A Boolean approach for novel hypoxia-related gene discovery.
A Boolean approach for novel hypoxia-related gene discovery.
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DOI：
10.1371/journal.pone.0273524
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发表时间：
2022
期刊：
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
无论是心血管疾病、癌症、呼吸系统疾病还是中风，缺氧在大多数发病和死亡的主要原因的病因和发病机制中起着重要作用。尽管对缺氧信号通路的研究很活跃，但对调节机制的理解，特别是在特定组织中，仍然是难以捉摸的。随着数千个潜在的不同基因组数据集的可访问性，计算方法被用来生成新的假设。在此，我们利用布尔蕴涵关系，一个强大的方法来探测对称和不对称相关基因，以确定新的缺氧相关基因。我们使用了一个众所周知的缺氧反应基因，VEGFA，与非常大的人类表达数据集（n = 25，955），以确定新的缺氧反应候选基因。此外，我们使用暴露于1%O2环境2、8、24和48小时的人内皮细胞进行体外分析，以验证最佳候选基因。在前几位候选基因（n = 19）中，84%的基因先前被报道为缺氧相关，验证了我们的结果。然而，我们确定FAM114A1作为一个新的候选基因显着上调的内皮细胞在8，24和48小时的1%O2环境。其他证据，特别是内含子miRNA和许多HRE的定位进一步支持和加强了我们的发现。目前FAM114A1的结果提供了一个例子，展示了强大的计算方法的效用，如布尔蕴涵，在假设建立和发现中发挥了重要作用。
Hypoxia plays a major role in the etiology and pathogenesis of most of the leading causes of morbidity and mortality, whether cardiovascular diseases, cancer, respiratory diseases or stroke. Despite active research on hypoxia-signaling pathways, the understanding of regulatory mechanisms, especially in specific tissues, still remain elusive. With the accessibility of thousands of potentially diverse genomic datasets, computational methods are utilized to generate new hypotheses. Here we utilized Boolean implication relationship, a powerful method to probe symmetrically and asymmetrically related genes, to identify novel hypoxia related genes. We used a well-known hypoxia-responsive gene, VEGFA, with very large human expression datasets (n = 25,955) to identify novel hypoxia-responsive candidate gene/s. Further, we utilized in-vitro analysis using human endothelial cells exposed to 1% O2 environment for 2, 8, 24 and 48 hours to validate top candidate genes. Out of the top candidate genes (n = 19), 84% genes were previously reported as hypoxia related, validating our results. However, we identified FAM114A1 as a novel candidate gene significantly upregulated in the endothelial cells at 8, 24 and 48 hours of 1% O2 environment. Additional evidence, particularly the localization of intronic miRNA and numerous HREs further support and strengthen our finding. Current results on FAM114A1 provide an example demonstrating the utility of powerful computational methods, like Boolean implications, in playing a major role in hypothesis building and discovery.
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影响因子：
4.4
作者：
Abe H;Semba H;Takeda N
通讯作者：
Takeda N
影响因子：
2.1
作者：
ErŽen B;Šilar M;Šabovič M
通讯作者：
Šabovič M
影响因子：
20.3
作者：
Manalo, DJ;Rowan, A;Semenza, GL
通讯作者：
Semenza, GL
DOI：
10.1111/j.1749-6632.2012.06668.x
发表时间：
2012-01-01
期刊：
THROMBOLYSIS AND ACUTE STROKE TREATMENT: PREPARING FOR THE NEXT DECADE
影响因子：
--
作者：
Heiss, Wolf-Dieter
通讯作者：
Heiss, Wolf-Dieter
影响因子：
4.4
作者：
Chandel, NS;Trzyna, WC;Schumacker, PT
通讯作者：
Schumacker, PT