Unique perfect phylogeny is NP-hard

We answer, in the affirmative, the following question proposed by Mike Steel as a $100 challenge: "Is the following problem NP-hard? Given a ternary phylogenetic X-tree T and a collection Q of quartet subtrees on X, is T the only tree that displays Q ?

Potential Maximal Clique Algorithms for Perfect Phylogeny Problems

Kloks, Kratsch, and Spinrad showed how treewidth and minimum-fill, NP-hard combinatorial optimization problems related to minimal triangulations, are broken into subproblems by block subgraphs defined by minimal separators. These ideas were expanded on by Bouchitt\'e and Todinca, who used potential maximal cliques to solve these problems using a dynamic programming approach in time polynomial in the number of minimal separators of a graph. It is known that solutions to the perfect phylogeny problem, maximum compatibility problem, and unique perfect phylogeny problem are characterized by minimal triangulations of the partition intersection graph. In this paper, we show that techniques similar to those proposed by Bouchitt\'e and Todinca can be used to solve the perfect phylogeny problem with missing data, the two- state maximum compatibility problem with missing data, and the unique perfect phylogeny problem with missing data in time polynomial in the number of minimal separators of the partition intersection graph

Constructing computer virus phylogenies

There has been much recent algorithmic work on the problem of reconstructing the evolutionary history of biological species. Computer virus specialists are interested in finding the evolutionary history of computer viruses - a virus is often written using code fragments from one or more other viruses, which are its immediate ancestors. A phylogeny for a collection of computer viruses is a directed acyclic graph whose nodes are the viruses and whose edges map ancestors to descendants and satisfy the property that each code fragment is "invented" only once. To provide a simple explanation for the data, we consider the problem of constructing such a phylogeny with a minimum number of edges. In general this optimization problem is NP-complete; some associated approximation problems are also hard, but others are easy. When tree solutions exist, they can be constructed and randomly sampled in polynomial time

A New Quartet Tree Heuristic for Hierarchical Clustering

We consider the problem of constructing an an optimal-weight tree from the 3*(n choose 4) weighted quartet topologies on n objects, where optimality means that the summed weight of the embedded quartet topologiesis optimal (so it can be the case that the optimal tree embeds all quartets as non-optimal topologies). We present a heuristic for reconstructing the optimal-weight tree, and a canonical manner to derive the quartet-topology weights from a given distance matrix. The method repeatedly transforms a bifurcating tree, with all objects involved as leaves, achieving a monotonic approximation to the exact single globally optimal tree. This contrasts to other heuristic search methods from biological phylogeny, like DNAML or quartet puzzling, which, repeatedly, incrementally construct a solution from a random order of objects, and subsequently add agreement values.Comment: 22 pages, 14 figure

Inference of single-cell phylogenies from lineage tracing data using Cassiopeia.

The pairing of CRISPR/Cas9-based gene editing with massively parallel single-cell readouts now enables large-scale lineage tracing. However, the rapid growth in complexity of data from these assays has outpaced our ability to accurately infer phylogenetic relationships. First, we introduce Cassiopeia-a suite of scalable maximum parsimony approaches for tree reconstruction. Second, we provide a simulation framework for evaluating algorithms and exploring lineage tracer design principles. Finally, we generate the most complex experimental lineage tracing dataset to date, 34,557 human cells continuously traced over 15 generations, and use it for benchmarking phylogenetic inference approaches. We show that Cassiopeia outperforms traditional methods by several metrics and under a wide variety of parameter regimes, and provide insight into the principles for the design of improved Cas9-enabled recorders. Together, these should broadly enable large-scale mammalian lineage tracing efforts. Cassiopeia and its benchmarking resources are publicly available at www.github.com/YosefLab/Cassiopeia

Tracing evolutionary links between species

The idea that all life on earth traces back to a common beginning dates back at least to Charles Darwin's {\em Origin of Species}. Ever since, biologists have tried to piece together parts of this `tree of life' based on what we can observe today: fossils, and the evolutionary signal that is present in the genomes and phenotypes of different organisms. Mathematics has played a key role in helping transform genetic data into phylogenetic (evolutionary) trees and networks. Here, I will explain some of the central concepts and basic results in phylogenetics, which benefit from several branches of mathematics, including combinatorics, probability and algebra.Comment: 18 pages, 6 figures (Invited review paper (draft version) for AMM

Clustering by compression

We present a new method for clustering based on compression. The method doesn't use subject-specific features or background knowledge, and works as follows: First, we determine a universal similarity distance, the normalized compression distance or NCD, computed from the lengths of compressed data files (singly and in pairwise concatenation). Second, we apply a hierarchical clustering method. The NCD is universal in that it is not restricted to a specific application area, and works across application area boundaries. A theoretical precursor, the normalized information distance, co-developed by one of the authors, is provably optimal but uses the non-computable notion of Kolmogorov complexity. We propose precise notions of similarity metric, normal compressor, and show that the NCD based on a normal compressor is a similarity metric that approximates universality. To extract a hierarchy of clusters from the distance matrix, we determine a dendrogram (binary tree) by a new quartet method and a fast heuristic to implement it. The method is implemented and available as public software, and is robust under choice of different compressors. To substantiate our claims of universality and robustness, we report evidence of successful application in areas as diverse as genomics, virology, languages, literature, music, handwritten digits, astronomy, and combinations of objects from completely different domains, using statistical, dictionary, and block sorting compressors. In genomics we presented new evidence for major questions in Mammalian evolution, based on whole-mitochondrial genomic analysis: the Eutherian orders and the Marsupionta hypothesis against the Theria hypothesis.Comment: LaTeX, 27 pages, 20 figure