Laboratory for Neurobiology of Psychiatric Disorders, Sagol Department of Neurobiology, University of Haifa, Haifa 3498838, Israel.
Int J Mol Sci. 2021 Sep 13;22(18):9870. doi: 10.3390/ijms22189870.
Angelman-like syndromes are a group of neurodevelopmental disorders that entail clinical presentation similar to Angelman Syndrome (AS). In our previous study, we showed that calcium signaling is disrupted in AS, and we identified calcium-target and calcium-regulating gene signatures that are able to differentiate between AS and their controls in different models. In the herein study, we evaluated these sets of calcium-target and calcium-regulating genes as signatures of AS-like and non-AS-like syndromes. We collected a number of RNA-seq datasets of various AS-like and non-AS-like syndromes and performed Principle Component Analysis (PCA) separately on the two sets of signature genes to visualize the distribution of samples on the PC1-PC2 plane. In addition to the evaluation of calcium signature genes, we performed differential gene expression analyses to identify calcium-related genes dysregulated in each of the studied syndromes. These analyses showed that the calcium-target and calcium-regulating signatures differentiate well between AS-like syndromes and their controls. However, in spite of the fact that many of the non-AS-like syndromes have multiple differentially expressed calcium-related genes, the calcium signatures were not efficient classifiers for non-AS-like neurodevelopmental disorders. These results show that features based on clinical presentation are reflected in signatures derived from bioinformatics analyses and suggest the use of bioinformatics as a tool for classification.
天使综合征样综合征是一组神经发育障碍，其临床表现与天使综合征（AS）相似。在我们之前的研究中，我们表明钙信号在 AS 中被破坏，并且我们确定了钙靶向和钙调节基因特征，这些特征能够区分不同模型中的 AS 与其对照。在本研究中，我们将这些钙靶向和钙调节基因集作为 AS 样和非 AS 样综合征的特征进行评估。我们收集了许多各种 AS 样和非 AS 样综合征的 RNA-seq 数据集，并分别对这两组特征基因进行主成分分析（PCA），以可视化样本在 PC1-PC2 平面上的分布。除了评估钙特征基因外，我们还进行了差异表达基因分析，以确定在每个研究综合征中失调的钙相关基因。这些分析表明，钙靶向和钙调节特征可以很好地区分 AS 样综合征及其对照。然而，尽管许多非 AS 样综合征有多个差异表达的钙相关基因，但钙特征对于非 AS 样神经发育障碍不是有效的分类器。这些结果表明基于临床表现的特征反映在生物信息学分析中得出的特征中，并表明将生物信息学用作分类工具。
