Cancer systems biology in the genome sequencing era: Part 1, dissecting and modeling of tumor clones and their networks

TL;DR

This paper discusses how recent genome sequencing advances enable the dissection and modeling of tumor clones, transforming cancer systems biology by focusing on clone-specific analysis and network modeling.

Contribution

It introduces new computational methods and conceptual frameworks for analyzing tumor heterogeneity and clone-specific networks in the era of genome sequencing.

Findings

Quantification of tumor subpopulations using sequencing data

Modeling of clone-based networks and their rewiring principles

Insights into cell survival networks of fast-growing clones

Abstract

Recent tumor genome sequencing confirmed that one tumor often consists of multiple cell subpopulations (clones) which bear different, but related, genetic profiles such as mutation and copy number variation profiles. Thus far, one tumor has been viewed as a whole entity in cancer functional studies. With the advances of genome sequencing and computational analysis, we are able to quantify and computationally dissect clones from tumors, and then conduct clone-based analysis. Emerging technologies such as single-cell genome sequencing and RNA-Seq could profile tumor clones. Thus, we should reconsider how to conduct cancer systems biology studies in the genome sequencing era. We will outline new directions for conducting cancer systems biology by considering that genome sequencing technology can be used for dissecting, quantifying and genetically characterizing clones from tumors. Topics discussed in Part 1 of this review include computationally quantifying of tumor subpopulations; clone-based network modeling, cancer hallmark-based networks and their high-order rewiring principles and the principles of cell survival networks of fast-growing clones.