TY - JOUR
T1 - Human Autoantigen Atlas
T2 - Searching for the Hallmarks of Autoantigens
AU - Wang, Dan
AU - Yang, Dong
AU - Yang, Liuhui
AU - Diao, Lihong
AU - Zhang, Yuqi
AU - Li, Yang
AU - Wang, Hongye
AU - Ren, Jing
AU - Cheng, Linlin
AU - Tan, Qiaoyun
AU - Zhang, Ran
AU - Han, Xiaohong
AU - Zhang, Xiaohan
AU - Wang, Bingwei
AU - Li, Dong
AU - Chen, Meng
AU - Hermjakob, Henning
AU - Li, Yongzhe
AU - LaBaer, Joshua
AU - Zhou, Zhou
AU - Yu, Xiaobo
N1 - Publisher Copyright:
© 2023 American Chemical Society.
PY - 2023/6/2
Y1 - 2023/6/2
N2 - Understanding autoimmunity to endogenous proteins is crucial in diagnosing and treating autoimmune diseases. In this work, we developed a user-friendly AAgAtlas portal (http://biokb.ncpsb.org.cn/aagatlas_portal/index.php#), which can be used to search for 8045 non-redundant autoantigens (AAgs) and 47 post-translationally modified AAgs against 1073 human diseases that are prioritized by a credential score developed by multisource evidence. Using AAgAtlas, the immunogenic properties of human AAgs was systematically elucidated according to their genetic, biophysical, cytological, expression profile, and evolutionary characteristics. The results indicated that human AAgs are evolutionally conserved in protein sequence and enriched in three hydrophilic and polar amino acid residues (K, D, and E) that are located at the protein surface. AAgs are enriched in proteins that are involved in nucleic acid binding, transferase, and the cytoskeleton. Genome, transcriptome, and proteome analyses further indicated that AAb production is associated with gene variance and abnormal protein expression related to the pathological activities of different tumors. Collectively, our data outlines the hallmarks of human AAgs that facilitate the understanding of humoral autoimmunity and the identification of biomarkers of human diseases.
AB - Understanding autoimmunity to endogenous proteins is crucial in diagnosing and treating autoimmune diseases. In this work, we developed a user-friendly AAgAtlas portal (http://biokb.ncpsb.org.cn/aagatlas_portal/index.php#), which can be used to search for 8045 non-redundant autoantigens (AAgs) and 47 post-translationally modified AAgs against 1073 human diseases that are prioritized by a credential score developed by multisource evidence. Using AAgAtlas, the immunogenic properties of human AAgs was systematically elucidated according to their genetic, biophysical, cytological, expression profile, and evolutionary characteristics. The results indicated that human AAgs are evolutionally conserved in protein sequence and enriched in three hydrophilic and polar amino acid residues (K, D, and E) that are located at the protein surface. AAgs are enriched in proteins that are involved in nucleic acid binding, transferase, and the cytoskeleton. Genome, transcriptome, and proteome analyses further indicated that AAb production is associated with gene variance and abnormal protein expression related to the pathological activities of different tumors. Collectively, our data outlines the hallmarks of human AAgs that facilitate the understanding of humoral autoimmunity and the identification of biomarkers of human diseases.
KW - autoantibody
KW - autoantigen
KW - autoimmune disease
KW - biomarker
KW - database
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U2 - 10.1021/acs.jproteome.2c00799
DO - 10.1021/acs.jproteome.2c00799
M3 - Article
C2 - 37183442
AN - SCOPUS:85160743512
SN - 1535-3893
VL - 22
SP - 1800
EP - 1815
JO - Journal of Proteome Research
JF - Journal of Proteome Research
IS - 6
ER -