Limits...
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.

Show MeSH

Related in: MedlinePlus

Analysis of CX samples and joint analysis of all samples. Turquoise densities are for samples from the right side of the tumor and the pink ones are for the left side. (A) Maximum depth of trees. Trees from the right side have posterior maximum depth between 2 and 3, while trees from the left side have posterior maximum depth between 3 and 4. (B) Total branch length of trees. Trees from the right side have slightly shorter total branch lengths than the trees from the left side. (C) Number of clones in a tree. Trees from the right side contain fewer clones than trees from the left side. (D) Mean number of clones versus mean maximum depth of trees. With these two summary statistics of trees, samples from the left and right can be separated very clearly.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig6: Analysis of CX samples and joint analysis of all samples. Turquoise densities are for samples from the right side of the tumor and the pink ones are for the left side. (A) Maximum depth of trees. Trees from the right side have posterior maximum depth between 2 and 3, while trees from the left side have posterior maximum depth between 3 and 4. (B) Total branch length of trees. Trees from the right side have slightly shorter total branch lengths than the trees from the left side. (C) Number of clones in a tree. Trees from the right side contain fewer clones than trees from the left side. (D) Mean number of clones versus mean maximum depth of trees. With these two summary statistics of trees, samples from the left and right can be separated very clearly.

Mentions: For the CX sample, we observed that the left side can be well separated from the right side in terms of maximum tree depth (P=0.027, t-test; Figure 6). Less pronounced, this separation was also found for the total branch length as well as for the number of clones and big clones. In the original study [9], the CX sample was identified as the largest tumor in the study. The size of this tumor could be a reason for the separation of the evolutionary history of the right side from the left side. Additionally, they identified CX as the tumor with the highest cancer stem cell fraction. We did not observe such a clear separation of left and right sides in any of the other samples. The left side of the tumor appears to evolve faster than the right side, because it has deeper trees with more clones and longer total branch lengths than the right side.Figure 6


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

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

Analysis of CX samples and joint analysis of all samples. Turquoise densities are for samples from the right side of the tumor and the pink ones are for the left side. (A) Maximum depth of trees. Trees from the right side have posterior maximum depth between 2 and 3, while trees from the left side have posterior maximum depth between 3 and 4. (B) Total branch length of trees. Trees from the right side have slightly shorter total branch lengths than the trees from the left side. (C) Number of clones in a tree. Trees from the right side contain fewer clones than trees from the left side. (D) Mean number of clones versus mean maximum depth of trees. With these two summary statistics of trees, samples from the left and right can be separated very clearly.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig6: Analysis of CX samples and joint analysis of all samples. Turquoise densities are for samples from the right side of the tumor and the pink ones are for the left side. (A) Maximum depth of trees. Trees from the right side have posterior maximum depth between 2 and 3, while trees from the left side have posterior maximum depth between 3 and 4. (B) Total branch length of trees. Trees from the right side have slightly shorter total branch lengths than the trees from the left side. (C) Number of clones in a tree. Trees from the right side contain fewer clones than trees from the left side. (D) Mean number of clones versus mean maximum depth of trees. With these two summary statistics of trees, samples from the left and right can be separated very clearly.
Mentions: For the CX sample, we observed that the left side can be well separated from the right side in terms of maximum tree depth (P=0.027, t-test; Figure 6). Less pronounced, this separation was also found for the total branch length as well as for the number of clones and big clones. In the original study [9], the CX sample was identified as the largest tumor in the study. The size of this tumor could be a reason for the separation of the evolutionary history of the right side from the left side. Additionally, they identified CX as the tumor with the highest cancer stem cell fraction. We did not observe such a clear separation of left and right sides in any of the other samples. The left side of the tumor appears to evolve faster than the right side, because it has deeper trees with more clones and longer total branch lengths than the right side.Figure 6

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