来自用户 sqc 的文献。
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1.
sqc (2025-07-31 23:53):
#paper, 《A global cancer data integrator reveals principles of synthetic lethality, sex disparity and immunotherapy》, 10.1186/s13073-021-00987-8, 本研究开发了一个名为 Cancer Data Integrator(CanDI)的 Python 框架,用于整合来自 CCLE、DepMap、PICKLES、CORUM 等多源公开数据,实现跨组学(基因组、转录组、蛋白组、代谢组)与功能基因组数据的无缝查询与联合分析。作者通过统一索引与类对象抽象,使用户无需数据库背景即可快速完成复杂条件筛选与可视化。利用 CanDI,研究者在卵巢癌和乳腺癌模型中发现了 BRCA1 突变背景下 Fanconi Anemia 通路的合成致死性;在 KRAS 与 EGFR 突变 NSCLC 模型中评估了基因条件必需性;首次系统揭示了男性与女性 KRAS 突变结直肠癌、胰腺癌和肺癌模型中的性别差异必需基因;并整合外部支气管上皮 RNA-seq 数据,提名了 12 个定位于细胞膜、在 KRAS/EGFR 突变 NSCLC 中显著上调的潜在免疫治疗靶点。CanDI 以灵活、可扩展的方式降低了大规模癌症数据整合门槛,为发现新靶点、解释性别差异及设计联合治疗策略提供了高效工具。
Abstract:
AbstractBackgroundAdvances in cancer biology are increasingly dependent on integration of heterogeneous datasets. Large-scale efforts have systematically mapped many aspects of cancer cell biology; however, it remains challenging for individual scientists … >>>
AbstractBackgroundAdvances in cancer biology are increasingly dependent on integration of heterogeneous datasets. Large-scale efforts have systematically mapped many aspects of cancer cell biology; however, it remains challenging for individual scientists to effectively integrate and understand this data.ResultsWe have developed a new data retrieval and indexing framework that allows us to integrate publicly available data from different sources and to combine publicly available data with new or bespoke datasets. Our approach, which we have named the cancer data integrator (CanDI), is straightforward to implement, is well documented, and is continuously updated which should enable individual users to take full advantage of efforts to map cancer cell biology. We show that CanDI empowered testable hypotheses of new synthetic lethal gene pairs, genes associated with sex disparity, and immunotherapy targets in cancer.ConclusionsCanDI provides a flexible approach for large-scale data integration in cancer research enabling rapid generation of hypotheses. The CanDI data integrator is available athttps://github.com/GilbertLabUCSF/CanDI. <<<
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2.
sqc (2025-06-28 15:11):
#paper 【doi】10.1038/s41590-024-01932-8 【发表年份】2024年 【期刊】Nature Immunology 【标题】Tumor editing suppresses innate and adaptive antitumor immunity and is reversed by inhibiting DNA methylation 【内容总结】 这篇论文研究了肿瘤在发生过程中通过基因调控逃避免疫监视的机制,并探索了DNA甲基化抑制剂恢复免疫控制的可能性。研究人员使用转基因乳腺癌小鼠模型,比较了早期(5–10天)和晚期(30–35天)肿瘤的单细胞RNA测序结果,发现晚期肿瘤中主要下调的是固有免疫和适应性免疫相关基因,特别是干扰素信号通路和相关刺激基因(ISGs),而与增殖相关的恶性基因表达几乎不变。进一步实验表明,DNA甲基化抑制剂低剂量地西他滨(decitabine, DAC)可以逆转这些免疫基因的沉默,显著抑制肿瘤生长,提高肿瘤浸润性T细胞(CD8+、CD4+、NK细胞)的数量、功能和记忆性,并降低免疫抑制性髓系细胞比例。此外,DAC能诱导肿瘤细胞中坏死性凋亡和焦亡相关基因(如Ripk3、Gsdmd、Gsdme)的表达和炎性细胞死亡,从而增强免疫清除效应。简单说就是,肿瘤通过DNA甲基化沉默免疫基因逃避免疫,而抑制甲基化可以“解锁”这些免疫通路,重新激活对肿瘤的天然和适应性免疫控制。
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