@hongmaple0820/med-scale-research-os 0.43.0

package/target-research-platform/bridge_runner.py

@@ -0,0 +1,310 @@
+#!/usr/bin/env python3
+"""
+SCALE Bridge Runner — Python 端桥接入点
+
+接收 TS 端通过 stdin 传入的 BridgeRequest JSON，
+调度 target-research-platform 的 Stage Pipeline，
+输出符合 BridgeResponse 协议的 JSON 到 stdout。
+
+用法:
+  # 被 TS 端自动调用，也可手动测试:
+  echo '{"protocol":"scale-analysis-v1","stage":"expression","input":{"gene_symbol":"CDK4","cancer_types":["BRCA"]},"timeout_ms":300000,"output_schema":"expression_result_v1","request_id":"test-001"}' | python bridge_runner.py
+
+  # 独立运行（等同 main.py --json）:
+  python bridge_runner.py stage1 --gene CDK4 --cancers BRCA
+"""
+import argparse
+import json
+import sys
+import time
+import traceback
+from pathlib import Path
+
+# 添加 target-research-platform/src 到路径
+PLATFORM_DIR = Path(__file__).parent
+sys.path.insert(0, str(PLATFORM_DIR))
+
+from src.analysis.stage1_expression import Stage1Pipeline
+from src.analysis.stage2_screening import Stage2Pipeline
+from src.analysis.stage3_deep_research import Stage3Pipeline
+from src.analysis.stage4_business import Stage4Pipeline
+
+
+PROTOCOL_VERSION = "scale-analysis-v1"
+
+# Stage → Pipeline class 映射
+STAGE_PIPELINE_MAP = {
+    "expression": ("stage1", Stage1Pipeline),
+    "screening": ("stage2", Stage2Pipeline),
+    "deep_research": ("stage3", Stage3Pipeline),
+    "business": ("stage4", Stage4Pipeline),
+}
+
+
+def _make_response(
+    request_id: str,
+    stage: str,
+    success: bool,
+    data=None,
+    error: str = None,
+    duration_ms: int = 0,
+    provenance: list = None,
+) -> dict:
+    """构建标准 BridgeResponse"""
+    resp = {
+        "protocol": PROTOCOL_VERSION,
+        "request_id": request_id,
+        "success": success,
+        "stage": stage,
+        "duration_ms": duration_ms,
+    }
+    if data is not None:
+        resp["data"] = data
+    if error is not None:
+        resp["error"] = error
+    if provenance is not None:
+        resp["provenance"] = provenance
+    return resp
+
+
+def _sanitize_for_json(obj):
+    """递归转换 numpy 类型为 Python 原生类型"""
+    import numpy as np
+    if isinstance(obj, dict):
+        return {k: _sanitize_for_json(v) for k, v in obj.items()}
+    elif isinstance(obj, list):
+        return [_sanitize_for_json(v) for v in obj]
+    elif isinstance(obj, np.bool_):
+        return bool(obj)
+    elif isinstance(obj, np.integer):
+        return int(obj)
+    elif isinstance(obj, np.floating):
+        return float(obj)
+    elif isinstance(obj, np.ndarray):
+        return obj.tolist()
+    return obj
+
+
+def execute_bridge_request(request: dict) -> dict:
+    """
+    执行桥接请求
+
+    Args:
+        request: BridgeRequest dict
+
+    Returns:
+        BridgeResponse dict
+    """
+    request_id = request.get("request_id", "unknown")
+    stage = request.get("stage", "")
+    input_data = request.get("input", {})
+
+    # 验证协议版本
+    if request.get("protocol") != PROTOCOL_VERSION:
+        return _make_response(
+            request_id, stage, False,
+            error=f"Unsupported protocol: {request.get('protocol')}"
+        )
+
+    # 验证阶段
+    if stage not in STAGE_PIPELINE_MAP:
+        return _make_response(
+            request_id, stage, False,
+            error=f"Unknown stage: {stage}. Supported: {list(STAGE_PIPELINE_MAP.keys())}"
+        )
+
+    cli_stage, pipeline_cls = STAGE_PIPELINE_MAP[stage]
