Browsing by Author "Chen, Yet-Ran"

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Application of Data-Independent Acquisition Approach to Study the Proteome Change from Early to Later Phases of Tomato Pathogenesis Responses
(2019-02-02)
Fan, Kai-Ting
;
Wang, Kuo-Hsin
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Chang, Wei-Hung
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Yang, Jhih-Ci
;
Yeh, Ching-Fang
Plants and pathogens are entangled in a continual arms race. Plants have evolved dynamic defence and immune mechanisms to resist infection and enhance immunity for second wave attacks from the same or different types of pathogenic species. In addition to evolutionarily and physiological changes, plant-pathogen interaction is also highly dynamic at the molecular level. Recently, an emerging quantitative mass spectrometry-based proteomics approach named data-independent acquisition (DIA), has been developed for the analysis of the proteome in a high-throughput fashion. In this study, the DIA approach was applied to quantitatively trace the change in the plant proteome from the early to the later stage of pathogenesis progression. This study revealed that at the early stage of the pathogenesis response, proteins directly related to the chaperon were regulated for the defence proteins. At the later stage, not only the defence proteins but also a set of the pathogen-associated molecular pattern-triggered immunity (PTI) and effector triggered immunity (ETI)-related proteins were highly induced. Our findings show the dynamics of the plant regulation of pathogenesis at the protein level and demonstrate the potential of using the DIA approach for tracing the dynamics of the plant proteome during pathogenesis responses.
Metabolic labelling of cholesteryl glucosides in Helicobacter pylori reveals how the uptake of human lipids enhances bacterial virulence
(2016-01-01)
Jan, Hau-Ming
;
Chen, Yi-Chi
;
Shih, Yu-Yin
;
Huang, Yu-Chen
;
Tu, Zhijay
Helicobacter pylori infects approximately half of the human population and is the main cause of various gastric diseases. This pathogen is auxotrophic for cholesterol, which it converts upon uptake to various cholesteryl alpha-glucoside derivatives, including cholesteryl 6'-acyl and 6'-phosphatidyl alpha-glucosides (CAGs and CPGs). Owing to a lack of sensitive analytical methods, it is not known if CAGs and CPGs play distinct physiological roles or how the acyl chain component affects function. Herein we established a metabolite-labelling method for characterising these derivatives qualitatively and quantitatively with a femtomolar detection limit. The development generated an MS/MS database of CGds, allowing for profiling of all the cholesterol-derived metabolites. The subsequent analysis led to the unprecedented information that these bacteria acquire phospholipids from the membrane of epithelial cells for CAG biosynthesis. The resulting increase in longer or/and unsaturated CAG acyl chains helps to promote lipid raft formation and thus delivery of the virulence factor CagA into the host cell, supporting the idea that the host/pathogen interplay enhances bacterial virulence. These findings demonstrate an important connection between the chain length of CAGs and the bacterial pathogenicity.
Proteogenomics of Non-smoking Lung Cancer in East Asia Delineates Molecular Signatures of Pathogenesis and Progression
(2020-07-09)
Chen, Yi-Ju
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Roumeliotis, Theodoros, I
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Chang, Ya-Hsuan
;
Chen, Ching-Tai
;
Han, Chia-Li
Lung cancer in East Asia is characterized by a high percentage of never-smokers, early onset and predominant EGFR mutations. To illuminate the molecular phenotype of this demographically distinct disease, we performed a deep comprehensive proteogenomic study on a prospectively collected cohort in Taiwan, representing early stage, predominantly female, non-smoking lung adenocarcinoma. Integrated genomic, proteomic, and phosphoproteomic analysis delineated the demographically distinct molecular attributes and hallmarks of tumor progression. Mutational signature analysis revealed age- and gender-related mutagenesis mechanisms, characterized by high prevalence of APOBEC mutational signature in younger females and over-representation of environmental carcinogen-like mutational signatures in older females. A proteomics-informed classification distinguished the clinical characteristics of early stage patients with EGFR mutations. Furthermore, integrated protein network analysis revealed the cellular remodeling underpinning clinical trajectories and nominated candidate biomarkers for patient stratification and therapeutic intervention. This multi-omic molecular architecture may help develop strategies for management of early stage never-smoker lung adenocarcinoma.