Application of personalized differential expression analysis in human cancer proteome

Owing to the recent technological advances, liquid chromatography-mass spectrometry (LC-MS)-based quantitative proteomics can measure expression of thousands of proteins from biological specimens. Currently, several studies have used the LC-MS-based proteomics to measure protein expression levels in human cancer. Identifying differentially expressed proteins (DEPs) between tumors and normal controls is a common way to investigate carcinogenesis mechanisms. However, most statistical methods used for DEPs analysis can only identify deregulated proteins at the population-level and ignore the heterogeneous differential expression of proteins in individual patients. Thus, to identify patient-specific molecular defects for personalized medicine, it is necessary to perform personalized differential analysis at the scale of a single sample. To date, there is a scarcity of systematic and easy-to-handle tool that could be used to evaluate the performance of individualized difference expression analysis algorithms in human cancer proteome. Herein, we developed a user-friendly tool kit, IDEP, to enable implementation and evaluation of personalized difference expression analysis algorithms. IDEP evaluates five rank-based tools (RankComp v1/v2, PENDA, Peng and Quantile) through classic computational and functional criteria in lung, gastric and liver cancer proteome. The results show that the within-sample relative expression orderings (REOs) of protein pairs in normal tissues were highly stable, which provided the basis for individual level DEPs analysis. Moreover, these individualized difference analysis tools could reach much higher efficiency in detecting sample-specific deregulated proteins than the group-based methods. Pathway enrichment and survival analysis results were dataset and analysis method dependent. In summary, IDEP has integrated necessary toolkits for individualized identification of DEPs and supported flexible methods evaluation analysis and visualization modules. It could provide a robust and scalable framework to extract personalized deregulation patterns and could also be used for the discovery of prognostic biomarkers for personalized medicine.

Comprehensive analysis of immune prognostic‐related genes in the tumor microenvironment of hepatocellular carcinoma

Background : The percentage of death resulted from hepatocellular carcinoma (HCC) remains high worldwide, despite surgical and chemotherapy treatment. Immunotherapy offers great promise in the treatment of a rapidly expanding spectrum of HCC. Therefore, further exploration of the immune-related signatures in the tumor microenvironment, which plays a vital role in tumor initiation and progression for immunotherapy is currently needed. Methods: In this present research, 866 immune-related difference expression genes (DEGs) were identified by integrating the DEGs between TCGA HCC and normal tissue and the immune genes from databases (Innate DB; Imm Port), and 144 candidate prognostic genes were defined through weighted gene co-expression network analysis (WGCNA). Results: Seven prognostic immune-related DEGs were determined by LASSO Cox PH model, which were followed by constructing the ImmuneRiskScore model based on the prognostic immune-related DEGs. The prognostic index of the ImmuneRiskScore was validated then in the dependent dataset. Patients were divided into high- and low-risk groups according to ImmuneRiskScore. The difference in ImmuneRiskScore and infiltration of immune cells between groups was detected and the correlation analysis for immunotherapy biomarkers was further explored. Conclusion: The ImmuneRiskScore of HCC could provide a prognostic signature and reflect immune characteristics within tumor microenvironment. Furthermore, it also may provide novel immunotherapy predictive biomarker for HCC patients in the near future.

Comprehensive Analysis of Immune Prognostic‐Related Genes in the Tumor Microenvironment of Hepatocellular Carcinoma

Background: The percentage of death resulted from hepatocellular carcinoma (HCC) remains high worldwide, despite surgical and chemotherapy treatment. Immunotherapy offers great promise in the treatment of a rapidly expanding spectrum of HCC. Therefore, further exploration of the immune-related signatures in the tumor microenvironment, which plays a vital role in tumor initiation and progression for immunotherapy is currently needed. Methods: In this present research, 866 immune-related difference expression genes (DEGs) were identified by integrating the DEGs between TCGA HCC and normal tissue and the immune genes from databases (Innate DB; Imm Port), and 144 candidate prognostic genes were defined through weighted gene co-expression network analysis (WGCNA). Results: Seven prognostic immune-related DEGs were determined with LASSO Cox PH model, which was followed by constructing the ImmuneRiskScore model based on the prognostic immune-related DEGs. The prognostic index of the ImmuneRiskScore was validated then in the dependent dataset. Patients were divided into high- and low-risk groups according to ImmuneRiskScore. The difference in ImmuneRiskScore and infiltration of immune cells between groups was detected and the correlation analysis for immunotherapy biomarkers was further explored. Conclusion:The ImmuneRiskScore of HCC could provide a prognostic signature and reflect immune characteristics within tumor microenvironment. Furthermore, it also may provide novel immunotherapy predictive biomarker for HCC patients in the near future.