+
+    # 执行
+    start_time = time.time()
+    try:
+        output_dir = input_data.pop("output_dir", f"./output/{cli_stage}")
+        cache_dir = input_data.pop("cache_dir", "./cache")
+
+        pipeline = pipeline_cls(output_dir=output_dir, cache_dir=cache_dir)
+
+        # 根据阶段调用对应参数
+        if stage == "expression":
+            result = pipeline.run(
+                gene_symbol=input_data["gene_symbol"],
+                cancer_types=input_data["cancer_types"],
+                ensg_id=input_data.get("ensg_id"),
+            )
+        elif stage == "screening":
+            result = pipeline.run(
+                disease=input_data["disease"],
+                known_targets=input_data.get("exclude_targets"),
+                top_n=input_data.get("top_n", 20),
+                normal_tissue_expression=input_data.get("normal_tissue_expression"),
+            )
+        elif stage == "deep_research":
+            result = pipeline.run(
+                target_name=input_data["target_name"],
+                ensg_id=input_data.get("ensg_id"),
+                disease=input_data.get("disease"),
+            )
+        elif stage == "business":
+            result = pipeline.run(
+                target_name=input_data["target_name"],
+                disease=input_data.get("disease"),
+                stage1_data=input_data.get("stage1_data"),
+                stage2_data=input_data.get("stage2_data"),
+                stage3_data=input_data.get("stage3_data"),
+                modality=input_data.get("modality", "small_molecule"),
+                risk_level=input_data.get("risk_level", "medium"),
+            )
+        else:
+            return _make_response(request_id, stage, False, error=f"Unhandled stage: {stage}")
+
+        duration_ms = int((time.time() - start_time) * 1000)
+
+        # 清洗 numpy 类型
+        result = _sanitize_for_json(result)
+
+        # 提取溯源信息（如果有）
+        provenance = None
+        if hasattr(pipeline, 'provenance_tracker') and pipeline.provenance_tracker:
+            provenance = pipeline.provenance_tracker.get_all_provenance()
+
+        return _make_response(
+            request_id, stage, result.get("success", True),
+            data=result,
+            duration_ms=duration_ms,
+            provenance=provenance,
+        )
+
+    except Exception as e:
+        duration_ms = int((time.time() - start_time) * 1000)
+        return _make_response(
+            request_id, stage, False,
+            error=str(e),
+            duration_ms=duration_ms,
+        )
+
+
+def run_from_stdin():
+    """从 stdin 读取 BridgeRequest JSON 并执行"""
+    try:
+        raw_input = sys.stdin.read().strip()
+        if not raw_input:
+            print(json.dumps({
+                "protocol": PROTOCOL_VERSION,
+                "request_id": "stdin",
+                "success": False,
+                "error": "No input received on stdin",
+                "stage": "",
+                "duration_ms": 0,
+            }), flush=True)
+            return
+
+        request = json.loads(raw_input)
+        response = execute_bridge_request(request)
+
+        # 输出到 stdout（TS 端从 stdout 读取）
+        print(json.dumps(response, ensure_ascii=False, default=str), flush=True)
+
+    except json.JSONDecodeError as e:
+        print(json.dumps({
+            "protocol": PROTOCOL_VERSION,
