分别在两种重要并行计算模型中给出计算有向基因组排列的反转距离新的并行算法.基于Hannenhalli和Pevzner理论,分3个主要部分设计并行算法:构建断点图、计算断点图中圈数、计算断点图中障碍的数目.在cREW-PRAM模型上,算法使用O(n^2)处理...分别在两种重要并行计算模型中给出计算有向基因组排列的反转距离新的并行算法.基于Hannenhalli和Pevzner理论,分3个主要部分设计并行算法:构建断点图、计算断点图中圈数、计算断点图中障碍的数目.在cREW-PRAM模型上,算法使用O(n^2)处理器,时间复杂度为D(log^2n);在基于流水光总线的可重构线性阵列系统(linear array with a reconfigurable pipelined bus system,LARPBS)模型上,算法使用O(n^3)处理器,计算时间复杂度为D(logn).展开更多
Prostate cancer is a leading cause of global cancer-related death but attempts to improve diagnoses and develop novel therapies have been confounded by significant patient heterogeneity. In recent years, the applicati...Prostate cancer is a leading cause of global cancer-related death but attempts to improve diagnoses and develop novel therapies have been confounded by significant patient heterogeneity. In recent years, the application of next-generation sequencing to hundreds of prostate tumours has defined novel molecular subtypes and characterized extensive genomic aberration underlying disease initiation and progression. It is now clear that the heterogeneity observed in the clinic is underpinned by a molecular landscape rife with complexity, where genomic rearrangements and rare mutations combine to amplify transcriptomic diversity. This review dissects our current understanding of prostate cancer 'omics', including the sentinel role of copy number variation, the growing spectrum of oncogenic fusion genes, the potential influence of chromothripsis, and breakthroughs in defining mutation-associated subtypes. Increasing evidence suggests that genomic lesions frequently converge on specific cellular functions and signalling pathways, yet recurrent gene aberration appears rare. Therefore, it is critical that we continue to define individual tumour genomes, especially in the context of their expressed transcriptome. Only through improved characterisation of tumour to tumour variability can we advance to an age of precision therapy and personalized oncology.展开更多
Genome-scale assignment of orthologous genes is a fundamental and challenging problem in computational biology and has a wide range of applications in comparative genomics, functional genomics, and systems biology. Ma...Genome-scale assignment of orthologous genes is a fundamental and challenging problem in computational biology and has a wide range of applications in comparative genomics, functional genomics, and systems biology. Many methods based on sequence similarity, phylogenetic analysis, chromosomal syntenic information, and genome rearrangement have been proposed in recent years for ortholog assignment. Although these methods produce results that largely agree with each other, their results may still contain significant differences. In this article, we consider the recently proposed parsimony approach for assigning orthologs between closely related genomes based on genome rearrangement, which essentially attempts to transform one genome into another by the smallest number of genome rearrangement events including reversal, translocation, fusion, and fission, as well as gene duplication events. We will highlight some of the challenging algorithmic problems that arise in the approach including (i) minimum common substring partition, (ii) signed reversal distance with duplicates, and (iii) signed transposition distance with duplicates. The most recent progress towards the solution of these problems will be reviewed and some open questions will he posed. We will also discuss some possible extensions of the approach to the simultaneous comparison of multiple genomes.展开更多
Stochastic introgression of alien DNA may impose a genomic stress to the recipient genome. Herein, we report that apparent de novo genomic rearrangements in 10 of 13 selected endogenous, lowcopy, and potentially activ...Stochastic introgression of alien DNA may impose a genomic stress to the recipient genome. Herein, we report that apparent de novo genomic rearrangements in 10 of 13 selected endogenous, lowcopy, and potentially active long terminal repeat (LTR) retrotransposons occurred in one or more of three rice lines studied that were introgressed by wild rice (Zizania latifolia Griseb.). For nine retrotransposons in which both the reverse-transcriptase (RT) region and the LTR region were available, largely concordant rearrangements occurred at both regions in five elements and at the RT region only in the remaining four elements. A marked proportion of the genomic changes was shared by two or all three introgression lines that were derived from a single F~ plant. This indicates that most of the genomic changes occurred at early developmental stages of the F~ somatic cells, which then gave rise to germline cells, and, hence, ensured inheritance of the changes to later generations. Possible causes and potential implications of the introgression-induced genomic rearrangements in LTR retrotransposons are discussed in the context of plant genome evolution and breeding.展开更多
Reversals, transpositions and transreversals are common events in genome rearrangement. The genome rearrangement sorting problem is to transform one genome into another using the minimum number of given rearrangement ...Reversals, transpositions and transreversals are common events in genome rearrangement. The genome rearrangement sorting problem is to transform one genome into another using the minimum number of given rearrangement operations. An integer permutation is used to represent a genome in many cases. It can be divided into disjoint strips with each strip denoting a block of consecutive integers. A singleton is a strip of one integer. And the genome rearrange- ment problem turns into the problem of sorting a permutation into the identity permutation equivalently. Hannenhalli and Pevzner designed a polynomial time algorithm for the unsigned reversal sorting problem on those permutations with O(logn) singletons. In this paper, first we describe one case in which Hannenhalli and Pevzner's algorithm may fail and propose a corrected approach. In addition, we propose a (1 + ε)-approximation algorithm for sorting unsigned permutations with O(log n) singletons by reversals of weight 1 and transpositions/transreversals of weight 2.展开更多
In view of the fact that the problem of sorting unsigned permutation by reversal is NP-hard, while the problem of sorting signed permutation by reversal can be solved easily, in this paper, we first transform an unsig...In view of the fact that the problem of sorting unsigned permutation by reversal is NP-hard, while the problem of sorting signed permutation by reversal can be solved easily, in this paper, we first transform an unsigned permutation of length n,π (π1 ,… ,πn), into a set S(π) containing 2^n signed permutations, so that the reversal distance of π is equal to the reversal distance of the optimal signed permutation in S(π). Then analyze the structural features of S(π) by creating a directed graph and induce a new computing model of this question. Finally, an improved genetic algorithm for solving the new model is proposed. Experimental results show that the proposed model and algorithm is very efficient in practice.展开更多
文摘分别在两种重要并行计算模型中给出计算有向基因组排列的反转距离新的并行算法.基于Hannenhalli和Pevzner理论,分3个主要部分设计并行算法:构建断点图、计算断点图中圈数、计算断点图中障碍的数目.在cREW-PRAM模型上,算法使用O(n^2)处理器,时间复杂度为D(log^2n);在基于流水光总线的可重构线性阵列系统(linear array with a reconfigurable pipelined bus system,LARPBS)模型上,算法使用O(n^3)处理器,计算时间复杂度为D(logn).
