Modeling non coding background sequences appropriately is important for the detection of regulatory elements from DNA sequences. Based on the chi square statistic test, some explanations about why to choose higher ...Modeling non coding background sequences appropriately is important for the detection of regulatory elements from DNA sequences. Based on the chi square statistic test, some explanations about why to choose higher order Markov chain model and how to automatically select the proper order are given in this paper. The chi square test is first run on synthetic data sets to show that it can efficiently find the proper order of Markov chain. Using chi square test, distinct higher order context dependences inherent in ten sets of sequences of yeast S.cerevisiae from other literature have been found. So the Markov chain with higher order would be more suitable for modeling the non coding background sequences than an independent model.展开更多
In developing distributed systems, conformance testing is required to determine whether an implementation under test (IUT) conforms to its specification. With distributed test architectures involving multiple remote...In developing distributed systems, conformance testing is required to determine whether an implementation under test (IUT) conforms to its specification. With distributed test architectures involving multiple remote testers, testing approaches may become more complicated because of issues known as controllability and observability problems. Based on a finite state machine (FSM) representation of the system's specification, this paper proposes a new method to generate a test sequence utilizing multiple UIO sequences. The method is essentially guided by the way of minimizing the use of external coordination messages and input/output operations. Experiments are given to evaluate the proposed method.展开更多
In order to solve the problem of artificial generation and low efficiency of test sequences for zone controller (ZC), a model-based automatic generation method of test sequence is proposed. Firstly, the timed automata...In order to solve the problem of artificial generation and low efficiency of test sequences for zone controller (ZC), a model-based automatic generation method of test sequence is proposed. Firstly, the timed automata model is established based on function analysis of the zone controller, and the correctness of the model is verified by UPPAAL. Then by parsing the timed automata model files, state information and transition conditions can be extracted to generate test case sets. Finally, according to the serialization conditions of test cases, the test cases are serialized into test sequences by using the improved depth first search algorithm. A case, the ZC controls the train running within its jurisdiction, shows that the method is correct and can effectively improve the efficiency of test sequence generation.展开更多
A novel interoperability test sequences optimization scheme is proposed in which the genetic algorithm (GA) is used to obtain the minimal-length interoperability test sequences. During our work, the basic interopera...A novel interoperability test sequences optimization scheme is proposed in which the genetic algorithm (GA) is used to obtain the minimal-length interoperability test sequences. During our work, the basic interoperability test sequences are generated based on the minimal-complete-coverage criterion, which removes the redundancy from conformance test sequences. Then interoperability sequences minimization problem can be considered as an instance of the set covering problem, and the GA is applied to remove redundancy in interoperability transitions. The results show that compared to conventional algorithm, the proposed algorithm is more practical to avoid the state space explosion problem, for it can reduce the length of the test sequences and maintain the same transition coverage.展开更多
This paper presents modified version of a realistic test tool suitable to Design For Testability (DFT) and Built-ln Self Test (BIST) environments. A comprehensive tool is developed in the form of a test simulator....This paper presents modified version of a realistic test tool suitable to Design For Testability (DFT) and Built-ln Self Test (BIST) environments. A comprehensive tool is developed in the form of a test simulator. The simulator is capable of providing a required goal of test for the Circuit Under Test (CUT). The simulator uses the approach of fault diagnostics with fault grading procedures to provide the optimum tests. The current version of the simulator embeds features of exhaustive and pseudo-random test generation schemes along with the search solutions of cost effective test goals. The simulator provides facilities of realizing all possible pseudo-random sequence generators with all possible combinations of seeds. The tool is developed on a common Personal Computer (PC) platform and hence no special software is required. Thereby, it is a low cost tool hence economical. The tool is very much suitable for determining realistic test sequences for a targeted goal of testing for any CUT. The developed tool incorporates flexible Graphical User Interface (GUI) procedures and can be operated without any special programming skill. The tool is debugged and tested with the results of many bench mark circuits. Further, this developed tool can be utilized for educational purposes for many courses such as fault-tolerant computing, fault diagnosis, digital electronics, and safe-reliable-testable digital logic designs.展开更多
