• Title/Summary/Keyword: Mutation robustness

Search Result 13, Processing Time 0.017 seconds

Clinical significance of APOB inactivation in hepatocellular carcinoma

  • Lee, Gena;Jeong, Yun Seong;Kim, Do Won;Kwak, Min Jun;Koh, Jiwon;Joo, Eun Wook;Lee, Ju-Seog;Kah, Susie;Sim, Yeong-Eun;Yim, Sun Young
    • Experimental and Molecular Medicine
    • /
    • v.50 no.11
    • /
    • pp.7.1-7.12
    • /
    • 2018
  • Recent findings from The Cancer Genome Atlas project have provided a comprehensive map of genomic alterations that occur in hepatocellular carcinoma (HCC), including unexpected mutations in apolipoprotein B (APOB). We aimed to determine the clinical significance of this non-oncogenetic mutation in HCC. An Apob gene signature was derived from genes that differed between control mice and mice treated with siRNA specific for Apob (1.5-fold difference; P < 0.005). Human gene expression data were collected from four independent HCC cohorts (n = 941). A prediction model was constructed using Bayesian compound covariate prediction, and the robustness of the APOB gene signature was validated in HCC cohorts. The correlation of the APOB signature with previously validated gene signatures was performed, and network analysis was conducted using ingenuity pathway analysis. APOB inactivation was associated with poor prognosis when the APOB gene signature was applied in all human HCC cohorts. Poor prognosis with APOB inactivation was consistently observed through cross-validation with previously reported gene signatures (NCIP A, HS, high-recurrence SNUR, and high RS subtypes). Knowledge-based gene network analysis using genes that differed between low-APOB and high-APOB groups in all four cohorts revealed that low-APOB activity was associated with upregulation of oncogenic and metastatic regulators, such as HGF, MTIF, ERBB2, FOXM1, and CD44, and inhibition of tumor suppressors, such as TP53 and PTEN. In conclusion, APOB inactivation is associated with poor outcome in patients with HCC, and APOB may play a role in regulating multiple genes involved in HCC development.

Evaluating Reverse Logistics Networks with Centralized Centers : Hybrid Genetic Algorithm Approach (집중형센터를 가진 역물류네트워크 평가 : 혼합형 유전알고리즘 접근법)

  • Yun, YoungSu
    • Journal of Intelligence and Information Systems
    • /
    • v.19 no.4
    • /
    • pp.55-79
    • /
    • 2013
  • In this paper, we propose a hybrid genetic algorithm (HGA) approach to effectively solve the reverse logistics network with centralized centers (RLNCC). For the proposed HGA approach, genetic algorithm (GA) is used as a main algorithm. For implementing GA, a new bit-string representation scheme using 0 and 1 values is suggested, which can easily make initial population of GA. As genetic operators, the elitist strategy in enlarged sampling space developed by Gen and Chang (1997), a new two-point crossover operator, and a new random mutation operator are used for selection, crossover and mutation, respectively. For hybrid concept of GA, an iterative hill climbing method (IHCM) developed by Michalewicz (1994) is inserted into HGA search loop. The IHCM is one of local search techniques and precisely explores the space converged by GA search. The RLNCC is composed of collection centers, remanufacturing centers, redistribution centers, and secondary markets in reverse logistics networks. Of the centers and secondary markets, only one collection center, remanufacturing center, redistribution center, and secondary market should be opened in reverse logistics networks. Some assumptions are considered for effectively implementing the RLNCC The RLNCC is represented by a mixed integer programming (MIP) model using indexes, parameters and decision variables. The objective function of the MIP model is to minimize the total cost which is consisted of transportation cost, fixed cost, and handling cost. The transportation cost is obtained by transporting the returned products between each centers and secondary markets. The fixed cost is calculated by opening or closing decision at each center and secondary markets. That is, if there are three collection centers (the opening costs of collection center 1 2, and 3 are 10.5, 12.1, 8.9, respectively), and the collection center 1 is opened and the remainders are all closed, then the fixed cost is 10.5. The handling cost means the cost of treating the products returned from customers at each center and secondary markets which are opened at each RLNCC stage. The RLNCC is solved by the proposed HGA approach. In numerical experiment, the proposed HGA and a conventional competing approach is compared with each other using various measures of performance. For the conventional competing approach, the GA approach by Yun (2013) is used. The GA approach has not any local search technique such as the IHCM proposed the HGA approach. As measures of performance, CPU time, optimal solution, and optimal setting are used. Two types of the RLNCC with different numbers of customers, collection centers, remanufacturing centers, redistribution centers and secondary markets are presented for comparing the performances of the HGA and GA approaches. The MIP models using the two types of the RLNCC are programmed by Visual Basic Version 6.0, and the computer implementing environment is the IBM compatible PC with 3.06Ghz CPU speed and 1GB RAM on Windows XP. The parameters used in the HGA and GA approaches are that the total number of generations is 10,000, population size 20, crossover rate 0.5, mutation rate 0.1, and the search range for the IHCM is 2.0. Total 20 iterations are made for eliminating the randomness of the searches of the HGA and GA approaches. With performance comparisons, network representations by opening/closing decision, and convergence processes using two types of the RLNCCs, the experimental result shows that the HGA has significantly better performance in terms of the optimal solution than the GA, though the GA is slightly quicker than the HGA in terms of the CPU time. Finally, it has been proved that the proposed HGA approach is more efficient than conventional GA approach in two types of the RLNCC since the former has a GA search process as well as a local search process for additional search scheme, while the latter has a GA search process alone. For a future study, much more large-sized RLNCCs will be tested for robustness of our approach.

