Joint IRB-BSC-CRG Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), Barcelona 08028, Spain.
Genomic Instability and Cancer Laboratory, Institute for Research in Biomedicine (IRB Barcelona), Barcelona 08028, Spain.
J Mol Biol. 2015 Mar 27;427(6 Pt B):1436-1450. doi: 10.1016/j.jmb.2015.01.014. Epub 2015 Jan 29.
Despite the remarkable progress achieved in the identification of specific genes involved in breast cancer (BC), our understanding of their complex functioning is still limited. In this manuscript, we systematically explore the existence of direct physical interactions between the products of BC core and associated genes. Our aim is to generate a protein interaction network of BC-associated gene products and suggest potential molecular mechanisms to unveil their role in the disease. In total, we report 599 novel high-confidence interactions among 44 BC core, 54 BC candidate/associated and 96 newly identified proteins. Our findings indicate that this network-based approach is indeed a robust inference tool to pinpoint new potential players and gain insight into the underlying mechanisms of those proteins with previously unknown roles in BC. To illustrate the power of our approach, we provide initial validation of two BC-associated proteins on the alteration of DNA damage response as a result of specific re-wiring interactions. Overall, our BC-related network may serve as a framework to integrate clinical and molecular data and foster novel global therapeutic strategies.
尽管在鉴定乳腺癌 (BC) 相关特定基因方面取得了显著进展，但我们对它们复杂功能的理解仍然有限。在本文中，我们系统地探索了 BC 核心基因和相关基因产物之间是否存在直接的物理相互作用。我们的目的是生成一个 BC 相关基因产物的蛋白质相互作用网络，并提出潜在的分子机制来揭示它们在疾病中的作用。总的来说，我们报告了 44 个 BC 核心基因、54 个 BC 候选/相关基因和 96 个新鉴定蛋白之间的 599 个新的高可信度相互作用。我们的研究结果表明，这种基于网络的方法确实是一种强大的推断工具，可以确定新的潜在参与者，并深入了解那些在 BC 中具有未知作用的蛋白质的潜在机制。为了说明我们方法的强大，我们初步验证了两个与 BC 相关的蛋白质在特定重布线相互作用下对 DNA 损伤反应的改变。总的来说，我们的 BC 相关网络可以作为一个框架，整合临床和分子数据，并促进新的全局治疗策略。
