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1 | 1 | """Define route(s) for the variant-level matching (VLM) protocol""" |
2 | 2 |
|
| 3 | +import gzip |
| 4 | +import logging |
| 5 | +import tempfile |
| 6 | +import uuid |
3 | 7 | from pathlib import Path |
4 | | -from typing import Annotated |
| 8 | +from typing import Annotated, BinaryIO, Literal |
5 | 9 |
|
6 | | -from fastapi import Query, Request |
| 10 | +from anyvar.utils.liftover_utils import ReferenceAssembly |
| 11 | +from fastapi import HTTPException, Query, Request, UploadFile |
7 | 12 | from ga4gh.va_spec.base.core import CohortAlleleFrequencyStudyResult |
| 13 | +from pydantic import BaseModel |
8 | 14 |
|
9 | 15 | from anyvlm.anyvar.base_client import BaseAnyVarClient |
10 | 16 | from anyvlm.functions.build_vlm_response import build_vlm_response_from_caf_data |
11 | 17 | from anyvlm.functions.get_caf import get_caf |
| 18 | +from anyvlm.functions.ingest_vcf import VcfAfColumnsError |
| 19 | +from anyvlm.functions.ingest_vcf import ingest_vcf as ingest_vcf_function |
12 | 20 | from anyvlm.main import app |
13 | | -from anyvlm.schemas.vlm import ( |
14 | | - VlmResponse, |
15 | | -) |
| 21 | +from anyvlm.schemas.vlm import VlmResponse |
16 | 22 | from anyvlm.utils.types import ( |
17 | 23 | ChromosomeName, |
18 | 24 | EndpointTag, |
|
21 | 27 | UcscAssemblyBuild, |
22 | 28 | ) |
23 | 29 |
|
| 30 | +# Create alias for easier mocking in tests |
| 31 | +ingest_vcf = ingest_vcf_function |
| 32 | + |
| 33 | +_logger = logging.getLogger(__name__) |
| 34 | + |
| 35 | +# Constants |
| 36 | +MAX_FILE_SIZE = 5 * 1024 * 1024 * 1024 # 5GB |
| 37 | +UPLOAD_CHUNK_SIZE = 1024 * 1024 # 1MB |
| 38 | +REQUIRED_INFO_FIELDS = {"AC", "AN", "AC_Het", "AC_Hom", "AC_Hemi"} |
| 39 | + |
| 40 | + |
| 41 | +# ==================== |
| 42 | +# Response Models |
| 43 | +# ==================== |
| 44 | + |
| 45 | + |
| 46 | +class VcfIngestionResponse(BaseModel): |
| 47 | + """Response model for VCF ingestion endpoint.""" |
| 48 | + |
| 49 | + status: Literal["success", "error"] |
| 50 | + message: str |
| 51 | + details: str | None = None |
| 52 | + |
| 53 | + |
| 54 | +# ==================== |
| 55 | +# Validation Helpers |
| 56 | +# ==================== |
| 57 | + |
| 58 | + |
| 59 | +def validate_filename_extension(filename: str) -> None: |
| 60 | + """Validate that filename has .vcf.gz extension. |
| 61 | +
|
| 62 | + :param filename: name of uploaded file |
| 63 | + :raise ValueError: if extension is not .vcf.gz |
| 64 | + """ |
| 65 | + if not filename.endswith(".vcf.gz"): |
| 66 | + raise ValueError("Only .vcf.gz files are accepted") |
| 67 | + |
| 68 | + |
| 69 | +def validate_gzip_magic_bytes(file_obj: BinaryIO) -> None: |
| 70 | + """Validate that file has gzip magic bytes. |
| 71 | +
|
| 72 | + :param file_obj: file-like object to validate |
| 73 | + :raise ValueError: if file is not gzipped |
| 74 | + """ |
| 75 | + header = file_obj.read(2) |
| 76 | + file_obj.seek(0) # Reset file pointer |
| 77 | + |
| 78 | + if header != b"\x1f\x8b": |
| 79 | + raise ValueError("File is not a valid gzip file") |
| 80 | + |
| 81 | + |
| 82 | +def validate_file_size(size: int) -> None: |
| 83 | + """Validate that file size is within limits. |
| 84 | +
|
| 85 | + :param size: file size in bytes |
| 86 | + :raise ValueError: if file exceeds maximum size |
| 87 | + """ |
| 88 | + if size > MAX_FILE_SIZE: |
| 89 | + max_gb = MAX_FILE_SIZE / (1024**3) |