+            "request_id": "stdin",
+            "success": False,
+            "error": f"Invalid JSON input: {e}",
+            "stage": "",
+            "duration_ms": 0,
+        }), flush=True)
+    except Exception as e:
+        print(json.dumps({
+            "protocol": PROTOCOL_VERSION,
+            "request_id": "stdin",
+            "success": False,
+            "error": f"Unexpected error: {e}",
+            "error_details": {
+                "type": type(e).__name__,
+                "message": str(e),
+                "traceback": traceback.format_exc(),
+            },
+            "stage": "",
+            "duration_ms": 0,
+        }), flush=True)
+
+
+def run_from_cli():
+    """通过命令行参数运行（兼容 main.py 接口）"""
+    parser = argparse.ArgumentParser(description="SCALE Bridge Runner")
+    parser.add_argument("stage", choices=["stage1", "stage2", "stage3", "stage4", "stdin"],
+                       help="分析阶段或 'stdin' 模式")
+    parser.add_argument("--gene", help="基因符号 (stage1)")
+    parser.add_argument("--cancers", nargs="+", help="癌种列表 (stage1)")
+    parser.add_argument("--disease", help="疾病名称 (stage2/3/4)")
+    parser.add_argument("--target", help="靶点名称 (stage3/4)")
+    parser.add_argument("--ensg", help="Ensembl基因ID")
+    parser.add_argument("--output", default="./output", help="输出目录")
+    parser.add_argument("--cache", default="./cache", help="缓存目录")
+    parser.add_argument("--json", action="store_true", help="JSON格式输出")
+
+    args = parser.parse_args()
+
+    if args.stage == "stdin":
+        run_from_stdin()
+        return
+
+    # 构建桥接请求
+    stage_map = {
+        "stage1": "expression",
+        "stage2": "screening",
+        "stage3": "deep_research",
+        "stage4": "business",
+    }
+    stage = stage_map[args.stage]
+
+    input_data = {"output_dir": args.output, "cache_dir": args.cache}
+    if stage == "expression":
+        input_data["gene_symbol"] = args.gene
+        input_data["cancer_types"] = args.cancers or []
+        if args.ensg:
+            input_data["ensg_id"] = args.ensg
+    elif stage == "screening":
+        input_data["disease"] = args.disease
+    elif stage == "deep_research":
+        input_data["target_name"] = args.target
+        if args.ensg:
+            input_data["ensg_id"] = args.ensg
+        if args.disease:
+            input_data["disease"] = args.disease
+    elif stage == "business":
+        input_data["target_name"] = args.target
+        if args.disease:
+            input_data["disease"] = args.disease
+
+    request = {
+        "protocol": PROTOCOL_VERSION,
+        "stage": stage,
+        "input": input_data,
+        "timeout_ms": 300000,
+        "output_schema": f"{stage}_result_v1",
+        "request_id": f"cli-{int(time.time())}",
+    }
+
+    response = execute_bridge_request(request)
+
+    if args.json:
+        print(json.dumps(response, ensure_ascii=False, default=str, indent=2))
+    else:
+        if response["success"]:
+            print(f"✓ Stage {stage} completed in {response['duration_ms']}ms")
+            if response.get("data"):
+                data = response["data"]
+                summary = data.get("summary", {})
+                print(f"  Gene: {summary.get('gene', 'N/A')}")
+                print(f"  Findings: {len(summary.get('key_findings', []))}")
+        else:
+            print(f"✗ Stage {stage} failed: {response.get('error', 'Unknown error')}")
