4.7 Article

Human Autoantigen Atlas: Searching for the Hallmarks of Autoantigens

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JOURNAL OF PROTEOME RESEARCH
卷 22, 期 6, 页码 1800-1815

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AMER CHEMICAL SOC
DOI: 10.1021/acs.jproteome.2c00799

关键词

autoantibody; autoantigen; autoimmune disease; database; biomarker

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Understanding autoimmunity to endogenous proteins is crucial in diagnosing and treating autoimmune diseases. A user-friendly AAgAtlas portal was developed, which provides information on autoantigens (AAgs) and post-translationally modified AAgs associated with human diseases. The portal allows for a systematic investigation of the immunogenic properties of AAgs, including their genetic, biophysical, cytological, expression profile, and evolutionary characteristics. This information can aid in understanding humoral autoimmunity and identifying biomarkers for human diseases.
Understanding autoimmunity to endogenous proteins iscrucial indiagnosing and treating autoimmune diseases. In this work, we developeda 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 against1073 human diseases that are prioritized by a credential score developedby multisource evidence. Using AAgAtlas, the immunogenic propertiesof human AAgs was systematically elucidated according to their genetic,biophysical, cytological, expression profile, and evolutionary characteristics.The results indicated that human AAgs are evolutionally conservedin protein sequence and enriched in three hydrophilic and polar aminoacid 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 proteomeanalyses further indicated that AAb production is associated withgene variance and abnormal protein expression related to the pathologicalactivities of different tumors. Collectively, our data outlines thehallmarks of human AAgs that facilitate the understanding of humoralautoimmunity and the identification of biomarkers of human diseases.

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