Laboratory of Bioinformatics, BioMathematics and Biostatistics (LR16IPT09), Pasteur Institute of Tunisia, University of Tunis El Manar, 1002 Tunis, Tunisia.
Laboratory of Biotechnology and Bio-Geo Resources Valorization (LR11ES31), Higher Institute for Biotechnology, University of Manouba-Biotechpole of Sidi Thabet, 2020, Sidi Thabet, Ariana, Tunisia.
Biomed Res Int. 2020 Nov 27;2020:4280467. doi: 10.1155/2020/4280467. eCollection 2020.
Orphan diseases (ODs) are progressive genetic disorders, which affect a small number of people. The principal fundamental aspects related to these diseases include insufficient knowledge of mechanisms involved in the physiopathology necessary to access correct diagnosis and to develop appropriate healthcare. Unlike ODs, complex diseases (CDs) have been widely studied due to their high incidence and prevalence allowing to understand the underlying mechanisms controlling their physiopathology. Few studies have focused on the relationship between ODs and CDs to identify potential shared pathways and related molecular mechanisms which would allow improving disease diagnosis, prognosis, and treatment. We have performed a computational approach to studying CDs and ODs relationships through (1) connecting diseases to genes based on genes-diseases associations from public databases, (2) connecting ODs and CDs through binary associations based on common associated genes, and (3) linking ODs and CDs to common enriched pathways. Among the most shared significant pathways between ODs and CDs, we found pathways in cancer, p53 signaling, mismatch repair, mTOR signaling, B cell receptor signaling, and apoptosis pathways. Our findings represent a reliable resource that will contribute to identify the relationships between drugs and disease-pathway networks, enabling to optimise patient diagnosis and disease treatment.
罕见病（ODs）是一种进行性遗传疾病，影响少数人群。与这些疾病相关的主要基本方面包括对生理病理学中涉及的机制缺乏了解，这些机制是进行正确诊断和制定适当医疗保健措施所必需的。与 ODs 不同，复杂疾病（CDs）由于其高发病率和患病率而得到了广泛研究，从而可以了解控制其生理病理学的潜在机制。很少有研究关注 ODs 和 CDs 之间的关系，以确定潜在的共享途径和相关的分子机制，从而可以改善疾病的诊断、预后和治疗。我们通过（1）根据公共数据库中的基因-疾病关联将疾病与基因联系起来，（2）通过基于共同相关基因的二元关联将 ODs 和 CDs 联系起来，（3）将 ODs 和 CDs 与常见的富集途径联系起来，对 CDs 和 ODs 之间的关系进行了计算方法研究。在 ODs 和 CDs 之间最常见的显著途径中，我们发现了癌症、p53 信号转导、错配修复、mTOR 信号转导、B 细胞受体信号转导和细胞凋亡途径。我们的研究结果代表了一个可靠的资源，有助于识别药物与疾病途径网络之间的关系，从而能够优化患者的诊断和疾病治疗。
