The Human Proteome Project (HPP) was launched in 2010 to enhance accurate annotation of the genome-encoded proteome. Ten years later, the HPP releases its first blueprint of the human proteome, annotating 90% of all known proteins at high-stringency and discussing the implications of proteomics for precision medicine.
Biological Mass Spectrometry
Mass spectrometry was long considered a specialist technology for physicists and chemists, but is now used across biological research. Two major driving forces of this development are Electrospray Ionization and the Orbitrap mass analyzer. On the occasion of their 30th and 20th anniversary in 2019, we assembled this collection of Nature Communications articles. As the advances of mass spectrometry are closely connected to the emergence of proteomics, we updated this collection in 2020 to celebrate 10 years of the Human Proteome Project.
The Opinion section includes an Editorial as well as Commentaries from Matthias Mann and Alexander Makarov, giving personal accounts of the invention and evolution of Electrospray Ionization and Orbitrap, respectively. The sections Protein Mass Spectrometry and Beyond Proteins feature various applications of Electrospray Ionization- and Orbitrap-based mass spectrometry. Recent advances in characterizing the human proteome in health and disease are presented in The Human Proteome section.
Standardization and harmonization of distributed multi-center proteotype analysis supporting precision medicine studies
Distributed multi-omic digitization of clinical specimen across multiple sites is a prerequisite for turning molecular precision medicine into reality. Here, the authors show that coordinated proteotype data acquisition is feasible using standardized MS data acquisition and analysis strategies.
Clinical proteomics critically depends on the ability to acquire highly reproducible data over an extended period of time. Here, the authors assess reproducibility over four months across different mass spectrometers and develop a computational approach to mitigate variation among instruments over time.
Mass spectrometry-based proteomics typically relies on highly sensitive nano-flow liquid chromatography (LC) but this can reduce robustness and reproducibility. Here, the authors show that micro-flow LC enables robust and reproducible high-throughput proteomics experiments at a very moderate loss of sensitivity.
The human skin is a highly complex organ comprising multiple tissue layers and diverse cell types. Here, the authors present a spatially-resolved quantitative proteomic atlas of the healthy human skin, characterizing the protein profiles of four skin layers and nine cell types.
Top-down proteomics can provide unique insights into the biological variations of protein biomarkers but detecting low-abundance proteins in body fluids remains challenging. Here, the authors develop a nanoparticle-based top-down proteomics approach enabling enrichment and detailed analysis of cardiac troponin I in human serum.
Large-scale, unbiased proteomics studies of biological samples like plasma are constrained by the complexity of the proteome. Herein, the authors develop a highly parallel protein quantitation platform leveraging multi nanoparticle protein coronas for deep proteome sampling and biomarker discovery.
Heart failure is a major health issue worldwide. Here, Egerstedt et al. perform proteomic profiling of human plasma at different stages of heart failure, providing a comprehensive analysis of changes in the plasma proteome during disease progression.
An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, the authors sample a longitudinal wellness cohort and analyse blood molecular profiles as well as gut microbiota composition.
Integrated proteogenomic deep sequencing and analytics accurately identify non-canonical peptides in tumor immunopeptidomes
Non-canonical HLA-bound peptides from presumed non-coding regions are potential targets for cancer immunotherapy, but their discovery remains challenging. Here, the authors integrate exome sequencing, transcriptomics, ribosome profiling, and immunopeptidomics to identify tumor-specific non-canonical HLA-bound peptides.
Connecting genomics and proteomics allows the development of more efficient and specific treatments for cancer. Here, the authors develop proteogenomic methods to defining cancer signaling in-vivo starting from core needle biopsies and with application to a HER2 breast cancer focused clinical trial.
Quantitative proteomic landscape of metaplastic breast carcinoma pathological subtypes and their relationship to triple-negative tumors
Metaplastic breast carcinoma (MBC) is among the most aggressive subtypes of triple-negative breast cancer (TNBC) but the underlying proteome profiles are unknown. Here, the authors characterize the protein signatures of human MBC tissue samples and their relationship to TNBC and normal breast tissue.