@cooolr/mcp-virtual-liver 1.0.0

package/index.js

@@ -0,0 +1,636 @@
+#!/usr/bin/env node
+/**
+ * 虚拟肝脏 AI Agent — MCP Skill Server
+ *
+ * 7 个分析 Skill 封装为 MCP Tool，供 FastAGI 等平台的模型节点调用。
+ * 模型已有图谱/组学数据在上下文中，将数据传给 Tool 做结构化分析，Tool 返回结果。
+ */
+import { McpServer } from "@modelcontextprotocol/sdk/server/mcp.js";
+import { StdioServerTransport } from "@modelcontextprotocol/sdk/server/stdio.js";
+import { z } from "zod";
+
+const server = new McpServer({
+  name: "virtual-liver-skills",
+  version: "1.0.0",
+  description: "虚拟肝脏多组学分析 Skill 工具集，包含基因画像、通路富集、多组学一致性检验、假说生成等 7 个分析能力",
+});
+
+// ════════════════════════════════════════════════════════════════
+// Skill 1: 基因功能全景分析
+// ════════════════════════════════════════════════════════════════
+server.tool(
+  "gene_profiling",
+  `基因功能全景分析：将基因的多维知识图谱数据整合为结构化画像。
+这是所有分析的入口 Skill，应最先调用。
+
+输入：基因名称 + 图谱中查到的各维度数据（通路、GO功能、细胞表达、语义标签、疾病、文献、代谢关联）。
+输出：结构化的基因功能画像。
+
+后续根据分析需求选择：
+- 问通路 → pathway_enrichment
+- 问机制 → omics_consistency_check → hypothesis_generation`,
+  {
+    gene_symbol: z.string().describe("基因符号，如 SMPD3"),
+    gene_full_name: z.string().optional().describe("基因全名"),
+    ec_number: z.string().optional().describe("EC 酶分类号"),
+    encoded_protein: z.string().optional().describe("编码蛋白名称"),
+    pathways: z.array(z.object({
+      name: z.string(),
+      role: z.string().optional(),
+    })).optional().describe("参与的代谢通路列表"),
+    go_functions: z.array(z.object({
+      term: z.string(),
+      category: z.enum(["BP", "MF", "CC"]).optional(),
+    })).optional().describe("GO 功能注释"),
+    cell_expression: z.array(z.object({
+      cell_type: z.string(),
+      level: z.string(),
+    })).optional().describe("肝脏细胞类型表达"),
+    semantic_tags: z.array(z.object({
+      tag: z.string(),
+      category: z.string().optional(),
+      confidence: z.number().optional(),
+    })).optional().describe("肝语义标签"),
+    diseases: z.array(z.string()).optional().describe("关联疾病"),
+    metabolites: z.array(z.object({
+      name: z.string(),
+      relation: z.string(),
+      direction: z.string().optional(),
+    })).optional().describe("关联代谢物"),
+  },
+  async (args) => {
+    const lines = [`## 基因画像: ${args.gene_symbol}\n`];
+
+    // 基本信息
+    lines.push("### 基本信息");
+    lines.push(`- 全名: ${args.gene_full_name || "未知"}`);
+    if (args.ec_number) lines.push(`- EC号: ${args.ec_number}`);
+    if (args.encoded_protein) lines.push(`- 编码蛋白: ${args.encoded_protein}`);
+
+    // 通路
+    if (args.pathways?.length) {
+      lines.push(`\n### 代谢通路 (${args.pathways.length}条)`);
+      for (const p of args.pathways) {
+        lines.push(`- ${p.name}${p.role ? ` (角色: ${p.role})` : ""}`);
+      }
+    }
+
+    // GO
+    if (args.go_functions?.length) {
+      lines.push(`\n### GO功能注释 (${args.go_functions.length}条)`);
+      const grouped = {};
