PMID- 34289030 OWN - NLM STAT- MEDLINE DCOM- 20230413 LR - 20230517 IS - 1367-4811 (Electronic) IS - 1367-4803 (Print) IS - 1367-4803 (Linking) VI - 37 IP - 24 DP - 2021 Dec 11 TI - Tumor heterogeneity assessed by sequencing and fluorescence in situ hybridization (FISH) data. PG - 4704-4711 LID - 10.1093/bioinformatics/btab504 [doi] AB - 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. AVAILABILITY AND IMPLEMENTATION: Source code is available on Github at https://github.com/CMUSchwartzLab/FISH_deconvolution. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. CI - (c) The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. FAU - Lei, Haoyun AU - Lei H AD - Computational Biology Department, Carnegie Mellon University, Pittsburgh, PA 15213, USA. FAU - Gertz, E Michael AU - Gertz EM AD - Cancer Data Science Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. FAU - Schaffer, Alejandro A AU - Schaffer AA AD - Cancer Data Science Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. FAU - Fu, Xuecong AU - Fu X AD - Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213, USA. FAU - Tao, Yifeng AU - Tao Y AD - Computational Biology Department, Carnegie Mellon University, Pittsburgh, PA 15213, USA. FAU - Heselmeyer-Haddad, Kerstin AU - Heselmeyer-Haddad K AD - Shenzhen Luohu People's Hospital, Shenzhen 518000, China. FAU - Torres, Irianna AU - Torres I AD - Shenzhen Luohu People's Hospital, Shenzhen 518000, China. FAU - Li, Guibo AU - Li G AD - Genetics Branch, Cancer Genomics Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. FAU - Xu, Liqin AU - Xu L AD - Department of Biology, University of Copenhagen, 1599 Copenhagen, Denmark. FAU - Hou, Yong AU - Hou Y AD - Genetics Branch, Cancer Genomics Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. FAU - Wu, Kui AU - Wu K AD - Genetics Branch, Cancer Genomics Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. FAU - Shi, Xulian AU - Shi X AD - Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213, USA. FAU - Dean, Michael AU - Dean M AD - Department of Biotechnology and Biomedicine, Technical University of Denmark, 2800 Kongens Lyngby, Denmark. FAU - Ried, Thomas AU - Ried T AD - Shenzhen Luohu People's Hospital, Shenzhen 518000, China. FAU - Schwartz, Russell AU - Schwartz R AUID- ORCID: 0000-0002-4970-2252 AD - Computational Biology Department, Carnegie Mellon University, Pittsburgh, PA 15213, USA. AD - Laboratory of Translational Genomics, Division of Cancer Epidemiology & Genetics, National Cancer Institute, U.S. National Institutes of Health, Gaithersburg, MD 20814, USA. LA - eng GR - R01 HG010589/HG/NHGRI NIH HHS/United States GR - R21 CA216452/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - England TA - Bioinformatics JT - Bioinformatics (Oxford, England) JID - 9808944 SB - IM MH - Humans MH - In Situ Hybridization, Fluorescence MH - Phylogeny MH - *Software MH - Algorithms MH - *Neoplasms/pathology PMC - PMC8665747 EDAT- 2021/07/22 06:00 MHDA- 2023/04/13 06:42 PMCR- 2022/07/21 CRDT- 2021/07/21 17:31 PHST- 2020/09/22 00:00 [received] PHST- 2021/05/19 00:00 [revised] PHST- 2021/07/05 00:00 [accepted] PHST- 2023/04/13 06:42 [medline] PHST- 2021/07/22 06:00 [pubmed] PHST- 2021/07/21 17:31 [entrez] PHST- 2022/07/21 00:00 [pmc-release] AID - 6325015 [pii] AID - btab504 [pii] AID - 10.1093/bioinformatics/btab504 [doi] PST - ppublish SO - Bioinformatics. 2021 Dec 11;37(24):4704-4711. doi: 10.1093/bioinformatics/btab504.