Chikina Maria D, Huttenhower Curtis, Murphy Coleen T, Troyanskaya Olga G
Department of Molecular Biology, Princeton University, Princeton, New Jersey, USA.
PLoS Comput Biol. 2009 Jun;5(6):e1000417. doi: 10.1371/journal.pcbi.1000417. Epub 2009 Jun 19.
Tissue-specific gene expression plays a fundamental role in metazoan biology and is an important aspect of many complex diseases. Nevertheless, an organism-wide map of tissue-specific expression remains elusive due to difficulty in obtaining these data experimentally. Here, we leveraged existing whole-animal Caenorhabditis elegans microarray data representing diverse conditions and developmental stages to generate accurate predictions of tissue-specific gene expression and experimentally validated these predictions. These patterns of tissue-specific expression are more accurate than existing high-throughput experimental studies for nearly all tissues; they also complement existing experiments by addressing tissue-specific expression present at particular developmental stages and in small tissues. We used these predictions to address several experimentally challenging questions, including the identification of tissue-specific transcriptional motifs and the discovery of potential miRNA regulation specific to particular tissues. We also investigate the role of tissue context in gene function through tissue-specific functional interaction networks. To our knowledge, this is the first study producing high-accuracy predictions of tissue-specific expression and interactions for a metazoan organism based on whole-animal data.
组织特异性基因表达在多细胞动物生物学中起着基础性作用,并且是许多复杂疾病的一个重要方面。然而,由于通过实验获取这些数据存在困难,全生物体范围的组织特异性表达图谱仍然难以捉摸。在这里,我们利用现有的代表不同条件和发育阶段的秀丽隐杆线虫全动物微阵列数据,来生成组织特异性基因表达的准确预测,并通过实验验证了这些预测。这些组织特异性表达模式对于几乎所有组织而言都比现有的高通量实验研究更为准确;它们还通过解决特定发育阶段和小组织中存在的组织特异性表达来补充现有实验。我们利用这些预测来解决几个实验上具有挑战性的问题,包括鉴定组织特异性转录基序以及发现特定于特定组织的潜在miRNA调控。我们还通过组织特异性功能相互作用网络研究组织背景在基因功能中的作用。据我们所知,这是第一项基于全动物数据对后生动物的组织特异性表达和相互作用进行高精度预测的研究。