+      for (const g of args.go_functions) {
+        const cat = g.category || "未分类";
+        (grouped[cat] = grouped[cat] || []).push(g.term);
+      }
+      for (const [cat, terms] of Object.entries(grouped)) {
+        lines.push(`- ${cat}: ${terms.join("; ")}`);
+      }
+    }
+
+    // 细胞表达
+    if (args.cell_expression?.length) {
+      lines.push(`\n### 肝脏细胞表达谱`);
+      const sorted = [...args.cell_expression].sort((a, b) => {
+        const order = { "高": 3, "中": 2, "低": 1, "无": 0 };
+        return (order[b.level] || 0) - (order[a.level] || 0);
+      });
+      for (const c of sorted) lines.push(`- ${c.cell_type}: ${c.level}`);
+    }
+
+    // 语义标签
+    if (args.semantic_tags?.length) {
+      lines.push(`\n### 肝语义标签`);
+      for (const t of args.semantic_tags) {
+        let s = `- ${t.tag}`;
+        if (t.category) s += ` [${t.category}]`;
+        if (t.confidence) s += ` (置信度: ${t.confidence})`;
+        lines.push(s);
+      }
+    }
+
+    // 疾病
+    if (args.diseases?.length) {
+      lines.push(`\n### 疾病关联`);
+      for (const d of args.diseases) lines.push(`- ${d}`);
+    }
+
+    // 代谢物
+    if (args.metabolites?.length) {
+      lines.push(`\n### 关联代谢物`);
+      for (const m of args.metabolites) {
+        lines.push(`- ${m.name} (${m.relation})${m.direction ? ` ${m.direction}` : ""}`);
+      }
+    }
+
+    return { content: [{ type: "text", text: lines.join("\n") }] };
+  }
+);
+
+// ════════════════════════════════════════════════════════════════
+// Skill 2: 多基因通路富集分析
+// ════════════════════════════════════════════════════════════════
+server.tool(
+  "pathway_enrichment",
+  `多基因通路富集分析：对一组差异基因/蛋白执行通路富集和交叉分析。
+
+输入：基因列表，每个基因包含名称、变化方向、参与通路。
+输出：富集通路排名（命中≥2基因）、桥接基因（跨≥2通路）、代谢物桥梁。
+
+用于回答：
+- "这些差异蛋白有什么共同通路？"
+- "哪些通路被显著影响？"
+- "哪些基因是跨通路枢纽？"`,
+  {
+    genes: z.array(z.object({
+      name: z.string().describe("基因/蛋白名"),
+      direction: z.enum(["up", "down", "unknown"]).describe("变化方向"),
+      pathways: z.array(z.string()).describe("该基因参与的通路列表"),
+    })).describe("差异基因列表"),
+  },
+  async ({ genes }) => {
+    // 构建通路-基因矩阵
+    const pathwayGenes = {};
+    const genePathways = {};
+
+    for (const g of genes) {
+      const label = `${g.name}(${g.direction === "up" ? "↑" : g.direction === "down" ? "↓" : "?"})`;
+      genePathways[g.name] = { pathways: g.pathways, label };
+      for (const pw of g.pathways) {
+        (pathwayGenes[pw] = pathwayGenes[pw] || []).push(label);
+      }
+    }
+
+    // 按命中数排序
+    const ranked = Object.entries(pathwayGenes)
+      .sort(([, a], [, b]) => b.length - a.length);
+
+    const lines = [
+      `## 通路富集分析\n`,
+      `输入基因: ${genes.length} 个, 覆盖通路: ${ranked.length} 条\n`,
+      `### 富集通路 (按命中基因数排序)`,
+    ];
+
+    for (const [pw, glist] of ranked) {
+      const enriched = glist.length >= 2 ? " ★富集" : "";
