feat: integrate gnomAD v4 gene constraints (#367)

src/genes/cli/data.rs

@@ -1171,7 +1171,7 @@ pub mod gnomad_constraints {
  // If parsed as T or None, return that.
  MaybeNA::Value(value) => Ok(value),
 
- // Otherwise, if value is string an "n/a", return None (and fail if it is any other
+ // Otherwise, if value is string an "NA", return None (and fail if it is any other
  // string)
  MaybeNA::NAString(string) => {
  if string == "NA" {
@@ -2162,9 +2162,16 @@ mod tests {
  Ok(())
  }
 
- #[test]
- fn deserialize_gnomad_constraints() -> Result<(), anyhow::Error> {
- let path_tsv = "tests/genes/gnomad_constraints/gnomad_constraints.tsv";
+ #[rstest::rstest]
+ #[case::gnomad_v2("2.1")]
+ #[case::gnomad_v4("4.0")]
+ fn deserialize_gnomad_constraints(
+ #[case] gnomad_constraints_version: &str,
+ ) -> Result<(), anyhow::Error> {
+ crate::common::set_snapshot_suffix!("{}", &gnomad_constraints_version);
+ let path_tsv = format!(
+ "tests/genes/gnomad_constraints/v{gnomad_constraints_version}/gnomad_constraints.tsv",
+ );
  let str_tsv = std::fs::read_to_string(path_tsv)?;
  let mut rdr = csv::ReaderBuilder::new()
  .delimiter(b'\t')

src/genes/cli/import.rs

@@ -138,7 +138,10 @@ fn load_gnomad_constraints(
  info!(" loading gnomAD constraints from {}", path);
  let mut result = HashMap::new();
 
- let mut reader = csv::ReaderBuilder::new().delimiter(b'\t').from_path(path)?;
+ let mut reader = csv::ReaderBuilder::new()
+ .delimiter(b'\t')
+ .flexible(true)
+ .from_path(path)?;
  for record in reader.deserialize::<gnomad_constraints::Record>() {
  let record = record?;
  result.insert(record.ensembl_gene_id.clone(), record);
@@ -1145,8 +1148,10 @@ pub mod test {
  use clap_verbosity_flag::Verbosity;
  use temp_testdir::TempDir;
 
- #[test]
- fn smoke_test() -> Result<(), anyhow::Error> {
+ #[rstest::rstest]
+ #[case::gnomad_v2("2.1")]
+ #[case::gnomad_v4("4.0")]
+ fn smoke_test(#[case] gnomad_constraints_version: &str) -> Result<(), anyhow::Error> {
  let tmp_dir = TempDir::default();
  let common_args = common::cli::Args {
  verbose: Verbosity::new(1, 0),
@@ -1159,8 +1164,8 @@ pub mod test {
  path_in_clingen_38: String::from(
  "tests/genes/clingen/ClinGen_gene_curation_list_GRCh38.tsv",
  ),
- path_in_gnomad_constraints: String::from(
- "tests/genes/gnomad_constraints/gnomad_constraints.tsv",
+ path_in_gnomad_constraints: format!(
+ "tests/genes/gnomad_constraints/v{gnomad_constraints_version}/gnomad_constraints.tsv",
  ),
  path_in_dbnsfp: String::from("tests/genes/dbnsfp/genes.tsv"),
  path_in_hgnc: String::from("tests/genes/hgnc/hgnc_info.jsonl"),

src/genes/cli/snapshots/annonars__genes__cli__data__tests__deserialize_gnomad_constraints@4.0.snap

