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
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
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
Genomes are incredibly dynamic within diverse eukaryotes and programmed genome rearrangements(PGR)play important roles in generating genomic diversity.However,genomes and chromosomes in metazoans are usually large in ...Genomes are incredibly dynamic within diverse eukaryotes and programmed genome rearrangements(PGR)play important roles in generating genomic diversity.However,genomes and chromosomes in metazoans are usually large in size which prevents our understanding of the origin and evolution of PGR.To expand our knowledge of genomic diversity and the evolutionary origin of complex genome rearrangements,we focus on ciliated protists(ciliates).Ciliates are single-celled eukaryotes with highly fragmented somatic chromosomes and massively scrambled germline genomes.PGR in ciliates occurs extensively by removing massive amounts of repetitive and selfish DNA elements found in the silent germline genome dur-ing development of the somatic genome.We report the partial germline genomes of two spirotrich ciliate species,namely Strombidium cf.sulcatum and Halteria grandinella,along with the most compact and highly fragmented somatic genome for S.cf.sulcatum.We provide the first insights into the genome rearrangements of these two species and compare these features with those of other ciliates.Our analyses reveal:(1)DNA sequence loss through evolution and during PGR in S.cf.sulcatum has combined to produce the most compact and efficient nanochromosomes observed to date;(2)the compact,transcriptome-like somatic genome in both species results from extensive removal of a relatively large number of shorter germline-specific DNA sequences;(3)long chromosome breakage site motifs are duplicated and retained in the somatic genome,revealing a complex model of chromosome fragmentation in spirotrichs;(4)gene scrambling and alternative pro-cessing are found throughout the core spirotrichs,offering unique opportunities to increase genetic diversity and regulation in this group.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
Porcine endogenous retroviruses(PERVs)are proviruses that have medical value in xenotransplantation.However,the evolutionary process leading to the generation of modern PERVs is not well understood.In this study,we in...Porcine endogenous retroviruses(PERVs)are proviruses that have medical value in xenotransplantation.However,the evolutionary process leading to the generation of modern PERVs is not well understood.In this study,we in silico mined 14 pig genomes and other available 304 mammalian genomes,which led to the documentation of 185 full-length PERVs or PERV-like sequences.Notably,we found that lesser Egyptian jerboa(Jaculus jaculus),rock hyrax(Procavia capensis)and eight Muridae species all harbored ancestral PERV-like sequences,indicative of ancient cross-species transmission events from none-porcine species to pigs.We also revealed that 11 genomic rearrangement events were mediated via PERVs,during the process of porcine evolution.In conclusion,these new findings help us to understand the complex evolution of the modern PERVs.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
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 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.
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funded by the Laoshan Laboratory(No.LSKJ202203202)the National Natural Science Foundation of China(32270539,31922013,31961123002)+3 种基金the Natural Science Foundation of Shandong Province(ZR2020JQ13)Royal Society/NSFC International Exchanges Cost Share Project(IEC\NSFC\201024)National Institutes of Health(P40OD010964)the Fundamental Research Funds for the Central Universities(202141004).
文摘Genomes are incredibly dynamic within diverse eukaryotes and programmed genome rearrangements(PGR)play important roles in generating genomic diversity.However,genomes and chromosomes in metazoans are usually large in size which prevents our understanding of the origin and evolution of PGR.To expand our knowledge of genomic diversity and the evolutionary origin of complex genome rearrangements,we focus on ciliated protists(ciliates).Ciliates are single-celled eukaryotes with highly fragmented somatic chromosomes and massively scrambled germline genomes.PGR in ciliates occurs extensively by removing massive amounts of repetitive and selfish DNA elements found in the silent germline genome dur-ing development of the somatic genome.We report the partial germline genomes of two spirotrich ciliate species,namely Strombidium cf.sulcatum and Halteria grandinella,along with the most compact and highly fragmented somatic genome for S.cf.sulcatum.We provide the first insights into the genome rearrangements of these two species and compare these features with those of other ciliates.Our analyses reveal:(1)DNA sequence loss through evolution and during PGR in S.cf.sulcatum has combined to produce the most compact and efficient nanochromosomes observed to date;(2)the compact,transcriptome-like somatic genome in both species results from extensive removal of a relatively large number of shorter germline-specific DNA sequences;(3)long chromosome breakage site motifs are duplicated and retained in the somatic genome,revealing a complex model of chromosome fragmentation in spirotrichs;(4)gene scrambling and alternative pro-cessing are found throughout the core spirotrichs,offering unique opportunities to increase genetic diversity and regulation in this group.
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.
基金supported by the Special Key Project of Biosafety Technologies(2017YFC1200800)for the National Major Research&Development Program of ChinaJ.C.is supported by National Natural Science Foundation of China under grant no.31671324 and CAS Pioneer Hundred Talents Program.
文摘Porcine endogenous retroviruses(PERVs)are proviruses that have medical value in xenotransplantation.However,the evolutionary process leading to the generation of modern PERVs is not well understood.In this study,we in silico mined 14 pig genomes and other available 304 mammalian genomes,which led to the documentation of 185 full-length PERVs or PERV-like sequences.Notably,we found that lesser Egyptian jerboa(Jaculus jaculus),rock hyrax(Procavia capensis)and eight Muridae species all harbored ancestral PERV-like sequences,indicative of ancient cross-species transmission events from none-porcine species to pigs.We also revealed that 11 genomic rearrangement events were mediated via PERVs,during the process of porcine evolution.In conclusion,these new findings help us to understand the complex evolution of the modern PERVs.
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.