Reachability testing is an approach to testing concurrent programs, which can systematically exercise every partially ordered SYN-sequence without constructing the static model. In fact, not all the SYN-sequences need...Reachability testing is an approach to testing concurrent programs, which can systematically exercise every partially ordered SYN-sequence without constructing the static model. In fact, not all the SYN-sequences need to be tested. This paper proposed a SYN-sequence selection strategy for reachability testing, which can reduce the number of SYN-sequences generated without decreasing the effectiveness of detecting programs' errors. We described a simple algorithm to implement the strategy, and then discussed several optimizations to the algorithm. Experiments have been carried out in a case study to verify the efficacy of the strategy.展开更多
Next generation sequencing is currently a cornerstone of genetic testing in routine diagnostics,allowing for the detection of sequence variants with so far unprecedented large scale,mainly in genetically heterogenous ...Next generation sequencing is currently a cornerstone of genetic testing in routine diagnostics,allowing for the detection of sequence variants with so far unprecedented large scale,mainly in genetically heterogenous diseases,such as neurological disorders.It is a fast-moving field,where new wet enrichment protocols and bioinformatics tools are constantly being developed to overcome initial limitations.Despite the as yet undiscussed advantages,however,there are still some challenges in data analysis and the interpretation of variants.In this review,we address the current state of next generation sequencing diagnostic testing for inherited human disorders,particularly giving an overview of the available high-throughput sequencing approaches;including targeted,whole-exome and whole-genome sequencing;and discussing the main critical aspects of the bioinformatic process,from raw data analysis to molecular diagnosis.展开更多
The introduction of next-generation sequencing(NGS) technology in testing for hereditary cancer susceptibility allows testing of multiple cancer susceptibility genes simultaneously. While there are many potential bene...The introduction of next-generation sequencing(NGS) technology in testing for hereditary cancer susceptibility allows testing of multiple cancer susceptibility genes simultaneously. While there are many potential benefits to utilizing this technology in the hereditary cancer clinic, including efficiency of time and cost, there are also important limitations that must be considered. The best panel for the given clinical situation should be selected to minimize the number of variants of unknown significance. The inclusion in panels of low penetrance or newly identified genes without specific actionability can be problematic for interpretation.Genetic counselors are an essential part of the hereditary cancer risk assessment team, helping the medical team select the most appropriate test and interpret the often complex results. Genetic counselors obtain an extended family history, counsel patients on the available tests and the potential implications of results for themselves and their family members(pre-test counseling), explain to patients the implications of the test results(post-test counseling), and assist in testing family members at risk.展开更多
This Paper presents a data fusion method with distributed sequence detection for on hypothasis testingtheory including the data fusion algorithm of sequence detection based on least error probability rule, the decisio...This Paper presents a data fusion method with distributed sequence detection for on hypothasis testingtheory including the data fusion algorithm of sequence detection based on least error probability rule, the decision ruleand the calcation formula of the detction times and the simulation result of system performance as well.展开更多
Over the past few years, many researchers have attempted to develop non-invasive prenatal testing methods in order to investigate the genetic status of the fetus. The aim is to avoid invasive procedures such as chorio...Over the past few years, many researchers have attempted to develop non-invasive prenatal testing methods in order to investigate the genetic status of the fetus. The aim is to avoid invasive procedures such as chorionic villus and amniotic fluid sampling, which result in a significant risk for pregnancy loss. The discovery of cell free fetal DNA circulating in the maternal blood has great potential for the development of non-invasive prenatal testing(NIPT) methodologies. Such strategies have been successfully applied for the determination of the fetal rhesus status and inherited monogenic disease but the field of fetal aneuploidy investigation seems to be more challenging. The main reason for this is that the maternal cell free DNA in the mother's plasma is far more abundant, and because it is identical to half of the corresponding fetal DNA. Approaches developed are mainly based on next generation sequencing(NGS) technologies and epigenetic genetic modifications, such as fetal-maternal DNA differential methylation. At present, genetic services for non-invasive fetal aneuploidy detection are offered using NGS-based approaches but, for reasons that are presented herein, they still serve as screening tests which are not readily accessed by the majority of couples. Here we discuss the limitations of both strategies for NIPT and the future potential of the methods developed.展开更多
