Merge pull request #634 from broadinstitute/jg/add_mane_select_to_sum…

…mary_stats

Add Mane select filtering option to `get_summary_counts`

gnomad/assessment/summary_stats.py

@@ -10,6 +10,7 @@
     LOF_CSQ_SET,
     add_most_severe_consequence_to_consequence,
     filter_vep_to_canonical_transcripts,
+    filter_vep_to_mane_select_transcripts,
     get_most_severe_consequence_for_summary,
     process_consequences,
 )
@@ -167,6 +168,8 @@ def get_summary_counts(
     freq_field: str = "freq",
     filter_field: str = "filters",
     filter_decoy: bool = False,
+    canonical_only: bool = True,
+    mane_select_only: bool = False,
     index: int = 0,
 ) -> hl.Table:
     """
@@ -186,8 +189,9 @@ def get_summary_counts(
 
     Before calculating summary counts, function:
         - Filters out low confidence regions
-        - Filters to canonical transcripts
         - Uses the most severe consequence
+        - Filters to canonical transcripts (if `canonical_only` is True) or MANE Select
+          transcripts (if `mane_select_only` is True)
 
     Assumes that:
         - Input HT is annotated with VEP.
@@ -198,10 +202,17 @@ def get_summary_counts(
     :param ht: Input Table.
     :param freq_field: Name of field in HT containing frequency annotation (array of structs). Default is "freq".
     :param filter_field: Name of field in HT containing variant filter information. Default is "filters".
+    :param canonical_only: Whether to filter to canonical transcripts. Default is True.
+    :param mane_select_only: Whether to filter to MANE Select transcripts. Default is False.
     :param filter_decoy: Whether to filter decoy regions. Default is False.
     :param index: Which index of freq_expr to use for annotation. Default is 0.
     :return: Table grouped by frequency bin and aggregated across summary count categories.
     """
+    if canonical_only and mane_select_only:
+        raise ValueError(
+            "Only one of `canonical_only` and `mane_select_only` can be True."
+        )
+
     logger.info("Checking if multi-allelic variants have been split...")
     max_alleles = ht.aggregate(hl.agg.max(hl.len(ht.alleles)))
     if max_alleles > 2:
@@ -212,10 +223,14 @@ def get_summary_counts(
     ht = ht.filter((hl.len(ht[filter_field]) == 0))
     ht = filter_low_conf_regions(ht, filter_decoy=filter_decoy)
 
-    logger.info(
-        "Filtering to canonical transcripts and getting VEP summary annotations..."
-    )
-    ht = filter_vep_to_canonical_transcripts(ht)
+    if canonical_only:
+        logger.info("Filtering to canonical transcripts...")
+        ht = filter_vep_to_canonical_transcripts(ht)
+    elif mane_select_only:
+        logger.info("Filtering to mane select transcripts...")
+        ht = filter_vep_to_mane_select_transcripts(ht)
+
+    logger.info("Getting VEP summary annotations...")
     ht = get_most_severe_consequence_for_summary(ht)
 
     logger.info("Annotating with frequency bin information...")

gnomad/utils/vep.py

@@ -382,6 +382,29 @@ def filter_vep_to_canonical_transcripts(
     )
 
 
+def filter_vep_to_mane_select_transcripts(
+    mt: Union[hl.MatrixTable, hl.Table],
+    vep_root: str = "vep",
+    filter_empty_csq: bool = False,
+) -> Union[hl.MatrixTable, hl.Table]:
+    """
+    Filter VEP transcript consequences to those in the MANE Select transcript.
+
+    :param mt: Input Table or MatrixTable.
+    :param vep_root: Name used for VEP annotation. Default is 'vep'.
+    :param filter_empty_csq: Whether to filter out rows where 'transcript_consequences' is empty. Default is False.
+    :return: Table or MatrixTable with VEP transcript consequences filtered.
+    """
+    return filter_vep_transcript_csqs(
+        mt,
+        vep_root,
+        synonymous=False,
+        canonical=False,
+        mane_select=True,
+        filter_empty_csq=filter_empty_csq,
+    )
+
+
 def filter_vep_to_synonymous_variants(
     mt: Union[hl.MatrixTable, hl.Table],
     vep_root: str = "vep",