PMID- 25060187
OWN - NLM
STAT- MEDLINE
DCOM- 20150720
LR  - 20240104
IS  - 1549-5469 (Electronic)
IS  - 1088-9051 (Print)
IS  - 1088-9051 (Linking)
VI  - 24
IP  - 11
DP  - 2014 Nov
TI  - TITAN: inference of copy number architectures in clonal cell populations from 
      tumor whole-genome sequence data.
PG  - 1881-93
LID - 10.1101/gr.180281.114 [doi]
AB  - The evolution of cancer genomes within a single tumor creates mixed cell 
      populations with divergent somatic mutational landscapes. Inference of tumor 
      subpopulations has been disproportionately focused on the assessment of somatic 
      point mutations, whereas computational methods targeting evolutionary dynamics of 
      copy number alterations (CNA) and loss of heterozygosity (LOH) in whole-genome 
      sequencing data remain underdeveloped. We present a novel probabilistic model, 
      TITAN, to infer CNA and LOH events while accounting for mixtures of cell 
      populations, thereby estimating the proportion of cells harboring each event. We 
      evaluate TITAN on idealized mixtures, simulating clonal populations from 
      whole-genome sequences taken from genomically heterogeneous ovarian tumor sites 
      collected from the same patient. In addition, we show in 23 whole genomes of 
      breast tumors that the inference of CNA and LOH using TITAN critically informs 
      population structure and the nature of the evolving cancer genome. Finally, we 
      experimentally validated subclonal predictions using fluorescence in situ 
      hybridization (FISH) and single-cell sequencing from an ovarian cancer patient 
      sample, thereby recapitulating the key modeling assumptions of TITAN.
CI  - (c) 2014 Ha et al.; Published by Cold Spring Harbor Laboratory Press.
FAU - Ha, Gavin
AU  - Ha G
AD  - Department of Molecular Oncology, British Columbia Cancer Agency, Vancouver, BC 
      V5Z 1L3, Canada; Bioinformatics Training Program, University of British Columbia, 
      Vancouver, BC V5Z 4S6, Canada; sshah@bccrc.ca.
FAU - Roth, Andrew
AU  - Roth A
AD  - Department of Molecular Oncology, British Columbia Cancer Agency, Vancouver, BC 
      V5Z 1L3, Canada; Bioinformatics Training Program, University of British Columbia, 
      Vancouver, BC V5Z 4S6, Canada;
FAU - Khattra, Jaswinder
AU  - Khattra J
AD  - Department of Molecular Oncology, British Columbia Cancer Agency, Vancouver, BC 
      V5Z 1L3, Canada;
FAU - Ho, Julie
AU  - Ho J
AD  - Centre for Translational and Applied Genomics, Vancouver, BC V5Z 4E6, Canada;
FAU - Yap, Damian
AU  - Yap D
AD  - Department of Molecular Oncology, British Columbia Cancer Agency, Vancouver, BC 
      V5Z 1L3, Canada;
FAU - Prentice, Leah M
AU  - Prentice LM
AD  - Centre for Translational and Applied Genomics, Vancouver, BC V5Z 4E6, Canada;
FAU - Melnyk, Nataliya
AU  - Melnyk N
AD  - Centre for Translational and Applied Genomics, Vancouver, BC V5Z 4E6, Canada;
FAU - McPherson, Andrew
AU  - McPherson A
AD  - Department of Molecular Oncology, British Columbia Cancer Agency, Vancouver, BC 
      V5Z 1L3, Canada; Bioinformatics Training Program, University of British Columbia, 
      Vancouver, BC V5Z 4S6, Canada;
FAU - Bashashati, Ali
AU  - Bashashati A
AD  - Department of Molecular Oncology, British Columbia Cancer Agency, Vancouver, BC 
      V5Z 1L3, Canada;
