PO.BCS01.12 · 生物信息与计算

TNMplot 2.0:面向肿瘤学靶点发现的分期解析与泛癌转录组分析

TNMplot 2.0: Stage-resolved and pan-cancer transcriptomic analytics for target discovery in oncology

海报缩略图:TNMplot 2.0:面向肿瘤学靶点发现的分期解析与泛癌转录组分析
编号 5523 展板 28 时间 4/21 02:00–05:00 区域 Section 4 主讲 Balazs Gyorffy, MD;PhD
分会场 New Software Tools for Data Analysis
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作者与单位 Authors & Affiliations

Aron Baratha, Balazs Gyorffy

Semmelweis University, Budapest, Hungary

摘要 Abstract

中文摘要
背景。TNMplot.com 是一个基于网络的资源,整合了来自 56,938 个样本的 RNA-Seq 和基因芯片数据,能够在 22 种癌症类型中对正常组织、原发肿瘤和转移组织之间进行差异基因表达分析。在此,我们建立了 TNMplot 数据库的更新版本,具备推进药理学和转化肿瘤学研究的新功能。 方法。我们利用来自乳腺癌(n=2,331)、结直肠癌(n=648)、肺癌(n=1,399)、皮肤癌(n=82)和前列腺癌(n=61)的 4,521 个肿瘤,实现了一个基于分期的表达模块。我们增加了泛癌点阵可视化,并扩展了多基因工具,包括密度分析、相关性矩阵、相关性谱、特征评估和 targetgram 分析。利用整合的数据库,我们进行了并行的 RNA-seq 和微阵列验证,以识别可成药候选靶点。 结果。分期模块用于评估与肿瘤进展和治疗时机相关的单个基因。多基因和泛癌功能能够快速绘制可成药通路和共表达结构。跨平台筛选凸显了 MET(p = 5.1e-69)、FGFR4(p = 1.59e-49)和 EZH2(p = 1.08e-54)作为在晚期结肠癌中可用于药物再利用的稳健的进展相关候选靶点。对失调的结肠癌基因进行的另一项筛选,通过 ≥2 倍的表达变化和 ChEMBL 匹配,识别出 16 个 FDA 批准的药物靶点,其中 LY6E 和 CDK1 各自超过了 3 倍的差异阈值。完整的合并数据库已整合到我们的分析平台,可在 www.tnmplot.com 访问。 结论。升级后的 TNMplot 平台提供了一个统一、高保真的环境,用于在多种癌症中进行进展分析、生物标志物发现和药理学靶点优先级排序。该数据库的一个独特之处在于对 RNA-seq 和基因阵列队列的并行分析,能够对候选生物标志物进行稳健的跨平台验证。
查看英文原文 English abstract
BACKGROUND. TNMplot.com is a web-based resource that integrates RNA-Seq and gene-chip data from 56,938 samples, enabling differential gene expression analysis among normal, primary tumor, and metastatic tissues across 22 cancer types. Here, an updated version of the TNMplot database was established featuring new capabilities that advance pharmacological and translational oncology research. METHODS. We implemented a stage-based expression module using 4,521 tumors from breast (n=2,331), colorectal (n=648), lung (n=1,399), skin (n=82), and prostate (n=61) cancer. We added pan-cancer dot-matrix visualization and extended multi-gene tools including density analyses, correlation matrices, correlation profiling, signature evaluation, and targetgram analysis. Using the integrated database, we performed parallel RNA-seq and microarray validation to identify druggable candidates. RESULTS. The stage module was used to evaluate isolated genes linked to tumor progression and therapeutic timing. Multi-gene and pan-cancer functions enabled rapid mapping of druggable pathways and co-expression structures. Cross-platform filtering highlighted MET (p = 5.1e-69), FGFR4 (p = 1.59e-49), and EZH2 (p = 1.08e-54) as robust progression-associated candidates for repurposing in advanced colon cancer. A separate screening of dysregulated colon cancer genes identified 16 FDA-approved drug targets through ≥2-fold expression changes and ChEMBL matching, with LY6E and CDK1 each surpassing a 3-fold differential threshold. The complete combined database was integrated into our analysis platform available at www.tnmplot.com. CONCLUSIONS. The upgraded TNMplot platform provides a unified, high-fidelity environment for progression analysis, biomarker discovery, and pharmacological target prioritization across multiple cancers. A unique feature of the database is the parallel analysis of RNA-seq and gene array cohorts, enabling robust cross-platform validation of candidate biomarkers.
利益披露 Disclosure
A. Baratha, None.. B. Gyorffy, None.

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