Browsing by Author "Tseng, Yu-Yao"

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A homologous mapping method for three-dimensional reconstruction of protein networks reveals disease-associated mutations
(2018-03-19)
Huang, Sing-Han
;
Lo, Yu-Shu
;
Luo, Yong-Chun
;
Tseng, Yu-Yao
;
Yang, Jinn-Moon
Background: One of the crucial steps toward understanding the associations among molecular interactions, pathways, and diseases in a cell is to investigate detailed atomic protein-protein interactions (PPIs) in the structural interactome. Despite the availability of large-scale methods for analyzing PPI networks, these methods often focused on PPI networks using genome-scale data and/or known experimental PPIs. However, these methods are unable to provide structurally resolved interaction residues and their conservations in PPI networks. Results: Here, we reconstructed a human three-dimensional (3D) structural PPI network (hDiSNet) with the detailed atomic binding models and disease-associated mutations by enhancing our PPI families and 3D-domain interologs from 60,618 structural complexes and complete genome database with 6,352,363 protein sequences across 2274 species. hDiSNet is a scale-free network (gamma = 2.05), which consists of 5177 proteins and 19,239 PPIs with 5843 mutations. These 19,239 structurally resolved PPIs not only expanded the number of PPIs compared to present structural PPI network, but also achieved higher agreement with gene ontology similarities and higher co-expression correlation than the ones of 181,868 experimental PPIs recorded in public databases. Among 5843 mutations, 1653 and 790 mutations involved in interacting domains and contacting residues, respectively, are highly related to diseases. Our hDiSNet can provide detailed atomic interactions of human disease and their associated proteins with mutations. Our results show that the disease-related mutations are often located at the contacting residues forming the hydrogen bonds or conserved in the PPI family. In addition, hDiSNet provides the insights of the FGFR (EGFR)-MAPK pathway for interpreting the mechanisms of breast cancer and ErbB signaling pathway in brain cancer. Conclusions: Our results demonstrate that hDiSNet can explore structural-based interactions insights for understanding the mechanisms of disease-associated proteins and their mutations. We believe that our method is useful to reconstruct structurally resolved PPI networks for interpreting structural genomics and disease associations.
Identification of the PCa28 gene signature as a predictor in prostate cancer
(2018-01-01)
Lee, Jung-Yu
;
Lin, Si-Yu
;
Chuang, Yi-Hsuan
;
Huang, Sing-Han
;
Tseng, Yu-Yao
Prostate cancer (PCa) is the second-leading cause of cancer death among men in the worldwide. Most PCa is slowly growing and usually early symptomless. About 70% of PCa patients were diagnosed at later stage and metastasis has been observed. Additionally, the cure rate of PCa closely relies on the early diagnosis with biomarkers. Prostatic Specific Antigen (PSA) is currently the only clinical biomarker for PCa diagnosis. However, the PSA test has inherent limitations and has about 75% of false-positive results. The identification of a set of genes (as biomarkers) for diagnosis and prognosis is an urgent clinical issue for PCa. Here, we integrated genome-wide analysis and protein-protein interaction network to identify potential genes for early diagnostic biomarkers of PCa. First, we collected gene expression datasets of 145 PCa samples, consisting of both tumor and corresponding normal tissues, from two different sources in Gene Expression Omnibus (GEO). We found 158 and 268 significantly highly and lowly expressed genes, respectively, in tumor samples. Moreover, we proposed cluster score (CS) and predicting score (PS) to select 28 prostate cancer-related genes (called PCa28). The results indicate that PCa28 can discriminate between the normal/tumor tissues and are specific for prostate cancer. Finally, we examined 8 genes in PCa28 on four PCa cell lines by real time quantitative polymerase chain reaction (RT-qPCR). Experimental results show that up-regulated genes have higher expression level in tumor cells in comparison to normal cells, and down-regulated genes have lower expression level in tumor cells. We believe that our method is useful and PCa28 are potential biomarkers that provide the clues to develop targeting therapy for PCa.
Identification of the PCA29 gene signature as a predictor in prostate cancer
(2019-06-01)
Lee, Jung-Yu
;
Lin, Si-Yu
;
Lin, Chun-Yu
;
Chuang, Yi-Huan
;
Huang, Sing-Han
Prostate cancer (PCa) is the second leading cause of cancer death among men worldwide. About 70% of PCa patients were diagnosed at later stage, and metastasis has been observed. Additionally, the cure rate of PCa closely relies on the early diagnosis with biomarkers. The identification of biomarkers for diagnosis and prognosis is an urgent clinical issue for PCa. Here, we developed a novel scoring strategy, including cluster score (CS) and predicting score (PS), to identify 29 PCa genes (called PCa29) for early diagnostic biomarkers from two datasets in Gene Expression Omnibus. The result indicates that PCa29 can discriminate between normal and tumor tissues and are specific for prostate cancer. To validate PCa29, we found that 97% of PCa29 were consistently significant with these gene expressions in The Cancer Genome Atlas; furthermore, similar to 70% of PCa29 are consensus to the protein expression in The Human Protein Atlas. Finally, we examined 10 genes in PCa29 on three PCa cell lines by real-time quantitative polymerase chain reaction. The experimental results show that the trend of the differential PCa29 expression is consistent with the analyzed results from our novel scoring method. We believe that our method is useful and PCa29 are potential biomarkers that provide the clues to develop targeting therapy for PCa.