FAU - Laks, Emma
AU  - Laks E
AD  - Department of Molecular Oncology, British Columbia Cancer Agency, Vancouver, BC 
      V5Z 1L3, Canada;
FAU - Biele, Justina
AU  - Biele J
AD  - Department of Molecular Oncology, British Columbia Cancer Agency, Vancouver, BC 
      V5Z 1L3, Canada;
FAU - Ding, Jiarui
AU  - Ding J
AD  - Department of Molecular Oncology, British Columbia Cancer Agency, Vancouver, BC 
      V5Z 1L3, Canada; Department of Computer Science, University of British Columbia, 
      Vancouver, BC V6T 1Z4, Canada;
FAU - Le, Alan
AU  - Le A
AD  - Department of Molecular Oncology, British Columbia Cancer Agency, Vancouver, BC 
      V5Z 1L3, Canada;
FAU - Rosner, Jamie
AU  - Rosner J
AD  - Department of Molecular Oncology, British Columbia Cancer Agency, Vancouver, BC 
      V5Z 1L3, Canada;
FAU - Shumansky, Karey
AU  - Shumansky K
AD  - Department of Molecular Oncology, British Columbia Cancer Agency, Vancouver, BC 
      V5Z 1L3, Canada;
FAU - Marra, Marco A
AU  - Marra MA
AD  - Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC V5Z 1L3, 
      Canada;
FAU - Gilks, C Blake
AU  - Gilks CB
AD  - Genetic Pathology Evaluation Centre, Vancouver General Hospital, Vancouver, BC 
      V6H 3Z6, Canada;
FAU - Huntsman, David G
AU  - Huntsman DG
AD  - Centre for Translational and Applied Genomics, Vancouver, BC V5Z 4E6, Canada; 
      Department of Pathology and Laboratory Medicine, University of British Columbia, 
      Vancouver, BC V6T 2B5, Canada;
FAU - McAlpine, Jessica N
AU  - McAlpine JN
AD  - Department of Gynecology and Obstetrics, University of British Columbia, 
      Vancouver, BC V5Z 1M9, Canada.
FAU - Aparicio, Samuel
AU  - Aparicio S
AD  - Department of Molecular Oncology, British Columbia Cancer Agency, Vancouver, BC 
      V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of 
      British Columbia, Vancouver, BC V6T 2B5, Canada;
FAU - Shah, Sohrab P
AU  - Shah SP
AD  - Department of Molecular Oncology, British Columbia Cancer Agency, Vancouver, BC 
      V5Z 1L3, Canada; Department of Computer Science, University of British Columbia, 
      Vancouver, BC V6T 1Z4, Canada; Department of Pathology and Laboratory Medicine, 
      University of British Columbia, Vancouver, BC V6T 2B5, Canada; sshah@bccrc.ca.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140724
PL  - United States
TA  - Genome Res
JT  - Genome research
JID - 9518021
SB  - IM
MH  - *Algorithms
MH  - Clone Cells/metabolism/pathology
MH  - Computational Biology/*methods
MH  - *DNA Copy Number Variations
MH  - Female
MH  - Genomics/methods
MH  - Genotype
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/methods
MH  - Loss of Heterozygosity
MH  - *Models, Genetic
MH  - Neoplasms/*genetics
MH  - Ovarian Neoplasms/genetics
MH  - Polymorphism, Single Nucleotide
MH  - Reproducibility of Results
MH  - Sequence Analysis, DNA/methods
MH  - Triple Negative Breast Neoplasms/genetics
PMC - PMC4216928
EDAT- 2014/07/26 06:00
MHDA- 2015/07/21 06:00
PMCR- 2014/11/01
CRDT- 2014/07/26 06:00
PHST- 2014/07/26 06:00 [entrez]
PHST- 2014/07/26 06:00 [pubmed]
PHST- 2015/07/21 06:00 [medline]
PHST- 2014/11/01 00:00 [pmc-release]
AID - gr.180281.114 [pii]
AID - 10.1101/gr.180281.114 [doi]
PST - ppublish
SO  - Genome Res. 2014 Nov;24(11):1881-93. doi: 10.1101/gr.180281.114. Epub 2014 Jul 
      24.