- Date : [[2022-09-20]]
- 参考：Frontiers | CD8 T cell trajectory subtypes decode tumor heterogeneity and provide treatment recommendations for hepatocellular carcinoma[1]
1-单细胞数据
收集3,817 CD45 immune cells GEO Accession viewer (nih.gov)[2]
image-20220918114840230
对全部的T 细胞再次进行聚类，鉴别出CD4 与CD8 亚型：
image-20220918120443879
拟时序结合免疫检查点基因显示CD8 T 细胞像耗竭状态演化过程：
image-20220918120600805
2-利用CD8 分化相关基因聚类
利用monocle 提取与上述轨迹变化相关的基因，利用NMF 方法对TCGA 数据进行分类：
image-20220920090159173
发现三个亚群与生存显著相关：
image-20220920090330392
3-鉴别与模块关联基因
利用WGCNA，鉴别出与聚类表型相关的模块：
image-20220920090626417
发现与每个clust 相关的模块：
image-20220920090814002
‘Therefore, we characterized C1 as lipid metabolic HCC and C2 as cell proliferative HCC, whereas C3 was defined as immune inflammatory HCC.
ps：（WGCNA 方法相对可以更加可靠的赋予每个clust 生物学意义）
通过直接聚类对样本进行分群，并通过wgcna 等方法找到每个分群的关键基因，并用ntp 评价，也是一个构建模型不错的思路。（相比用这些分群的基因来做cox回归等构建模型）
4-通过NTP 方法评价
通过聚类结果与wgcna 找到的模块marker 基因对其他数据集进行分类，并评价分类效果：
image-20220920091142506
image-20220920092004636
5-三种分群的突变及拷贝数
image-20220920092137519
6-免疫浸润与治疗情况
image-20220920092443831
几种打分方法：
image-20220920092706179
he Submap was utilized to measure the expression profile similarity between HCC patients and immunotherapeutic patients, which was consistent with the similarity of clinical responses
发现C3 与免疫激活相关：Subsequently, the characteristic genes of C3 were extracted to serve as the measured score, named as cluster-associated immunotherapy score (CAIS).
通过四个免疫治疗队列，评价C3 clust 响应免疫治疗的效果：
image-20220920092902700
另外还看了TACE 和sorafenib 两种药物治疗组别：
image-20220920093931682
利用cmap 等数据库看潜在治疗药物：
image-20220920094318017
从单细胞亚群（轨迹分化）到预后模型。
参考资料
[1]
Frontiers | CD8 T cell trajectory subtypes decode tumor heterogeneity and provide treatment recommendations for hepatocellular carcinoma: https://www.frontiersin.org/articles/10.3389/fimmu.2022.964190/full
[2]
GEO Accession viewer (nih.gov): https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE140228
