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Dolphyin

Authors: Daniel W. Feng and Mohammed El-Kebir


Abstract

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Daniel W. Feng, Mohammed El-Kebir. Dolphyin (Software, Source Code). Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2025)


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@misc{dagstuhl-artifact-24317,
   title = {{Dolphyin}}, 
   author = {Feng, Daniel W. and El-Kebir, Mohammed},
   note = {Software, swhId: \href{https://archive.softwareheritage.org/swh:1:dir:61c0cd5f22da3a8e10cc6fdac70dd7d93ecb6be5;origin=https://github.com/elkebir-group/Dolphyin;visit=swh:1:snp:40995a37bef2ff3ba9886e82d6e8c8f3e0253b9a;anchor=swh:1:rev:fbf400f4100a33ee4aeb47286cefb957abd9b77d}{\texttt{swh:1:dir:61c0cd5f22da3a8e10cc6fdac70dd7d93ecb6be5}} (visited on 2025-08-15)},
   url = {https://github.com/elkebir-group/Dolphyin},
   doi = {10.4230/artifacts.24317},
}
Document
Dolphyin: A Combinatorial Algorithm for Identifying 1-Dollo Phylogenies in Cancer

Authors: Daniel W. Feng and Mohammed El-Kebir

Published in: LIPIcs, Volume 344, 25th International Conference on Algorithms for Bioinformatics (WABI 2025)


Abstract
Several recent cancer phylogeny inference methods have used the k-Dollo evolutionary model for single-nucleotide variants. Specifically, in this problem one is given an m × n binary matrix B and seeks a rooted tree T with m leaves that correspond to the m rows of B, and each node of T is labeled by a binary state for each of the n characters subject to the restriction that each character is gained at most once (0-to-1 transition) and subsequently lost at most k times (1-to-0 transitions). The 1-Dollo variant, also known as the persistent perfect phylogeny where one is restricted to at most k = 1 losses per character, has been studied extensively, but its hardness remains an open question. Here, we prove that the 1-Dollo Linear Phylogeny (1DLP) problem, where we additionally require the resulting 1-Dollo phylogeny T to be linear, is equivalent to verifying whether the input matrix B adheres to the Consecutive Ones Property (C1P), which can be solved in polynomial time. Due to the equivalence, several known NP-hardness results for relevant variants of C1P carry over to 1DLP, including the minimization of false negatives (0-to-1 modifications to the input matrix B) or the allowance of 2 gains and 2 losses. We furthermore show how we can recursively decompose any, not necessarily linear, 1-Dollo phylogeny T into several 1-Dollo linear phylogenies, connected by matching branching points. We extend this characterization to matrices B that admit 1-Dollo phylogenies, giving necessary and sufficient conditions for the existence of a novel decomposition of B into several submatrices and corresponding branching points. This decomposition forms the basis of Dolphyin, a new exponential-time algorithm for inferring 1-Dollo phylogenies that efficiently leverages the determination of linear 1-Dollo phylogenies as a subroutine. Dolphyin can also be applied to input matrices B with false negatives. We demonstrate that Dolphyin is runtime-competitive with a previous integer linear programming based algorithm SPhyR on simulated datasets. We additionally analyze simulated datasets with false negative errors and find that in the median case, Dolphyin infers 1-Dollo phylogenies with inferred error rates at or below the ground truth rate. Finally, we apply Dolphyin to 99 acute myeloid leukemia single-cell sequencing datasets, finding that the majority of the cancers can be explained by 1-Dollo phylogenies with false negative error rates in line with the used sequencing technology. Availability. Dolphyin is available at: https://github.com/elkebir-group/Dolphyin.

Cite as

Daniel W. Feng and Mohammed El-Kebir. Dolphyin: A Combinatorial Algorithm for Identifying 1-Dollo Phylogenies in Cancer. In 25th International Conference on Algorithms for Bioinformatics (WABI 2025). Leibniz International Proceedings in Informatics (LIPIcs), Volume 344, pp. 9:1-9:23, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2025)


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@InProceedings{feng_et_al:LIPIcs.WABI.2025.9,
  author =	{Feng, Daniel W. and El-Kebir, Mohammed},
  title =	{{Dolphyin: A Combinatorial Algorithm for Identifying 1-Dollo Phylogenies in Cancer}},
  booktitle =	{25th International Conference on Algorithms for Bioinformatics (WABI 2025)},
  pages =	{9:1--9:23},
  series =	{Leibniz International Proceedings in Informatics (LIPIcs)},
  ISBN =	{978-3-95977-386-7},
  ISSN =	{1868-8969},
  year =	{2025},
  volume =	{344},
  editor =	{Brejov\'{a}, Bro\v{n}a and Patro, Rob},
  publisher =	{Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
  address =	{Dagstuhl, Germany},
  URL =		{https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2025.9},
  URN =		{urn:nbn:de:0030-drops-239356},
  doi =		{10.4230/LIPIcs.WABI.2025.9},
  annote =	{Keywords: Intra-tumor heterogeneity, persistent perfect phylogeny, consecutive ones property, combinatorics}
}
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