Borchers C H, Kast J, Foster L J, Siu K W M, Overall C M, Binkowski T A, Hildebrand W H, Scherer A, Mansoor M, Keown P A
University of Victoria/Genome BC Proteomics Centre, Victoria, BC, Canada.
Biomedical Research Centre, University of British Columbia, Vancouver, BC, Canada.
J Proteomics. 2014 Apr 4;100:60-7. doi: 10.1016/j.jprot.2013.08.001. Epub 2013 Aug 8.
The Human Proteome Project (HPP) is designed to generate a comprehensive map of the protein-based molecular architecture of the human body, to provide a resource to help elucidate biological and molecular function, and to advance diagnosis and treatment of diseases. Within this framework, the chromosome-based HPP (C-HPP) has allocated responsibility for mapping individual chromosomes by country or region, while the biology/disease HPP (B/D-HPP) coordinates these teams in cross-functional disease-based groups. Chromosome 6 (Ch6) provides an excellent model for integration of these two tasks. This metacentric chromosome has a complement of 1002-1034 genes that code for known, novel or putative proteins. Ch6 is functionally associated with more than 120 major human diseases, many with high population prevalence, devastating clinical impact and profound societal consequences. The unique combination of genomic, proteomic, metabolomic, phenomic and health services data being drawn together within the Ch6 program has enormous potential to advance personalized medicine by promoting robust biomarkers, subunit vaccines and new drug targets. The strong liaison between the clinical and laboratory teams, and the structured framework for technology transfer and health policy decisions within Canada will increase the speed and efficacy of this transition, and the value of this translational research.
Canada has been selected to play a leading role in the international Human Proteome Project, the global counterpart of the Human Genome Project designed to understand the structure and function of the human proteome in health and disease. Canada will lead an international team focusing on chromosome 6, which is functionally associated with more than 120 major human diseases, including immune and inflammatory disorders affecting the brain, skeletal system, heart and blood vessels, lungs, kidney, liver, gastrointestinal tract and endocrine system. Many of these chronic and persistent diseases have a high population prevalence, devastating clinical impact and profound societal consequences. As a result, they impose a multi-billion dollar economic burden on Canada and on all advanced societies through direct costs of patient care, the loss of health and productivity, and extensive caregiver burden. There is no definitive treatment at the present time for any of these disorders. The manuscript outlines the research which will involve a systematic assessment of all chromosome 6 genes, development of a knowledge base, and development of assays and reagents for all chromosome 6 proteins. We feel that the informatic infrastructure and MRM assays developed will place the chromosome 6 consortium in an excellent position to be a leading player in this major international research initiative. This article is part of a Special Issue: Can Proteomics Fill the Gap Between Genomics and Phenotypes?
人类蛋白质组计划（HPP）旨在生成一幅关于人体基于蛋白质的分子结构的全面图谱，提供一种有助于阐明生物学和分子功能的资源，并推动疾病的诊断和治疗。在此框架内，基于染色体的HPP（C-HPP）已按国家或地区分配了绘制各条染色体图谱的职责，而生物学/疾病HPP（B/D-HPP）则在基于疾病的跨职能小组中协调这些团队。6号染色体（Ch6）为整合这两项任务提供了一个绝佳的模型。这条中着丝粒染色体含有1002 - 1034个基因，这些基因编码已知、新发现或推测的蛋白质。Ch6在功能上与120多种主要人类疾病相关，其中许多疾病在人群中患病率高，具有毁灭性的临床影响和深远的社会后果。Ch6项目中汇聚的基因组、蛋白质组、代谢组、表型组和健康服务数据的独特组合，通过推动强大的生物标志物、亚单位疫苗和新药物靶点的研发，在推进个性化医疗方面具有巨大潜力。临床团队与实验室团队之间的紧密联系，以及加拿大境内技术转移和卫生政策决策的结构化框架，将提高这一转变的速度和效率，以及这项转化研究的价值。
加拿大已被选中在国际人类蛋白质组计划中发挥主导作用，该计划是人类基因组计划在全球的对应项目，旨在了解人类蛋白质组在健康和疾病中的结构与功能。加拿大将领导一个国际团队专注于6号染色体，该染色体在功能上与120多种主要人类疾病相关，包括影响大脑、骨骼系统、心脏和血管、肺、肾、肝、胃肠道和内分泌系统的免疫和炎症性疾病。这些慢性和持续性疾病中的许多在人群中患病率高，具有毁灭性的临床影响和深远的社会后果。因此，它们通过患者护理的直接成本、健康和生产力的损失以及广泛的护理负担，给加拿大和所有发达社会带来了数十亿美元的经济负担。目前对于这些疾病中的任何一种都没有确切的治疗方法。本文概述了相关研究，该研究将涉及对所有6号染色体基因进行系统评估、建立一个知识库，以及开发针对所有6号染色体蛋白质的检测方法和试剂。我们认为，所开发的信息基础设施和多反应监测（MRM）检测方法将使6号染色体联盟在这一重大国际研究计划中处于领先地位。本文是一期特刊的一部分：蛋白质组学能否填补基因组学与表型之间的空白？