+      lines.push(`- **${pw}** (${glist.length}基因${enriched}): ${glist.join(", ")}`);
+    }
+
+    // 桥接基因
+    const bridges = Object.entries(genePathways)
+      .filter(([, info]) => info.pathways.length >= 2);
+
+    if (bridges.length) {
+      lines.push(`\n### 桥接基因 (参与≥2通路)`);
+      for (const [gene, info] of bridges) {
+        lines.push(`- **${info.label}**: ${info.pathways.join(" + ")}`);
+      }
+    } else {
+      lines.push(`\n### 桥接基因\n无单基因跨≥2通路。需检查是否有代谢物作为跨通路桥梁。`);
+    }
+
+    // 通路内矛盾检测
+    lines.push(`\n### 通路内方向分析`);
+    for (const [pw, glist] of ranked) {
+      if (glist.length < 2) continue;
+      const ups = glist.filter(g => g.includes("↑")).length;
+      const downs = glist.filter(g => g.includes("↓")).length;
+      if (ups > 0 && downs > 0) {
+        lines.push(`- ⚠️ **${pw}**: ${ups}个↑ + ${downs}个↓ — 通路内方向不一致，需分析限速步骤`);
+      } else {
+        lines.push(`- ✅ **${pw}**: 方向一致 (${ups > 0 ? "均↑" : "均↓"})`);
+      }
+    }
+
+    return { content: [{ type: "text", text: lines.join("\n") }] };
+  }
+);
+
+// ════════════════════════════════════════════════════════════════
+// Skill 3: 肝细胞表达谱分析
+// ════════════════════════════════════════════════════════════════
+server.tool(
+  "liver_expression_analysis",
+  `肝细胞表达谱分析：分析基因在 11 种肝脏细胞类型中的表达模式。
+
+输入：一个或多个基因的细胞类型表达数据。
+输出：表达模式分类（广泛/特异/中等）、细胞类型排序、共表达模式。
+
+11种肝脏细胞：肝细胞、胆管细胞、血管内皮细胞、肝星状细胞、单核细胞、巨噬细胞、库普弗细胞、T细胞、B细胞、浆细胞、NK细胞。
+数据来源：Human Protein Atlas (HPA) 单细胞 RNA-seq。`,
+  {
+    genes: z.array(z.object({
+      name: z.string(),
+      expression: z.array(z.object({
+        cell_type: z.string(),
+        level: z.string().describe("表达水平: 高/中/低/无 或 nCPM 数值"),
+      })),
+    })).describe("基因表达数据列表"),
+  },
+  async ({ genes }) => {
+    const lines = [`## 肝细胞表达谱分析\n`];
+
+    for (const gene of genes) {
+      const expressed = gene.expression.filter(e =>
+        e.level !== "无" && e.level !== "0" && e.level !== "not detected"
+      );
+      const pattern = expressed.length >= 6 ? "广泛表达"
+        : expressed.length <= 2 ? "细胞特异"
+        : "中等分布";
+
+      lines.push(`### ${gene.name} — ${pattern} (${expressed.length}/11 细胞类型检出)`);
+      for (const e of gene.expression) {
+        lines.push(`- ${e.cell_type}: ${e.level}`);
+      }
+      lines.push("");
+    }
+
+    // 多基因共表达
+    if (genes.length >= 2) {
+      lines.push("### 共表达分析");
+      const allCellTypes = [...new Set(genes.flatMap(g => g.expression.map(e => e.cell_type)))];
+      for (const ct of allCellTypes) {
+        const expressedGenes = genes.filter(g =>
+          g.expression.some(e => e.cell_type === ct && e.level !== "无" && e.level !== "0")
+        );
+        if (expressedGenes.length >= 2) {
+          lines.push(`- **${ct}**: ${expressedGenes.map(g => g.name).join(", ")} 共表达`);
+        }
+      }
+    }
+
