Merge branch 'main' into TypoMolecConseq

app/__init__.py

@@ -2,9 +2,13 @@
 import flask
 from flask_cors import CORS
 import os
+from .fasta import download_fasta
 
 
 def create_app():
+    # First ensure we have the fasta files locally
+    download_fasta()
+
     # App and API
     options = {
         'swagger_url': '/',

app/common.py

@@ -2,12 +2,12 @@
 from threading import Lock
 from uuid import uuid4
 import pyliftover
-import requests
 from datetime import datetime
 import pymongo
 from flask import abort
 from itertools import groupby
 import re
+from .input_normalization import normalize
 
 # MongoDB Client URIs
 FHIR_genomics_data_client_uri = "mongodb+srv://download:download@cluster0.8ianr.mongodb.net/FHIRGenomicsData"
@@ -116,8 +116,6 @@ def get_liftover(from_db, to_db):
 
 SUPPORTED_GENOMIC_SOURCE_CLASSES = ['germline', 'somatic']
 
-NCBI_VARIATION_SERVICES_BASE_URL = 'https://api.ncbi.nlm.nih.gov/variation/v0/'
-
 CHROMOSOME_CSV_FILE = 'app/_Dict_Chromosome.csv'
 
 # Utility Functions
@@ -163,26 +161,6 @@ def merge_ranges(ranges):
     return merged_ranges
 
 
-def get_hgvs_contextuals_url(hgvs):
-    return f"{NCBI_VARIATION_SERVICES_BASE_URL}hgvs/{hgvs}/contextuals"
-
-
-def get_spdi_all_equivalent_contextual_url(contextual_SPDI):
-    return f'{NCBI_VARIATION_SERVICES_BASE_URL}spdi/{contextual_SPDI}/all_equivalent_contextual'
-
-
-def get_spdi_canonical_representative_url(contextual_SPDI):
-    return f'{NCBI_VARIATION_SERVICES_BASE_URL}spdi/{contextual_SPDI}/canonical_representative'
-
-
-def build_spdi(seq_id, position, deleted_sequence, inserted_sequence):
-    return f"{seq_id}:{position}:{deleted_sequence}:{inserted_sequence}"
-
-
-def get_spdi_elements(response_object):
-    return (response_object['seq_id'], response_object['position'], response_object['deleted_sequence'], response_object['inserted_sequence'])
-
-
 def validate_subject(patient_id):
     if not patients_db.find_one({"patientID": patient_id}):
         abort(400, f"Patient ({patient_id}) not found.")
@@ -196,7 +174,7 @@ def get_variant(variant):
     variant = variant.lstrip()
 
     if variant.count(":") == 1:  # HGVS expression
-        SPDIs = hgvs_2_contextual_SPDIs(variant)
+        SPDIs = normalize(variant)
         if not SPDIs:
             abort(400, f'Cannot normalize variant: {variant}')
         elif not SPDIs["GRCh37"] and not SPDIs["GRCh38"]:
@@ -205,7 +183,7 @@ def get_variant(variant):
             normalized_variant = {"variant": variant, "GRCh37": SPDIs["GRCh37"], "GRCh38": SPDIs["GRCh38"]}
 
     elif variant.count(":") == 3:  # SPDI expression
-        SPDIs = SPDI_2_contextual_SPDIs(variant)
+        SPDIs = normalize(variant)
         if not SPDIs:
             abort(400, f'Cannot normalize variant: {variant}')
         elif not SPDIs["GRCh37"] and not SPDIs["GRCh38"]:
@@ -1001,136 +979,6 @@ def get_intersected_regions(bed_id, build, chrom, start, end, intersected_region
             intersected_regions.append(f'{ref_seq}:{max(start, csePair["Start"])}-{min(end, csePair["End"])}')
 
