PMID- 23812984 OWN - NLM STAT- MEDLINE DCOM- 20131217 LR - 20220309 IS - 1367-4811 (Electronic) IS - 1367-4803 (Print) IS - 1367-4803 (Linking) VI - 29 IP - 13 DP - 2013 Jul 1 TI - Phylogenetic analysis of multiprobe fluorescence in situ hybridization data from tumor cell populations. PG - i189-98 LID - 10.1093/bioinformatics/btt205 [doi] AB - MOTIVATION: Development and progression of solid tumors can be attributed to a process of mutations, which typically includes changes in the number of copies of genes or genomic regions. Although comparisons of cells within single tumors show extensive heterogeneity, recurring features of their evolutionary process may be discerned by comparing multiple regions or cells of a tumor. A useful source of data for studying likely progression of individual tumors is fluorescence in situ hybridization (FISH), which allows one to count copy numbers of several genes in hundreds of single cells. Novel algorithms for interpreting such data phylogenetically are needed, however, to reconstruct likely evolutionary trajectories from states of single cells and facilitate analysis of tumor evolution. RESULTS: In this article, we develop phylogenetic methods to infer likely models of tumor progression using FISH copy number data and apply them to a study of FISH data from two cancer types. Statistical analyses of topological characteristics of the tree-based model provide insights into likely tumor progression pathways consistent with the prior literature. Furthermore, tree statistics from the resulting phylogenies can be used as features for prediction methods. This results in improved accuracy, relative to unstructured gene copy number data, at predicting tumor state and future metastasis. AVAILABILITY: Source code for software that does FISH tree building (FISHtrees) and the data on cervical and breast cancer examined here are available at ftp://ftp.ncbi.nlm.nih.gov/pub/FISHtrees. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. FAU - Chowdhury, Salim Akhter AU - Chowdhury SA AD - Joint Carnegie Mellon/University of Pittsburgh Ph.D. Program in Computational Biology, Lane Center for Computational Biology, Carnegie Mellon University, Pittsburgh, PA 15213, USA. sachowdh@andrew.cmu.edu FAU - Shackney, Stanley E AU - Shackney SE FAU - Heselmeyer-Haddad, Kerstin AU - Heselmeyer-Haddad K FAU - Ried, Thomas AU - Ried T FAU - Schaffer, Alejandro A AU - Schaffer AA FAU - Schwartz, Russell AU - Schwartz R LA - eng GR - 1R01AI076318/AI/NIAID NIH HHS/United States GR - R01 AI076318/AI/NIAID NIH HHS/United States GR - 1R01CA140214/CA/NCI NIH HHS/United States GR - R01 CA140214/CA/NCI NIH HHS/United States GR - Z99 CA999999/Intramural NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, N.I.H., Intramural PL - England TA - Bioinformatics JT - Bioinformatics (Oxford, England) JID - 9808944 SB - IM MH - Algorithms MH - Breast Neoplasms/classification/*genetics/pathology MH - Disease Progression MH - Female MH - *Gene Dosage MH - Humans MH - In Situ Hybridization, Fluorescence/*methods MH - *Phylogeny MH - Software MH - Uterine Cervical Neoplasms/classification/*genetics/pathology PMC - PMC3694640 EDAT- 2013/07/03 06:00 MHDA- 2013/12/18 06:00 PMCR- 2013/06/19 CRDT- 2013/07/02 06:00 PHST- 2013/07/02 06:00 [entrez] PHST- 2013/07/03 06:00 [pubmed] PHST- 2013/12/18 06:00 [medline] PHST- 2013/06/19 00:00 [pmc-release] AID - btt205 [pii] AID - 10.1093/bioinformatics/btt205 [doi] PST - ppublish SO - Bioinformatics. 2013 Jul 1;29(13):i189-98. doi: 10.1093/bioinformatics/btt205.