Vantini Michele, Mannerström Henrik, Rautio Sini, Ahlfors Helena, Stockinger Brigitta, Lähdesmäki Harri
Department of Computer Science, Aalto University, Konemiehentie 2, Espoo, 02 150, Finland.
The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, United Kingdom.
Comput Biol Med. 2022 Apr;143:105268. doi: 10.1016/j.compbiomed.2022.105268. Epub 2022 Jan 26.
High-throughput technologies produce gene expression time-series data that need fast and specialized algorithms to be processed. While current methods already deal with different aspects, such as the non-stationarity of the process and the temporal correlation, they often fail to take into account the pairing among replicates. We propose PairGP, a non-stationary Gaussian process method to compare gene expression time-series across several conditions that can account for paired longitudinal study designs and can identify groups of conditions that have different gene expression dynamics. We demonstrate the method on both simulated data and previously unpublished RNA sequencing (RNA-seq) time-series with five conditions. The results show the advantage of modeling the pairing effect to better identify groups of conditions with different dynamics. The pairing effect model displays good capabilities of selecting the most probable grouping of conditions even in the presence of a high number of conditions. The developed method is of general application and can be applied to any gene expression time series dataset. The model can identify common replicate effects among the samples coming from the same biological replicates and model those as separate components. Learning the pairing effect as a separate component, not only allows us to exclude it from the model to get better estimates of the condition effects, but also to improve the precision of the model selection process. The pairing effect that was accounted before as noise, is now identified as a separate component, resulting in more accurate and explanatory models of the data.
高通量技术产生的基因表达时间序列数据需要快速且专门的算法来处理。虽然当前方法已经处理了不同方面的问题,比如过程的非平稳性和时间相关性,但它们往往没有考虑重复样本之间的配对关系。我们提出了PairGP,一种非平稳高斯过程方法,用于比较多种条件下的基因表达时间序列,该方法能够考虑配对纵向研究设计,并能够识别具有不同基因表达动态的条件组。我们在模拟数据和之前未发表的包含五种条件的RNA测序(RNA-seq)时间序列上演示了该方法。结果显示了对配对效应进行建模以更好地识别具有不同动态的条件组的优势。即使在存在大量条件的情况下,配对效应模型在选择最可能的条件分组方面也表现出良好的能力。所开发的方法具有广泛的适用性,可应用于任何基因表达时间序列数据集。该模型可以识别来自相同生物学重复的样本之间的共同重复效应,并将其作为单独的成分进行建模。将配对效应作为一个单独的成分来学习,不仅使我们能够将其从模型中排除以更好地估计条件效应,还能提高模型选择过程的精度。之前被视为噪声的配对效应,现在被识别为一个单独的成分,从而产生更准确且更具解释性的数据模型。
Comput Biol Med. 2022-4
Early Hum Dev. 2020-11
Cochrane Database Syst Rev. 2022-2-1
Stat Appl Genet Mol Biol. 2010
Nucleic Acids Res. 2012-1-28
Proc Natl Acad Sci U S A. 2014-12-23
Genes (Basel). 2021-2-27