Proteomics analysis and proteogenomic characterization of different physiopathological human lenses
Abstract Background The aim of the present study was to identify the proteomic differences among human lenses in different physiopathological states and to screen for susceptibility genes/proteins via proteogenomic characterization. Methods The total proteomes identified across the regenerative lens...
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BMC
2017-12-01
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| Series: | BMC Ophthalmology |
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| Online Access: | http://link.springer.com/article/10.1186/s12886-017-0642-9 |
| _version_ | 1831562834148851712 |
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| author | Xiaohang Wu Zhenzhen Liu Xiayin Zhang Dongni Wang Erping Long Jinghui Wang Wangting Li Weiyi Lai Qianzhong Cao Kunhua Hu Weirong Chen Haotian Lin Yizhi Liu |
| author_facet | Xiaohang Wu Zhenzhen Liu Xiayin Zhang Dongni Wang Erping Long Jinghui Wang Wangting Li Weiyi Lai Qianzhong Cao Kunhua Hu Weirong Chen Haotian Lin Yizhi Liu |
| author_sort | Xiaohang Wu |
| collection | DOAJ |
| description | Abstract Background The aim of the present study was to identify the proteomic differences among human lenses in different physiopathological states and to screen for susceptibility genes/proteins via proteogenomic characterization. Methods The total proteomes identified across the regenerative lens with secondary cataract (RLSC), congenital cataract (CC) and age-related cataract (ARC) groups were compared to those of normal lenses using isobaric tagging for relative and absolute protein quantification (iTRAQ). The up-regulated proteins between the groups were subjected to biological analysis. Whole exome sequencing (WES) was performed to detect genetic variations. Results The most complete human lens proteome to date, which consisted of 1251 proteins, including 55.2% previously unreported proteins, was identified across the experimental groups. Bioinformatics functional annotation revealed the common involvement of cellular metabolic processes, immune responses and protein folding disturbances among the groups. RLSC-over-expressed proteins were characteristically enriched in the intracellular immunological signal transduction pathways. The CC groups featured biological processes relating to gene expression and vascular endothelial growth factor (VEGF) signaling transduction, whereas the molecular functions corresponding to external stress were specific to the ARC groups. Combined with WES, the proteogenomic characterization narrowed the list to 16 candidate causal molecules. Conclusions These findings revealed common final pathways with diverse upstream regulation of cataractogenesis in different physiopathological states. This proteogenomic characterization shows translational potential for detecting susceptibility genes/proteins in precision medicine. |
| first_indexed | 2024-12-17T10:44:51Z |
| format | Article |
| id | doaj.art-05ef8d4a8e424a418eff308aa19705a2 |
| institution | Directory Open Access Journal |
| issn | 1471-2415 |
| language | English |
| last_indexed | 2024-12-17T10:44:51Z |
| publishDate | 2017-12-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Ophthalmology |
| spelling | doaj.art-05ef8d4a8e424a418eff308aa19705a22022-12-21T21:52:09ZengBMCBMC Ophthalmology1471-24152017-12-0117111310.1186/s12886-017-0642-9Proteomics analysis and proteogenomic characterization of different physiopathological human lensesXiaohang Wu0Zhenzhen Liu1Xiayin Zhang2Dongni Wang3Erping Long4Jinghui Wang5Wangting Li6Weiyi Lai7Qianzhong Cao8Kunhua Hu9Weirong Chen10Haotian Lin11Yizhi Liu12State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen UniversityState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen UniversityState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen UniversityState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen UniversityState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen UniversityState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen UniversityState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen UniversityState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen UniversityState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen UniversityDepartment of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen UniversityState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen UniversityState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen UniversityState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen UniversityAbstract Background The aim of the present study was to identify the proteomic differences among human lenses in different physiopathological states and to screen for susceptibility genes/proteins via proteogenomic characterization. Methods The total proteomes identified across the regenerative lens with secondary cataract (RLSC), congenital cataract (CC) and age-related cataract (ARC) groups were compared to those of normal lenses using isobaric tagging for relative and absolute protein quantification (iTRAQ). The up-regulated proteins between the groups were subjected to biological analysis. Whole exome sequencing (WES) was performed to detect genetic variations. Results The most complete human lens proteome to date, which consisted of 1251 proteins, including 55.2% previously unreported proteins, was identified across the experimental groups. Bioinformatics functional annotation revealed the common involvement of cellular metabolic processes, immune responses and protein folding disturbances among the groups. RLSC-over-expressed proteins were characteristically enriched in the intracellular immunological signal transduction pathways. The CC groups featured biological processes relating to gene expression and vascular endothelial growth factor (VEGF) signaling transduction, whereas the molecular functions corresponding to external stress were specific to the ARC groups. Combined with WES, the proteogenomic characterization narrowed the list to 16 candidate causal molecules. Conclusions These findings revealed common final pathways with diverse upstream regulation of cataractogenesis in different physiopathological states. This proteogenomic characterization shows translational potential for detecting susceptibility genes/proteins in precision medicine.http://link.springer.com/article/10.1186/s12886-017-0642-9Human lensRegenerative lenses with secondary cataract (RLSC)ProteomicsProteogenomic analysis |
| spellingShingle | Xiaohang Wu Zhenzhen Liu Xiayin Zhang Dongni Wang Erping Long Jinghui Wang Wangting Li Weiyi Lai Qianzhong Cao Kunhua Hu Weirong Chen Haotian Lin Yizhi Liu Proteomics analysis and proteogenomic characterization of different physiopathological human lenses BMC Ophthalmology Human lens Regenerative lenses with secondary cataract (RLSC) Proteomics Proteogenomic analysis |
| title | Proteomics analysis and proteogenomic characterization of different physiopathological human lenses |
| title_full | Proteomics analysis and proteogenomic characterization of different physiopathological human lenses |
| title_fullStr | Proteomics analysis and proteogenomic characterization of different physiopathological human lenses |
| title_full_unstemmed | Proteomics analysis and proteogenomic characterization of different physiopathological human lenses |
| title_short | Proteomics analysis and proteogenomic characterization of different physiopathological human lenses |
| title_sort | proteomics analysis and proteogenomic characterization of different physiopathological human lenses |
| topic | Human lens Regenerative lenses with secondary cataract (RLSC) Proteomics Proteogenomic analysis |
| url | http://link.springer.com/article/10.1186/s12886-017-0642-9 |
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