Visualizing tumor evolution with the fishplot package for R
Christopher A. Miller,Joshua F. McMichael,Ha X. Dang,Christopher G. Maher,Li Ding,Timothy J. Ley,Elaine R. Mardis,Richard K. Wilson +7 more
TLDR
The simplicity, power, and flexibility of this tool make it valuable for visualizing tumor evolution, and it has potential utility in both research and clinical settings.Abstract:
Massively-parallel sequencing at depth is now enabling tumor heterogeneity and evolution to be characterized in unprecedented detail. Tracking these changes in clonal architecture often provides insight into therapeutic response and resistance. In complex cases involving multiple timepoints, standard visualizations, such as scatterplots, can be difficult to interpret. Current data visualization methods are also typically manual and laborious, and often only approximate subclonal fractions. We have developed an R package that accurately and intuitively displays changes in clonal structure over time. It requires simple input data and produces illustrative and easy-to-interpret graphs suitable for diagnosis, presentation, and publication. The simplicity, power, and flexibility of this tool make it valuable for visualizing tumor evolution, and it has potential utility in both research and clinical settings. The fishplot package is available at https://github.com/chrisamiller/fishplot
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Citations
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Journal ArticleDOI
Whole-Exome Sequencing of Cell-Free DNA Reveals Temporo-spatial Heterogeneity and Identifies Treatment-Resistant Clones in Neuroblastoma
Mathieu Chicard,Léo Colmet-Daage,Nathalie Clément,Adrien Danzon,Mylène Bohec,Virginie Bernard,Sylvain Baulande,Angela Bellini,Paul Deveau,Gaëlle Pierron,Eve Lapouble,Isabelle Janoueix-Lerosey,Michel Peuchmaur,Nadège Corradini,Anne-Sophie Defachelles,Dominique Valteau-Couanet,Jean Michon,Valérie Combaret,Olivier Delattre,Olivier Delattre,Gudrun Schleiermacher,Gudrun Schleiermacher +21 more
TL;DR: Modelization of mutated allele fractions in cfDNA indicated distinct patterns of clonal evolution, with either a minor, treatment-resistant clone expanding to a major clone at relapse, or minor clones collaborating toward tumor progression.
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Radiologic and Genomic Evolution of Individual Metastases during HER2 Blockade in Colorectal Cancer
Giulia Siravegna,Luca Lazzari,Giovanni Crisafulli,Andrea Sartore-Bianchi,Benedetta Mussolin,Andrea Cassingena,Cosimo Martino,Richard B. Lanman,Rebecca J. Nagy,Stephen R. Fairclough,Giuseppe Rospo,Giorgio Corti,Alice Bartolini,Pamela Arcella,Monica Montone,Francesca Lodi,Annalisa Lorenzato,Alice Vanzati,Emanuele Valtorta,Giovanni Cappello,Andrea Bertotti,Sara Lonardi,Vittorina Zagonel,Francesco Leone,Mariangela Russo,Antonella Balsamo,Mauro Truini,Federica Di Nicolantonio,Alessio Amatu,Erica Bonazzina,Silvia Ghezzi,Daniele Regge,Angelo Vanzulli,Livio Trusolino,Salvatore Siena,Silvia Marsoni,Alberto Bardelli +36 more
TL;DR: Genomic and functional analyses on samples and cell models from eight metastases of a patient co-recruited to a postmortem study unveiled lesion-specific evolutionary trees and pharmacologic vulnerabilities.
Journal ArticleDOI
ClonEvol: clonal ordering and visualization in cancer sequencing.
Ha X. Dang,Brian S. White,Steven M. Foltz,Christopher A. Miller,J. Luo,Ryan C. Fields,Christopher G. Maher +6 more
TL;DR: ClonEvol outperformed three of the state of the art tools for clonal evolution inference, showing more robust error tolerance and producing more accurate trees in a simulation, and has broad applicability for longitudinal monitoring of clonal populations in tumor biopsies, or noninvasively, to guide precision medicine.
Journal ArticleDOI
Diverse resistance mechanisms to the third-generation ALK inhibitor lorlatinib in ALK-rearranged lung cancer
Gonzalo Recondo,Gonzalo Recondo,Laura Mezquita,Francesco Facchinetti,Francesco Facchinetti,David Planchard,Anas Gazzah,Ludovic Bigot,Ludovic Bigot,Ahsan Z. Rizvi,Ahsan Z. Rizvi,Rosa L. Frias,Rosa L. Frias,Jean Paul Thiery,Jean-Yves Scoazec,Jean-Yves Scoazec,Tony Sourisseau,Tony Sourisseau,Karen Howarth,Olivier Deas,D. O. Samofalova,Justine Galissant,Justine Galissant,Pauline Tesson,Pauline Tesson,Floriane Braye,Floriane Braye,C. Naltet,Pernelle Lavaud,Linda Mahjoubi,Aurelie Abou Lovergne,Aurelie Abou Lovergne,Gilles Vassal,Rastilav Bahleda,Antoine Hollebecque,Claudio Nicotra,Maud Ngo-Camus,Stefan Michiels,Ludovic Lacroix,Catherine Richon,Nathalie Auger,Thierry de Baere,Lambros Tselikas,Eric Solary,Eric Angevin,Alexander M.M. Eggermont,Fabrice Andre,Fabrice Andre,Christophe Massard,Christophe Massard,Ken A. Olaussen,Ken A. Olaussen,Jean-Charles Soria,Jean-Charles Soria,Benjamin Besse,Benjamin Besse,Luc Friboulet,Luc Friboulet +57 more
TL;DR: This study shows that mechanisms of resistance to lorlatinib are diverse and complex, requiring new therapeutic strategies to tailor treatment upon disease progression, and identifies a novel bypass mechanism of resistance caused by NF2 loss-of-function mutations, conferring sensitivity to treatment with mTOR inhibitors.
Journal ArticleDOI
Optimizing cancer genome sequencing and analysis
Malachi Griffith,Christopher A. Miller,Obi L. Griffith,Krysiak Kilannin,Zachary L. Skidmore,Avinash Ramu,Jason Walker,Ha X. Dang,Trani Lee,David E. Larson,Ryan Demeter,Michael C. Wendl,Joshua F. McMichael,Rachel Austin,Vincent Magrini,McGrath Sean,Amy Ly,Shashikant Kulkarni,Matt Cordes,Catrina Fronick,Robert S. Fulton,Christopher G. Maher,Li Ding,Jeffery M. Klco,Elaine R. Mardis,Timothy J. Ley,Richard K. Wilson +26 more
TL;DR: This dataset, representing the most comprehensively sequenced tumor described to date, will serve as an invaluable community resource (dbGaP accession id phs000159) and reassess optimal sequencing strategies.
References
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SciClone: inferring clonal architecture and tracking the spatial and temporal patterns of tumor evolution.
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