Dear Editor,The tuberculin skin test(TST)reagents have continuously improved,with the ESAT6-CFP10(EC)test having recently been introduced,but are seldom based on the direction of the delayed-type hypersensitivity(DTH)...Dear Editor,The tuberculin skin test(TST)reagents have continuously improved,with the ESAT6-CFP10(EC)test having recently been introduced,but are seldom based on the direction of the delayed-type hypersensitivity(DTH)mechanism.Previous studies only partially showed the infiltration and activation of immune cells and the production of cytokines of the skin induration[1,2],and lack the detailed measurements of cell proportions and gene expression in the DTH response.Therefore,in this study,we revealed the comprehensive characteristics of DTH by single-cell RNA sequencing(scRNA-seq)in the guinea pig tuberculosis(TB)model[Experimental Animal Welfare Ethics Committee,Beijing Tuberculosis and Thoracic Tumor Research Institute(2021-064)].展开更多
Recent advancements in next generation sequencing have allowed for genetic information become more readily available in the clinical setting for those affected by cancer and by treating clinicians.Given the lack of ac...Recent advancements in next generation sequencing have allowed for genetic information become more readily available in the clinical setting for those affected by cancer and by treating clinicians.Given the lack of access to geneticists,medical oncologists and other treating physicians have begun ordering and interpreting genetic tests for individuals with cancer through the process of"mainstreaming".While this process has allowed for quicker access to genetic tests,the process of"mainstreaming"has also brought several challenges including the dissemination of variants of unknown significance results,ordering of appropriate tests,and accurate interpretation of genetic results with appropriate followup testing and interventions.In this editorial,we seek to explore the process of informed consent of individuals before obtaining genetic testing and offer potential solutions to optimize the informed consent process including categorization of results as well as a layered consent model.展开更多
Screening for maternal syphilis has been an essential component of routine antenatal screening tests in most countries for many years. This is not only because of the virulence of the spirochete which causes the infec...Screening for maternal syphilis has been an essential component of routine antenatal screening tests in most countries for many years. This is not only because of the virulence of the spirochete which causes the infection but also because of its vertical transmission rate and the potential severe adverse complications/morbidity that can result from its transmission to the fetus. Although the incidence of maternal syphilis and its fetal sequalae in low-income countries has been considerable for several years, the disease has been almost non-existent in high income countries with wide antenatal screening coverage and effective treatment programmes for Syphilis. The recent alarming increase in the incidence of maternal syphilis in high income countries has spawned a renewed public health interest in the infection, with several countries updating and strengthening public health guidance in an attempt to stem this dramatic trend. This is a short clinical update for the practising obstetrician on how to manage the antenatal patient with a positive syphilis screening test.展开更多
The objectives of this study were to construct a database of expressed sequence tag (EST)-simple sequence repeat (SSR) markers to identify lettuce cultivars. A set of 370 EST-SSR primer pairs were applied for fingerpr...The objectives of this study were to construct a database of expressed sequence tag (EST)-simple sequence repeat (SSR) markers to identify lettuce cultivars. A set of 370 EST-SSR primer pairs were applied for fingerprinting the lettuce cultivars. Fifty-eight EST-SSR markers showed hy-per-variability and were able to differentiate 92 cultivars. A total of 176 polymorphic amplified fragments were obtained by the 58 markers, and two to eight SSR alleles were detected for each l°Cus with an average of three alleles per locus. Average polymorphism information content (PIC) was 0.425, ranging from 0.022 to 0.743. Cluster analysis was based on Jaccard’s distance coefficients using the method of unweighted pair group. In this method we used arithmetical averages (UPGMA) algorithm categorized 4 major groups, which were in accordance to morphological traits. The eight cultivars of three groups with 100% genetic similarity through SSR analysis were investigated by phenotypic traits. These cultivars including these pairs are very similar in 27 morphological characteristics. Therefore, these EST-SSR markers could be used to select similar cultivars through management of reference collection to complement distinctiveness test of lettuce cultivars.展开更多
