SPoRE: a mathematical model to predict double strand breaks and axis protein sites in meiosis.

SPoRE: a mathematical model to predict double strand breaks and axis protein sites in meiosis.
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DOI:
10.1186/s12859-014-0391-1
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发表时间:
2014-12-11
期刊:
影响因子:
3
通讯作者:
Carbone A
Carbone A
中科院分区:
生物学4区
文献类型:
--
作者:
Champeimont R;Carbone A

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同源染色体之间的减数分裂重组提供了遗传变异的自然组合,是进化的主要推动力。它通过程序性DNA双链断裂(DSB)启动,涉及到特定的轴向染色体结构。到目前为止,重组区域的确定主要是通过实验来确定的,既昂贵又耗时。孢子是一个数学模型,它描述了DSB和AXIS蛋白位点的非均匀定位,并区分了高和低蛋白密度。它是基于基因组信号的组合,基于从湿实验室实验中已知的,其贡献被精确量化。它模拟了轴蛋白在基因5‘端的积累,并对其沿基因的扩散和对流进行了离散近似。它用基因间隔区长度和GC含量来模拟DSB在近似基因启动子位置的积累。孢子可以用于预测,而且它以一种明显的方式被参数化,这使得它很容易从生物学的角度来理解。与酿酒酵母的实验数据相比,孢子预测轴蛋白和DSB的位置具有很高的灵敏度和精度,轴蛋白密度的平均局部相关r=0.63,DSB密度的平均局部相关r=0.62。孢子爆发了以前的基于核苷酸模式的DSB预测因子,它在DSB预测中的成功率达到85%,而现有工具在基准数据集上获得的成功率为54%。孢子可从以下网址获得:http://www.lcqb.upmc.fr/SPoRE/.本文的在线版本(doi:10.1186/s12859-0140391-1)包含补充材料,授权用户可以使用。
Meiotic recombination between homologous chromosomes provides natural combinations of genetic variations and is a main driving force of evolution. It is initiated via programmed DNA double-strand breaks (DSB) and involves a specific axial chromosomal structure. So far, recombination regions have been mainly determined by experiments, both expensive and time-consuming. SPoRE is a mathematical model that describes the non-uniform localisation of DSB and axis proteins sites, and distinguishes high versus low protein density. It is based on a combination of genomic signals, based on what is known from wet-lab experiments, whose contribution is precisely quantified. It models axis proteins accumulation at gene 5’-ends with a discrete approximation of their diffusion and convection along genes. It models DSB accumulation at approximated gene promoter positions with intergenic region length and GC-content. SPoRE can be used for prediction and it is parameterised in an obvious way that makes it easy to understand from a biological viewpoint. When compared to Saccharomyces cerevisiae experimental data, SPoRE predicts axis protein and DSB positions with high sensitivity and precision, axis protein density with an average local correlation r=0.63 and DSB density with an average local correlation r=0.62. SPoRE outbreaks previous DSB predictors, which are based on nucleotide patterning, and it reaches 85% of success rate in DSB prediction compared to 54% obtained by available tools on a benchmarked dataset. SPoRE is available at the address http://www.lcqb.upmc.fr/SPoRE/. The online version of this article (doi:10.1186/s12859-014-0391-1) contains supplementary material, which is available to authorized users.
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