The availability of human genome sequence has transformed biomedical research over the past decade. However, an equivalent map for the human proteome with direct measurements of proteins and peptides does not exist yet. Here, we present a draft map of the human proteome using high resolution Fourier transform mass spectrometry. In-depth proteomic profiling of 30 histologically normal human samples including 17 adult tissues, 7 fetal tissues and 6 purified primary hematopoietic cells resulted in identification of proteins encoded by 17,294 genes accounting for ~84% of the total annotated protein-coding genes in humans. A unique and comprehensive strategy for proteogenomic analysis enabled us to discover a number of novel protein-coding regions, which includes translated pseudogenes, non-coding RNAs and upstream ORFs. This large human proteome catalog (available as an interactive web-based resource at http://www.humanproteomemap.org) will complement available human genome and transcriptome data to accelerate biomedical research in health and disease.

Purpose Development of novel biomarkers for AD is important for early diagnosis, monitoring disease progression and therapeutic response. The aim of this study was to identify the potential CSF biomarkers for Alzheimer's disease (AD) and evaluate these markers on independent CSF samples using a parallel reaction monitoring mass spectrometry (PRM-MS) assay. Experimental design In this study, we employed high-resolution mass spectrometry and tandem mass tag (TMT) multiplexing technology to identify proteins that might serve as candidate biomarkers for Alzheimer’s disease. Identified potential biomarkers were validated using a parallel reaction monitoring mass spectrometry (PRM-MS) assay. Results We identified 2,327 proteins in the cerebrospinal fluid (CSF) of which 139 were observed to be significantly different in their abundance in the CSF of AD patients versus controls. The proteins whose abundance was altered in AD included a number of known AD marker proteins such as MAPT, NPTX2, SCG2, VGF, GFAP, SST and NCAM1 as well as novel biomarkers such as GSN, PKM and YWHAG. We then sought to validate these findings in a separate set of CSF specimens from AD dementia patients and controls. For the AD group, significant increases were found for YWHAG and PKM, and a significant decrease was observed for VGF by multiplexed targeted parallel reaction monitoring (PRM) experiments. NPTX2 in combination with PKM or with YWHAG led to the best results with AUCs of 0.935 and 0.933, respectively. Conclusions and clinical relevance The identified altered CSF proteins in AD CSF samples will be useful to understand AD pathogenesis.