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BitPhylogeny: a probabilistic framework for reconstructing intra-tumor phylogenies.

Yuan K, Sakoparnig T, Markowetz F, Beerenwinkel N - Genome Biol. (2015)

Bottom Line: Here, we present BitPhylogenyBitPhylogeny, a probabilistic framework to reconstruct intra-tumor evolutionary pathways.Using a full Bayesian approach, we jointly estimate the number and composition of clones in the sample as well as the most likely tree connecting them.We validate our approach in the controlled setting of a simulation study and compare it against several competing methods.

View Article: PubMed Central - PubMed

ABSTRACT
Cancer has long been understood as a somatic evolutionary process, but many details of tumor progression remain elusive. Here, we present BitPhylogenyBitPhylogeny, a probabilistic framework to reconstruct intra-tumor evolutionary pathways. Using a full Bayesian approach, we jointly estimate the number and composition of clones in the sample as well as the most likely tree connecting them. We validate our approach in the controlled setting of a simulation study and compare it against several competing methods. In two case studies, we demonstrate how BitPhylogeny BitPhylogeny reconstructs tumor phylogenies from methylation patterns in colon cancer and from single-cell exomes in myeloproliferative neoplasm.

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Analysis of CT samples.(A) Level-wise mass distribution of CT samples. For each tree, the bars show the level sums of the mixture model masses for all eight samples of the CT tumor. The red bars correspond to the posterior means of the root masses. The blue, green and pink bars correspond to the means of the sums of the second, third and fourth tree levels, respectively. (B) Maximum depth of trees of the individual samples. Turquoise densities are from the right side of the tumor and the pink ones are from the left side. Trees from the left side of the tumor have peaked posterior densities at a depth of either 3 or 4, while the posterior densities from the right side are less peaked. (C) Total branch length of trees of individual samples. The trees from the left side, which peak at depth 3 in (B), have shorter total branch lengths than the tree that peaks at depth 4 or the trees from the right side of the tumor.
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Fig5: Analysis of CT samples.(A) Level-wise mass distribution of CT samples. For each tree, the bars show the level sums of the mixture model masses for all eight samples of the CT tumor. The red bars correspond to the posterior means of the root masses. The blue, green and pink bars correspond to the means of the sums of the second, third and fourth tree levels, respectively. (B) Maximum depth of trees of the individual samples. Turquoise densities are from the right side of the tumor and the pink ones are from the left side. Trees from the left side of the tumor have peaked posterior densities at a depth of either 3 or 4, while the posterior densities from the right side are less peaked. (C) Total branch length of trees of individual samples. The trees from the left side, which peak at depth 3 in (B), have shorter total branch lengths than the tree that peaks at depth 4 or the trees from the right side of the tumor.

Mentions: Among the CT samples, we find that the left side displays more topological diversity than the right side (Figure 5). The samples from the right side have most of their mass assigned to levels two and three, though the tumor mass in the left side in one sample, CT_L7, is mostly at the second level. In CT_L3, most of the tumor mass is at the third level and in CT_L2 a considerable proportion of the tumor mass, about 18%, is assigned to the fourth level. The fourth sample of the left side, CT_L8, exhibits a mass distribution similar to the right side. The pairwise symmetrized KullbackÔÇôLeibler divergences, a measure of topological diversity, among samples from the left colon side were larger than those within the right side (P=0.002, Wilcoxon rank sum test).Figure 5


BitPhylogeny: a probabilistic framework for reconstructing intra-tumor phylogenies.

Yuan K, Sakoparnig T, Markowetz F, Beerenwinkel N - Genome Biol. (2015)

Analysis of CT samples.(A) Level-wise mass distribution of CT samples. For each tree, the bars show the level sums of the mixture model masses for all eight samples of the CT tumor. The red bars correspond to the posterior means of the root masses. The blue, green and pink bars correspond to the means of the sums of the second, third and fourth tree levels, respectively. (B) Maximum depth of trees of the individual samples. Turquoise densities are from the right side of the tumor and the pink ones are from the left side. Trees from the left side of the tumor have peaked posterior densities at a depth of either 3 or 4, while the posterior densities from the right side are less peaked. (C) Total branch length of trees of individual samples. The trees from the left side, which peak at depth 3 in (B), have shorter total branch lengths than the tree that peaks at depth 4 or the trees from the right side of the tumor.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4359483&req=5

Fig5: Analysis of CT samples.(A) Level-wise mass distribution of CT samples. For each tree, the bars show the level sums of the mixture model masses for all eight samples of the CT tumor. The red bars correspond to the posterior means of the root masses. The blue, green and pink bars correspond to the means of the sums of the second, third and fourth tree levels, respectively. (B) Maximum depth of trees of the individual samples. Turquoise densities are from the right side of the tumor and the pink ones are from the left side. Trees from the left side of the tumor have peaked posterior densities at a depth of either 3 or 4, while the posterior densities from the right side are less peaked. (C) Total branch length of trees of individual samples. The trees from the left side, which peak at depth 3 in (B), have shorter total branch lengths than the tree that peaks at depth 4 or the trees from the right side of the tumor.
Mentions: Among the CT samples, we find that the left side displays more topological diversity than the right side (Figure 5). The samples from the right side have most of their mass assigned to levels two and three, though the tumor mass in the left side in one sample, CT_L7, is mostly at the second level. In CT_L3, most of the tumor mass is at the third level and in CT_L2 a considerable proportion of the tumor mass, about 18%, is assigned to the fourth level. The fourth sample of the left side, CT_L8, exhibits a mass distribution similar to the right side. The pairwise symmetrized KullbackÔÇôLeibler divergences, a measure of topological diversity, among samples from the left colon side were larger than those within the right side (P=0.002, Wilcoxon rank sum test).Figure 5

Bottom Line: Here, we present BitPhylogenyBitPhylogeny, a probabilistic framework to reconstruct intra-tumor evolutionary pathways.Using a full Bayesian approach, we jointly estimate the number and composition of clones in the sample as well as the most likely tree connecting them.We validate our approach in the controlled setting of a simulation study and compare it against several competing methods.

View Article: PubMed Central - PubMed

ABSTRACT
Cancer has long been understood as a somatic evolutionary process, but many details of tumor progression remain elusive. Here, we present BitPhylogenyBitPhylogeny, a probabilistic framework to reconstruct intra-tumor evolutionary pathways. Using a full Bayesian approach, we jointly estimate the number and composition of clones in the sample as well as the most likely tree connecting them. We validate our approach in the controlled setting of a simulation study and compare it against several competing methods. In two case studies, we demonstrate how BitPhylogeny BitPhylogeny reconstructs tumor phylogenies from methylation patterns in colon cancer and from single-cell exomes in myeloproliferative neoplasm.

Show MeSH
Related in: MedlinePlus