Fix broken gCNV Annotation pipeline (#960)

* Add the get-gencode script

* use the pre-downloaded gencode data in gCNV and SV

* Bump version: 1.29.4 → 1.29.5

.bumpversion.cfg

@@ -1,5 +1,5 @@
 [bumpversion]
-current_version = 1.29.4
+current_version = 1.29.5
 commit = True
 tag = False
 

.github/workflows/docker.yaml

@@ -15,7 +15,7 @@ permissions:
   contents: read
 
 env:
-  VERSION: 1.29.4
+  VERSION: 1.29.5
 
 jobs:
   docker:

configs/defaults/gatk_sv_multisample.toml

@@ -3,6 +3,9 @@ name = 'gatk_sv'
 ref_fasta = 'gs://cpg-common-main/references/hg38/v0/dragen_reference/Homo_sapiens_assembly38_masked.fasta'
 status_reporter = 'metamist'
 
+# update this when cpg_workflows.scripts.get_gencode_gtf.sh is re-run
+gencode_gtf_file = 'gs://cpg-common-main/references/hg38/v0/gencode_47.gtf.gz'
+
 # Write dataset MTs for these datasets. Required for the AnnotateDatasetSv stage.
 # write_mt_for_datasets = []
 

configs/defaults/gcnv.toml

@@ -13,6 +13,9 @@ num_samples_per_scatter_block = 10
 gncv_max_events = 320
 gncv_max_pass_events = 30
 
+# update this when cpg_workflows.scripts.get_gencode_gtf.sh is re-run
+gencode_gtf_file = 'gs://cpg-common-main/references/hg38/v0/gencode_47.gtf.gz'
+
 [images]
 gatk_docker = "australia-southeast1-docker.pkg.dev/cpg-common/images/sv/gatk:2023-07-13-4.4.0.0-43-gd79823f9c-NIGHTLY-SNAPSHOT"
 gatk_gcnv = 'australia-southeast1-docker.pkg.dev/cpg-common/images/sv/gatk:4.2.6.1-57-g9e03432'

cpg_workflows/jobs/gcnv.py

@@ -11,7 +11,7 @@
 from cpg_utils.config import config_retrieve, get_config, image_path
 from cpg_utils.hail_batch import command, fasta_res_group, get_batch, query_command
 from cpg_workflows.filetypes import CramPath
-from cpg_workflows.query_modules import seqr_loader, seqr_loader_cnv
+from cpg_workflows.query_modules import seqr_loader
 from cpg_workflows.resources import HIGHMEM
 from cpg_workflows.scripts import upgrade_ped_with_inferred
 from cpg_workflows.utils import can_reuse, chunks
@@ -670,7 +670,7 @@ def update_vcf_attributes(input_tmp: str, output_file: str):
 def annotate_dataset_jobs_cnv(
     mt_path: Path,
     sgids: list[str],
-    out_mt_path: Path,
+    out_mt_path: str,
     tmp_prefix: Path,
     job_attrs: dict | None = None,
 ) -> list[Job]:
@@ -688,7 +688,7 @@ def annotate_dataset_jobs_cnv(
     subset_j: Job | None = None
     if not subset_mt_path.exists():
         subset_j = get_batch().new_job('subset cohort to dataset', (job_attrs or {}) | {'tool': 'hail query'})
-        subset_j.image(image_path('cpg_workflows'))
+        subset_j.image(config_retrieve(['workflow', 'driver_image']))
         subset_j.command(
             query_command(
                 seqr_loader,
@@ -701,16 +701,15 @@ def annotate_dataset_jobs_cnv(
         )
 