miR-147b-modulated expression of vestigial regulates wing development in the bird cherry-oat aphid Rhopalosiphum padimiR-147b-modulated expression of vestigial regulates wing development in the bird cherry-oat aphid Rhopalosiphum padi

Background: Most aphids exhibit wing polyphenism in which wingless and winged morphs produce depending on the population density and host plant quality. Although the influence of environmental factors on wing polyphenism of aphids have been extensively investigated, molecular mechanisms underlining morph differentiation (i.e. wing development /degeneration), one downstream aspect of the wing polyphenism , has been poorly understood. Results: We examined the expression levels of the twenty genes involved in wing development network, and only vestigial (vg ) showed significantly different expression levels in both whole-body and wall-body of third instar nymphs, with 5.4- and 16.14- fold higher expression in winged lines compared to wingless lines, respectively in Rhopalosiphum padi . vg expression was higher in winged lines compared to wingless lines in third, fourth instar nymphs and adults. Larger difference expression was observed in third (21.38-fold) and fourth (20.91-fold) instar nymphs relative to adults (3.12-fold). Suppression of vg using RNAi repressed the wing development of third winged morphs. Furthermore, dual luciferase reporter assay revealed that the miR-147 can target the vg mRNA. Modulation of miR-147b levels by microinjection of its agomir (mimic) decreased vg expression levels and repressed wing development. Conclusions : Our findings suggest that vg is essential for wing development in R. padi and that miR-147b modulates its expression. .

miR-147b-modulated expression of vestigial regulates wing development in the bird cherry-oat aphid Rhopalosiphum padi

Background: Most aphids exhibit wing polyphenism in which wingless and winged morphs produce depending on the population density and host plant quality. Although the influence of environmental factors on wing polyphenism of aphids have been extensively investigated, molecular mechanisms underlining morph differentiation (i.e. wing development /degeneration), one downstream aspect of the wing polyphenism, has been poorly understood. Results: We examined the expression levels of the twenty genes involved in wing development network, and only vestigial (vg) showed significantly different expression levels in both whole-body and wall-body of third instar nymphs, with 5.4- and 16.14- fold higher expression in winged lines compared to wingless lines, respectively in Rhopalosiphum padi. vg expression was higher in winged lines compared to wingless lines in third, fourth instar nymphs and adults. Larger difference expression was observed in third (21.38-fold) and fourth (20.91-fold) instar nymphs relative to adults (3.12-fold). Suppression of vg using RNAi repressed the wing development of third winged morphs. Furthermore, dual luciferase reporter assay revealed that the miR-147 can target the vg mRNA. Modulation of miR-147b levels by microinjection of its agomir (mimic) decreased vg expression levels and repressed wing development. Conclusions: Our findings suggest that vg is essential for wing development in R. padi and that miR-147b modulates its expression.

A Modeling Method of Multiphase Synchronous Generator for Shipboards Power System Based on PSCAD/EMTDC

The synchronous generators of shipboards power system are generally multiphase (mostly twelve phases), it means necessary to building the model by code programming because there aren’t this ready-made component in EMTDC or other digital simulation software. In this paper, a programming method for numerical calculation of synchronous generator and interfacing program codes to PSCAD/EMTDC are described. According to generic rotate machine Park equation, trapezoid integral is adopted to make the math differential equations discrete to numerical difference expression. The paper emphatically deduces discrete algorithm for getting numerical transient solutions of synchronous generator model. For the sake of the verification for this modeling method, a three-phase synchronous generator model based on code program modeling is taken as test demonstration.