We have proposed a new method for quantitative structure-activity relationship (QSAR) analysis. T... more We have proposed a new method for quantitative structure-activity relationship (QSAR) analysis. This tool, termed GEMPLS, combines a genetic evolutionary method with partial least squares (PLS). We designed a new genetic operator and used Mahalanobis distance to improve predicted accuracy and speed up a solution for QSAR. The number of latent variables (lv) was encoded into the chromosome of GA, instead of scanning the best lv for PLS. We applied GEMPLS on a comparative binding energy (COMBINE) analysis system of 48 inhibitors of the HIV-1 protease. Using GEMPLS, the cross-validated correlation coefficient (q 2) is 0.9053 and external SDEP (SDEP ex) is 0.61. The results indicate that GEMPLS is very comparative to GAPLS and GEMPLS is faster than GAPLS for this data set. GEMPLS yielded the QSAR models, in which selected residues are consistent with some experimental evidences.
Proceedings of the 7th annual conference on Genetic and evolutionary computation, 2005
Edge Assembly Crossover (EAX) is by far the most successful crossover operator in solving the tra... more Edge Assembly Crossover (EAX) is by far the most successful crossover operator in solving the traveling salesman problem (TSP) with Genetic Algorithms (GAs). Various improvements have been proposed for EAX in GA. However, some of the improvements have to make compromises between performance and solution quality. In this work, we have combined several improvements proposed in the past, including heterogeneous pair selection (HpS), iterative child generation (ICG), and 2-opt. We also incorporate 2-opt into EAX, and restricted the 2-opt local searches to sub-tours in the intermediates generated by EAX. Our proposed method can improve the performance of EAX with decreased number of generations, error rates, and computation time. The applications of conventional 2-opt and our restricted 2opt concurrently have additive effect on the performance gain, and this performance improvement is more obvious in larger problems. The proposed method also enhanced the solution quality of EAX. The significances of the restricted 2-opt and the conventional 2-opt in EAX were analyzed and discussed.
Proceedings. 1998 IEEE International Conference on Robotics and Automation (Cat. No.98CH36146), 1998
This paper explores the use of neural networks to control robots in tasks requiring sequential an... more This paper explores the use of neural networks to control robots in tasks requiring sequential and leaming behavior. We propose a Family Competition Evolutionary Algorithm (FCEA) to evolve networks that can integrate these different types of behavior in a smooth and continuous manner. The approach integrates selfadaptive Gaussian mutation, self-adaptive Cauchy mutation, decreasing-based Gaussian mutation, and family competition. In order to illustrate the power of the approach, we apply this approach to two different task domains: the "artificial ant" problem and a sequential behavior probleman agent learns to play football. From the experimental results, we find our approach performs much better than other evolutionary algorithms in these two tasks. The main contribution of the paper, based on the results from our experiments, is that our approach can evolve neural networks to provide a means of integrating sequencing and learning within a single control system.
Background: Schizophrenic patients show lower incidences of cancer, implicating schizophrenia may... more Background: Schizophrenic patients show lower incidences of cancer, implicating schizophrenia may be a protective factor against cancer. To study the genetic correlation between the two diseases, a specific PPI network was constructed with candidate genes of both schizophrenia and hepatocellular carcinoma. The network, designated schizophrenia-hepatocellular carcinoma network (SHCN), was analysed and cliques were identified as potential functional modules or complexes. The findings were compared with information from pathway databases such as KEGG, Reactome, PID and ConsensusPathDB. Results: The functions of mediator genes from SHCN show immune system and cell cycle regulation have important roles in the eitology mechanism of schizophrenia. For example, the over-expressing schizophrenia candidate genes, SIRPB1, SYK and LCK, are responsible for signal transduction in cytokine production; immune responses involving IL-2 and TREM-1/DAP12 pathways are relevant for the etiology mechanism of schizophrenia. Novel treatments were proposed by searching the target genes of FDA approved drugs with genes in potential protein complexes and pathways. It was found that Vitamin A, retinoid acid and a few other immune response agents modulated by RARA and LCK genes may be potential treatments for both schizophrenia and hepatocellular carcinoma. Conclusions: This is the first study showing specific mediator genes in the SHCN which may suppress tumors. We also show that the schizophrenic protein interactions and modulation with cancer implicates the importance of immune system for etiology of schizophrenia.
