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通过单细胞测序加深对肿瘤进化的认识。

Advances in understanding tumour evolution through single-cell sequencing.

机构信息

Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland; Swiss Institute of Bioinformatics, Basel, Switzerland.

出版信息

Biochim Biophys Acta Rev Cancer. 2017 Apr;1867(2):127-138. doi: 10.1016/j.bbcan.2017.02.001. Epub 2017 Feb 11.

Abstract

The mutational heterogeneity observed within tumours poses additional challenges to the development of effective cancer treatments. A thorough understanding of a tumour's subclonal composition and its mutational history is essential to open up the design of treatments tailored to individual patients. Comparative studies on a large number of tumours permit the identification of mutational patterns which may refine forecasts of cancer progression, response to treatment and metastatic potential. The composition of tumours is shaped by evolutionary processes. Recent advances in next-generation sequencing offer the possibility to analyse the evolutionary history and accompanying heterogeneity of tumours at an unprecedented resolution, by sequencing single cells. New computational challenges arise when moving from bulk to single-cell sequencing data, leading to the development of novel modelling frameworks. In this review, we present the state of the art methods for understanding the phylogeny encoded in bulk or single-cell sequencing data, and highlight future directions for developing more comprehensive and informative pictures of tumour evolution. This article is part of a Special Issue entitled: Evolutionary principles - heterogeneity in cancer?, edited by Dr. Robert A. Gatenby.

摘要

肿瘤内观察到的突变异质性对开发有效的癌症治疗方法提出了额外的挑战。彻底了解肿瘤的亚克隆组成及其突变历史对于设计针对个体患者的治疗方法至关重要。对大量肿瘤进行的比较研究可以确定可能改善癌症进展、治疗反应和转移潜力预测的突变模式。肿瘤的组成受进化过程的影响。下一代测序的最新进展提供了通过对单细胞进行测序,以空前的分辨率分析肿瘤进化历史和伴随的异质性的可能性。当从批量测序数据转移到单细胞测序数据时,会出现新的计算挑战,从而导致新的建模框架的发展。在这篇综述中,我们介绍了理解批量或单细胞测序数据中编码的系统发育的最新方法,并强调了开发更全面和信息丰富的肿瘤进化图的未来方向。本文是一个特刊的一部分,题为:进化原理-癌症中的异质性?,由罗伯特·加滕比博士编辑。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/217f/5813714/ff21ee40bc29/gr1.jpg

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