A comprehensive map and functional annotation of the normal human cerebrospinal fluid proteome

Yang Zhang; Zhengguang Guo; Lili Zou; Yehong Yang; Liwei Zhang; Nan Ji; Chen Shao; Wei Sun; Yajie Wang

doi:10.1016/j.jprot.2015.01.017

A comprehensive map and functional annotation of the normal human cerebrospinal fluid proteome

J Proteomics. 2015 Apr 24:119:90-9. doi: 10.1016/j.jprot.2015.01.017. Epub 2015 Feb 7.

Authors

Yang Zhang¹, Zhengguang Guo², Lili Zou³, Yehong Yang³, Liwei Zhang⁴, Nan Ji⁴, Chen Shao⁵, Wei Sun⁶, Yajie Wang⁷

Affiliations

¹ Department of Neurosurgery, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, 6 Tian Tan Xi Li, Beijing 100050, China. Electronic address: zhangyang8025@yeah.net.
² Core Facility of Instrument, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, China. Electronic address: gzg0625@sina.com.
³ Core Facility of Instrument, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, China.
⁴ Department of Neurosurgery, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, 6 Tian Tan Xi Li, Beijing 100050, China.
⁵ National Key Laboratory of Medical Molecular Biology, Department of Physiology and Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, China.
⁶ Core Facility of Instrument, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, China. Electronic address: sunwei1018@hotmail.com.
⁷ Core Laboratory for Clinical Medical Research, Beijing Tiantan Hospital, Capital Medical University, 6 Tian Tan Xi Li, Beijing 100050, China; Department of Clinical Laboratory Diagnosis, Beijing Tiantan Hospital, Capital Medical University, 6 Tian Tan Xi Li, Beijing 100050, China. Electronic address: tiantanwyj@aliyun.com.

PMID: 25661039
DOI: 10.1016/j.jprot.2015.01.017

Abstract

Knowledge about the normal human cerebrospinal fluid (CSF) proteome serves as a baseline reference for CSF biomarker discovery and provides insight into CSF physiology. In this study, high-pH reverse-phase liquid chromatography (hp-RPLC) was first integrated with a TripleTOF 5600 mass spectrometer to comprehensively profile the normal CSF proteome. A total of 49,836 unique peptides and 3256 non-redundant proteins were identified. To obtain high-confidence results, 2513 proteins with at least 2 unique peptides were further selected as bona fide CSF proteins. Nearly 30% of the identified CSF proteins have not been previously reported in the normal CSF proteome. More than 25% of the CSF proteins were components of CNS cell microenvironments, and network analyses indicated their roles in the pathogenesis of neurological diseases. The top canonical pathway in which the CSF proteins participated was axon guidance signaling. More than one third of the CSF proteins (788 proteins) were related to neurological diseases, and these proteins constitute potential CSF biomarker candidates. The mapping results can be freely downloaded at http://122.70.220.102:8088/csf/, which can be used to navigate the CSF proteome.

Biological significance: This study identified and functionally annotated the largest high-precision dataset of the CSF proteome, which offers a baseline reference for CSF biomarker discovery and reveals insight into CSF physiology.

Keywords: Cerebrospinal fluid; Functional annotation; Proteome.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cerebrospinal Fluid / metabolism*
Databases, Protein
Humans
Molecular Sequence Annotation*
Proteome / metabolism*

Substances

Proteome