@@ -0,0 +1,194 @@
+---
+source: src/genes/cli/data.rs
+expression: records
+---
+- ensembl_gene_id: ENSG00000121410
+ entrez_id: "1"
+ gene_symbol: A1BG
+ exp_lof: 43.008
+ exp_mis: 646.45
+ exp_syn: 295.68
+ mis_z: -0.86948
+ obs_lof: 45
+ obs_mis: 707
+ obs_syn: 316
+ oe_lof: 1.0463
+ oe_lof_lower: 0.823
+ oe_lof_upper: 1.342
+ oe_mis: 1.0937
+ oe_mis_lower: 1.027
+ oe_mis_upper: 1.164
+ oe_syn: 1.0687
+ oe_syn_lower: 0.974
+ oe_syn_upper: 1.173
+ pli: 0.00000000000000017129
+ syn_z: -0.64437
+- ensembl_gene_id: ENSG00000148584
+ entrez_id: "29974"
+ gene_symbol: A1CF
+ exp_lof: 69.896
+ exp_mis: 744.8
+ exp_syn: 272.29
+ mis_z: 1.2281
+ obs_lof: 45
+ obs_mis: 653
+ obs_syn: 272
+ oe_lof: 0.64381
+ oe_lof_lower: 0.506
+ oe_lof_upper: 0.825
+ oe_mis: 0.87674
+ oe_mis_lower: 0.821
+ oe_mis_upper: 0.935
+ oe_syn: 0.99895
+ oe_syn_lower: 0.904
+ oe_syn_upper: 1.104
+ pli: 0.00000000074328
+ syn_z: 0.0094264
+- ensembl_gene_id: ENSG00000175899
+ entrez_id: "2"
+ gene_symbol: A2M
+ exp_lof: 147.1
+ exp_mis: 1631.7
+ exp_syn: 624.65
+ mis_z: 2.7451
+ obs_lof: 95
+ obs_mis: 1328
+ obs_syn: 541
+ oe_lof: 0.64584
+ oe_lof_lower: 0.546
+ oe_lof_upper: 0.766
+ oe_mis: 0.81386
+ oe_mis_lower: 0.777
+ oe_mis_upper: 0.852
+ oe_syn: 0.86608
+ oe_syn_lower: 0.806
+ oe_syn_upper: 0.93
+ pli: 0.000000000000000000091331
+ syn_z: 1.8251
+- ensembl_gene_id: ENSG00000166535
+ entrez_id: "144568"
+ gene_symbol: A2ML1
+ exp_lof: 175.89
+ exp_mis: 1784.1
+ exp_syn: 680.92
+ mis_z: 1.6427
+ obs_lof: 146
+ obs_mis: 1594
+ obs_syn: 636
+ oe_lof: 0.83121
+ oe_lof_lower: 0.725
+ oe_lof_upper: 0.954
+ oe_mis: 0.89347
+ oe_mis_lower: 0.857
+ oe_mis_upper: 0.931
+ oe_syn: 0.93402
+ oe_syn_lower: 0.874
+ oe_syn_upper: 0.997
+ pli: 0.00000000000000000000000000000000000000015734
+ syn_z: 0.93881
+- ensembl_gene_id: ENSG00000184389
+ entrez_id: "127550"
+ gene_symbol: A3GALT2
+ exp_lof: 26.534
+ exp_mis: 381.4
+ exp_syn: 160.06
+ mis_z: -4.0864
+ obs_lof: 41
+ obs_mis: 600
+ obs_syn: 253
+ oe_lof: 1.0228
+ oe_lof_lower: 0.699
+ oe_lof_upper: 1.53
+ oe_mis: 1.5732
+ oe_mis_lower: 1.471
+ oe_mis_upper: 1.683
+ oe_syn: 1.5807
+ oe_syn_lower: 1.426
+ oe_syn_upper: 1.754
+ pli: 0.0000010075
+ syn_z: -4.0061
+- ensembl_gene_id: ENSG00000128274
+ entrez_id: "53947"
+ gene_symbol: A4GALT
+ exp_lof: 21.691
+ exp_mis: 494.59
+ exp_syn: 225.34
+ mis_z: -0.28586
+ obs_lof: 22
+ obs_mis: 512
+ obs_syn: 257
+ oe_lof: 0.61691
+ oe_lof_lower: 0.303
+ oe_lof_upper: 1.394
+ oe_mis: 1.0352
+ oe_mis_lower: 0.962
+ oe_mis_upper: 1.114
+ oe_syn: 1.1405
+ oe_syn_lower: 1.029
+ oe_syn_upper: 1.265
+ pli: 0.075456
+ syn_z: -1.1499
+- ensembl_gene_id: ENSG00000118017
+ entrez_id: "51146"
+ gene_symbol: A4GNT
+ exp_lof: 27.359
+ exp_mis: 436.48
+ exp_syn: 167.83
+ mis_z: 1.0569
+ obs_lof: 14
+ obs_mis: 376
+ obs_syn: 156
+ oe_lof: 0.70139
+ oe_lof_lower: 0.383
+ oe_lof_upper: 1.377
+ oe_mis: 0.86143
+ oe_mis_lower: 0.791
+ oe_mis_upper: 0.938
+ oe_syn: 0.92954
+ oe_syn_lower: 0.815
+ oe_syn_upper: 1.062
+ pli: 0.019099
+ syn_z: 0.49778
+- ensembl_gene_id: ENSG00000094914
+ entrez_id: "8086"
+ gene_symbol: AAAS
+ exp_lof: 81.872
+ exp_mis: 722.62
+ exp_syn: 280.11
+ mis_z: 0.87764
+ obs_lof: 61
+ obs_mis: 658
+ obs_syn: 271
+ oe_lof: 0.74507
+ oe_lof_lower: 0.605
+ oe_lof_upper: 0.922
+ oe_mis: 0.91057
+ oe_mis_lower: 0.853
+ oe_mis_upper: 0.971
+ oe_syn: 0.96747
+ oe_syn_lower: 0.875
+ oe_syn_upper: 1.07
+ pli: 0.0000000000000008615
+ syn_z: 0.29692
+- ensembl_gene_id: ENSG00000081760
+ entrez_id: "65985"
+ gene_symbol: AACS
+ exp_lof: 82.529
+ exp_mis: 896.85
+ exp_syn: 349.3
+ mis_z: 0.4736
+ obs_lof: 65
+ obs_mis: 858
+ obs_syn: 333
+ oe_lof: 0.7876
+ oe_lof_lower: 0.644
+ oe_lof_upper: 0.968
+ oe_mis: 0.95668
+ oe_mis_lower: 0.904
+ oe_mis_upper: 1.012
+ oe_syn: 0.95333
+ oe_syn_lower: 0.871
+ oe_syn_upper: 1.044
+ pli: 0.0000000000000000085337
+ syn_z: 0.4756
+

