Department of Bioinformatics, Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran.
Institute of Parasitology, McGill University, Montreal, QC, Canada.
Comput Biol Med. 2014 Nov;54:24-31. doi: 10.1016/j.compbiomed.2014.08.020. Epub 2014 Aug 26.
The human Y chromosome contains a small number of genes that play a critical role in the determination of male-specific organs. Today's advances have provided valuable resources for defining the functions of this chromosome in both normal and cancerous prostates. Despite the fact that generation of high-throughput expression data is becoming usual; the systematic methods of data analysis in a biological context are still an impediment. Here we have shown that constructing co-expression networks using Y-chromosome genes provides an alternative strategy for the detection of new candidate genes involved in prostate cancer. In our approach, independent co-expression networks from normal and cancerous stages are reconstructed using a reverse engineering approach. We then highlight crucial pathways, biological processes, and genes involved in the prostate cancer by analyzing each network individually and in concert. Thus, we have identified 18 critical pathways and processes related to prostate cancer, many of which have previously been shown to be involved in cancer. In particular, we identify 22 Y-chromosome genes putatively linked to prostate cancer, 13 of which have been already verified experimentally. Our novel network-based approach is useful for accurate inference of processes and essential regulators that mediate molecular changes during cancer progression.
人类的 Y 染色体包含少量的基因,这些基因在决定男性特有的器官方面起着关键作用。如今的进展为定义这条染色体在正常和癌变前列腺中的功能提供了宝贵的资源。尽管生成高通量表达数据已经变得很常见,但在生物学背景下进行系统的数据分析方法仍然是一个障碍。在这里,我们已经表明,使用 Y 染色体基因构建共表达网络为检测新的候选基因提供了一种替代策略,这些基因涉及前列腺癌。在我们的方法中,使用反向工程方法分别重建来自正常和癌变阶段的独立共表达网络。然后,我们通过单独和协同分析每个网络,突出显示涉及前列腺癌的关键途径、生物过程和基因。因此,我们确定了 18 个与前列腺癌相关的关键途径和过程,其中许多已经被证明与癌症有关。特别是,我们确定了 22 个可能与前列腺癌相关的 Y 染色体基因,其中 13 个已经通过实验验证。我们的新网络方法可用于准确推断在癌症进展过程中介导分子变化的过程和基本调节剂。