Reddy Panga Jaipal, Ray Sandipan, Srivastava Sanjeeva
Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay , Powai, Mumbai, India .
OMICS. 2015 May;19(5):276-82. doi: 10.1089/omi.2015.0035.
Given the diverse range of transcriptional and post-transcriptional mechanisms of gene regulation, the estimates of the human proteome is likely subject to scientific surprises as the field of proteomics has gained momentum worldwide. In this regard, the establishment of the "Human Proteome Draft" using high-resolution mass spectrometry (MS), tissue microarrays, and immunohistochemistry by three independent research groups (laboratories of Pandey, Kuster, and Uhlen) accelerated the pace of proteomics research. The Chromosome Centric Human Proteome Project (C-HPP) has taken initiative towards the completion of the Human Proteome Project (HPP) so as to understand the proteomics correlates of common complex human diseases and biological diversity, not to mention person-to-person and population differences in response to drugs, nutrition, vaccines, and other health interventions and host-environment interactions. Although high-resolution MS-based and antibody microarray approaches have shown enormous promises, we are still unable to map the whole human proteome due to the presence of numerous "missing proteins." In December 2014, at the Indian Institute of Technology Bombay, Mumbai the 6(th) Annual Meeting of the Proteomics Society, India (PSI) and the International Proteomics Conference was held. As part of this interdisciplinary summit, a panel discussion session on "The Quest of the Human Proteome and Missing Proteins" was organized. Eminent scientists in the field of proteomics and systems biology, including Akhilesh Pandey, Gilbert S. Omenn, Mark S. Baker, and Robert L. Mortiz, shed light on different aspects of the human proteome drafts and missing proteins. Importantly, the possible reasons for the "missing proteins" in shotgun MS workflow were identified and debated by experts as low tissue expression, lack of enzymatic digestion site, or protein lost during extraction, among other contributing factors. To capture the missing proteins, the experts' collective view was to study the wider tissue range with multiple digesting enzymes and follow targeted proteomics workflow in particular. On the innovation trajectory from the proteomics laboratory to novel proteomics diagnostics and therapeutics in society, we will also need new conceptual frames for translation science and innovation strategy in proteomics. These will embody both technical as well as rigorous social science and humanities considerations to understand the correlates of the proteome from cell to society.
鉴于基因调控在转录和转录后机制方面具有多样性，随着蛋白质组学领域在全球范围内蓬勃发展，对人类蛋白质组的估计可能会出现一些科学上的意外发现。在这方面，三个独立研究小组（潘迪实验室、库斯特实验室和乌伦实验室）利用高分辨率质谱（MS）、组织微阵列和免疫组织化学技术建立了“人类蛋白质组草图”，加快了蛋白质组学研究的步伐。染色体中心人类蛋白质组计划（C-HPP）已率先推动人类蛋白质组计划（HPP）的完成，以便了解常见复杂人类疾病和生物多样性的蛋白质组学关联，更不用说个体之间以及群体在药物、营养、疫苗和其他健康干预措施的反应以及宿主与环境相互作用方面的差异。尽管基于高分辨率MS和抗体微阵列的方法显示出巨大潜力，但由于存在大量“缺失蛋白质”，我们仍然无法绘制出完整的人类蛋白质组图谱。2014年12月，在印度孟买的印度理工学院举行了印度蛋白质组学协会（PSI）第六届年会和国际蛋白质组学会议。作为这次跨学科峰会的一部分，组织了一场关于“人类蛋白质组与缺失蛋白质的探索”的小组讨论会议。蛋白质组学和系统生物学领域的知名科学家，包括阿基莱什·潘迪、吉尔伯特·S·奥门、马克·S·贝克和罗伯特·L·莫里茨，对人类蛋白质组草图和缺失蛋白质的不同方面进行了深入探讨。重要的是，专家们确定并讨论了鸟枪法MS工作流程中“缺失蛋白质”的可能原因，如低组织表达、缺乏酶切位点或提取过程中蛋白质丢失等其他影响因素。为了捕获缺失蛋白质，专家们的共同观点是使用多种消化酶研究更广泛的组织范围，尤其要遵循靶向蛋白质组学工作流程。在从蛋白质组学实验室到社会新型蛋白质组学诊断和治疗方法的创新轨迹上，我们还需要蛋白质组学翻译科学和创新战略的新的概念框架。这些框架将体现技术以及严谨的社会科学和人文考量，以便从细胞到社会理解蛋白质组的关联。