A new evolutionary algorithm is introduced for training both feedforward and recurrent neural net... more A new evolutionary algorithm is introduced for training both feedforward and recurrent neural networks. The proposed approach, called the Family Competition Evolutionary Algorithm (FCEA), automatically achieves the balance of the solution quality and convergence speed by integrating multiple mutations, family competition and adaptive rules. We experimentally analyse the proposed approach by showing that its components can cooperate with one another, and possess good local and global properties. Following the description of implementation details, our approach is then applied to several benchmark problems, including an artificial ant problem, parity problems and a two-spiral problem. Experimental results indicate that the new approach is able to stably solve these problems, and is very competitive with the comparative evolutionary algorithms.
A robust evolutionary approach, called the Family Competition Evolutionary Algorithm (FCEA), is d... more A robust evolutionary approach, called the Family Competition Evolutionary Algorithm (FCEA), is described for the synthesis of optical thin-film designs. Based on family competition and adaptive rules, the proposed approach consists of global and local strategies by integrating decreasing mutations and self-adaptive mutations. The method is applied to three different optical coating designs with complex spectral quantities. Numerical results indicate that the proposed approach performs very robustly and is very competitive with other approaches.
In this paper the Family Competition Genetic Algorithm (FCGA) is applied to analyze DNAmicroarray... more In this paper the Family Competition Genetic Algorithm (FCGA) is applied to analyze DNAmicroarray data. DNA Microarray technology is a significant impact on genomics study. The proposed approach consists of global and local strategies by integrating the family competition, edge assembly crossover, and neighbor-join mutation. Experiments are performed to compare the FCGA with several methods in some realworld biological data sets. Numerical results indicate that FCGA performs very robustly and is very competitive with other approaches. Using FCGA, we are able to find a gene order to display the microarray data in a meaningful way.
The accuracy of the Content should not be relied upon and should be independently verified with p... more The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sublicensing, systematic supply, or distribution in any form to anyone is expressly forbidden.
Background Neutrophil antigens are involved in a variety of clinical conditions including transfu... more Background Neutrophil antigens are involved in a variety of clinical conditions including transfusion-related acute lung injury (TRALI) and other transfusion-related diseases. Recently, there are five characterized groups of human neutrophil antigen (HNA) systems, the HNA1 to 5. Characterization of all neutrophil antigens from whole genome sequencing (WGS) data may be accomplished for revealing complete genotyping formats of neutrophil antigens collectively at genome level with molecular variations which may respectively be revealed with available genotyping techniques for neutrophil antigens conventionally. Results We developed a computing method for the genotyping of human neutrophil antigens. Six samples from two families, available from the 1000 Genomes projects, were used for a HNA typing test. There are 500 ~ 3000 reads per sample filtered from the adopted human WGS datasets in order for identifying single nucleotide polymorphisms (SNPs) of neutrophil antigens. The visualizati...
Background The recent increase in the use of high-throughput two-hybrid analysis has generated la... more Background The recent increase in the use of high-throughput two-hybrid analysis has generated large quantities of data on protein interactions. Specifically, the availability of information about experimental protein-protein interactions and other protein features on the Internet enables human protein-protein interactions to be computationally predicted from co-evolution events (interolog). This study also considers other protein interaction features, including sub-cellular localization, tissue-specificity, the cell-cycle stage and domain-domain combination. Computational methods need to be developed to integrate these heterogeneous biological data to facilitate the maximum accuracy of the human protein interaction prediction. Results This study proposes a relative conservation score by finding maximal quasi-cliques in protein interaction networks, and considering other interaction features to formulate a scoring method. The scoring method can be adopted to discover which protein p...
Background DNA-binding proteins are of utmost importance to gene regulation. The identification o... more Background DNA-binding proteins are of utmost importance to gene regulation. The identification of DNA-binding domains is useful for understanding the regulation mechanisms of DNA-binding proteins. In this study, we proposed a method to determine whether a domain or a protein can has DNA binding capability by considering evolutionary conservation of DNA-binding residues. Results Our method achieves high precision and recall for 66 families of DNA-binding domains, with a false positive rate less than 5% for 250 non-DNA-binding proteins. In addition, experimental results show that our method is able to identify the different DNA-binding behaviors of proteins in the same SCOP family based on the use of evolutionary conservation of DNA-contact residues. Conclusion This study shows the conservation of DNA-contact residues in DNA-binding domains. We conclude that the members in the same subfamily bind DNA specifically and the members in different subfamilies often recognize different DNA ...
