文献名:Comprehensive identification of mutational cancer driver genes across 12 tumor types
本文比较了四种寻找癌症驱动基因的方法,并且得到了综合性的、可靠的291个HCDs 基因列表。
数据来源于3205个肿瘤样本,共涉及到12种癌症。
Cancer Gene Census (CGC) 数据库里面已经有了接近500个cancer genes
癌症基因组研究分析可以得到数以万计的somatic mutations,但是其中很少一部分才是驱动肿瘤发生,发展的突变。
而且大多数driver genes的突变频率很低,又由于肿瘤的异质性,大量样本的研究是必须的。
主流的四种找癌症驱动基因的方法如下:
1、Most common methods identify genes that are mutated more frequently than expected from the background mutation rate (recurrence)
2、Other methods - a bias towards the accumulation of functional mutations (FM bias)
3、other methods exploit the tendency to sustain mutations in certain regions of the protein sequence (CLUST bias)
4、other approaches exploit the overrepresentation of mutations in specific functional residues, such as phosphorylation sites (ACTIVE bias)
它们的代表软件是MuSiC, OncodriveFM, OncodriveCLUST and ActiveDriver
本文把这四种方法进行了比较,并且综合了它们的结果。
In summary, we provide a very reliable list of 291 HCDs and a second one, of 144 CDs, more comprehensive but with an expectedly higher false-positives rate
One hundred and sixty-five of these candidates are novel findings not included in the CGC.
然后,作者对这291个HCDs基因进行了功能分析,其中,它们主要集中在以下五个生物功能
Chromatin remodeling,
mRNA processing,
Cell signaling/proliferation,
Cell adhesion,
DNA repair/Cell cycle
然后把四种方法综合得到的291个HCDs基因与Cancer Gene Census (CGC) 数据库里面已经有的接近500个cancer genes进行综合比较
本文首次展示了综合多种癌症驱动基因寻找方法的可能性,这种综合是基于两个事实:
1,各种方法找癌症驱动基因本来就没有金标准,所以综合多种方法,更comprehensive。
2,综合多种方法能更好的比较评估所找到的癌症驱动基因的准确性。