Roos Andreas, Thompson Rachel, Horvath Rita, Lochmüller Hanns, Sickmann Albert
John Walton Muscular Dystrophy Research Centre, International Centre for Life, Institute of Genetic Medicine, Newcastle upon Tyne, England, UK.
Leibniz-Institut für Analytische Wissenschaften - ISAS - e.V., Dortmund, Germany.
Proteomics Clin Appl. 2018 Mar;12(2). doi: 10.1002/prca.201700073. Epub 2017 Oct 23.
Despite recent rapid advances in sequencing technologies, a significant proportion of patients with rare genetic disorders do not receive a genetic diagnosis after exhaustive testing, and even fewer have a potential therapeutic target identified. Taking rare neuromuscular and neurodegenerative disorders as a paradigm that can be extended to other rare Mendelian disorders, this viewpoint explores the opportunities that are brought about by the integration of genomics and proteomics, as well as the limitations and remaining challenges of this newly emerging field of proteogenomics. The relevance of combining proteomic findings with genetic results for diagnosis and gene discovery is illustrated, highlighting the insights the combined analysis provides into the underlying biology and aetiology as well as the limitations of the experimental techniques. A final discussion focuses on the importance of mechanisms to enable the sharing, reuse, and analysis of source experimental data and describes some of the international initiatives that are making progress in this area.
尽管测序技术最近取得了快速进展，但相当一部分患有罕见遗传疾病的患者在经过详尽检测后仍未得到基因诊断，而确定有潜在治疗靶点的患者更少。以罕见神经肌肉和神经退行性疾病为范例（该范例可扩展到其他罕见孟德尔疾病），本文观点探讨了基因组学和蛋白质组学整合所带来的机遇，以及这个新兴的蛋白质基因组学领域的局限性和尚存的挑战。文中阐述了将蛋白质组学研究结果与基因检测结果相结合用于诊断和基因发现的相关性，强调了联合分析在揭示潜在生物学机制和病因方面所提供的见解以及实验技术的局限性。最后讨论聚焦于实现源实验数据共享、再利用和分析机制的重要性，并介绍了在这一领域取得进展的一些国际倡议。
