Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
Department of Geosciences and Geography, University of Helsinki, Helsinki, Finland.
PLoS Comput Biol. 2021 Sep 10;17(9):e1008947. doi: 10.1371/journal.pcbi.1008947. eCollection 2021 Sep.
Although most genes share their chromosomal neighbourhood with other genes, distribution of genes has not been explored in the context of individual organ development; the common focus of developmental biology studies. Because developmental processes are often associated with initially subtle changes in gene expression, here we explored whether neighbouring genes are informative in the identification of differentially expressed genes. First, we quantified the chromosomal neighbourhood patterns of genes having related functional roles in the mammalian genome. Although the majority of protein coding genes have at least five neighbours within 1 Mb window around each gene, very few of these neighbours regulate development of the same organ. Analyses of transcriptomes of developing mouse molar teeth revealed that whereas expression of genes regulating tooth development changes, their neighbouring genes show no marked changes, irrespective of their level of expression. Finally, we test whether inclusion of gene neighbourhood in the analyses of differential expression could provide additional benefits. For the analyses, we developed an algorithm, called DELocal that identifies differentially expressed genes by comparing their expression changes to changes in adjacent genes in their chromosomal regions. Our results show that DELocal removes detection bias towards large changes in expression, thereby allowing identification of even subtle changes in development. Future studies, including the detection of differential expression, may benefit from, and further characterize the significance of gene-gene neighbour relationships.
尽管大多数基因都与其染色体附近的其他基因共享位置,但基因的分布尚未在单个器官发育的背景下进行探索,这是发育生物学研究的共同重点。因为发育过程通常与基因表达的最初细微变化有关,所以我们在这里探讨了邻近基因是否可以提供关于差异表达基因的信息。首先,我们在哺乳动物基因组中具有相关功能作用的基因中量化了其染色体附近的模式。尽管大多数编码蛋白的基因在每个基因周围 1Mb 窗口内至少有 5 个相邻基因,但这些相邻基因中很少有调节相同器官发育的基因。对发育中的小鼠磨牙的转录组分析表明,虽然调节牙齿发育的基因的表达发生变化,但它们的相邻基因的表达没有明显变化,无论其表达水平如何。最后,我们测试了在差异表达分析中包含基因邻域是否可以提供额外的好处。为此,我们开发了一种名为 DELocal 的算法,该算法通过比较其表达变化与染色体区域中相邻基因的变化来识别差异表达的基因。我们的结果表明,DELocal 消除了对表达大变化的检测偏差,从而可以识别出发育过程中的细微变化。未来的研究,包括差异表达的检测,可能会受益于并进一步表征基因-基因邻域关系的重要性。