SexAnnoDB，人类癌的多摩学数据的性别特定法规的知识基础

分子水平的性差异对癌症生物学和结果深远影响。患者性别显着影响药物反应，男女对同一药物的反应有分歧。尽管人类组织中性别差异的数据库，但了解癌症性别差异的法规仍然有限。这些资源缺乏有关性别偏见分子的详细机理研究。在这项研究中，我们对27种癌症类型的分子区别和调节网络进行了全面检查，并深入研究了性偏见的作用。我们的分析涵盖了性行为竞争性的内源性RNA网络，涉及性别偏见的RNA结合蛋白蛋白质外观的调节网络跳过事件，性偏见的转录因子调节网络，以及性别偏见的性偏见定量表达表达性表达性特征，性别偏见的性别鉴定性鉴定性性疾病，鉴定性别性甲基甲基化的性别典型的甲基化甲基化性甲基化的甲基化性特征，特性属于性能，特性，特性，特性，特性，特性，特性，特性，特征，鉴定性质治疗药物靶基因。这些分析中的所有发现均可在SEXANNODB（https://ccsm.uth.edu/sexannodb/）上访问。从这些分析中，我们定义了126个癌症治疗靶标性相关基因。其中，有9个基因在mRNA和蛋白质水平上均显示出性别偏见。具体而言，S100A9是五种药物的靶标，其中FDA已批准钙用于治疗结肠和直肠癌。转录因子（TF） - 基因调节网络分析表明，SARC雄性组的四个TF针对S100A9，并上调了这些患者的S100A9的表达。启动子区域甲基化状态仅与KIRP女性患者的S100A9表达有关。高甲基化抑制了S100A9的表达，并导致这些女性患者的S100A9下调。Comhearsive网络和关联分析表明，转录组水平的性别差异部分是相应性别偏见的表观遗传和遗传分子的结果。总体而言，SexAnnoDB提供了一个特定于学科的搜索平台，该平台可能有可能帮助基本的实验研究人员或医生制定个性化的治疗计划。

Sexual differences across molecular levels profoundly impact cancer biology and outcomes. Patient gender significantly influences drug responses, with divergent reactions between men and women to the same drugs. Despite databases on sex differences in human tissues, understanding regulations of sex disparities in cancer is limited. These resources lack detailed mechanistic studies on sex-biased molecules.In this study, we conducted a comprehensive examination of molecular distinctions and regulatory networks across 27 cancer types, delving into sex-biased effects. Our analyses encompassed sex-biased competitive endogenous RNA networks, regulatory networks involving sex-biased RNA binding protein-exon skipping events, sex-biased transcription factor-gene regulatory networks, as well as sex-biased expression quantitative trait loci, sex-biased expression quantitative trait methylation, sex-biased splicing quantitative trait loci, and the identification of sex-biased cancer therapeutic drug target genes. All findings from these analyses are accessible on SexAnnoDB ( https://ccsm.uth.edu/SexAnnoDB/ ).From these analyses, we defined 126 cancer therapeutic target sex-associated genes. Among them, 9 genes showed sex-biased at both the mRNA and protein levels. Specifically, S100A9 was the target of five drugs, of which calcium has been approved by the FDA for the treatment of colon and rectal cancers. Transcription factor (TF)-gene regulatory network analysis suggested that four TFs in the SARC male group targeted S100A9 and upregulated the expression of S100A9 in these patients. Promoter region methylation status was only associated with S100A9 expression in KIRP female patients. Hypermethylation inhibited S100A9 expression and was responsible for the downregulation of S100A9 in these female patients.Comprehensive network and association analyses indicated that the sex differences at the transcriptome level were partially the result of corresponding sex-biased epigenetic and genetic molecules. Overall, SexAnnoDB offers a discipline-specific search platform that could potentially assist basic experimental researchers or physicians in developing personalized treatment plans.