The problem of sequential fault diagnosis is to construct a diagnosis tree that can isolate the failure sources with minimal test cost. Pervious sequential fault diagnosis strategy generating algorithms only consider ...The problem of sequential fault diagnosis is to construct a diagnosis tree that can isolate the failure sources with minimal test cost. Pervious sequential fault diagnosis strategy generating algorithms only consider the execution cost at application stage, which may result in a solution with poor quality from the view of life cycle cost. Furthermore, due to the fact that uncertain information exists extensively in the real-world systems, the tests are always imperfect. In order to reduce the cost of fault diagnosis in the realistic systems, the sequential fault diagnosis problem with imperfect tests considering life cycle cost is presented and formulated in this work, which is an intractable NP-hard AND/OR decision tree construction problem. An algorithm based on AND/OR graph search is proposed to solve this problem. Heuristic search based on information theory is applied to generate the sub-tree in the algorithm. Some practical issues such as the method to improve the computational efficiency and the diagnosis strategy with multi-outcome tests are discussed. The algorithm is tested and compared with previous algorithms on the simulated systems with different scales and uncertainty. Application on a wheel momentum system of a spacecraft is studied in detail. Both the simulation and application results suggest that the cost of the diagnosis strategy can be reduced significantly by using the proposed algorithm, especially when the placement cost of the tests constitutes a large part of the total cost.展开更多
文摘Modeling non coding background sequences appropriately is important for the detection of regulatory elements from DNA sequences. Based on the chi square statistic test, some explanations about why to choose higher order Markov chain model and how to automatically select the proper order are given in this paper. The chi square test is first run on synthetic data sets to show that it can efficiently find the proper order of Markov chain. Using chi square test, distinct higher order context dependences inherent in ten sets of sequences of yeast S.cerevisiae from other literature have been found. So the Markov chain with higher order would be more suitable for modeling the non coding background sequences than an independent model.
基金Project supported by the National Natural Science Foundation of China (Grant No.60673115), and the Open Foundation of State Key Laboratory of Software Engineering (Grant No.SKLSE05-13)
文摘In developing distributed systems, conformance testing is required to determine whether an implementation under test (IUT) conforms to its specification. With distributed test architectures involving multiple remote testers, testing approaches may become more complicated because of issues known as controllability and observability problems. Based on a finite state machine (FSM) representation of the system's specification, this paper proposes a new method to generate a test sequence utilizing multiple UIO sequences. The method is essentially guided by the way of minimizing the use of external coordination messages and input/output operations. Experiments are given to evaluate the proposed method.
文摘In order to solve the problem of artificial generation and low efficiency of test sequences for zone controller (ZC), a model-based automatic generation method of test sequence is proposed. Firstly, the timed automata model is established based on function analysis of the zone controller, and the correctness of the model is verified by UPPAAL. Then by parsing the timed automata model files, state information and transition conditions can be extracted to generate test case sets. Finally, according to the serialization conditions of test cases, the test cases are serialized into test sequences by using the improved depth first search algorithm. A case, the ZC controls the train running within its jurisdiction, shows that the method is correct and can effectively improve the efficiency of test sequence generation.
文摘A novel interoperability test sequences optimization scheme is proposed in which the genetic algorithm (GA) is used to obtain the minimal-length interoperability test sequences. During our work, the basic interoperability test sequences are generated based on the minimal-complete-coverage criterion, which removes the redundancy from conformance test sequences. Then interoperability sequences minimization problem can be considered as an instance of the set covering problem, and the GA is applied to remove redundancy in interoperability transitions. The results show that compared to conventional algorithm, the proposed algorithm is more practical to avoid the state space explosion problem, for it can reduce the length of the test sequences and maintain the same transition coverage.
文摘This paper presents modified version of a realistic test tool suitable to Design For Testability (DFT) and Built-ln Self Test (BIST) environments. A comprehensive tool is developed in the form of a test simulator. The simulator is capable of providing a required goal of test for the Circuit Under Test (CUT). The simulator uses the approach of fault diagnostics with fault grading procedures to provide the optimum tests. The current version of the simulator embeds features of exhaustive and pseudo-random test generation schemes along with the search solutions of cost effective test goals. The simulator provides facilities of realizing all possible pseudo-random sequence generators with all possible combinations of seeds. The tool is developed on a common Personal Computer (PC) platform and hence no special software is required. Thereby, it is a low cost tool hence economical. The tool is very much suitable for determining realistic test sequences for a targeted goal of testing for any CUT. The developed tool incorporates flexible Graphical User Interface (GUI) procedures and can be operated without any special programming skill. The tool is debugged and tested with the results of many bench mark circuits. Further, this developed tool can be utilized for educational purposes for many courses such as fault-tolerant computing, fault diagnosis, digital electronics, and safe-reliable-testable digital logic designs.