tests/genes/gnomad_constraints/v4.0/gnomad_constraints.tsv

@@ -0,0 +1,10 @@
+ensembl_gene_id entrez_id gene_symbol exp_lof exp_mis exp_syn mis_z obs_lof obs_mis obs_syn oe_lof oe_lof_lower oe_lof_upper oe_mis oe_mis_lower oe_mis_upper oe_syn oe_syn_lower oe_syn_upper pLI syn_z exac_pLI exac_obs_lof exac_exp_lof exac_oe_lof
+ENSG00000121410 1 A1BG 4.3008e+01 6.4645e+02 2.9568e+02 -8.6948e-01 45 707 316 1.0463e+00 8.2300e-01 1.3420e+00 1.0937e+00 1.0270e+00 1.1640e+00 1.0687e+00 9.7400e-01 1.1730e+00 1.7129e-16 -6.4437e-01 NA NA NA NA
+ENSG00000148584 29974 A1CF 6.9896e+01 7.4480e+02 2.7229e+02 1.2281e+00 45 653 272 6.4381e-01 5.0600e-01 8.2500e-01 8.7674e-01 8.2100e-01 9.3500e-01 9.9895e-01 9.0400e-01 1.1040e+00 7.4328e-10 9.4264e-03 NA NA NA NA
+ENSG00000175899 2 A2M 1.4710e+02 1.6317e+03 6.2465e+02 2.7451e+00 95 1328 541 6.4584e-01 5.4600e-01 7.6600e-01 8.1386e-01 7.7700e-01 8.5200e-01 8.6608e-01 8.0600e-01 9.3000e-01 9.1331e-20 1.8251e+00 NA NA NA NA
+ENSG00000166535 144568 A2ML1 1.7589e+02 1.7841e+03 6.8092e+02 1.6427e+00 146 1594 636 8.3121e-01 7.2500e-01 9.5400e-01 8.9347e-01 8.5700e-01 9.3100e-01 9.3402e-01 8.7400e-01 9.9700e-01 1.5734e-40 9.3881e-01 NA NA NA NA
+ENSG00000184389 127550 A3GALT2 2.6534e+01 3.8140e+02 1.6006e+02 -4.0864e+00 41 600 253 1.0228e+00 6.9900e-01 1.5300e+00 1.5732e+00 1.4710e+00 1.6830e+00 1.5807e+00 1.4260e+00 1.7540e+00 1.0075e-06 -4.0061e+00 NA NA NA NA
+ENSG00000128274 53947 A4GALT 2.1691e+01 4.9459e+02 2.2534e+02 -2.8586e-01 22 512 257 6.1691e-01 3.0300e-01 1.3940e+00 1.0352e+00 9.6200e-01 1.1140e+00 1.1405e+00 1.0290e+00 1.2650e+00 7.5456e-02 -1.1499e+00 NA NA NA NA
+ENSG00000118017 51146 A4GNT 2.7359e+01 4.3648e+02 1.6783e+02 1.0569e+00 14 376 156 7.0139e-01 3.8300e-01 1.3770e+00 8.6143e-01 7.9100e-01 9.3800e-01 9.2954e-01 8.1500e-01 1.0620e+00 1.9099e-02 4.9778e-01 NA NA NA NA
+ENSG00000094914 8086 AAAS 8.1872e+01 7.2262e+02 2.8011e+02 8.7764e-01 61 658 271 7.4507e-01 6.0500e-01 9.2200e-01 9.1057e-01 8.5300e-01 9.7100e-01 9.6747e-01 8.7500e-01 1.0700e+00 8.6150e-16 2.9692e-01 NA NA NA NA
+ENSG00000081760 65985 AACS 8.2529e+01 8.9685e+02 3.4930e+02 4.7360e-01 65 858 333 7.8760e-01 6.4400e-01 9.6800e-01 9.5668e-01 9.0400e-01 1.0120e+00 9.5333e-01 8.7100e-01 1.0440e+00 8.5337e-18 4.7560e-01 NA NA NA NA