use crate::annotate::seqvars::consequence::VcfVariant;
use crate::common::contig::ContigManager;
use crate::db::keys;
use anyhow::Error;
use prost::Message;
use rocksdb::DBWithThreadMode;
use serde::{Deserialize, Serialize};
use std::fmt::Display;
use std::io::Cursor;
use std::path::Path;
use std::sync::Arc;
#[derive(Debug)]
pub struct ClinvarAnnotator {
db: DBWithThreadMode<rocksdb::MultiThreaded>,
contig_manager: Arc<ContigManager>,
}
impl ClinvarAnnotator {
pub fn new(
db: DBWithThreadMode<rocksdb::MultiThreaded>,
contig_manager: Arc<ContigManager>,
) -> Self {
Self { db, contig_manager }
}
pub(crate) fn from_path(
path: impl AsRef<Path> + Display,
contig_manager: Arc<ContigManager>,
) -> anyhow::Result<Self> {
tracing::info!("Opening ClinVar database");
tracing::debug!("RocksDB path = {}", &path);
let options = rocksdb::Options::default();
let db_clinvar =
rocksdb::DB::open_cf_for_read_only(&options, &path, ["meta", "clinvar"], false)?;
Ok(Self::new(db_clinvar, contig_manager))
}
pub fn annotate_record_clinvar(&self, key: &[u8]) -> Result<Option<ClinvarResult>, Error> {
if let Some(raw_value) = self
.db
.get_cf(self.db.cf_handle("clinvar").as_ref().unwrap(), key)?
{
let record_list = annonars::pbs::clinvar::minimal::ExtractedVcvRecordList::decode(
&mut Cursor::new(&raw_value),
)?;
let mut vcv = Vec::new();
let mut germline_classification = Vec::new();
for r in record_list.records.iter() {
let accession = r
.accession
.as_ref()
.ok_or_else(|| anyhow::anyhow!("must have VCV"))?;
vcv.push(format!("{}.{}", accession.accession, accession.version));
if let Some(gc) = &r
.classifications
.as_ref()
.ok_or_else(|| anyhow::anyhow!("has classifications"))?
.germline_classification
{
let description = gc
.description
.as_ref()
.ok_or_else(|| anyhow::anyhow!("description missing"))?;
germline_classification.push(description.to_string());
}
}
Ok(Some(ClinvarResult {
vcv,
germline_classification,
}))
} else {
Ok(None)
}
}
pub(crate) fn annotate(&self, vcf_var: &keys::Var) -> anyhow::Result<Option<ClinvarResult>> {
if let Some(chrom) = self.contig_manager.get_annonars_chrom(&vcf_var.chrom) {
let key: Vec<u8> = annonars::common::keys::Var::from(
chrom,
vcf_var.pos,
&vcf_var.reference,
&vcf_var.alternative,
)
.into();
return self.annotate_record_clinvar(&key);
}
Ok(None)
}
#[cfg(feature = "server")]
pub(crate) fn annotate_variant(
&self,
vcf_var: &VcfVariant,
) -> anyhow::Result<Option<crate::server::run::actix_server::seqvars_clinvar::ClinvarResultEntry>>
{
let Some(chrom) = self.contig_manager.get_annonars_chrom(&vcf_var.chromosome) else {
return Ok(None);
};
let vcf_var = annonars::common::keys::Var::from(
chrom,
vcf_var.position,
&vcf_var.reference,
&vcf_var.alternative,
);
let key: Vec<u8> = vcf_var.clone().into();
match self
.db
.get_cf(self.db.cf_handle("clinvar").as_ref().unwrap(), key)?
{
Some(raw_value) => {
let record_list = annonars::pbs::clinvar::minimal::ExtractedVcvRecordList::decode(
&mut Cursor::new(&raw_value),
)?;
let mut clinvar_vcvs = Vec::new();
let mut clinvar_germline_classifications = Vec::new();
for clinvar_record in record_list.records.iter() {
let accession = clinvar_record
.accession
.as_ref()
.ok_or_else(|| anyhow::anyhow!("must have VCV"))?;
let vcv = format!("{}.{}", accession.accession, accession.version);
let classifications = clinvar_record
.classifications
.as_ref()
.ok_or_else(|| anyhow::anyhow!("must have classifications"))?;
if let Some(germline_classification) = &classifications.germline_classification
{
let description = germline_classification
.description
.as_ref()
.ok_or_else(|| anyhow::anyhow!("description missing"))?
.to_string();
clinvar_vcvs.push(vcv);
clinvar_germline_classifications.push(description);
}
}
Ok(Some(
crate::server::run::actix_server::seqvars_clinvar::ClinvarResultEntry {
clinvar_vcv: clinvar_vcvs,
clinvar_germline_classification: clinvar_germline_classifications,
},
))
}
_ => Ok(None),
}
}
}
#[derive(Debug, Clone, Default, Serialize, Deserialize)]
pub struct ClinvarResult {
pub vcv: Vec<String>,
pub germline_classification: Vec<String>,
}
#[cfg(test)]
mod tests {
use super::*;
#[rstest::rstest]
#[case("17")]
#[case("chr17")]
#[case("NC_000017.10")]
fn test_annotate_contig_alias(#[case] chrom: &str) -> Result<(), anyhow::Error> {
let annotator = ClinvarAnnotator::from_path(
"tests/data/annotate/db/grch37/seqvars/clinvar",
Arc::new(ContigManager::new("grch37")),
)?;
let var = keys::Var::new(chrom.into(), 41215920, "G".into(), "T".into());
let result = annotator.annotate(&var)?.unwrap();
assert_eq!(result.vcv, ["VCV000055407.47"]);
Ok(())
}
}