The Biology/Disease-driven Human Proteome Project (B/D-HPP): Enabling Protein Research for the Life Sciences Community Ruedi Aebersold, †,‡,§ Gary D. Bader, §,∥ Aled M. Edwards, §,⊥,# Jennifer E. van Eyk, §,¶ Martin Kussmann, §,×,□,● Jun Qin, §,△,■ and Gilbert S. Omenn ○,◆ † Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland ‡ Faculty of Science, University of Zurich, Zurich, Switzerland ∥ The Donnelly Centre, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada ⊥ Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada # Division of Cancer Genomics and Proteomics, Ontario Cancer Institute, Toronto M5G 2M9, Canada ¶ Johns Hopkins Bayview Proteomics Center, Department of Medicine, Division of Cardiology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States × Proteomics and Metabonomics Core, Nestle ́ Institute of Health Sciences, Lausanne, Switzerland □ Faculty of Life Sciences, Ecole Polytechnique Fé de ́ rale Lausanne (EPFL), Lausanne, Switzerland ● Faculty of Science, Aarhus University, Aarhus, Denmark △ State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, China ■ Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, United States ○ Departments of Computational Medicine and Bioinformatics, Internal Medicine, and Human Genetics, and School of Public Health, University of Michigan, Ann Arbor, Michigan 48109-2218, United States; chair, HUPO Human Proteome Project ◆ Institute for Systems Biology, Seattle, Washington 98101, United States ABSTRACT: The biology and disease oriented branch of the Human Proteome Project (B/D-HPP) was established by the Human Proteome Organization (HUPO) with the main goal of supporting the broad application of state-of the- art measurements of proteins and proteomes by life scientists studying the molecular mechanisms of biological processes and human disease. This will be accomplished through the generation of research and informational resources that will support the routine and definitive measurement of the process or disease relevant proteins. The B/D-HPP is highly complementary to the C-HPP and will provide datasets and biological characterization useful to the C-HPP teams. In this manuscript we describe the goals, the plans, and the current status of the of the B/D-HPP. KEYWORDS: Human proteome project, proteomics, mass spectrometry, affinity reagents, network biology, human disease, biological processes ■ PROTEOMICS AND ITS IMPACT ON EXPERIMENTAL BIOLOGY With the announcement of the first draft of the human genome sequence in 2000, life science research achieved an important milestone. With the nearly completed human genome sequence the genetic basis for the ensemble of molecules that constitute a living human cell and execute all its biochemical processes of life had become available, in principle. However, it is the how, when and where the genetic information is translated into the different classes of biomolecules and the question how these molecules interact that ultimately define a particular phenotype. These questions have remained the subject of intense research, particularly via genomic approaches. Recent progress exten- sively reported by the ENCODE II program has revealed regulatory roles of genome elements, various RNA molecules, and proteins. 1,2 It is generally understood that proteins play an essential role in connecting genotype and phenotype. However, the specific mechanisms by which genomic variation is translated into specific (disease) phenotypes remain essentially unknown. For example, in cancer genomics studies, a key objective is to find recurrently mutated or aberrantly expressed genes and their Special Issue: Chromosome-centric Human Proteome Project Received: December 7, 2012 Published: December 21, 2012 Perspective pubs.acs.org/jpr © 2012 American Chemical Society 23 dx.doi.org/10.1021/pr301151m | J. Proteome Res. 2013, 12, 23−27