Optimization of Multiclass Support Vector Machine using Genetic Algorithm: Application to the Prediction of Corporate Credit Rating (유전자 알고리즘을 이용한 다분류 SVM의 최적화: 기업신용등급 예측에의 응용)

  • Ahn, Hyunchul
    • Information Systems Review
    • /
    • v.16 no.3
    • /
    • pp.161-177
    • /
    • 2014
  • Corporate credit rating assessment consists of complicated processes in which various factors describing a company are taken into consideration. Such assessment is known to be very expensive since domain experts should be employed to assess the ratings. As a result, the data-driven corporate credit rating prediction using statistical and artificial intelligence (AI) techniques has received considerable attention from researchers and practitioners. In particular, statistical methods such as multiple discriminant analysis (MDA) and multinomial logistic regression analysis (MLOGIT), and AI methods including case-based reasoning (CBR), artificial neural network (ANN), and multiclass support vector machine (MSVM) have been applied to corporate credit rating.2) Among them, MSVM has recently become popular because of its robustness and high prediction accuracy. In this study, we propose a novel optimized MSVM model, and appy it to corporate credit rating prediction in order to enhance the accuracy. Our model, named 'GAMSVM (Genetic Algorithm-optimized Multiclass Support Vector Machine),' is designed to simultaneously optimize the kernel parameters and the feature subset selection. Prior studies like Lorena and de Carvalho (2008), and Chatterjee (2013) show that proper kernel parameters may improve the performance of MSVMs. Also, the results from the studies such as Shieh and Yang (2008) and Chatterjee (2013) imply that appropriate feature selection may lead to higher prediction accuracy. Based on these prior studies, we propose to apply GAMSVM to corporate credit rating prediction. As a tool for optimizing the kernel parameters and the feature subset selection, we suggest genetic algorithm (GA). GA is known as an efficient and effective search method that attempts to simulate the biological evolution phenomenon. By applying genetic operations such as selection, crossover, and mutation, it is designed to gradually improve the search results. Especially, mutation operator prevents GA from falling into the local optima, thus we can find the globally optimal or near-optimal solution using it. GA has popularly been applied to search optimal parameters or feature subset selections of AI techniques including MSVM. With these reasons, we also adopt GA as an optimization tool. To empirically validate the usefulness of GAMSVM, we applied it to a real-world case of credit rating in Korea. Our application is in bond rating, which is the most frequently studied area of credit rating for specific debt issues or other financial obligations. The experimental dataset was collected from a large credit rating company in South Korea. It contained 39 financial ratios of 1,295 companies in the manufacturing industry, and their credit ratings. Using various statistical methods including the one-way ANOVA and the stepwise MDA, we selected 14 financial ratios as the candidate independent variables. The dependent variable, i.e. credit rating, was labeled as four classes: 1(A1); 2(A2); 3(A3); 4(B and C). 80 percent of total data for each class was used for training, and remaining 20 percent was used for validation. And, to overcome small sample size, we applied five-fold cross validation to our dataset. In order to examine the competitiveness of the proposed model, we also experimented several comparative models including MDA, MLOGIT, CBR, ANN and MSVM. In case of MSVM, we adopted One-Against-One (OAO) and DAGSVM (Directed Acyclic Graph SVM) approaches because they are known to be the most accurate approaches among various MSVM approaches. GAMSVM was implemented using LIBSVM-an open-source software, and Evolver 5.5-a commercial software enables GA. Other comparative models were experimented using various statistical and AI packages such as SPSS for Windows, Neuroshell, and Microsoft Excel VBA (Visual Basic for Applications). Experimental results showed that the proposed model-GAMSVM-outperformed all the competitive models. In addition, the model was found to use less independent variables, but to show higher accuracy. In our experiments, five variables such as X7 (total debt), X9 (sales per employee), X13 (years after founded), X15 (accumulated earning to total asset), and X39 (the index related to the cash flows from operating activity) were found to be the most important factors in predicting the corporate credit ratings. However, the values of the finally selected kernel parameters were found to be almost same among the data subsets. To examine whether the predictive performance of GAMSVM was significantly greater than those of other models, we used the McNemar test. As a result, we found that GAMSVM was better than MDA, MLOGIT, CBR, and ANN at the 1% significance level, and better than OAO and DAGSVM at the 5% significance level.