DPHL: A DIA Pan-human Protein Mass Spectrometry Library for Robust Biomarker Discovery

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipeline and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to generate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

INternational ORthopaedic MUlticentre Study (INORMUS) in Fracture Care: Protocol for a large prospective observational study

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Despite the fact that orthopaedic trauma injuries represent a serious cause of mortality and morbidity worldwide, there are few data in low-middle income countries quantifying the burden of fractures and describing current treatment practices. To address this critical knowledge gap, a large multinational prospective observational study of 40,000 patients with musculoskeletal trauma in Africa, Asia, and Latin America is proposed. The International Orthopaedic Multicentre Study in Fracture Care (INORMUS) study seeks to determine the incidence of major complications (mortality, reoperation, and infection) within 30 days after a musculoskeletal injury and to determine patient, treatment, and system factors associated with these major complications in low-middle income countries. This study coincides with the World Health Organization\u27s Global Road Traffic Safety Decade (2011-2020) and other international efforts to reduce the burden of injury on developing populations. Insight gained from the INORMUS study will not only inform the global burden of orthopaedic trauma but also drive the development of future randomized trials to evaluate simple solutions and practical interventions to decrease deaths and improve the quality of life for trauma patients worldwide