+            sys.exit(1)
+
+
+if __name__ == "__main__":
+    # 如果有 stdin 数据且无命令行参数，使用 stdin 模式
+    if not sys.stdin.isatty() and len(sys.argv) == 1:
+        run_from_stdin()
+    else:
+        run_from_cli()

package/target-research-platform/config.yaml

@@ -0,0 +1,148 @@
+# 靶点研究平台配置文件
+# 所有可配置参数集中管理，便于环境切换和调优
+
+# === 通用设置 ===
+app:
+  name: "靶点研究平台"
+  version: "0.5.0"
+  debug: false
+  log_level: "INFO"           # DEBUG / INFO / WARNING / ERROR
+  log_file: null              # 日志文件路径，null 表示仅控制台输出
+
+# === API 客户端 ===
+api:
+  # 请求超时（秒）
+  timeout: 30
+  # 缓存目录
+  cache_dir: "./cache"
+  # 缓存有效期（秒），0 表示永不过期
+  cache_ttl: 86400
+  # 请求限流间隔（秒）
+  rate_limit_interval: 0.34
+
+  # NCBI E-utilities
+  ncbi:
+    base_url: "https://eutils.ncbi.nlm.nih.gov/entrez/eutils"
+    api_key: ""               # 从 .env 文件读取，或直接填入
+
+  # OpenTargets
+  opentargets:
+    graphql_url: "https://api.platform.opentargets.org/api/v4/graphql"
+    rest_url: "https://api.opentargets.org/api/v4"
+
+  # ClinicalTrials.gov
+  clinicaltrials:
+    base_url: "https://clinicaltrials.gov/api/v2/studies"
+
+  # GTEx
+  gtex:
+    base_url: "https://gtexportal.org/rest/v1"
+
+  # TCGA
+  tcga:
+    base_url: "https://api.gdc.cancer.gov"
+
+# === Stage 1: 表达分析 ===
+stage1:
+  output_dir: "./output/stage1"
+  # 正常组织 TPM 阈值（低于此值才算肿瘤特异性）
+  normal_tissue_tpm_threshold: 10.0
+  # 生存分析 p 值阈值
+  survival_p_threshold: 0.05
+  # 免疫相关性分析最小样本数
+  immune_min_samples: 30
+
+# === Stage 2: 靶点筛选 ===
+stage2:
+  output_dir: "./output/stage2"
+  # GEO 数据集搜索
+  geo:
+    max_datasets_to_try: 5          # 最多尝试多少个数据集
+    min_samples_per_group: 3        # 每组最少样本数
+    prefer_rnaseq: true             # 优先 RNA-seq 数据集
+  # 差异表达阈值
+  de:
+    # Level 1: 严格标准
+    strict_adj_p: 0.05
+    strict_log2fc: 1.0
+    # Level 2: 宽松标准
+    relaxed_adj_p: 0.2
+    relaxed_log2fc: 0.5
+    # Level 3: 名义标准
+    nominal_p: 0.05
+    nominal_log2fc: 0.3
+  # 正常组织过滤
+  normal_filter:
+    tpm_threshold: 50              # 正常组织 TPM > 此值的基因被过滤
+  # 自适应权重
+  adaptive_weights:
+    de_weight_min: 0.2
+    de_weight_max: 0.6
+    sigmoid_midpoint: 0.3
+    sigmoid_steepness: 10.0
+  # 成药性评估
+  druggability:
+    fallback_genes: ["CDK4", "CDK6", "EGFR", "BRAF", "KRAS"]
+    top_n: 20
+
+# === Stage 3: 深度研究 ===
+stage3:
+  output_dir: "./output/stage3"
+  # 竞争格局
+  competitive:
+    max_trials: 100
+    # 临床阶段映射
+    phase_mapping:
+      "APPROVAL": 4
+      "PHASE_3": 3
+      "PHASE_2": 2
+      "PHASE_1": 1
+      "PHASE_0": 0
+
+# === Stage 4: 商业规划 ===
+stage4:
+  output_dir: "./output/stage4"
+  # 药物开发阶段标准时间（月）
+  phase_durations:
+    target_validation: 12
+    hit_to_lead: 12
+    lead_optimization: 18
+    pcc_nomination: 6
+    ind_enabling: 18
+    phase1: 18
+    phase2: 24
+    phase3: 36
+    nda_submission: 12
+    approval: 12
+  # 成本差异化
+  cost_differentiation:
+    # 成药性影响早期阶段
+    low_druggability_multiplier: 1.3
+    high_druggability_multiplier: 0.85
+    # 竞争格局影响临床阶段
+    approved_drugs_multiplier: 0.9
+    high_competition_multiplier: 1.15
+    # 药物形式成本
+    modality_cost:
+      small_molecule: 1.0
+      antibody: 1.3
+      cell_therapy: 2.0
+      gene_therapy: 2.5
+
+# === 期刊论文 / 医学 Skills 富化 ===
+manuscript:
+  # LLM 深度文献评述（OpenAI 兼容 API）
+  llm_api_key: ""              # OPENAI_API_KEY 或 MANUSCRIPT_LLM_API_KEY
