PREDICTION OF HUMAN MESSENGER-RNA DONOR AND ACCEPTOR SITES FROM THE DNA-SEQUENCE
PREDICTION OF HUMAN MESSENGER-RNA DONOR AND ACCEPTOR SITES FROM THE DNA-SEQUENCE
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DOI：
10.1016/0022-2836(91)90380-o
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发表时间：
1991-07-05
影响因子：
5.6
通讯作者：
KNUDSEN, S
中科院分区：
文献类型：
--
作者：
BRUNAK, S;ENGELBRECHT, J;KNUDSEN, S
人工神经网络已被应用于预测剪接位点的位置在人前mRNA。一个联合预测方案，其中预测的内含子和外显子之间的过渡区调节剪接位点分配的截止水平能够预测剪接位点的位置与置信水平远远好于以前在文献中报道。预测人类基因中供体和受体位点的问题受到大量假阳性的阻碍：这里检查这些假剪接位点的分布，并将其与体内剪接机制的可能情况联系起来。当所提出的方法检测到95%的真实供体和受体位点时，其产生小于0.1%的错误供体位点分配和小于0.4%的错误受体位点分配。对于本研究中使用的大数据集，这意味着平均每个真供体位点有一个半假供体位点，每个真受体位点有六个假受体位点。与联合分配方法，超过五分之一的真正的供体网站和真正的受体网站的四分之一左右，可以检测到没有伴随任何假阳性预测。高度确信的剪接位点无法用广泛使用的权重矩阵方法或单独的剪接位点网络来分离。观察到编码/非编码和单独的剪接位点网络的置信水平之间的互补关系，许多弱剪接位点在编码/非编码信号中具有尖锐的过渡，许多较强的剪接位点在编码和非编码之间具有更不明确的过渡。
Artificial neural networks have been applied to the prediction of splice site location in human pre-mRNA. A joint prediction scheme where prediction of transition regions between introns and exons regulates a cutoff level for splice site assignment was able to predict splice site locations with confidence levels far better than previously reported in the literature. The problem of predicting donor and acceptor sites in human genes is hampered by the presence of numerous amounts of false positives: here the distribution of these false splice sites is examined and linked to a possible scenario for the splicing mechanismin vivo. When the presented method detects 95% of the true donor and acceptor sites, it makes less than 0·1 % false donor site assignments and less than 0·4% false acceptor site assignments. For the large data set used in this study, this means that on average there are one and a half false donor sites per true donor site and six false acceptor sites per true acceptor site. With the joint assignment method, more than a fifth of the true donor sites and around one fourth of the true acceptor sites could be detected without accompaniment of any false positive predictions. Highly confident splice sites could not be isolated with a widely used weight matrix method or by separate splice site networks. A complementary relation between the confidence levels of the coding/non-coding and the separate splice site networks was observed, with many weak splice sites having sharp transitions in the coding/non-coding signal and many stronger splice sites having more ill-defined transitions between coding and non-coding.