+    return { content: [{ type: "text", text: lines.join("\n") }] };
+  }
+);
+
+// ════════════════════════════════════════════════════════════════
+// Skill 4: 肝语义功能聚类
+// ════════════════════════════════════════════════════════════════
+server.tool(
+  "semantic_clustering",
+  `肝语义功能聚类：按肝脏特异的语义标签体系（6大类19小类）对基因集合进行功能分类。
+
+语义标签体系：
+- 代谢: 脂代谢、糖代谢、胆汁酸代谢、氨基酸代谢、药物代谢、能量代谢
+- 应激: 氧化应激、内质网应激
+- 再生: 肝再生、细胞增殖
+- 免疫: 炎症反应、免疫调节
+- 细胞死亡: 凋亡、自噬
+- 转运: 离子转运、脂质转运、蛋白转运
+
+输入：基因列表及其语义标签（或 GO 注释映射后的标签）。
+输出：大类分布、小类排名、多标签交叉基因。`,
+  {
+    genes: z.array(z.object({
+      name: z.string(),
+      tags: z.array(z.string()).describe("该基因的语义小类标签，如 '脂代谢', '氧化应激'"),
+    })).describe("基因及其语义标签"),
+  },
+  async ({ genes }) => {
+    const SUB_TO_CAT = {
+      "脂代谢": "代谢", "糖代谢": "代谢", "胆汁酸代谢": "代谢",
+      "氨基酸代谢": "代谢", "药物代谢": "代谢", "能量代谢": "代谢",
+      "氧化应激": "应激", "内质网应激": "应激",
+      "肝再生": "再生", "细胞增殖": "再生",
+      "炎症反应": "免疫", "免疫调节": "免疫",
+      "凋亡": "细胞死亡", "自噬": "细胞死亡",
+      "离子转运": "转运", "脂质转运": "转运", "蛋白转运": "转运",
+    };
+
+    const catGenes = {};
+    const subGenes = {};
+    const geneCats = {};
+
+    for (const gene of genes) {
+      geneCats[gene.name] = new Set();
+      for (const tag of gene.tags) {
+        const cat = SUB_TO_CAT[tag] || "其他";
+        (catGenes[cat] = catGenes[cat] || new Set()).add(gene.name);
+        (subGenes[tag] = subGenes[tag] || new Set()).add(gene.name);
+        geneCats[gene.name].add(cat);
+      }
+    }
+
+    const total = genes.length;
+    const lines = [`## 肝语义功能聚类 (${total} 基因)\n`];
+
+    // 大类分布
+    lines.push("### 大类分布");
+    const sortedCats = Object.entries(catGenes)
+      .map(([cat, set]) => [cat, [...set]])
+      .sort(([, a], [, b]) => b.length - a.length);
+
+    for (const [cat, geneList] of sortedCats) {
+      const pct = (geneList.length / total * 100).toFixed(0);
+      lines.push(`- **${cat}**: ${geneList.length}基因 (${pct}%) — ${geneList.slice(0, 5).join(", ")}`);
+    }
+
+    // 小类排名
+    lines.push("\n### 小类排名 (Top 10)");
+    const sortedSubs = Object.entries(subGenes)
+      .map(([sub, set]) => [sub, [...set]])
+      .sort(([, a], [, b]) => b.length - a.length)
+      .slice(0, 10);
+
+    for (const [sub, geneList] of sortedSubs) {
+      const cat = SUB_TO_CAT[sub] || "其他";
+      lines.push(`- ${sub} [${cat}]: ${geneList.length}基因 — ${geneList.join(", ")}`);
+    }
+
+    // 多标签交叉
+    const crossGenes = Object.entries(geneCats)
+      .filter(([, cats]) => cats.size >= 2);
+
+    if (crossGenes.length) {
+      lines.push("\n### 多标签交叉基因 (跨≥2大类)");
+      for (const [gene, cats] of crossGenes) {
+        lines.push(`- **${gene}**: ${[...cats].join(" + ")}`);
+      }
+    }
+
+    return { content: [{ type: "text", text: lines.join("\n") }] };
+  }
+);
+
+// ════════════════════════════════════════════════════════════════
