feat(IPVC-2228): Extract mito gene data from genbank file (#14)

pyproject.toml

@@ -47,6 +47,8 @@ dependencies = [
   "configparser",
   "docopt",
   "eutils>=0.3.2",
+  "importlib_resources",
+  "more_itertools",
   "nose",
   "prettytable",
   "psycopg2-binary",

sbin/ncbi_process_mito.py

@@ -0,0 +1,335 @@
+"""
+Download mito fasta and gbff file. Use BioPython to parse the features in the Mitochondrial genbank file to get
+the attributes of a region of the genome that correspond to genes along with their attributes. Output gene/tx/alignment
+details to intermediate file needed to update UTA database and SeqRepo.
+
+    FEATURES             Location/Qualifiers
+     source          1..16569
+                     /organism="Homo sapiens"
+                     /organelle="mitochondrion"
+                     /mol_type="genomic DNA"
+                     /isolation_source="caucasian"
+                     /db_xref="taxon:9606"
+                     /tissue_type="placenta"
+                     /country="United Kingdom: Great Britain"
+                     /note="this is the rCRS"
+     D-loop          complement(join(16024..16569,1..576))
+     gene            577..647
+                     /gene="TRNF"
+                     /nomenclature="Official Symbol: MT-TF | Name:
+                     mitochondrially encoded tRNA phenylalanine | Provided by:
+                     HGNC:HGNC:7481"
+                     /db_xref="GeneID:4558"
+                     /db_xref="HGNC:HGNC:7481"
+                     /db_xref="MIM:590070"
+     tRNA            577..647
+                     /gene="TRNF"
+                     /product="tRNA-Phe"
+                     /note="NAR: 1455"
+                     /anticodon=(pos:611..613,aa:Phe,seq:gaa)
+                     /codon_recognized="UUC"
+                     /db_xref="GeneID:4558"
+                     /db_xref="HGNC:HGNC:7481"
+                     /db_xref="MIM:590070"
+     gene            648..1601
+                     /gene="RNR1"
+                     /gene_synonym="MTRNR1"
+                     /nomenclature="Official Symbol: MT-RNR1 | Name:
+                     mitochondrially encoded 12S RNA | Provided by:
+                     HGNC:HGNC:7470"
+                     /db_xref="GeneID:4549"
+                     /db_xref="HGNC:HGNC:7470"
+                     /db_xref="MIM:561000"
+     rRNA            648..1601
+                     /gene="RNR1"
+                     /gene_synonym="MTRNR1"
+                     /product="s-rRNA"
+                     /note="12S rRNA; 12S ribosomal RNA"
+                     /db_xref="GeneID:4549"
+                     /db_xref="HGNC:HGNC:7470"
+                     /db_xref="MIM:561000"
+                     ...
+"""
+import argparse
+import dataclasses
+import importlib_resources
+import logging
+import logging.config
+from typing import Dict, Optional
+
+from Bio.Seq import Seq
+import Bio.SeqIO
+from Bio.SeqFeature import SeqFeature
+from Bio.SeqRecord import SeqRecord
+from bioutils.digests import seq_md5
+from more_itertools import first, one
+
+from uta.formats.geneaccessions import GeneAccessions, GeneAccessionsWriter
+from uta.formats.seqinfo import SeqInfo, SeqInfoWriter
+from uta.formats.txinfo import TxInfo, TxInfoWriter
+from uta.formats.exonset import ExonSet, ExonSetWriter
+from uta.tools.eutils import download_from_eutils, NcbiFileFormatEnum
+
+
+@dataclasses.dataclass
+class MitoGeneData:
+    gene_id: int
+    gene_symbol: str
+    name: str
+    tx_ac: str
+    tx_seq: str
+    tx_start: int
+    tx_end: int
+    alt_ac: str
+    alt_start: int
+    alt_end: int
+    strand: str
+    origin: str = "NCBI"
+    alignment_method: str = "splign"
+    transl_table: Optional[str] = None
+    transl_except: Optional[str] = None
+    pro_ac: Optional[str] = None
+    pro_seq: Optional[str] = None
+
+    def exons_se_i(self) -> str:
+        return f"{self.tx_start},{self.tx_end}"
+
+    def cds_se_i(self) -> str:
+        return self.exons_se_i() if self.pro_ac else ""
+
+    def alt_exons_se_i(self) -> str:
+        return f"{self.alt_start},{self.alt_end}"
+
+
+logging_conf_fn = importlib_resources.files("uta").joinpath("etc/logging.conf")
+logging.config.fileConfig(logging_conf_fn)
+logging.getLogger().setLevel(logging.INFO)
+logger = logging.getLogger(__name__)
+
+
+def parse_args():