+  llm_base_url: ""             # OPENAI_BASE_URL，默认 https://api.openai.com/v1
+  llm_model: "gpt-4o-mini"     # MANUSCRIPT_LLM_MODEL
+  # AMiner 学术补充（引用链/期刊信号）https://open.aminer.cn/open/board
+  aminer_token: ""             # AMINER_TOKEN
+  enrich_pubmed: true          # PubMed efetch：摘要 + MeSH + 发表类型
+  enrich_aminer: true          # AMiner 引用链（需 token）
+  max_literature_papers: 12
+
+# === Dashboard ===
+dashboard:
+  host: "127.0.0.1"
+  port: 3012
+  output_dir: "./output"

package/target-research-platform/data/immune_infiltration/ACC.csv

@@ -0,0 +1,201 @@
+sample_id,B_cell,CD4_T_cell,CD8_T_cell,Neutrophil,Macrophage,Dendritic_cell,NK_cell,Monocyte,Mast_cell,Eosinophil
+TCGA-AC-0001-01A,0.0864,0.1897,0.0902,0.0782,0.1261,0.0751,0.0647,0.0581,0.015,0.0175
+TCGA-AC-0002-01A,0.0404,0.0796,0.0875,0.0737,0.2606,0.0484,0.0167,0.1032,0.0206,0.015
+TCGA-AC-0003-01A,0.0615,0.0393,0.0941,0.0741,0.2793,0.0395,0.0302,0.0673,0.0221,0.0048
+TCGA-AC-0004-01A,0.024,0.0512,0.0414,0.1056,0.1257,0.1017,0.0383,0.0554,0.0189,0.009
+TCGA-AC-0005-01A,0.0385,0.1363,0.0546,0.024,0.1009,0.025,0.0371,0.0599,0.0193,0.0069
+TCGA-AC-0006-01A,0.0394,0.0844,0.0508,0.0499,0.2936,0.0469,0.0377,0.0197,0.0271,0.0145
+TCGA-AC-0007-01A,0.0208,0.1179,0.0576,0.0534,0.123,0.0468,0.034,0.0708,0.0207,0.0113
+TCGA-AC-0008-01A,0.0429,0.2088,0.1209,0.0227,0.0729,0.0457,0.0488,0.016,0.0545,0.0072
+TCGA-AC-0009-01A,0.0354,0.1553,0.1178,0.023,0.1008,0.0184,0.0271,0.0644,0.0224,0.0132
+TCGA-AC-0010-01A,0.0456,0.1265,0.1482,0.0854,0.1018,0.033,0.0477,0.0917,0.0257,0.0178
+TCGA-AC-0011-01A,0.0934,0.0494,0.0714,0.0253,0.2283,0.0227,0.0265,0.0425,0.0111,0.0044
+TCGA-AC-0012-01A,0.031,0.085,0.0584,0.0725,0.0717,0.0511,0.0277,0.0537,0.0122,0.0099
+TCGA-AC-0013-01A,0.0315,0.1005,0.0655,0.0317,0.2388,0.0237,0.0298,0.0836,0.0176,0.0186
+TCGA-AC-0014-01A,0.0389,0.0611,0.0242,0.0367,0.1153,0.0227,0.0518,0.0945,0.0124,0.0085
+TCGA-AC-0015-01A,0.0559,0.0877,0.1776,0.0327,0.0762,0.0849,0.0394,0.0672,0.0201,0.0089
+TCGA-AC-0016-01A,0.0671,0.1477,0.104,0.0757,0.1151,0.1001,0.025,0.0606,0.0316,0.0098
+TCGA-AC-0017-01A,0.1113,0.0364,0.0913,0.0419,0.1044,0.0618,0.0425,0.07,0.0262,0.0074
+TCGA-AC-0018-01A,0.0924,0.1179,0.1041,0.0654,0.1299,0.0243,0.0546,0.1144,0.0086,0.0161
+TCGA-AC-0019-01A,0.0241,0.1868,0.0777,0.044,0.0883,0.055,0.0511,0.0349,0.0192,0.0083
+TCGA-AC-0020-01A,0.0901,0.3707,0.0841,0.0308,0.2833,0.0336,0.0618,0.0566,0.0388,0.0142
+TCGA-AC-0021-01A,0.0679,0.1324,0.1948,0.0343,0.1063,0.0119,0.0362,0.0537,0.0128,0.016
+TCGA-AC-0022-01A,0.032,0.1339,0.0544,0.0365,0.1435,0.0394,0.0982,0.0359,0.0254,0.0107
+TCGA-AC-0023-01A,0.0382,0.1522,0.0872,0.015,0.055,0.0176,0.0512,0.0574,0.0248,0.0102
+TCGA-AC-0024-01A,0.0562,0.0455,0.074,0.0367,0.0771,0.0426,0.073,0.0635,0.0315,0.009
+TCGA-AC-0025-01A,0.0499,0.0742,0.0934,0.0363,0.206,0.057,0.0951,0.0396,0.0081,0.0123
+TCGA-AC-0026-01A,0.0266,0.0471,0.129,0.0854,0.184,0.041,0.0672,0.1048,0.0205,0.0074
+TCGA-AC-0027-01A,0.0613,0.0193,0.0523,0.0324,0.1047,0.041,0.0327,0.1191,0.026,0.008
+TCGA-AC-0028-01A,0.0551,0.214,0.1013,0.0296,0.125,0.0423,0.049,0.0416,0.0174,0.0156
+TCGA-AC-0029-01A,0.0423,0.0531,0.0861,0.0423,0.2436,0.0421,0.0831,0.0159,0.0157,0.0063
+TCGA-AC-0030-01A,0.0674,0.0558,0.0754,0.0507,0.0785,0.0771,0.0505,0.0314,0.025,0.0149
+TCGA-AC-0031-01A,0.0758,0.109,0.0769,0.0196,0.1329,0.0459,0.0296,0.0742,0.0097,0.0119
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