplicate")


def GenomeSTRIPLikeRedundancyAnnotator(SVSet, reader,
                                       duplicatescore_threshold=-2,
                                       genotyper="svtyper"):
    """ Annotating duplicate candidates based on the genotype likelihoods
      - genotype likelihoods can be provided by svtyper or genomestrip
    """

    add_redundancy_infos_header(reader)
    setLikeliTag(genotyper)

    variants = defaultdict()
    for sv in SVSet:
        variants[sv.id] = sv

    pybed_variants = vcf_to_pybed(SVSet)
    self_overlap = pybed_variants.intersect(pybed_variants,
                                            f=0.5, r=True, wo=True)

    seen = defaultdict(tuple)
    duplicates = defaultdict(list)
    overlapping = defaultdict(tuple)
    reference = defaultdict()
    for o in self_overlap:
        print("Here ?", o)
        if o[3] == o[7]:
            continue
        a, b = ordered(o[3], o[7])
        if seen[(a, b)]:
            continue
        seen[(a, b)] = True
        u = variants[a]
        v = variants[b]
        score = duplicatescore(u, v)
        # print("Comparing %s and %s : %3.8f" % (u.id, v.id, score))
        if score > duplicatescore_threshold:
            ref, dupli, s1, s2 = getduplicates_GQ(u, v)
            # print("%s prefered to %s %3.8f" % (ref.id, dupli.id, score))
            reference[ref] = 1
            overlap_size = int(o[-1])
            overlap = getoverlap(dupli, overlap_size)
            if maxGQ(ref) > 0 and passed(dupli):
                # are dismissed
                # - reference variant with 0 genotype quality for all markers
                # - duplicate that are already tagged as filtered out
                # dupli.id is considered as a duplicate of ref.id
                duplicates[dupli.id].append((ref.id, score, overlap))
        else:
            overlap_size = int(o[-1])
            overlap_u = getoverlap(u, overlap_size)
            overlap_v = getoverlap(v, overlap_size)
            overlapping[(u, v)] = {'dupli_score': score,
                                   'overlap_left': overlap_u,
                                   'overlap_right': overlap_v,
                                   }
    for u in SVSet:
        if u.id in duplicates:
            print("tagged as duplicate %s" % u.id)
            duplis = sorted([a for (a, s, o) in duplicates[u.id]])
            score = max([s for (a, s, o) in duplicates[u.id]])
            overlap = max([o for (a, s, o) in duplicates[u.id]])
            add_duplicate_info_sv(u, overlap, score, duplis)


def add_duplicate_info_sv(sv, duplicateoverlap, duplicatescore, duplicates):
    """
        simply adding two information to the sv infos
    """
    if isnan(duplicatescore):
        sv.record.info['DUPLICATESCORE'] = float('nan')
    else:
        sv.record.info['DUPLICATESCORE'] = duplicatescore
    sv.record.info['DUPLICATEOVERLAP'] = duplicateoverlap
    sv.record.info['DUPLICATES'] = duplicates


def add_overlap_info_sv(sv, overlap, duplicatescore):
    """
        simply adding two information to the sv infos
    """
    if isnan(duplicatescore):
        sv.record.info['DUPLICATESCORE'] = float('nan')
    else:
        sv.record.info['DUPLICATESCORE'] = duplicatescore
    sv.record.info['NONDUPLICATEOVERLAP'] = overlap


def add_filter_infos_header(reader):
    # FILTERS
    # Adding specific filters
    reader.addFilter("CALLRATE", "Call rate <0.75")
    reader.addFilter("MONOMORPH", "All samples have the same genotype")
    reader.addFilter("DUPLICATE", "GSDUPLICATESCORE>0")
    reader.addFilter("OVERLAP", "NONDUPLICATEOVERLAP>0.7")


def GenomeSTRIPLikefiltering(SVSet, reader):
    """ Filtering the candidate CNVs according to the following criteria
          - non duplicate sites
          - variant sites
          - call rate > 0.8
          - at least one variant (homozygous or heterozygote) has a genotype
            quality > 20
          - the variant is not everywhere heterozygote or homozygote
            (use NONVARIANTSCORE in both cases)
    """

    add_filter_infos_header(reader)

    for sv in SVSet:
        info = sv.record.info
        if callRate(sv) < 0.75:
            sv.filter.add("CALLRATE")
        if not Polymorph(sv):
            sv.filter.add("MONOMORPH")
        if 'NONDUPLICATEOVERLAP' in info and info['NONDUPLICATEOVERLAP'] > 0.7:
            sv.filter.add("OVERLAP")
        if "DUPLICATESCORE" in info is not None and info['DUPLICATESCORE'] > -2:
            sv.filter.add("DUPLICATE")