Title
Tumor heterogeneity assessed by sequencing and fluorescence in situ hybridization (FISH) data
Abstract
Motivation: Computational reconstruction of clonal evolution in cancers has become a crucial tool for understanding how tumors initiate and progress and how this process varies across patients. The field still struggles, however, with special challenges of applying phylogenetic methods to cancers, such as the prevalence and importance of copy number alteration (CNA) and structural variation events in tumor evolution, which are difficult to profile accurately by prevailing sequencing methods in such a way that subsequent reconstruction by phylogenetic inference algorithms is accurate. Results: In this work, we develop computational methods to combine sequencing with multiplex interphase fluorescence in situ hybridization to exploit the complementary advantages of each technology in inferring accurate models of clonal CNA evolution accounting for both focal changes and aneuploidy at whole-genome scales. By integrating such information in an integer linear programming framework, we demonstrate on simulated data that incorporation of FISH data substantially improves accurate inference of focal CNA and ploidy changes in clonal evolution from deconvolving bulk sequence data. Analysis of real glioblastoma data for which FISH, bulk sequence and single cell sequence are all available confirms the power of FISH to enhance accurate reconstruction of clonal copy number evolution in conjunction with bulk and optionally single-cell sequence data.
Year
DOI
Venue
2021
10.1093/bioinformatics/btab504
BIOINFORMATICS
DocType
Volume
Issue
Conference
37
24
ISSN
Citations 
PageRank 
1367-4803
0
0.34
References 
Authors
0
15
Name
Order
Citations
PageRank
Haoyun Lei110.69
E. Michael Gertz220427.45
Alejandro A. Schäffer3827136.66
Xuecong Fu411.37
Yifeng Tao501.01
Kerstin Heselmeyer-Haddad600.34
Irianna Torres700.34
Guibo Li811.04
Liqin Xu900.34
Yong Hou1000.34
Kui Wu1111.04
Xulian Shi1211.04
Michael Dean1300.34
Thomas Ried1400.34
Russell Schwartz1554868.68