Improved identification of concordant and discordant gene expression signatures using an updated rank-rank hypergeometric overlap approach.
Improved identification of concordant and discordant gene expression signatures using an updated rank-rank hypergeometric overlap approach.
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DOI：
10.1038/s41598-018-27903-2
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发表时间：
2018-06-25
影响因子：
4.6
通讯作者：
Seney ML
中科院分区：
文献类型：
--
作者：
Cahill KM;Huo Z;Tseng GC;Logan RW;Seney ML
大规模基因表达谱的最新进展需要生物统计学方法的同步发展，以揭示有意义的生物学关系。大多数分析依赖于显著性阈值来识别差异表达基因。我们使用“无阈值”比较的方法来比较基因表达数据集。识别数据集之间共享的基因的显著性截断可能过于严格，并且可能错过具有潜在生物学相关性的基因表达的一致模式。Rank-Rank超几何重叠（rho）是一种无阈值方法，在包括神经科学在内的几个研究领域越来越受欢迎。基因根据其p值和效应大小方向进行排序，并对排序列表进行比较，以便在连续的显著性梯度上识别显著重叠的基因，而不是在单一的任意截止点上。我们更新了之前的rho分析，通过准确地检测两个数据集之间相同和相反方向变化的基因重叠。在这里，我们使用模拟和真实数据来显示以前算法的缺点以及我们的新算法的实用性。例如，我们展示了检测精神疾病患者死后大脑中不一致转录模式的能力。新的R包，RRHO2，提供了一个新的，更直观的和谐和不和谐基因重叠的可视化。
Recent advances in large-scale gene expression profiling necessitate concurrent development of biostatistical approaches to reveal meaningful biological relationships. Most analyses rely on significance thresholds for identifying differentially expressed genes. We use an approach to compare gene expression datasets using ‘threshold-free’ comparisons. Significance cut-offs to identify genes shared between datasets may be too stringent and may miss concordant patterns of gene expression with potential biological relevance. A threshold-free approach gaining popularity in several research areas, including neuroscience, is Rank–Rank Hypergeometric Overlap (RRHO). Genes are ranked by their p-value and effect size direction, and ranked lists are compared to identify significantly overlapping genes across a continuous significance gradient rather than at a single arbitrary cut-off. We have updated the previous RRHO analysis by accurately detecting overlap of genes changed in the same and opposite directions between two datasets. Here, we use simulated and real data to show the drawbacks of the previous algorithm as well as the utility of our new algorithm. For example, we show the power of detecting discordant transcriptional patterns in the postmortem brain of subjects with psychiatric disorders. The new R package, RRHO2, offers a new, more intuitive visualization of concordant and discordant gene overlap.
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影响因子：
14.9
作者：
Ritchie ME;Phipson B;Wu D;Hu Y;Law CW;Shi W;Smyth GK
通讯作者：
Smyth GK
影响因子：
3.8
作者：
Mok S;Tsoi J;Koya RC;Hu-Lieskovan S;West BL;Bollag G;Graeber TG;Ribas A
通讯作者：
Ribas A
男性和女性抑郁症的分子特征相反。
影响因子：
10.6
作者：
Seney ML;Huo Z;Cahill K;French L;Puralewski R;Zhang J;Logan RW;Tseng G;Lewis DA;Sibille E
通讯作者：
Sibille E
影响因子：
16.6
作者：
Li, Jie;Lenferink, Anne E. G.;Deng, Yinghai;Collins, Catherine;Cui, Qinghua;Purisima, Enrico O.;O'Connor-McCourt, Maureen D.;Wang, Edwin
通讯作者：
Wang, Edwin
DOI：
10.1016/j.gpb.2017.02.002
发表时间：
2017-04
期刊：
Genomics, proteomics & bioinformatics
影响因子：
--
作者：
McGee SR;Tibiche C;Trifiro M;Wang E
通讯作者：
Wang E