Program in Emerging Infectious Diseases, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore.
Centre for Computational Biology, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore.
Brief Bioinform. 2024 Jul 25;25(5). doi: 10.1093/bib/bbae452.
High-throughput experiments often produce ranked gene outputs, with forward genetic screening being a notable example. While there are various tools for analyzing individual datasets, those that perform comparative and meta-analytical examination of such ranked gene lists remain scarce. Here, we introduce Gene Rank Meta Analyzer (GeneRaMeN), an R Shiny tool utilizing rank statistics to facilitate the identification of consensus, unique, and correlated genes across multiple hit lists. We focused on two key topics to showcase GeneRaMeN: virus host factors and cancer dependencies. Using GeneRaMeN 'Rank Aggregation', we integrated 24 published and new flavivirus genetic screening datasets, including dengue, Japanese encephalitis, and Zika viruses. This meta-analysis yielded a consensus list of flavivirus host factors, elucidating the significant influence of cell line selection on screening outcomes. Similar analysis on 13 SARS-CoV-2 CRISPR screening datasets highlighted the pivotal role of meta-analysis in revealing redundant biological pathways exploited by the virus to enter human cells. Such redundancy was further underscored using GeneRaMeN's 'Rank Correlation', where a strong negative correlation was observed for host factors implicated in one entry pathway versus the alternate route. Utilizing GeneRaMeN's 'Rank Uniqueness', we analyzed human coronaviruses 229E, OC43, and SARS-CoV-2 datasets, identifying host factors uniquely associated with a defined subset of the screening datasets. Similar analyses were performed on over 1000 Cancer Dependency Map (DepMap) datasets spanning 19 human cancer types to reveal unique cancer vulnerabilities for each organ/tissue. GeneRaMeN, an efficient tool to integrate and maximize the usability of genetic screening datasets, is freely accessible via https://ysolab.shinyapps.io/GeneRaMeN.
高通量实验通常会产生基因排序输出,正向遗传筛选就是一个显著的例子。虽然有各种工具可用于分析单个数据集,但用于对这些排序基因列表进行比较和元分析的工具仍然很少。在这里,我们介绍 Gene Rank Meta Analyzer(GeneRaMeN),这是一个利用秩统计来促进识别多个命中列表中一致、独特和相关基因的 R Shiny 工具。我们重点介绍了两个关键主题,以展示 GeneRaMeN:病毒宿主因子和癌症依赖性。使用 GeneRaMeN 的“秩聚合”,我们整合了 24 个已发表和新的黄病毒遗传筛选数据集,包括登革热、日本脑炎和寨卡病毒。这项荟萃分析产生了一个黄病毒宿主因子的共识列表,阐明了细胞系选择对筛选结果的重大影响。对 13 个 SARS-CoV-2 CRISPR 筛选数据集的类似分析强调了元分析在揭示病毒进入人体细胞所利用的冗余生物学途径方面的重要性。使用 GeneRaMeN 的“秩相关性”进一步强调了这种冗余性,观察到一个进入途径所涉及的宿主因子与另一个途径呈强烈负相关。利用 GeneRaMeN 的“秩独特性”,我们分析了人类冠状病毒 229E、OC43 和 SARS-CoV-2 数据集,确定了与定义的筛选数据集子集唯一相关的宿主因子。对跨越 19 种人类癌症类型的超过 1000 个 Cancer Dependency Map(DepMap)数据集进行了类似的分析,揭示了每个器官/组织的独特癌症脆弱性。GeneRaMeN 是一种高效的工具,可用于整合和最大化遗传筛选数据集的可用性,可通过 https://ysolab.shinyapps.io/GeneRaMeN 免费访问。