+// Skill 5: 多组学一致性检验（核心 Skill）
+// ════════════════════════════════════════════════════════════════
+server.tool(
+  "omics_consistency_check",
+  `多组学一致性检验：将差异蛋白(↑↓)与差异代谢物(↑↓)逐对比对，检查生物学逻辑一致性。
+这是多组学整合分析最核心的步骤。矛盾是最有价值的发现——矛盾意味着存在未知机制。
+
+判定规则：
+- 合成酶↑ + 产物↑ = ✅一致
+- 合成酶↑ + 产物↓ = ❌矛盾 → 查消耗途径或翻译后抑制
+- 降解酶↓ + 底物↑ = ✅一致（降解减少→积累）
+- 降解酶↓ + 底物↓ = ❌矛盾 → 查其他降解途径
+- 转运蛋白↓ + 上游↑ = ✅一致（转运受阻→堆积）
+- 同通路内唯一↓的限速酶 + 其他酶↑ = 无效代偿（瓶颈未解除）
+
+输入：蛋白-代谢物配对列表，包含方向和酶类型。
+输出：一致对/矛盾对/限速步骤判定/矛盾解释。`,
+  {
+    pairs: z.array(z.object({
+      protein: z.string().describe("蛋白名"),
+      protein_direction: z.enum(["up", "down"]).describe("蛋白变化方向"),
+      metabolite: z.string().describe("代谢物名"),
+      metabolite_direction: z.enum(["up", "down"]).describe("代谢物变化方向"),
+      enzyme_type: z.enum(["synthesis", "degradation", "transport", "oxidation"]).describe("酶功能类型: 合成酶/降解酶/转运蛋白/氧化酶"),
+      pathway: z.string().optional().describe("所属通路"),
+    })).describe("蛋白-代谢物配对"),
+  },
+  async ({ pairs }) => {
+    const RULES = {
+      "synthesis|up|up": { status: "✅", reason: "合成酶↑→产物↑，逻辑一致" },
+      "synthesis|up|down": { status: "❌", reason: "合成酶↑但产物↓ → 产物被快速消耗、酶活性被翻译后抑制、或底物不足" },
+      "synthesis|down|down": { status: "✅", reason: "合成酶↓→产物↓，逻辑一致" },
+      "synthesis|down|up": { status: "❌", reason: "合成酶↓但产物↑ → 存在替代合成途径、或降解减少" },
+      "degradation|up|down": { status: "✅", reason: "降解酶↑→底物↓，逻辑一致" },
+      "degradation|up|up": { status: "❌", reason: "降解酶↑但底物↑ → 合成速率 > 降解速率" },
+      "degradation|down|up": { status: "✅", reason: "降解酶↓→底物积累↑，逻辑一致" },
+      "degradation|down|down": { status: "❌", reason: "降解酶↓但底物↓ → 查其他降解途径或合成端下降" },
+      "transport|down|up": { status: "✅", reason: "转运受阻→上游堆积↑" },
+      "transport|down|down": { status: "❌", reason: "转运受阻但上游↓ → 合成端也受影响" },
+      "transport|up|down": { status: "✅", reason: "转运增强→上游被清除↓" },
+      "transport|up|up": { status: "❌", reason: "转运增强但上游↑ → 供给 > 转运能力" },
+      "oxidation|up|down": { status: "✅", reason: "氧化酶↑→底物被氧化分解↓" },
+      "oxidation|up|up": { status: "❌", reason: "氧化酶↑但底物↑ → 氧化受限（辅因子不足？底物转运受阻？）" },
+      "oxidation|down|up": { status: "✅", reason: "氧化酶↓→底物积累↑" },
+      "oxidation|down|down": { status: "❌", reason: "氧化酶↓但底物↓ → 查上游合成是否也受阻" },
+    };
+
+    const consistent = [];
+    const contradictions = [];
+
+    for (const p of pairs) {
+      const key = `${p.enzyme_type}|${p.protein_direction}|${p.metabolite_direction}`;
+      const rule = RULES[key] || { status: "❓", reason: "无匹配规则" };
+      const dir = (d) => d === "up" ? "↑" : "↓";
+
+      const entry = {
+        text: `${p.protein}(${dir(p.protein_direction)}) → ${p.metabolite}(${dir(p.metabolite_direction)})`,
+        reason: rule.reason,
+        pathway: p.pathway || "",
+      };
+
+      if (rule.status === "✅") consistent.push(entry);
+      else contradictions.push(entry);