| 90 | + raise ValueError(f"File too large. Maximum size: {max_gb:.1f}GB") |
| 91 | + |
| 92 | + |
| 93 | +def validate_vcf_header(file_path: Path) -> None: |
| 94 | + """Validate VCF file format and required INFO fields. |
| 95 | +
|
| 96 | + :param file_path: path to VCF file |
| 97 | + :raise ValueError: if VCF is malformed or missing required fields |
| 98 | + """ |
| 99 | + with gzip.open(file_path, "rt") as f: |
| 100 | + # Check first line is VCF format declaration |
| 101 | + first_line = f.readline().strip() |
| 102 | + if not first_line.startswith("##fileformat=VCF"): |
| 103 | + raise ValueError("Not a valid VCF file (missing format declaration)") |
| 104 | + |
| 105 | + # Scan headers for required INFO fields |
| 106 | + found_fields = set() |
24 | 107 |
|
25 | | -def ingest_vcf(vcf_path: Path) -> None: |
26 | | - """Ingest variants and cohort allele frequency data from an input VCF |
| 108 | + for line in f: |
| 109 | + if line.startswith("##INFO=<ID="): |
| 110 | + # Extract field ID |
| 111 | + field_id = line.split("ID=")[1].split(",")[0] |
| 112 | + found_fields.add(field_id) |
| 113 | + elif line.startswith("#CHROM"): |
| 114 | + # End of headers |
| 115 | + break |
27 | 116 |
|
28 | | - :param vcf_path: VCF file location |
| 117 | + missing = REQUIRED_INFO_FIELDS - found_fields |
| 118 | + if missing: |
| 119 | + raise ValueError( |
| 120 | + f"VCF missing required INFO fields: {', '.join(sorted(missing))}" |
| 121 | + ) |
| 122 | + |
| 123 | + |
| 124 | +# ==================== |
| 125 | +# File Handling |
| 126 | +# ==================== |
| 127 | + |
| 128 | + |
| 129 | +async def save_upload_file_temp(upload_file: UploadFile) -> Path: |
| 130 | + """Save uploaded file to temporary location using streaming. |
| 131 | +
|
| 132 | + :param upload_file: FastAPI UploadFile object |
| 133 | + :return: path to saved temporary file |
| 134 | + :raise: Any exceptions during file operations (caller should handle cleanup) |
| 135 | + """ |
| 136 | + temp_dir = Path(tempfile.gettempdir()) |
| 137 | + temp_path = temp_dir / f"anyvlm_{uuid.uuid4()}.vcf.gz" |
| 138 | + |
| 139 | + try: |
| 140 | + # Stream upload to disk (memory efficient) |
| 141 | + with open(temp_path, "wb") as f: |
| 142 | + while chunk := await upload_file.read(UPLOAD_CHUNK_SIZE): |
| 143 | + f.write(chunk) |
| 144 | + return temp_path |
| 145 | + except Exception: |
| 146 | + # Cleanup on error |
| 147 | + if temp_path.exists(): |
| 148 | + temp_path.unlink() |
| 149 | + raise |
| 150 | + |
| 151 | + |
| 152 | +# ==================== |
| 153 | +# Endpoints |
| 154 | +# ==================== |
| 155 | + |
| 156 | + |
| 157 | +@app.post( |
| 158 | + "/ingest_vcf", |
| 159 | + summary="Upload and ingest VCF file", |
| 160 | + description="Upload a compressed VCF file (.vcf.gz) to register variants and store allele frequency data", |
| 161 | + tags=[EndpointTag.SEARCH], |
| 162 | + response_model=VcfIngestionResponse, |
| 163 | +) |
| 164 | +async def ingest_vcf_endpoint( |
| 165 | + request: Request, |
| 166 | + file: UploadFile, |
| 167 | + assembly: Annotated[ |
| 168 | + ReferenceAssembly, |
| 169 | + Query(..., description="Reference genome assembly (GRCh37 or GRCh38)"), |
| 170 | + ], |
| 171 | +) -> VcfIngestionResponse: |
| 172 | + """Upload and ingest a VCF file with allele frequency data. |
| 173 | +
|
| 174 | + :param request: FastAPI request object |