Background Schizophrenia, bipolar disorder, and major depression are devastating mental diseases,... more Background Schizophrenia, bipolar disorder, and major depression are devastating mental diseases, each with distinctive yet overlapping epidemiologic characteristics. Microarray and proteomics data have revealed genes which expressed abnormally in patients. Several single nucleotide polymorphisms (SNPs) and mutations are associated with one or more of the three diseases. Nevertheless, there are few studies on the interactions among the disease-associated genes and proteins. Results This study, for the first time, incorporated microarray and protein-protein interaction (PPI) databases to construct the PPI network of abnormally expressed genes in postmortem brain samples of schizophrenia, bipolar disorder, and major depression patients. The samples were collected from Brodmann area (BA) 10 of the prefrontal cortex. Abnormally expressed disease genes were selected by t-tests comparing the disease and control samples. These genes were involved in housekeeping functions (e.g. translation...
Background Protein-protein interactions (PPIs) are critical to every aspect of biological process... more Background Protein-protein interactions (PPIs) are critical to every aspect of biological processes. Expansion of all PPIs from a set of given queries often results in a complex PPI network lacking spatiotemporal consideration. Moreover, the reliability of available PPI resources, which consist of low- and high-throughput data, for network construction remains a significant challenge. Even though a number of software tools are available to facilitate PPI network analysis, an integrated tool is crucial to alleviate the burden on querying across multiple web servers and software tools. Results We have constructed an integrated web service, POINeT, to simplify the process of PPI searching, analysis, and visualization. POINeT merges PPI and tissue-specific expression data from multiple resources. The tissue-specific PPIs and the numbers of research papers supporting the PPIs can be filtered with user-adjustable threshold values and are dynamically updated in the viewer. The network cons...
Summary: Predicting disulfide connectivity precisely helps towards the solution of protein struct... more Summary: Predicting disulfide connectivity precisely helps towards the solution of protein structure prediction. In this study, a descriptor derived from the sequential distance between oxidized cysteines (denoted as DOC) is proposed. An approach using support vector machine (SVM) method based on weighted graph matching was further developed to predict the disulfide connectivity pattern in proteins. When DOC was applied, prediction accuracy of 63% for our SVM models could be achieved, which is significantly higher than those obtained from previous approaches. The results show that using the non-local descriptor DOC coupled with local sequence profiles significantly improves the prediction accuracy. These improvements demonstrate that DOC, with a proper scaling scheme, is an effective feature for the prediction of disulfide connectivity. The method developed in this work is available at the web server PreCys (prediction of cys–cys linkages of proteins). Availability: Contact: cyka...
We have proposed a new method for quantitative structure-activity relationship (QSAR) analysis. T... more We have proposed a new method for quantitative structure-activity relationship (QSAR) analysis. This tool, termed GEMPLS, combines a genetic evolutionary method with partial least squares (PLS). We designed a new genetic operator and used Mahalanobis distance to improve predicted accuracy and speed up a solution for QSAR. The number of latent variables (lv) was encoded into the chromosome of GA, instead of scanning the best lv for PLS. We applied GEMPLS on a comparative binding energy (COMBINE) analysis system of 48 inhibitors of the HIV-1 protease. Using GEMPLS, the cross-validated correlation coefficient (q 2) is 0.9053 and external SDEP (SDEP ex) is 0.61. The results indicate that GEMPLS is very comparative to GAPLS and GEMPLS is faster than GAPLS for this data set. GEMPLS yielded the QSAR models, in which selected residues are consistent with some experimental evidences.
Proceedings of the 7th annual conference on Genetic and evolutionary computation, 2005
Edge Assembly Crossover (EAX) is by far the most successful crossover operator in solving the tra... more Edge Assembly Crossover (EAX) is by far the most successful crossover operator in solving the traveling salesman problem (TSP) with Genetic Algorithms (GAs). Various improvements have been proposed for EAX in GA. However, some of the improvements have to make compromises between performance and solution quality. In this work, we have combined several improvements proposed in the past, including heterogeneous pair selection (HpS), iterative child generation (ICG), and 2-opt. We also incorporate 2-opt into EAX, and restricted the 2-opt local searches to sub-tours in the intermediates generated by EAX. Our proposed method can improve the performance of EAX with decreased number of generations, error rates, and computation time. The applications of conventional 2-opt and our restricted 2opt concurrently have additive effect on the performance gain, and this performance improvement is more obvious in larger problems. The proposed method also enhanced the solution quality of EAX. The significances of the restricted 2-opt and the conventional 2-opt in EAX were analyzed and discussed.