+    }
+
+    // 限速步骤检测
+    const pathwayProteins = {};
+    for (const p of pairs) {
+      if (p.pathway) {
+        (pathwayProteins[p.pathway] = pathwayProteins[p.pathway] || []).push(p);
+      }
+    }
+
+    const bottlenecks = [];
+    for (const [pw, prots] of Object.entries(pathwayProteins)) {
+      const downs = prots.filter(p => p.protein_direction === "down");
+      const ups = prots.filter(p => p.protein_direction === "up");
+      if (downs.length === 1 && ups.length >= 1) {
+        bottlenecks.push({
+          pathway: pw,
+          bottleneck: downs[0].protein,
+          compensating: ups.map(p => p.protein).join(", "),
+        });
+      }
+    }
+
+    const lines = [`## 多组学一致性检验\n`];
+    lines.push(`### ✅ 一致 (${consistent.length}对)`);
+    for (const e of consistent) lines.push(`- ${e.text}: ${e.reason}`);
+
+    lines.push(`\n### ❌ 矛盾 (${contradictions.length}对)`);
+    for (const e of contradictions) lines.push(`- ${e.text}: ${e.reason}`);
+
+    if (bottlenecks.length) {
+      lines.push(`\n### 限速步骤 / 无效代偿`);
+      for (const b of bottlenecks) {
+        lines.push(`- **${b.pathway}**: 限速酶 ${b.bottleneck}(↓) — 代偿酶 ${b.compensating}(↑) → 代偿可能无效（瓶颈未解除）`);
+      }
+    }
+
+    lines.push(`\n### 分析建议`);
+    if (contradictions.length > 0) {
+      lines.push(`发现 ${contradictions.length} 个矛盾对，建议对每个矛盾寻找：`);
+      lines.push(`1. 是否有未检测到的中间代谢步骤`);
+      lines.push(`2. 是否存在翻译后调控（磷酸化、变构抑制）`);
+      lines.push(`3. 是否有替代通路分流`);
+    }
+
+    return { content: [{ type: "text", text: lines.join("\n") }] };
+  }
+);
+
+// ════════════════════════════════════════════════════════════════
+// Skill 6: 疾病关联分析
+// ════════════════════════════════════════════════════════════════
+server.tool(
+  "disease_association",
+  `疾病关联与临床意义分析：评估基因/蛋白的疾病关联，判断证据强度，提出临床转化方向。
+
+输入：基因名 + 关联疾病列表 + 支持文献。
+输出：疾病按证据强度排序 + 转化建议。`,
+  {
+    gene: z.string().describe("基因名"),
+    associations: z.array(z.object({
+      disease: z.string().describe("疾病名称"),
+      evidence: z.string().optional().describe("证据类型: confirmed/probable/potential"),
+      publications: z.array(z.string()).optional().describe("支持文献 PMID 列表"),
+      co_associated_genes: z.array(z.string()).optional().describe("同疾病关联的其他基因"),
+    })).describe("疾病关联列表"),
+  },
+  async ({ gene, associations }) => {
+    const lines = [`## 疾病关联分析: ${gene}\n`];
+
+    // 按证据强度排序
+    const order = { confirmed: 3, probable: 2, potential: 1 };
+    const sorted = [...associations].sort((a, b) =>
+      (order[b.evidence] || 0) - (order[a.evidence] || 0)
+    );
+
+    const strengthLabel = (e) => {
+      if (e === "confirmed") return "强 🟢";
+      if (e === "probable") return "中 🟡";
+      return "弱 ⚪";
+    };
+
+    lines.push("### 疾病关联排序");
+    lines.push("| 疾病 | 证据强度 | 文献数 | 共关联基因 |");
+    lines.push("|------|---------|--------|-----------|");