+    parser = argparse.ArgumentParser(description=__doc__)
+    parser.add_argument("accession", type=str)
+    parser.add_argument("--output-dir", "-o", default=".", type=str)
+    return parser.parse_args()
+
+
+def download_mito_files(output_dir: str, accession: str) -> Dict[str, str]:
+    logger.info(f"downloading files for {accession}")
+    mt_gb_filepath = f"{output_dir}/{accession}.gbff"
+    mt_fa_filepath = f"{output_dir}/{accession}.fna"
+
+    logger.info(f"downloading {NcbiFileFormatEnum.GENBANK} file to {mt_gb_filepath}")
+    download_from_eutils(accession, NcbiFileFormatEnum.GENBANK, mt_gb_filepath)
+
+    logger.info(f"downloading {NcbiFileFormatEnum.FASTA} file to {mt_fa_filepath}")
+    download_from_eutils(accession, NcbiFileFormatEnum.FASTA, mt_fa_filepath)
+
+    return {"gbff": mt_gb_filepath, "fna": mt_fa_filepath}
+
+
+def parse_db_xrefs(gb_feature: SeqFeature) -> Dict[str, str]:
+    """
+    Example:
+        Key: db_xref
+        Value: ['GeneID:4558', 'HGNC:HGNC:7481', 'MIM:590070']
+    """
+    return {
+        x.partition(":")[0].strip(): x.partition(":")[2].strip()
+        for x in gb_feature.qualifiers.get("db_xref", [])
+    }
+
+
+def parse_nomenclature_value(gb_feature: SeqFeature) -> Dict[str, str]:
+    """
+    Example:
+        Key: nomenclature
+        Value: ['Official Symbol: MT-TF | Name: mitochondrially encoded tRNA phenylalanine | Provided by: HGNC:HGNC:7481']
+    """
+    nomenclature_key = "nomenclature"
+    nomenclature_results: Dict[str, str] = {}
+    if nomenclature_key in gb_feature.qualifiers:
+        nomenclature_list = list(
+            map(
+                lambda x: x.strip(),
+                one(gb_feature.qualifiers[nomenclature_key]).split("|"),
+            )
+        )
+        nomenclature_results = {
+            x.partition(":")[0].strip(): x.partition(":")[2].strip()
+            for x in nomenclature_list
+        }
+
+    return nomenclature_results
+
+
+def get_mito_genes(gbff_filepath: str):
+    logger.info(f"processing NCBI GBFF file from {gbff_filepath}")
+    with open(gbff_filepath) as fh:
+        for record in Bio.SeqIO.parse(fh, "gb"):
+            for feature in record.features:
+                xrefs = parse_db_xrefs(feature)
+
+                feature_start, feature_end = (
+                    feature.location.start,
+                    feature.location.end,
+                )
+
+                # dependent on feature type, process data and output if appropriate
+                if feature.type == "gene":
+                    # assert subsequent features represent the same location
+                    assert feature_start == feature.location.start
+                    assert feature_end == feature.location.end
+                    # for gene feature do not yield anything, just set gene level attributes
+                    gene_id = int(xrefs["GeneID"])
+                    nomenclature = parse_nomenclature_value(feature)
+                    hgnc = nomenclature["Official Symbol"]
+                    name = nomenclature["Name"]
+
+                elif feature.type in ("tRNA", "rRNA", "CDS"):
+                    # assert subsequent features represent the same location and gene
+                    assert int(xrefs["GeneID"]) == gene_id
+                    assert feature_start == feature.location.start
+                    assert feature_end == feature.location.end
+                    # if feature type not CDS, set defaults
+                    pro_ac = None
+                    pro_seq = None
+                    transl_table = None
+                    transl_except = None
+
+                    # retrieve sequence, and reverse compliment if on reverse strand
+                    ac = f"{record.id}_{feature.location.start:05}_{feature.location.end:05}"
+                    feature_seq = record.seq[feature_start:feature_end]
+                    strand = "+"
+                    if feature.location.strand == -1:
+                        strand = "-"
+                        feature_seq = feature_seq.reverse_complement()
+
+                    if feature.type == "CDS":
+                        # override defaults for CDS features
+                        pro_ac = one(feature.qualifiers["protein_id"])
+                        pro_seq = str(one(feature.qualifiers["translation"]))
