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(1980/台)OnekeyAI平台一键复现中科院二区病理多模态组学研究方案

(1980/台)OnekeyAI平台一键复现中科院二区病理多模态组学研究方案

一、参考论文

使用的数据包括:

转录组数据TCGA-HNSC队列的mRNA表达谱(395例HPV阴性样本)。

临床数据TCGA-HNSC的总生存期(OS)、无进展间隔(PFI)、肿瘤分期、淋巴结转移、放疗信息等。

基因组数据:体细胞突变(含COSMIC突变特征)、拷贝数变异(CNV)、肿瘤突变负荷(TMB)、基因组改变分数。

单细胞RNA-seq数据:来自GEO的三个公共数据集(GSE181919、GSE182227、GSE234933),共34例HPV阴性样本的115,479个细胞。

空间转录组数据GEO数据集GSM5494476(GSE181300),用于配体-受体空间共定位分析。

组织病理图像TCGA-HNSC的348例HPV阴性病例的360张HE染色全切片图像(WSIs)。

二、复现及创新

OneKey平台复现论文的核心步骤

1. 数据准备与预处理

病理图像格式要求

必须是全切片图像(WSI),常见格式为.svs.ndpi.mrxs

不支持单张截图(如.jpg.png),除非是私有格式如.kfb(江丰生物),可通过工具转换为.svs

数据收集

使用公开数据集(如TCGA-HNSC)或私有数据。

需要准备患者标签(label)

2. WSI裁剪为Patch

工具WsiToPatch

参数说明

level:放大倍率,TCGA数据一般为20倍(对应 level=0 或 level=1)。

patch_size:裁剪大小,常用512×512像素。

strategy:若指定倍率失败,默认使用最高分辨率。

输出:每个WSI被裁剪为数千个patch,用于后续分析。

3. Patch预处理

删除白色背景

工具:PatchToPredict

参数:saturation_threshold 默认216,数值越大删除越严格。

颜色空间标准化

工具:StainNormalize

常用方法:Macenko(效果好但慢)、Vahadane(居中)、Reinhard(快但效果差)。

需要指定参考图像(reference)进行颜色归一化。

4. 无监督聚类(核心差异化步骤)

目的:识别具有生物学意义的病理区域(如肿瘤区、间质区、浸润前沿等)。

工具

FeatExtract:提取深度学习特征(使用预训练模型如ResNet50)。

FeatureCluster:对特征进行K-means聚类,指定聚类数(如6类)。

DimReduction + TSNE:可视化聚类结果。

输出:每个patch的聚类标签及距离聚类中心的距离。

5. 聚类结果筛选(Silicon病理区域选择)

人工干预

根据聚类结果和病理学知识,筛选出有意义的聚类(如肿瘤区、浸润前沿)。

删除无关区域(如肌肉、脂肪、背景)。

工具辅助

使用QuPath 或 PatchVisualizer 查看每个聚类的代表性patch。

可通过cluster_to_wsi 工具将聚类结果映射回原图,辅助判断。

6. 弱监督学习建模

目的:基于筛选后的patch,预测患者风险(高/低风险)。

工具WeaklySupervised

模型:支持多种CNN架构(ResNet18/50、Inception_v3)。

训练策略

使用患者级别标签(来自生信分析的风险分组)。

采用多实例学习(MIL)或特征聚合(如FeatAggregate)进行训练。

评估:对比筛选前后模型的AUC、准确率、混淆矩阵等。

7. 结果可视化与解释

Grad-CAM:生成热图,显示模型关注的病理区域(如血管浸润、间质浸润)。

聚类映射:将聚类结果可视化到WSI上,便于病理医生验证。

工具WSIHeatmapQuPathMatplotlib

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  1. CONNECT:[ UseTime:0.000560s ] mysql:host=127.0.0.1;port=3306;dbname=wenku;charset=utf8mb4
  2. SHOW FULL COLUMNS FROM `fenlei` [ RunTime:0.000916s ]
  3. SELECT * FROM `fenlei` WHERE `fid` = 0 [ RunTime:0.000387s ]
  4. SELECT * FROM `fenlei` WHERE `fid` = 63 [ RunTime:0.000281s ]
  5. SHOW FULL COLUMNS FROM `set` [ RunTime:0.000618s ]
  6. SELECT * FROM `set` [ RunTime:0.000221s ]
  7. SHOW FULL COLUMNS FROM `article` [ RunTime:0.000546s ]
  8. SELECT * FROM `article` WHERE `id` = 776032 LIMIT 1 [ RunTime:0.002721s ]
  9. UPDATE `article` SET `lasttime` = 1781992246 WHERE `id` = 776032 [ RunTime:0.003643s ]
  10. SELECT * FROM `fenlei` WHERE `id` = 64 LIMIT 1 [ RunTime:0.000242s ]
  11. SELECT * FROM `article` WHERE `id` < 776032 ORDER BY `id` DESC LIMIT 1 [ RunTime:0.000478s ]
  12. SELECT * FROM `article` WHERE `id` > 776032 ORDER BY `id` ASC LIMIT 1 [ RunTime:0.000959s ]
  13. SELECT * FROM `article` WHERE `id` < 776032 ORDER BY `id` DESC LIMIT 10 [ RunTime:0.000708s ]
  14. SELECT * FROM `article` WHERE `id` < 776032 ORDER BY `id` DESC LIMIT 10,10 [ RunTime:0.000645s ]
  15. SELECT * FROM `article` WHERE `id` < 776032 ORDER BY `id` DESC LIMIT 20,10 [ RunTime:0.007223s ]
0.104210s