Division of Genetics, Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
Nat Rev Cancer. 2020 Apr;20(4):233-246. doi: 10.1038/s41568-020-0240-7. Epub 2020 Feb 17.
A key goal of cancer systems biology is to use big data to elucidate the molecular networks by which cancer develops. However, to date there has been no systematic evaluation of how far these efforts have progressed. In this Analysis, we survey six major systems biology approaches for mapping and modelling cancer pathways with attention to how well their resulting network maps cover and enhance current knowledge. Our sample of 2,070 systems biology maps captures all literature-curated cancer pathways with significant enrichment, although the strong tendency is for these maps to recover isolated mechanisms rather than entire integrated processes. Systems biology maps also identify previously underappreciated functions, such as a potential role for human papillomavirus-induced chromosomal alterations in ovarian tumorigenesis, and they add new genes to known cancer pathways, such as those related to metabolism, Hippo signalling and immunity. Notably, we find that many cancer networks have been provided only in journal figures and not for programmatic access, underscoring the need to deposit network maps in community databases to ensure they can be readily accessed. Finally, few of these findings have yet been clinically translated, leaving ample opportunity for future translational studies. Periodic surveys of cancer pathway maps, such as the one reported here, are critical to assess progress in the field and identify underserved areas of methodology and cancer biology.
癌症系统生物学的一个主要目标是利用大数据阐明癌症发展的分子网络。然而，迄今为止，还没有系统地评估这些努力的进展程度。在本分析中，我们调查了六种主要的系统生物学方法，用于绘制和模拟癌症途径，重点关注其生成的网络图在多大程度上覆盖和增强了现有知识。我们的 2070 个系统生物学图谱样本包含了所有经过文献整理的具有显著富集的癌症途径，尽管这些图谱强烈倾向于恢复孤立的机制，而不是整个集成的过程。系统生物学图谱还确定了以前被低估的功能，例如人乳头瘤病毒诱导的染色体改变在卵巢肿瘤发生中的潜在作用，并且它们将新的基因添加到已知的癌症途径中，例如与代谢、Hippo 信号和免疫相关的途径。值得注意的是，我们发现许多癌症网络仅在期刊图中提供，而不是以编程方式访问，这强调了将网络图存入社区数据库以确保它们可以方便地访问的必要性。最后，这些发现中很少有已经被临床转化，为未来的转化研究留下了充足的机会。周期性地对癌症途径图谱进行调查，如这里报道的那样，对于评估该领域的进展和确定方法学和癌症生物学方面的不足领域至关重要。
