Visualizing tumor evolution with the fishplot package for R

Miller, Christopher A.; McMichael, Joshua F.; Dang, Ha X.; Maher, Christopher A.; Li, Ding; Ley, Timothy J.; Mardis, Elaine R.; Wilson, Richard K.

doi:10.1186/s12864-016-3195-z

Cited by 157 publications

(104 citation statements)

References 12 publications

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“…Clonality was assigned based on allele frequency of pathological variants, as reported from the targeted sequencing panel. Visualization was generated using the fishplot package in R version 3.4.0 …”

Section: Methodsmentioning

confidence: 99%

The combination of NPM1, DNMT3A, and IDH1/2 mutations leads to inferior overall survival in AML

et al. 2019

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Acute myeloid leukemia (AML) is a genetically heterogeneous disease with a clinical course predicted by recurrent cytogenetic abnormalities and/or gene mutations. The NPM1 insertion mutations define the largest distinct genetic subset, ∼30% of AML, and is considered a favorable risk marker if there is no (or low allelic ratio) FLT3 internal tandem duplication (FLT3 ITD) mutation. However, ∼40% of patients with mutated NPM1 without FLT3 ITD still relapse, and the factors that drive relapse are still not fully understood. We used a next‐generation sequencing panel to examine mutations at diagnosis; clearance of mutations after therapy, and gain/loss of mutations at relapse to prioritize mutations that contribute to relapse. Triple mutation of NPM1, DNMT3A and IDH1/2 showed a trend towards inferior overall survival in our discovery dataset, and was significantly associated with reduced OS in a large independent validation cohort. Analysis of relative variant allele frequencies suggests that early mutation and expansion of DNMT3A and IDH1/2 prior to acquisition of NPM1 mutation leads to increased risk of relapse. This subset of patients may benefit from allogeneic stem cell transplant or clinical trials with IDH inhibitors.

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Section: Methodsmentioning

confidence: 99%

The combination of NPM1, DNMT3A, and IDH1/2 mutations leads to inferior overall survival in AML

et al. 2019

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“…The tumor content in plasma and the contribution of each metastasis to the ctDNA released in the plasma were plotted using FishPlot package (Miller et al, 2016) of the software package R v 3.2.3 (www.r-project.org).…”

Section: Radiological Assessmentsmentioning

confidence: 99%

“…Peptides that were not identified in tissue were classified as ''not detected'' and showed with black color in the plot. The rearrangements contribution of each metastasis to the circulating TCR in the blood were plotted using FishPlot package (Miller et al, 2016) of the software package R v 3.2.3 (www.r-project.org).…”

Section: Radiological Assessmentsmentioning

confidence: 99%

Radiologic and Genomic Evolution of Individual Metastases during HER2 Blockade in Colorectal Cancer

et al. 2018

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Targeting HER2 is effective in 24% of ERBB2 amplified metastatic colorectal cancer; however, secondary resistance occurs in most of the cases. We studied the evolution of individual metastases during treatment to discover spatially resolved determinants of resistance. Circulating tumor DNA (ctDNA) analysis identified alterations associated with resistance in the majority of refractory patients. ctDNA profiles and lesion-specific radiographic reports revealed organ- or metastasis-private evolutionary patterns. When radiologic assessments documented progressive disease in target lesions, response to HER2 blockade was retained in other metastases. 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. Lesion size and contribution of distinct metastases to plasma ctDNA were correlated.

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“…The distance between sample times is relative to the actual number of days between them. This plot was created using fishplot v. 0.3 [71].…”

Section: Resultsmentioning

confidence: 99%

A Genome-Wide Association Analysis Reveals a Role for Recombination in the Evolution of Antimicrobial Resistance in Burkholderia multivorans

Caballero

Clark

Wang

et al. 2018

Preprint

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24 25 26 Running title: B. multivorans GWAS reveals a role for recombination in the evolution of 27 antimicrobial resistance 28 29 30 Abstract (300 words) 33 34Cystic fibrosis (CF) lung infections caused by members of the Burkholderia cepacia complex, 35 such as Burkholderia multivorans, are associated with high rates of mortality and morbidity. We 36 performed a population genomic study of 111 B. multivorans sputum isolates from a single CF 37 patient through three stages of infection including the initial incident infection, deep sampling of 38 a one-year period of chronic infection, and deep sampling of a post-transplant recolonization. 39 We reconstructed the evolutionary history of the population and used a lineage-controlled 40 genome-wide association study (GWAS) approach to identify genetic variants associated with 41 antibiotic resistance. We found that the incident isolate was more susceptible to agents from 42 three antimicrobial classes (β-lactams, aminoglycosides, quinolones), while the chronic isolates 43 diversified into distinct genetic lineages with reduced antimicrobial susceptibility to the same 44 agents. The post-transplant reinfection isolates displayed genetic and phenotypic signatures 45 that were distinct from sputum isolates from all CF lung specimens. There were numerous 46 examples of parallel pathoadaptation, in which individual loci, or even the same codon, were 47 independently mutated multiple times. This set of loci was enriched for functions associated with 48 virulence and resistance. Our GWAS approach identified one variant in the ampD locus (which 49 was independently mutated four times in our dataset) associated with resistance to β-lactams, 50 and two non-synonymous polymorphisms associated with resistance to both aminoglycosides 51 and quinolones, affecting an araC family transcriptional regulator, which was independently 52 mutated three times, and an outer member porin, which was independently mutated twice. We 53 also performed recombination analysis and identified a minimum of 14 recombination events. 54 Parallel pathoadaptive loci and polymorphisms associated with β-lactam resistance were over-55 represented in these recombinogenic regions. This study illustrates the power of deep, 56 longitudinal sampling coupled with evolutionary and lineage-corrected GWAS analyses to reveal 57 how pathogens adapt to their hosts. 58 3 Author Summary 59 60 Cystic fibrosis (CF) is a common lethal genetic disorder that affects individuals of European 61 descent and predisposes them to chronic lung infections. Among the organisms involved in 62 these infections, bacteria from the Burkholderia cepacia complex (BCC) are often associated 63 with poor clinical prognosis. This study examines how the most prevalent BCC species among 64 CF patients, B. multivorans, evolves within a CF patient and identifies mutations underlying 65antibiotic resistance and adaptation to both the native CF lung and a non-CF lung allograft. We 66 demonstrate that B. multivorans can diversify phen...

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Visualizing tumor evolution with the fishplot package for R

Cited by 157 publications

References 12 publications

The combination of NPM1, DNMT3A, and IDH1/2 mutations leads to inferior overall survival in AML

The combination of NPM1, DNMT3A, and IDH1/2 mutations leads to inferior overall survival in AML

Radiologic and Genomic Evolution of Individual Metastases during HER2 Blockade in Colorectal Cancer

A Genome-Wide Association Analysis Reveals a Role for Recombination in the Evolution of Antimicrobial Resistance in Burkholderia multivorans

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