基金Supported by the "Tenth-Five Years" National Science Pre-Research Foundation of China (41315.9.2)the Natural Science Founda-tion of Hubei Province (2005ABA266)
文摘Reachability testing is an approach to testing concurrent programs, which can systematically exercise every partially ordered SYN-sequence without constructing the static model. In fact, not all the SYN-sequences need to be tested. This paper proposed a SYN-sequence selection strategy for reachability testing, which can reduce the number of SYN-sequences generated without decreasing the effectiveness of detecting programs' errors. We described a simple algorithm to implement the strategy, and then discussed several optimizations to the algorithm. Experiments have been carried out in a case study to verify the efficacy of the strategy.
文摘Next generation sequencing is currently a cornerstone of genetic testing in routine diagnostics,allowing for the detection of sequence variants with so far unprecedented large scale,mainly in genetically heterogenous diseases,such as neurological disorders.It is a fast-moving field,where new wet enrichment protocols and bioinformatics tools are constantly being developed to overcome initial limitations.Despite the as yet undiscussed advantages,however,there are still some challenges in data analysis and the interpretation of variants.In this review,we address the current state of next generation sequencing diagnostic testing for inherited human disorders,particularly giving an overview of the available high-throughput sequencing approaches;including targeted,whole-exome and whole-genome sequencing;and discussing the main critical aspects of the bioinformatic process,from raw data analysis to molecular diagnosis.
文摘The introduction of next-generation sequencing(NGS) technology in testing for hereditary cancer susceptibility allows testing of multiple cancer susceptibility genes simultaneously. While there are many potential benefits to utilizing this technology in the hereditary cancer clinic, including efficiency of time and cost, there are also important limitations that must be considered. The best panel for the given clinical situation should be selected to minimize the number of variants of unknown significance. The inclusion in panels of low penetrance or newly identified genes without specific actionability can be problematic for interpretation.Genetic counselors are an essential part of the hereditary cancer risk assessment team, helping the medical team select the most appropriate test and interpret the often complex results. Genetic counselors obtain an extended family history, counsel patients on the available tests and the potential implications of results for themselves and their family members(pre-test counseling), explain to patients the implications of the test results(post-test counseling), and assist in testing family members at risk.
文摘This Paper presents a data fusion method with distributed sequence detection for on hypothasis testingtheory including the data fusion algorithm of sequence detection based on least error probability rule, the decision ruleand the calcation formula of the detction times and the simulation result of system performance as well.
文摘Over the past few years, many researchers have attempted to develop non-invasive prenatal testing methods in order to investigate the genetic status of the fetus. The aim is to avoid invasive procedures such as chorionic villus and amniotic fluid sampling, which result in a significant risk for pregnancy loss. The discovery of cell free fetal DNA circulating in the maternal blood has great potential for the development of non-invasive prenatal testing(NIPT) methodologies. Such strategies have been successfully applied for the determination of the fetal rhesus status and inherited monogenic disease but the field of fetal aneuploidy investigation seems to be more challenging. The main reason for this is that the maternal cell free DNA in the mother's plasma is far more abundant, and because it is identical to half of the corresponding fetal DNA. Approaches developed are mainly based on next generation sequencing(NGS) technologies and epigenetic genetic modifications, such as fetal-maternal DNA differential methylation. At present, genetic services for non-invasive fetal aneuploidy detection are offered using NGS-based approaches but, for reasons that are presented herein, they still serve as screening tests which are not readily accessed by the majority of couples. Here we discuss the limitations of both strategies for NIPT and the future potential of the methods developed.
基金supported by the National Natural Science Foundation(81871691)the Beijing Municipal Natural Science Foundation(KZ202110025034).