文摘Prostate cancer is a leading cause of global cancer-related death but attempts to improve diagnoses and develop novel therapies have been confounded by significant patient heterogeneity. In recent years, the application of next-generation sequencing to hundreds of prostate tumours has defined novel molecular subtypes and characterized extensive genomic aberration underlying disease initiation and progression. It is now clear that the heterogeneity observed in the clinic is underpinned by a molecular landscape rife with complexity, where genomic rearrangements and rare mutations combine to amplify transcriptomic diversity. This review dissects our current understanding of prostate cancer 'omics', including the sentinel role of copy number variation, the growing spectrum of oncogenic fusion genes, the potential influence of chromothripsis, and breakthroughs in defining mutation-associated subtypes. Increasing evidence suggests that genomic lesions frequently converge on specific cellular functions and signalling pathways, yet recurrent gene aberration appears rare. Therefore, it is critical that we continue to define individual tumour genomes, especially in the context of their expressed transcriptome. Only through improved characterisation of tumour to tumour variability can we advance to an age of precision therapy and personalized oncology.
基金supported by the NSF of USA under Grant No. IIS-0711129
文摘Genome-scale assignment of orthologous genes is a fundamental and challenging problem in computational biology and has a wide range of applications in comparative genomics, functional genomics, and systems biology. Many methods based on sequence similarity, phylogenetic analysis, chromosomal syntenic information, and genome rearrangement have been proposed in recent years for ortholog assignment. Although these methods produce results that largely agree with each other, their results may still contain significant differences. In this article, we consider the recently proposed parsimony approach for assigning orthologs between closely related genomes based on genome rearrangement, which essentially attempts to transform one genome into another by the smallest number of genome rearrangement events including reversal, translocation, fusion, and fission, as well as gene duplication events. We will highlight some of the challenging algorithmic problems that arise in the approach including (i) minimum common substring partition, (ii) signed reversal distance with duplicates, and (iii) signed transposition distance with duplicates. The most recent progress towards the solution of these problems will be reviewed and some open questions will he posed. We will also discuss some possible extensions of the approach to the simultaneous comparison of multiple genomes.
文摘Stochastic introgression of alien DNA may impose a genomic stress to the recipient genome. Herein, we report that apparent de novo genomic rearrangements in 10 of 13 selected endogenous, lowcopy, and potentially active long terminal repeat (LTR) retrotransposons occurred in one or more of three rice lines studied that were introgressed by wild rice (Zizania latifolia Griseb.). For nine retrotransposons in which both the reverse-transcriptase (RT) region and the LTR region were available, largely concordant rearrangements occurred at both regions in five elements and at the RT region only in the remaining four elements. A marked proportion of the genomic changes was shared by two or all three introgression lines that were derived from a single F~ plant. This indicates that most of the genomic changes occurred at early developmental stages of the F~ somatic cells, which then gave rise to germline cells, and, hence, ensured inheritance of the changes to later generations. Possible causes and potential implications of the introgression-induced genomic rearrangements in LTR retrotransposons are discussed in the context of plant genome evolution and breeding.
基金Supported by the National Natural Science Foundation of China under Grant No.60970003the Specialized Research Fund for the Doctoral Program of Higher Education of China under Grant No.20090131110009the Key Science-Technology Project of Shandong Province of China under Grant No.2006GG2201005
文摘Reversals, transpositions and transreversals are common events in genome rearrangement. The genome rearrangement sorting problem is to transform one genome into another using the minimum number of given rearrangement operations. An integer permutation is used to represent a genome in many cases. It can be divided into disjoint strips with each strip denoting a block of consecutive integers. A singleton is a strip of one integer. And the genome rearrange- ment problem turns into the problem of sorting a permutation into the identity permutation equivalently. Hannenhalli and Pevzner designed a polynomial time algorithm for the unsigned reversal sorting problem on those permutations with O(logn) singletons. In this paper, first we describe one case in which Hannenhalli and Pevzner's algorithm may fail and propose a corrected approach. In addition, we propose a (1 + ε)-approximation algorithm for sorting unsigned permutations with O(log n) singletons by reversals of weight 1 and transpositions/transreversals of weight 2.
基金Supported by the National Natural Science Foun-dation of China (30170214)
文摘In view of the fact that the problem of sorting unsigned permutation by reversal is NP-hard, while the problem of sorting signed permutation by reversal can be solved easily, in this paper, we first transform an unsigned permutation of length n,π (π1 ,… ,πn), into a set S(π) containing 2^n signed permutations, so that the reversal distance of π is equal to the reversal distance of the optimal signed permutation in S(π). Then analyze the structural features of S(π) by creating a directed graph and induce a new computing model of this question. Finally, an improved genetic algorithm for solving the new model is proposed. Experimental results show that the proposed model and algorithm is very efficient in practice.