Proceedings. 1998 IEEE International Conference on Robotics and Automation (Cat. No.98CH36146), 1998
This paper explores the use of neural networks to control robots in tasks requiring sequential an... more This paper explores the use of neural networks to control robots in tasks requiring sequential and leaming behavior. We propose a Family Competition Evolutionary Algorithm (FCEA) to evolve networks that can integrate these different types of behavior in a smooth and continuous manner. The approach integrates selfadaptive Gaussian mutation, self-adaptive Cauchy mutation, decreasing-based Gaussian mutation, and family competition. In order to illustrate the power of the approach, we apply this approach to two different task domains: the "artificial ant" problem and a sequential behavior probleman agent learns to play football. From the experimental results, we find our approach performs much better than other evolutionary algorithms in these two tasks. The main contribution of the paper, based on the results from our experiments, is that our approach can evolve neural networks to provide a means of integrating sequencing and learning within a single control system.
Background: Schizophrenic patients show lower incidences of cancer, implicating schizophrenia may... more Background: Schizophrenic patients show lower incidences of cancer, implicating schizophrenia may be a protective factor against cancer. To study the genetic correlation between the two diseases, a specific PPI network was constructed with candidate genes of both schizophrenia and hepatocellular carcinoma. The network, designated schizophrenia-hepatocellular carcinoma network (SHCN), was analysed and cliques were identified as potential functional modules or complexes. The findings were compared with information from pathway databases such as KEGG, Reactome, PID and ConsensusPathDB. Results: The functions of mediator genes from SHCN show immune system and cell cycle regulation have important roles in the eitology mechanism of schizophrenia. For example, the over-expressing schizophrenia candidate genes, SIRPB1, SYK and LCK, are responsible for signal transduction in cytokine production; immune responses involving IL-2 and TREM-1/DAP12 pathways are relevant for the etiology mechanism of schizophrenia. Novel treatments were proposed by searching the target genes of FDA approved drugs with genes in potential protein complexes and pathways. It was found that Vitamin A, retinoid acid and a few other immune response agents modulated by RARA and LCK genes may be potential treatments for both schizophrenia and hepatocellular carcinoma. Conclusions: This is the first study showing specific mediator genes in the SHCN which may suppress tumors. We also show that the schizophrenic protein interactions and modulation with cancer implicates the importance of immune system for etiology of schizophrenia.
A new evolutionary algorithm is introduced for training both feedforward and recurrent neural net... more A new evolutionary algorithm is introduced for training both feedforward and recurrent neural networks. The proposed approach, called the Family Competition Evolutionary Algorithm (FCEA), automatically achieves the balance of the solution quality and convergence speed by integrating multiple mutations, family competition and adaptive rules. We experimentally analyse the proposed approach by showing that its components can cooperate with one another, and possess good local and global properties. Following the description of implementation details, our approach is then applied to several benchmark problems, including an artificial ant problem, parity problems and a two-spiral problem. Experimental results indicate that the new approach is able to stably solve these problems, and is very competitive with the comparative evolutionary algorithms.
A robust evolutionary approach, called the Family Competition Evolutionary Algorithm (FCEA), is d... more A robust evolutionary approach, called the Family Competition Evolutionary Algorithm (FCEA), is described for the synthesis of optical thin-film designs. Based on family competition and adaptive rules, the proposed approach consists of global and local strategies by integrating decreasing mutations and self-adaptive mutations. The method is applied to three different optical coating designs with complex spectral quantities. Numerical results indicate that the proposed approach performs very robustly and is very competitive with other approaches.
In this paper the Family Competition Genetic Algorithm (FCGA) is applied to analyze DNAmicroarray... more In this paper the Family Competition Genetic Algorithm (FCGA) is applied to analyze DNAmicroarray data. DNA Microarray technology is a significant impact on genomics study. The proposed approach consists of global and local strategies by integrating the family competition, edge assembly crossover, and neighbor-join mutation. Experiments are performed to compare the FCGA with several methods in some realworld biological data sets. Numerical results indicate that FCGA performs very robustly and is very competitive with other approaches. Using FCGA, we are able to find a gene order to display the microarray data in a meaningful way.
The accuracy of the Content should not be relied upon and should be independently verified with p... more The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sublicensing, systematic supply, or distribution in any form to anyone is expressly forbidden.
Background Neutrophil antigens are involved in a variety of clinical conditions including transfu... more Background Neutrophil antigens are involved in a variety of clinical conditions including transfusion-related acute lung injury (TRALI) and other transfusion-related diseases. Recently, there are five characterized groups of human neutrophil antigen (HNA) systems, the HNA1 to 5. Characterization of all neutrophil antigens from whole genome sequencing (WGS) data may be accomplished for revealing complete genotyping formats of neutrophil antigens collectively at genome level with molecular variations which may respectively be revealed with available genotyping techniques for neutrophil antigens conventionally. Results We developed a computing method for the genotyping of human neutrophil antigens. Six samples from two families, available from the 1000 Genomes projects, were used for a HNA typing test. There are 500 ~ 3000 reads per sample filtered from the adopted human WGS datasets in order for identifying single nucleotide polymorphisms (SNPs) of neutrophil antigens. The visualizati...