文摘Dear Editor,The tuberculin skin test(TST)reagents have continuously improved,with the ESAT6-CFP10(EC)test having recently been introduced,but are seldom based on the direction of the delayed-type hypersensitivity(DTH)mechanism.Previous studies only partially showed the infiltration and activation of immune cells and the production of cytokines of the skin induration[1,2],and lack the detailed measurements of cell proportions and gene expression in the DTH response.Therefore,in this study,we revealed the comprehensive characteristics of DTH by single-cell RNA sequencing(scRNA-seq)in the guinea pig tuberculosis(TB)model[Experimental Animal Welfare Ethics Committee,Beijing Tuberculosis and Thoracic Tumor Research Institute(2021-064)].
文摘Recent advancements in next generation sequencing have allowed for genetic information become more readily available in the clinical setting for those affected by cancer and by treating clinicians.Given the lack of access to geneticists,medical oncologists and other treating physicians have begun ordering and interpreting genetic tests for individuals with cancer through the process of"mainstreaming".While this process has allowed for quicker access to genetic tests,the process of"mainstreaming"has also brought several challenges including the dissemination of variants of unknown significance results,ordering of appropriate tests,and accurate interpretation of genetic results with appropriate followup testing and interventions.In this editorial,we seek to explore the process of informed consent of individuals before obtaining genetic testing and offer potential solutions to optimize the informed consent process including categorization of results as well as a layered consent model.
文摘Screening for maternal syphilis has been an essential component of routine antenatal screening tests in most countries for many years. This is not only because of the virulence of the spirochete which causes the infection but also because of its vertical transmission rate and the potential severe adverse complications/morbidity that can result from its transmission to the fetus. Although the incidence of maternal syphilis and its fetal sequalae in low-income countries has been considerable for several years, the disease has been almost non-existent in high income countries with wide antenatal screening coverage and effective treatment programmes for Syphilis. The recent alarming increase in the incidence of maternal syphilis in high income countries has spawned a renewed public health interest in the infection, with several countries updating and strengthening public health guidance in an attempt to stem this dramatic trend. This is a short clinical update for the practising obstetrician on how to manage the antenatal patient with a positive syphilis screening test.
文摘The objectives of this study were to construct a database of expressed sequence tag (EST)-simple sequence repeat (SSR) markers to identify lettuce cultivars. A set of 370 EST-SSR primer pairs were applied for fingerprinting the lettuce cultivars. Fifty-eight EST-SSR markers showed hy-per-variability and were able to differentiate 92 cultivars. A total of 176 polymorphic amplified fragments were obtained by the 58 markers, and two to eight SSR alleles were detected for each l°Cus with an average of three alleles per locus. Average polymorphism information content (PIC) was 0.425, ranging from 0.022 to 0.743. Cluster analysis was based on Jaccard’s distance coefficients using the method of unweighted pair group. In this method we used arithmetical averages (UPGMA) algorithm categorized 4 major groups, which were in accordance to morphological traits. The eight cultivars of three groups with 100% genetic similarity through SSR analysis were investigated by phenotypic traits. These cultivars including these pairs are very similar in 27 morphological characteristics. Therefore, these EST-SSR markers could be used to select similar cultivars through management of reference collection to complement distinctiveness test of lettuce cultivars.
基金Project(C1320063131)supported by China Civil Space Foundation
文摘The problem of sequential fault diagnosis is to construct a diagnosis tree that can isolate the failure sources with minimal test cost. Pervious sequential fault diagnosis strategy generating algorithms only consider the execution cost at application stage, which may result in a solution with poor quality from the view of life cycle cost. Furthermore, due to the fact that uncertain information exists extensively in the real-world systems, the tests are always imperfect. In order to reduce the cost of fault diagnosis in the realistic systems, the sequential fault diagnosis problem with imperfect tests considering life cycle cost is presented and formulated in this work, which is an intractable NP-hard AND/OR decision tree construction problem. An algorithm based on AND/OR graph search is proposed to solve this problem. Heuristic search based on information theory is applied to generate the sub-tree in the algorithm. Some practical issues such as the method to improve the computational efficiency and the diagnosis strategy with multi-outcome tests are discussed. The algorithm is tested and compared with previous algorithms on the simulated systems with different scales and uncertainty. Application on a wheel momentum system of a spacecraft is studied in detail. Both the simulation and application results suggest that the cost of the diagnosis strategy can be reduced significantly by using the proposed algorithm, especially when the placement cost of the tests constitutes a large part of the total cost.