| 175 | + :param file: uploaded VCF file (must be .vcf.gz) |
| 176 | + :param assembly: reference assembly used in VCF |
| 177 | + :return: ingestion status response |
29 | 178 | """ |
30 | | - raise NotImplementedError |
| 179 | + temp_path: Path | None = None |
| 180 | + |
| 181 | + try: |
| 182 | + # Validate filename extension |
| 183 | + if not file.filename: |
| 184 | + raise HTTPException(400, "Filename is required") |
| 185 | + |
| 186 | + try: |
| 187 | + validate_filename_extension(file.filename) |
| 188 | + except ValueError as e: |
| 189 | + raise HTTPException(400, str(e)) from e |
| 190 | + |
| 191 | + # Validate content type (if provided) |
| 192 | + if file.content_type and file.content_type not in { |
| 193 | + "application/gzip", |
| 194 | + "application/x-gzip", |
| 195 | + "application/octet-stream", |
| 196 | + }: |
| 197 | + raise HTTPException( |
| 198 | + 400, |
| 199 | + f"Invalid content type: {file.content_type}", |
| 200 | + ) |
| 201 | + |
| 202 | + # Validate gzip magic bytes |
| 203 | + try: |
| 204 | + validate_gzip_magic_bytes(file.file) |
| 205 | + except ValueError as e: |
| 206 | + raise HTTPException(400, str(e)) from e |
| 207 | + |
| 208 | + # Check file size |
| 209 | + file.file.seek(0, 2) # Seek to end |
| 210 | + file_size = file.file.tell() |
| 211 | + file.file.seek(0) # Reset |
| 212 | + |
| 213 | + try: |
| 214 | + validate_file_size(file_size) |
| 215 | + except ValueError as e: |
| 216 | + raise HTTPException(400, str(e)) from e |
| 217 | + |
| 218 | + # Save to temporary file |
| 219 | + _logger.info("Saving uploaded file %s (%d bytes)", file.filename, file_size) |
| 220 | + temp_path = await save_upload_file_temp(file) |
| 221 | + |
| 222 | + # Validate VCF format and required fields |
| 223 | + try: |
| 224 | + validate_vcf_header(temp_path) |
| 225 | + except ValueError as e: |
| 226 | + raise HTTPException( |
| 227 | + 422, |
| 228 | + f"VCF validation failed: {str(e)}", |
| 229 | + ) from e |
| 230 | + |
| 231 | + # Process VCF |
| 232 | + anyvar_client = request.app.state.anyvar_client |
| 233 | + _logger.info("Starting VCF ingestion for %s", file.filename) |
| 234 | + |
| 235 | + try: |
| 236 | + ingest_vcf_function(temp_path, anyvar_client, assembly) |
| 237 | + except VcfAfColumnsError as e: |
| 238 | + _logger.exception("VCF missing required INFO columns") |
| 239 | + raise HTTPException( |
| 240 | + 422, f"VCF validation failed: {e}" |
| 241 | + ) from e |
| 242 | + except Exception as e: |
| 243 | + _logger.exception("VCF ingestion failed") |
| 244 | + raise HTTPException( |
| 245 | + 500, f"Ingestion failed: {e}" |
| 246 | + ) from e |
| 247 | + |
| 248 | + _logger.info("Successfully ingested VCF: %s", file.filename) |
| 249 | + return VcfIngestionResponse( |
| 250 | + status="success", |
| 251 | + message=f"Successfully ingested {file.filename}", |
| 252 | + ) |
| 253 | + |
| 254 | + except HTTPException: |
| 255 | + # Re-raise HTTP exceptions |
| 256 | + raise |
| 257 | + except Exception as e: |
| 258 | + _logger.exception("Unexpected error during VCF upload") |
| 259 | + raise HTTPException(500, f"Upload failed: {e}") from e |
| 260 | + finally: |
| 261 | + # Always cleanup temporary file |
| 262 | + if temp_path and temp_path.exists(): |
| 263 | + _logger.debug("Cleaning up temporary file: %s", temp_path) |
| 264 | + temp_path.unlink() |
31 | 265 |
|
32 | 266 |
|
33 | 267 | @app.get( |
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