Real-Time Definition of Non-Randomness in the Distribution of Genomic Events

被引:28
作者
Abel, Ulrich [1 ,2 ]
Deichmann, Annette [1 ]
Bartholomae, Cynthia [1 ]
Schwarzwaelder, Kerstin [1 ]
Glimm, Hanno [1 ]
Howe, Steven [2 ]
Thrasher, Adrian [3 ,4 ]
Garrigue, Alexandrine [5 ,6 ]
Hacein-Bey-Abina, Salima [5 ,6 ,7 ]
Cavazzana-Calvo, Marina [5 ,6 ,7 ]
Fischer, Alain [5 ,6 ,8 ]
Jaeger, Dirk [1 ]
von Kalle, Christof [1 ,9 ]
Schmidt, Manfred [1 ]
机构
[1] Natl Ctr Tumor Dis, Dept Translat Oncol, Heidelberg, Germany
[2] Tumor Ctr Heidelberg Mannheim, Dept Med Biostat, Heidelberg, Germany
[3] UCL, Mol Immunol Unit, Inst Child Hlth, London, England
[4] Great Ormond St Hosp NHS Trust, Dept Clin Immunol, London, England
[5] Univ Paris 05, INSERM Unit 768, Hop Necker, Paris, France
[6] Univ Paris 05, Fac Med, Paris, France
[7] Hop Necker Enfants Malad, Dept Biotherapies, Paris, France
[8] Hop Necker Enfants Malad, Unite Immunol & Hematol Pediat, Paris, France
[9] Cincinnati Childrens Res Fdn, Div Expt Hematol, Cincinnati, OH USA
来源
PLOS ONE | 2007年 / 2卷 / 06期
关键词
D O I
10.1371/journal.pone.0000570
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Features such as mutations or structural characteristics can be non-randomly or non-uniformly distributed within a genome. So far, computer simulations were required for statistical inferences on the distribution of sequence motifs. Here, we show that these analyses are possible using an analytical, mathematical approach. For the assessment of non-randomness, our calculations only require information including genome size, number of ( sampled) sequence motifs and distance parameters. We have developed computer programs evaluating our analytical formulas for the real-time determination of expected values and p-values. This approach permits a flexible cluster definition that can be applied to most effectively identify non-random or non-uniform sequence motif distribution. As an example, we show the effectivity and reliability of our mathematical approach in clinical retroviral vector integration site distribution.
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页数:5
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