Background The recent increase in the use of high-throughput two-hybrid analysis has generated la... more Background The recent increase in the use of high-throughput two-hybrid analysis has generated large quantities of data on protein interactions. Specifically, the availability of information about experimental protein-protein interactions and other protein features on the Internet enables human protein-protein interactions to be computationally predicted from co-evolution events (interolog). This study also considers other protein interaction features, including sub-cellular localization, tissue-specificity, the cell-cycle stage and domain-domain combination. Computational methods need to be developed to integrate these heterogeneous biological data to facilitate the maximum accuracy of the human protein interaction prediction. Results This study proposes a relative conservation score by finding maximal quasi-cliques in protein interaction networks, and considering other interaction features to formulate a scoring method. The scoring method can be adopted to discover which protein p...
Background DNA-binding proteins are of utmost importance to gene regulation. The identification o... more Background DNA-binding proteins are of utmost importance to gene regulation. The identification of DNA-binding domains is useful for understanding the regulation mechanisms of DNA-binding proteins. In this study, we proposed a method to determine whether a domain or a protein can has DNA binding capability by considering evolutionary conservation of DNA-binding residues. Results Our method achieves high precision and recall for 66 families of DNA-binding domains, with a false positive rate less than 5% for 250 non-DNA-binding proteins. In addition, experimental results show that our method is able to identify the different DNA-binding behaviors of proteins in the same SCOP family based on the use of evolutionary conservation of DNA-contact residues. Conclusion This study shows the conservation of DNA-contact residues in DNA-binding domains. We conclude that the members in the same subfamily bind DNA specifically and the members in different subfamilies often recognize different DNA ...
Background Schizophrenia, bipolar disorder, and major depression are devastating mental diseases,... more Background Schizophrenia, bipolar disorder, and major depression are devastating mental diseases, each with distinctive yet overlapping epidemiologic characteristics. Microarray and proteomics data have revealed genes which expressed abnormally in patients. Several single nucleotide polymorphisms (SNPs) and mutations are associated with one or more of the three diseases. Nevertheless, there are few studies on the interactions among the disease-associated genes and proteins. Results This study, for the first time, incorporated microarray and protein-protein interaction (PPI) databases to construct the PPI network of abnormally expressed genes in postmortem brain samples of schizophrenia, bipolar disorder, and major depression patients. The samples were collected from Brodmann area (BA) 10 of the prefrontal cortex. Abnormally expressed disease genes were selected by t-tests comparing the disease and control samples. These genes were involved in housekeeping functions (e.g. translation...
Background Protein-protein interactions (PPIs) are critical to every aspect of biological process... more Background Protein-protein interactions (PPIs) are critical to every aspect of biological processes. Expansion of all PPIs from a set of given queries often results in a complex PPI network lacking spatiotemporal consideration. Moreover, the reliability of available PPI resources, which consist of low- and high-throughput data, for network construction remains a significant challenge. Even though a number of software tools are available to facilitate PPI network analysis, an integrated tool is crucial to alleviate the burden on querying across multiple web servers and software tools. Results We have constructed an integrated web service, POINeT, to simplify the process of PPI searching, analysis, and visualization. POINeT merges PPI and tissue-specific expression data from multiple resources. The tissue-specific PPIs and the numbers of research papers supporting the PPIs can be filtered with user-adjustable threshold values and are dynamically updated in the viewer. The network cons...
Summary: Predicting disulfide connectivity precisely helps towards the solution of protein struct... more Summary: Predicting disulfide connectivity precisely helps towards the solution of protein structure prediction. In this study, a descriptor derived from the sequential distance between oxidized cysteines (denoted as DOC) is proposed. An approach using support vector machine (SVM) method based on weighted graph matching was further developed to predict the disulfide connectivity pattern in proteins. When DOC was applied, prediction accuracy of 63% for our SVM models could be achieved, which is significantly higher than those obtained from previous approaches. The results show that using the non-local descriptor DOC coupled with local sequence profiles significantly improves the prediction accuracy. These improvements demonstrate that DOC, with a proper scaling scheme, is an effective feature for the prediction of disulfide connectivity. The method developed in this work is available at the web server PreCys (prediction of cys–cys linkages of proteins). Availability: Contact: cyka...
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