+
+    for (const a of sorted) {
+      const pubCount = a.publications?.length || 0;
+      const coGenes = a.co_associated_genes?.slice(0, 3).join(", ") || "-";
+      lines.push(`| ${a.disease} | ${strengthLabel(a.evidence)} | ${pubCount} | ${coGenes} |`);
+    }
+
+    // 肝脏相关疾病
+    const liverKeywords = ["肝", "liver", "hepat", "cirrh", "fibrosis", "steatosis", "HCC"];
+    const liverDiseases = sorted.filter(a =>
+      liverKeywords.some(kw => a.disease.toLowerCase().includes(kw.toLowerCase()))
+    );
+
+    if (liverDiseases.length) {
+      lines.push("\n### 肝脏疾病（重点关注）");
+      for (const d of liverDiseases) {
+        lines.push(`- **${d.disease}**: 证据${strengthLabel(d.evidence)}`);
+        if (d.co_associated_genes?.length) {
+          lines.push(`  共关联基因: ${d.co_associated_genes.join(", ")}`);
+        }
+      }
+    }
+
+    return { content: [{ type: "text", text: lines.join("\n") }] };
+  }
+);
+
+// ════════════════════════════════════════════════════════════════
+// Skill 7: 机制假说生成
+// ════════════════════════════════════════════════════════════════
+server.tool(
+  "hypothesis_generation",
+  `机制假说生成：基于前序分析结果，运用推理模板构建机制链条并评分。
+应在完成 gene_profiling 和 omics_consistency_check 之后调用。
+
+4种推理模板：
+
+模板A - 代谢物直接功能：
+  基因变化 → 蛋白变化 → 代谢物变化 → 代谢物直接影响细胞功能 → 表型
+  （例：Cer↓ → PP2A活性↓ → Akt/mTOR↑ → 增殖）
+
+模板B - 代谢物-蛋白互作：
+  基因变化 → 代谢物变化 → 代谢物与靶蛋白结合 → 信号通路改变 → 表型
+  （例：malonyl-CoA↑ → 变构抑制Cpt1a → β-氧化阻断）
+
+模板C - 代谢重编程：
+  关键酶敲除 → 主通路阻断 → 代偿通路激活 → 代谢物谱整体改变 → 表型
+  （例：Mat1a↓ → SAM↓ → 转硫途径代偿Cbs↑ → GSH↑）
+
+模板D - 反馈调控：
+  代谢物A变化 → 反馈调控 → 酶B活性改变 → 代谢物C变化 → 表型
+
+评分维度（总分10）：
+  因果链完整性 0-3 / 数据一致性 0-3 / 文献支持 0-2 / 可验证性 0-2
+
+输入：假说列表，每个假说包含名称、推理模板、因果链步骤、证据。
+输出：评分排序 + 验证实验建议。`,
+  {
+    phenotype: z.string().describe("待解释的表型，如'SMPD3缺失促进肝脏再生'"),
+    hypotheses: z.array(z.object({
+      name: z.string().describe("假说名称"),
+      template: z.enum(["A", "B", "C", "D"]).describe("推理模板类型"),
+      chain: z.array(z.object({
+        step: z.string().describe("因果链步骤描述"),
+        evidence: z.enum(["data", "literature", "inference"]).describe("证据类型: 数据支持/文献支持/推测"),
+      })).describe("因果链步骤"),
+      has_metabolite_node: z.boolean().describe("链条中是否包含代谢物节点"),
+      key_experiments: z.array(z.string()).optional().describe("建议验证实验"),
+    })).describe("候选假说列表"),
+  },
+  async ({ phenotype, hypotheses }) => {
+    const lines = [`## 机制假说分析\n`, `待解释表型: **${phenotype}**\n`];
+
+    const scored = hypotheses.map(h => {
+      // 因果链完整性 (0-3)
+      const chainScore = Math.min(3, h.chain.length >= 4 ? 3 : h.chain.length >= 3 ? 2 : 1);
+      // 数据一致性 (0-3)
+      const dataSteps = h.chain.filter(s => s.evidence === "data").length;
+      const dataScore = Math.min(3, dataSteps);
+      // 文献支持 (0-2)
+      const litSteps = h.chain.filter(s => s.evidence === "literature").length;