 
-def hgvs_2_contextual_SPDIs(hgvs):
-
-    # convert hgvs to contextualSPDI
-    url = get_hgvs_contextuals_url(hgvs)
-    headers = {'Accept': 'application/json'}
-
-    r = requests.get(url, headers=headers)
-    if r.status_code != 200:
-        return False
-
-    response = r.json()
-    raw_data = response['data']
-    raw_SPDI = raw_data['spdis'][0]
-
-    seq_id, position, deleted_sequence, inserted_sequence = get_spdi_elements(raw_SPDI)
-
-    contextual_SPDI = build_spdi(seq_id, position, deleted_sequence, inserted_sequence)
-
-    # convert contextualSPDI to build37 and build38 contextual SPDIs
-    url = get_spdi_all_equivalent_contextual_url(contextual_SPDI)
-    headers = {'Accept': 'application/json'}
-
-    r = requests.get(url, headers=headers)
-    if r.status_code != 200:
-        return False
-
-    response = r.json()
-    raw_SPDI_List = response['data']['spdis']
-
-    b37SPDI = None
-    b38SPDI = None
-    for item in raw_SPDI_List:
-        if item['seq_id'].startswith("NC_"):
-            temp = get_build_and_chrom_by_ref_seq(item['seq_id'])
-            if temp:
-                seq_id, position, deleted_sequence, inserted_sequence = get_spdi_elements(item)
-
-                if temp['build'] == 'GRCh37':
-                    b37SPDI = build_spdi(seq_id, position, deleted_sequence, inserted_sequence)
-                elif temp['build'] == 'GRCh38':
-                    b38SPDI = build_spdi(seq_id, position, deleted_sequence, inserted_sequence)
-            else:
-                return False
-
-    return {"GRCh37": b37SPDI, "GRCh38": b38SPDI}
-
-
-def hgvs_2_canonical_SPDI(hgvs):
-
-    # convert hgvs to contextualSPDI
-    url = get_hgvs_contextuals_url(hgvs)
-    headers = {'Accept': 'application/json'}
-
-    r = requests.get(url, headers=headers)
-    if r.status_code != 200:
-        return False
-
-    response = r.json()
-    raw_data = response['data']
-    raw_SPDI = raw_data['spdis'][0]
-
-    seq_id, position, deleted_sequence, inserted_sequence = get_spdi_elements(raw_SPDI)
-
-    contextual_SPDI = build_spdi(seq_id, position, deleted_sequence, inserted_sequence)
-
-    # convert contextualSPDI to canonical SPDI
-    url = get_spdi_canonical_representative_url(contextual_SPDI)
-    headers = {'Accept': 'application/json'}
-
-    r = requests.get(url, headers=headers)
-    if r.status_code != 200:
-        return False
-
-    response = r.json()
-    raw_SPDI = response['data']
-
-    seq_id, position, deleted_sequence, inserted_sequence = get_spdi_elements(raw_SPDI)
-
-    canonical_SPDI = build_spdi(seq_id, position, deleted_sequence, inserted_sequence)
-
-    return {"canonicalSPDI": canonical_SPDI}
-
-
-def SPDI_2_contextual_SPDIs(spdi):
-    url = get_spdi_all_equivalent_contextual_url(spdi)
-    headers = {'Accept': 'application/json'}
-
-    r = requests.get(url, headers=headers)
-    if r.status_code != 200:
-        return False
-
-    response = r.json()
-    raw_SPDI_List = response['data']['spdis']
-
-    b37SPDI = None
-    b38SPDI = None
-    for item in raw_SPDI_List:
-        if item['seq_id'].startswith("NC_"):
-            temp = get_build_and_chrom_by_ref_seq(item['seq_id'])
-            if temp:
-                seq_id, position, deleted_sequence, inserted_sequence = get_spdi_elements(item)
-
-                if temp['build'] == 'GRCh37':
-                    b37SPDI = build_spdi(seq_id, position, deleted_sequence, inserted_sequence)
-                elif temp['build'] == 'GRCh38':
-                    b38SPDI = build_spdi(seq_id, position, deleted_sequence, inserted_sequence)
-            else:
-                return False
-
-    return {"GRCh37": b37SPDI, "GRCh38": b38SPDI}
-
-
-def SPDI_2_canonical_SPDI(spdi):
-    url = get_spdi_canonical_representative_url(spdi)
-    headers = {'Accept': 'application/json'}
-
-    r = requests.get(url, headers=headers)
-    if r.status_code != 200:
-        return False
-
-    response = r.json()
-    raw_SPDI = response['data']
-
-    seq_id, position, deleted_sequence, inserted_sequence = get_spdi_elements(raw_SPDI)
-
-    canonical_SPDI = build_spdi(seq_id, position, deleted_sequence, inserted_sequence)
-
-    return {"canonicalSPDI": canonical_SPDI}
-
-
 def query_clinvar_by_variants(normalized_variant_list, code_list, query, population=False):
     variant_list = []
     for item in normalized_variant_list:

app/endpoints.py

@@ -179,7 +179,11 @@ def find_subject_specific_variants(
     subject = subject.strip()
     common.validate_subject(subject)
 
