School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea.
School of Computer Science and Engineering, Kyungsung University, Busan 48434, Republic of Korea.
Nucleic Acids Res. 2019 May 21;47(9):e53. doi: 10.1093/nar/gkz139.
We present a novel approach to identify human microRNA (miRNA) regulatory modules (mRNA targets and relevant cell conditions) by biclustering a large collection of mRNA fold-change data for sequence-specific targets. Bicluster targets were assessed using validated messenger RNA (mRNA) targets and exhibited on an average 17.0% (median 19.4%) improved gain in certainty (sensitivity + specificity). The net gain was further increased up to 32.0% (median 33.4%) by incorporating functional networks of targets. We analyzed cancer-specific biclusters and found that the PI3K/Akt signaling pathway is strongly enriched with targets of a few miRNAs in breast cancer and diffuse large B-cell lymphoma. Indeed, five independent prognostic miRNAs were identified, and repression of bicluster targets and pathway activity by miR-29 was experimentally validated. In total, 29 898 biclusters for 459 human miRNAs were collected in the BiMIR database where biclusters are searchable for miRNAs, tissues, diseases, keywords and target genes.
我们提出了一种新的方法，通过对大量序列特异性靶标 mRNA 折叠变化数据进行双聚类，来识别人类 microRNA（miRNA）调节模块（mRNA 靶标和相关细胞条件）。使用经过验证的信使 RNA（mRNA）靶标评估双聚类靶标，平均提高了 17.0%（中位数为 19.4%）的确定性增益（敏感性+特异性）。通过整合靶标的功能网络，净增益进一步提高到 32.0%（中位数为 33.4%）。我们分析了癌症特异性的双聚类，发现 PI3K/Akt 信号通路在乳腺癌和弥漫性大 B 细胞淋巴瘤中富含少数 miRNA 的靶标。事实上，鉴定了五个独立的预后 miRNA，实验验证了 miR-29 对双聚类靶标和通路活性的抑制作用。总共收集了 459 个人类 miRNA 的 29898 个双聚类，BiMIR 数据库中可以对 miRNA、组织、疾病、关键字和靶基因进行双聚类搜索。