+      const litScore = Math.min(2, litSteps);
+      // 可验证性 (0-2)
+      const expScore = h.key_experiments?.length >= 2 ? 2 : h.key_experiments?.length === 1 ? 1 : 0;
+      // 代谢物节点 bonus / penalty
+      const metPenalty = h.has_metabolite_node ? 0 : -2;
+
+      const total = chainScore + dataScore + litScore + expScore + metPenalty;
+
+      return { ...h, chainScore, dataScore, litScore, expScore, metPenalty, total };
+    });
+
+    // 排序
+    scored.sort((a, b) => b.total - a.total);
+
+    const templateNames = { A: "代谢物直接功能", B: "代谢物-蛋白互作", C: "代谢重编程", D: "反馈调控" };
+
+    for (let i = 0; i < scored.length; i++) {
+      const h = scored[i];
+      lines.push(`### 假说${i + 1}: ${h.name} (${h.total}/10分)`);
+      lines.push(`推理模板: ${templateNames[h.template]} | 含代谢物节点: ${h.has_metabolite_node ? "是" : "否⚠️"}`);
+      lines.push(`评分: 因果链${h.chainScore}/3 + 数据${h.dataScore}/3 + 文献${h.litScore}/2 + 可验证${h.expScore}/2${h.metPenalty ? ` ${h.metPenalty}(无代谢物)` : ""}`);
+      lines.push("\n因果链:");
+      for (const s of h.chain) {
+        const icon = s.evidence === "data" ? "📊" : s.evidence === "literature" ? "📖" : "💡";
+        lines.push(`  ${icon} ${s.step}`);
+      }
+      if (h.key_experiments?.length) {
+        lines.push("\n验证实验:");
+        for (const exp of h.key_experiments) lines.push(`  - ${exp}`);
+      }
+      lines.push("");
+    }
+
+    // 排名表
+    lines.push("### 假说排名");
+    lines.push("| 排名 | 假说 | 模板 | 评分 | 关键依据 |");
+    lines.push("|------|------|------|------|---------|");
+    for (let i = 0; i < scored.length; i++) {
+      const h = scored[i];
+      const topEvidence = h.chain.find(s => s.evidence === "data")?.step || h.chain[0]?.step || "";
+      lines.push(`| ${i + 1} | ${h.name} | ${templateNames[h.template]} | **${h.total}/10** | ${topEvidence.slice(0, 40)} |`);
+    }
+
+    return { content: [{ type: "text", text: lines.join("\n") }] };
+  }
+);
+
+// ════════════════════════════════════════════════════════════════
+// 启动
+// ════════════════════════════════════════════════════════════════
+const transport = new StdioServerTransport();
+await server.connect(transport);

package/package.json

@@ -0,0 +1,31 @@
+{
+  "name": "@cooolr/mcp-virtual-liver",
+  "version": "1.0.0",
+  "description": "虚拟肝脏多组学分析 MCP Server — 7个Skill工具（基因画像、通路富集、多组学一致性检验、假说生成等）",
+  "main": "index.js",
+  "bin": {
+    "mcp-virtual-liver": "index.js"
+  },
+  "scripts": {
+    "start": "node index.js"
+  },
+  "keywords": [
+    "mcp",
+    "model-context-protocol",
+    "bioinformatics",
+    "liver",
+    "multi-omics",
+    "knowledge-graph",
+    "gene-analysis"
+  ],
+  "author": "cooolr",
+  "license": "MIT",
+  "type": "module",
+  "files": [
+    "index.js"
+  ],
+  "dependencies": {
+    "@modelcontextprotocol/sdk": "^1.27.1",
+    "zod": "^4.3.6"
+  }
+}