     annotate_j = get_batch().new_job('annotate dataset', (job_attrs or {}) | {'tool': 'hail query'})
-    annotate_j.image(image_path('cpg_workflows'))
+    annotate_j.image(config_retrieve(['workflow', 'driver_image']))
     annotate_j.command(
-        query_command(
-            seqr_loader_cnv,
-            seqr_loader_cnv.annotate_dataset_gcnv.__name__,
-            str(subset_mt_path),
-            str(out_mt_path),
-            setup_gcp=True,
-        ),
+        'seqr_loader_cnv '
+        f'--mt_out {out_mt_path} '
+        f'--checkpoint {str(tmp_prefix / "checkpoints")} '
+        'dataset '  # use the annotate_DATASET functionality
+        f'--mt_in {str(subset_mt_path)} ',
     )
+
     if subset_j:
         annotate_j.depends_on(subset_j)
         return [subset_j, annotate_j]

cpg_workflows/jobs/seqr_loader_sv.py

@@ -23,12 +23,15 @@ def annotate_cohort_jobs_sv(
 
     j = get_batch().new_job('Annotate cohort', job_attrs)
     j.image(get_config()['workflow']['driver_image'])
+    gencode_gz = get_config()['worfklow']['gencode_gtf_file']
+    gencode_gtf_local = get_batch().read_input(str(gencode_gz))
     j.command(
         query_command(
             seqr_loader_sv,
             seqr_loader_sv.annotate_cohort_sv.__name__,
             str(vcf_path),
             str(out_mt_path),
+            str(gencode_gtf_local),
             str(checkpoint_prefix),
             setup_gcp=True,
         ),

cpg_workflows/query_modules/seqr_loader_sv.py

@@ -4,15 +4,13 @@
 
 import gzip
 import logging
-
-import requests
+from os.path import join
 
 import hail as hl
 
-from cpg_utils import to_path
 from cpg_utils.config import get_config, reference_path
 from cpg_utils.hail_batch import genome_build
-from cpg_workflows.utils import checkpoint_hail, read_hail
+from cpg_workflows.utils import generator_chunks, read_hail
 
 # I'm just going to go ahead and steal these constants from their seqr loader
 BOTHSIDES_SUPPORT = 'BOTHSIDES_SUPPORT'
@@ -103,48 +101,16 @@ def get_cpx_interval(x):
     return hl.struct(type=type_chr[0], chrom=chr_pos[0], start=hl.int32(pos[0]), end=hl.int32(pos[1]))
 
 
-def download_gencode_gene_id_mapping(gencode_release: str) -> str:
-    """
-    This is an inefficient stand-in for now. Swap this out with a more permanent
-    location for this file in the resources bucket
-    Not suuuuuuper keen on storing a pickled representation, but a minimised JSON
-    would be a good middle ground. Parsed ~= 62000 {str: str}
-    Args:
-        gencode_release (str | int): Which gencode release do you want?
-    Returns:
-        str - path to localised GTF file
+def parse_gtf_from_local(gtf_path: str, chunk_size: int | None = None) -> hl.dict:
     """
+    Read over the localised GTF file and read into a dict
 
-    # this is the thing
-    local_gtf = 'localfile.gtf.gz'
-
-    # check for presence in config
-    if (config_gtf := get_config().get('gencode_gtf_path')) is not None:
-        # treat as GCP
-        if config_gtf.startswith('gs://'):
-            to_path(config_gtf).copy(local_gtf)
-            gtf_path = local_gtf
-        else:
-            gtf_path = config_gtf
-    else:
-        gtf_path = GENCODE_GTF_URL.format(gencode_release=gencode_release)
-
-    # if it wasn't a local file, download it
-    if gtf_path.startswith(('http://', 'https://')):
-        gz_stream = requests.get(gtf_path, stream=True)
-        with open(local_gtf, 'wb') as f:
-            f.writelines(gz_stream)
-        gz_stream.close()
-
-    # OK - I think that covers all the viable situations for now
-    return local_gtf
-
-
-def parse_gtf_from_local(gtf_path: str) -> hl.dict:
-    """
-    Read over the localised file and read into a dict
+    n.b. due to a limit in Spark of 20MB per String length, the dictionary here is actually too large to be used
+    in annotation expressions. To remedy this, the dictionary is returned as a list of fragments, and we can use each
+    one in turn, then create a checkpoint between them.
     Args:
         gtf_path ():
+        chunk_size (int): if specified, returns this dict as a list of dicts
     Returns:
         the gene lookup dictionary as a Hail DictExpression
     """
@@ -165,12 +131,24 @@ def parse_gtf_from_local(gtf_path: str) -> hl.dict:
             # parse info field
             info_fields_list = [x.strip().split() for x in record['info'].split(';') if x != '']
             info_fields = {k: v.strip('"') for k, v in info_fields_list}
+
+            # skip an ENSG: ENSG mapping, redundant...
+            if info_fields['gene_name'].startswith('ENSG'):
+                continue
             gene_id_mapping[info_fields['gene_name']] = info_fields['gene_id'].split('.')[0]
-    logging.info('Completed ingestion of gene-ID mapping')
-    return hl.literal(gene_id_mapping)
+
+    all_keys = list(gene_id_mapping.keys())
+    logging.info(f'Completed ingestion of gene-ID mapping, {len(all_keys)} entries')
+    if chunk_size is None:
+        return [hl.literal(gene_id_mapping)]
+
+    # hail can't impute the type of a generator, so do this in baby steps
+    sub_dictionaries = [{key: gene_id_mapping[key] for key in keys} for keys in generator_chunks(all_keys, chunk_size)]
+
+    return [hl.literal(each_dict) for each_dict in sub_dictionaries]
 
