Oncofuse: a computational framework for the prediction of the oncogenic potential of gene fusions
Oncofuse: a computational framework for the prediction of the oncogenic potential of gene fusions
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DOI：
10.1093/bioinformatics/btt445
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发表时间：
2013-10-15
期刊：
影响因子：
5.8
通讯作者：
Novo, Francisco J.
中科院分区：
文献类型：
--
作者：
Shugay, Mikhail;Ortiz de Mendibil, Inigo;Novo, Francisco J.
动机：染色体异常导致的基因融合是癌症的重要原因。某些癌症类型基因组变化的复杂性阻碍了用分子细胞遗传学方法鉴定基因融合，特别是在癌症中。随着下一代测序的出现，这种情况正在改变，它正在单个癌症基因组中检测到大量新的融合转录本。结果：在本研究中，我们利用最近发现的一些癌基因融合基因的基因组特征，建立了一条融合序列分类的流水线，即Oncofuse。该管道预测新的融合基因的致癌潜力，根据已知致癌融合中存在的特征计算融合序列作为致癌过程的“驱动力”的概率。交叉验证和对独立数据集的广泛验证测试表明，该方法具有健壮的行为，具有良好的精确度和召回率。我们相信，Oncofuse可以成为一种有用的工具，用于指导在下一代癌症转录体测序分析中发现的新融合序列的实验验证研究。
Motivation: Gene fusions resulting from chromosomal aberrations are an important cause of cancer. The complexity of genomic changes in certain cancer types has hampered the identification of gene fusions by molecular cytogenetic methods, especially in carcinomas. This is changing with the advent of next-generation sequencing, which is detecting a substantial number of new fusion transcripts in individual cancer genomes. However, this poses the challenge of identifying those fusions with greater oncogenic potential amid a background of 'passenger' fusion sequences.Results: In the present work, we have used some recently identified genomic hallmarks of oncogenic fusion genes to develop a pipeline for the classification of fusion sequences, namely, Oncofuse. The pipeline predicts the oncogenic potential of novel fusion genes, calculating the probability that a fusion sequence behaves as 'driver' of the oncogenic process based on features present in known oncogenic fusions. Cross-validation and extensive validation tests on independent datasets suggest a robust behavior with good precision and recall rates. We believe that Oncofuse could become a useful tool to guide experimental validation studies of novel fusion sequences found during next-generation sequencing analysis of cancer transcriptomes.