-    variants = list(map(common.get_variant, variants))
+    try:
+        variants = list(map(common.get_variant, variants))
+    except Exception as err:
+        print(f"Unexpected {err=}, {type(err)=}")
+        abort(422, 'Failed LiftOver')
 
     # Query
     query = {}
@@ -833,13 +837,22 @@ def find_subject_tx_implications(
     if ranges:
         ranges = list(map(common.get_range, ranges))
         common.get_lift_over_range(ranges)
-        variants = common.get_variants(ranges, query)
+        try:
+            variants = common.get_variants(ranges, query)
+        except Exception as err:
+            print(f"Unexpected {err=}, {type(err)=}")
+            abort(422, 'Failed LiftOver')
+
         if not variants:
             return jsonify({"resourceType": "Parameters"})
         normalized_variants = [{variant["BUILD"]: variant["SPDI"]} for variant in variants]
 
     if variants and not ranges:
-        normalized_variants = list(map(common.get_variant, variants))
+        try:
+            normalized_variants = list(map(common.get_variant, variants))
+        except Exception as err:
+            print(f"Unexpected {err=}, {type(err)=}")
+            abort(422, 'Failed LiftOver')
 
     # Result Object
     result = OrderedDict()
@@ -1105,13 +1118,22 @@ def find_subject_dx_implications(
     if ranges:
         ranges = list(map(common.get_range, ranges))
         common.get_lift_over_range(ranges)
-        variants = common.get_variants(ranges, query)
+        try:
+            variants = common.get_variants(ranges, query)
+        except Exception as err:
+            print(f"Unexpected {err=}, {type(err)=}")
+            abort(422, 'Failed LiftOver')
+
         if not variants:
             return jsonify({"resourceType": "Parameters"})
         normalized_variants = [{variant["BUILD"]: variant["SPDI"]} for variant in variants]
 
     if variants and not ranges:
-        normalized_variants = list(map(common.get_variant, variants))
+        try:
+            normalized_variants = list(map(common.get_variant, variants))
+        except Exception as err:
+            print(f"Unexpected {err=}, {type(err)=}")
+            abort(422, 'Failed LiftOver')
 
     # Result Object
     result = OrderedDict()
@@ -1373,7 +1395,11 @@ def find_population_specific_variants(
     # Parameters
     variants = list(map(lambda x: x.strip().split(","), variants))
     for i in range(len(variants)):
-        variants[i] = list(map(common.get_variant, variants[i]))
+        try:
+            variants[i] = list(map(common.get_variant, variants[i]))
+        except Exception as err:
+            print(f"Unexpected {err=}, {type(err)=}")
+            abort(422, 'Failed LiftOver')
 
     # Query
     query = {}
@@ -1884,7 +1910,11 @@ def find_population_tx_implications(
         return jsonify({"resourceType": "Parameters"})
 
     if variants:
-        variants = list(map(common.get_variant, variants))
+        try:
+            variants = list(map(common.get_variant, variants))
+        except Exception as err:
+            print(f"Unexpected {err=}, {type(err)=}")
+            abort(422, 'Failed LiftOver')
 
     condition_code_list = []
     if conditions:
@@ -2090,7 +2120,11 @@ def find_population_dx_implications(
         return jsonify({"resourceType": "Parameters"})
 
     if variants:
-        variants = list(map(common.get_variant, variants))
+        try:
+            variants = list(map(common.get_variant, variants))
+        except Exception as err:
+            print(f"Unexpected {err=}, {type(err)=}")
+            abort(422, 'Failed LiftOver')
 
     condition_code_list = []
     if conditions:

app/fasta.py

@@ -0,0 +1,23 @@
+from pathlib import Path
+from pyfastx import Fasta
+from urllib.request import urlretrieve
+
+
+def download_fasta():
+    try:
+        # Make sure the parent folder exists
+        Path('FASTA').mkdir(exist_ok=True)
+
+        for build in ['GRCh37', 'GRCh38']:
+            filename = build + '_latest_genomic.fna.gz'
+            filepath = 'FASTA/' + filename
+
+            # Download files
+            if not Path(filepath).is_file():
+                urlretrieve('https://ftp.ncbi.nlm.nih.gov/refseq/H_sapiens/annotation/' + build + '_latest/refseq_identifiers/' + filename, filepath)
+
+            # Build indexes
+            if not Path(filepath + '.fxi').is_file():
+                Fasta(filepath)
+    except Exception as error:
+        print(error)