 
-def annotate_cohort_sv(vcf_path: str, out_mt_path: str, checkpoint_prefix: str | None = None):
+def annotate_cohort_sv(vcf_path: str, out_mt_path: str, gencode_gz: str, checkpoint: str | None = None):
     """
     Translate an annotated SV VCF into a Seqr-ready format
     Relevant gCNV specific schema
@@ -180,7 +158,8 @@ def annotate_cohort_sv(vcf_path: str, out_mt_path: str, checkpoint_prefix: str |
     Args:
         vcf_path (str): Where is the VCF??
         out_mt_path (str): And where do you need output!?
-        checkpoint_prefix (str): CHECKPOINT!@!!
+        gencode_gz (str): The path to a compressed GENCODE GTF file
+        checkpoint (str): CHECKPOINT!@!!
     """
 
     logger = logging.getLogger('annotate_cohort_sv')
@@ -267,11 +246,11 @@ def annotate_cohort_sv(vcf_path: str, out_mt_path: str, checkpoint_prefix: str |
         mt = mt.annotate_rows(info=mt.info.annotate(CPX_TYPE=mt.sv_types[0]))
 
     # save those changes
-    mt = checkpoint_hail(mt, 'initial_annotation_round.mt', checkpoint_prefix)
+    if checkpoint:
+        mt = mt.checkpoint(join(checkpoint, 'initial_annotation_round.mt'))
 
     # get the Gene-Symbol mapping dict
-    gene_id_mapping_file = download_gencode_gene_id_mapping(get_config().get('gencode_release', '46'))
-    gene_id_mapping = parse_gtf_from_local(gene_id_mapping_file)
+    gene_id_mapping = parse_gtf_from_local(gencode_gz)[0]
 
     # OK, NOW IT'S BUSINESS TIME
     conseq_predicted_gene_cols = [

cpg_workflows/scripts/get_gencode_gtf.sh

@@ -0,0 +1,15 @@
+#!/usr/bin/env bash
+
+# use this get_gencode_gtf.sh script to download the latest GENCODE GTF file
+# and place it in the appropriate place in the CPG bucket
+
+set -ex
+
+GENCODE_VERSION=${1:-"47"}
+
+# download the GTF file
+wget -O gencode.gtf.gz "https://ftp.ebi.ac.uk/pub/databases/gencode/Gencode_human/release_${GENCODE_VERSION}/gencode.v${GENCODE_VERSION}.annotation.gtf.gz"
+
+# don't unzip the file - unzipping inflates from ~50MB to ~1.8GB, and transfer is probably the bottleneck
+# place the file in the place in the CPG bucket
+gsutil cp gencode.gtf "gs://cpg-common-main/references/hg38/v0/gencode_${GENCODE_VERSION}.gtf.gz"