+                        transl_table = one(feature.qualifiers["transl_table"])
+                        if "transl_except" in feature.qualifiers:
+                            transl_except = one(feature.qualifiers["transl_except"])
+
+                    # yield gene data
+                    yield MitoGeneData(
+                        gene_id=gene_id,
+                        gene_symbol=hgnc,
+                        name=name,
+                        tx_ac=ac,
+                        tx_seq=str(feature_seq),
+                        tx_start=0,
+                        tx_end=feature.location.end - feature.location.start,
+                        alt_ac=record.id,
+                        alt_start=feature_start,
+                        alt_end=feature_end,
+                        strand=strand,
+                        transl_table=transl_table,
+                        transl_except=transl_except,
+                        pro_ac=pro_ac,
+                        pro_seq=pro_seq,
+                    )
+
+
+def main(ncbi_accession: str, output_dir: str):
+    # get input files
+    input_files = download_mito_files(output_dir=output_dir, accession=ncbi_accession)
+
+    # extract Mitochondrial gene information
+    mito_genes = [mg for mf in input_files.values() for mg in get_mito_genes(mf)]
+    logger.info(f"found {len(mito_genes)} genes from parsing {input_files['gbff']}")
+
+    # write gene accessions
+    with open(f"{output_dir}/{ncbi_accession}.assocacs", "w") as o_file:
+        gaw = GeneAccessionsWriter(o_file)
+        for mg in mito_genes:
+            if mg.pro_ac is not None:
+                gaw.write(
+                    GeneAccessions(
+                        mg.gene_symbol, mg.tx_ac, mg.gene_id, mg.pro_ac, mg.origin
+                    )
+                )
+
+    # write sequence information
+    with open(f"{output_dir}/{ncbi_accession}.seqinfo", "w") as o_file:
+        siw = SeqInfoWriter(o_file)
+        for mg in mito_genes:
+            siw.write(
+                SeqInfo(
+                    seq_md5(mg.tx_seq),
+                    mg.origin,
+                    mg.tx_ac,
+                    mg.name,
+                    len(mg.tx_seq),
+                    None,
+                )
+            )
+            if mg.pro_ac is not None:
+                siw.write(
+                    SeqInfo(
+                        seq_md5(mg.pro_seq),
+                        mg.origin,
+                        mg.pro_ac,
+                        mg.name,
+                        len(mg.pro_seq),
+                        None,
+                    )
+                )
+
+    # write out transcript sequence fasta files.
+    with open(f"{output_dir}/{ncbi_accession}.rna.fna", "w") as o_file:
+        for mg in mito_genes:
+            record = SeqRecord(
+                Seq(mg.tx_seq),
+                id=mg.tx_ac,
+                description=mg.name,
+            )
+            o_file.write(record.format("fasta"))
+
+    # write out protein sequence fasta files.
+    with open(f"{output_dir}/{ncbi_accession}.protein.faa", "w") as o_file:
+        for mg in mito_genes:
+            if mg.pro_ac is not None:
+                record = SeqRecord(
+                    Seq(mg.pro_seq),
+                    id=mg.pro_ac,
+                    description=mg.name,
+                )
+                o_file.write(record.format("fasta"))
+
+    # write transcript information
+    with open(f"{output_dir}/{ncbi_accession}.txinfo", "w") as o_file:
+        tiw = TxInfoWriter(o_file)
+        for mg in mito_genes:
+            tiw.write(
+                TxInfo(
+                    mg.origin,
+                    mg.tx_ac,
+                    mg.gene_id,
+                    mg.gene_symbol,
+                    mg.cds_se_i(),
+                    mg.exons_se_i(),
+                )
+            )
+
+    # write exonset
+    with open(f"{output_dir}/{ncbi_accession}.exonset", "w") as o_file:
+        esw = ExonSetWriter(o_file)
+        for mg in mito_genes:
+            esw.write(
+                ExonSet(
+                    mg.tx_ac,
+                    mg.alt_ac,
+                    mg.alignment_method,
+                    mg.strand,
+                    mg.alt_exons_se_i(),
+                )
+            )
+
+
+if __name__ == "__main__":
+    args = parse_args()
+
+    main(args.accession, args.output_dir)