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

Learning mutational graphs of individual tumour evolution from single-cell and multi-region sequencing data

Background. A large number of algorithms is being developed to reconstruct evolutionary models of individual tumours from genome sequencing data. Most methods can analyze multiple samples collected either through bulk multi-region sequencing experiments or the sequencing of individual cancer cells. However, rarely the same method can support both data types. Results. We introduce TRaIT, a computational framework to infer mutational graphs that model the accumulation of multiple types of somatic alterations driving tumour evolution. Compared to other tools, TRaIT supports multi-region and single-cell sequencing data within the same statistical framework, and delivers expressive models that capture many complex evolutionary phenomena. TRaIT improves accuracy, robustness to data-specific errors and computational complexity compared to competing methods. Conclusions. We show that the application of TRaIT to single-cell and multi-region cancer datasets can produce accurate and reliable models of single-tumour evolution, quantify the extent of intra-tumour heterogeneity and generate new testable experimental hypotheses

Topological network alignment uncovers biological function and phylogeny

Sequence comparison and alignment has had an enormous impact on our understanding of evolution, biology, and disease. Comparison and alignment of biological networks will likely have a similar impact. Existing network alignments use information external to the networks, such as sequence, because no good algorithm for purely topological alignment has yet been devised. In this paper, we present a novel algorithm based solely on network topology, that can be used to align any two networks. We apply it to biological networks to produce by far the most complete topological alignments of biological networks to date. We demonstrate that both species phylogeny and detailed biological function of individual proteins can be extracted from our alignments. Topology-based alignments have the potential to provide a completely new, independent source of phylogenetic information. Our alignment of the protein-protein interaction networks of two very different species--yeast and human--indicate that even distant species share a surprising amount of network topology with each other, suggesting broad similarities in internal cellular wiring across all life on Earth.Comment: Algorithm explained in more details. Additional analysis adde

Complexity of Networks

Network or graph structures are ubiquitous in the study of complex systems. Often, we are interested in complexity trends of these system as it evolves under some dynamic. An example might be looking at the complexity of a food web as species enter an ecosystem via migration or speciation, and leave via extinction. In this paper, a complexity measure of networks is proposed based on the {\em complexity is information content} paradigm. To apply this paradigm to any object, one must fix two things: a representation language, in which strings of symbols from some alphabet describe, or stand for the objects being considered; and a means of determining when two such descriptions refer to the same object. With these two things set, the information content of an object can be computed in principle from the number of equivalent descriptions describing a particular object. I propose a simple representation language for undirected graphs that can be encoded as a bitstring, and equivalence is a topological equivalence. I also present an algorithm for computing the complexity of an arbitrary undirected network.Comment: Accepted for Australian Conference on Artificial Life (ACAL05). To appear in Advances in Natural Computation (World Scientific

Uniqueness, intractability and exact algorithms: reflections on level-k phylogenetic networks

Phylogenetic networks provide a way to describe and visualize evolutionary histories that have undergone so-called reticulate evolutionary events such as recombination, hybridization or horizontal gene transfer. The level k of a network determines how non-treelike the evolution can be, with level-0 networks being trees. We study the problem of constructing level-k phylogenetic networks from triplets, i.e. phylogenetic trees for three leaves (taxa). We give, for each k, a level-k network that is uniquely defined by its triplets. We demonstrate the applicability of this result by using it to prove that (1) for all k of at least one it is NP-hard to construct a level-k network consistent with all input triplets, and (2) for all k it is NP-hard to construct a level-k network consistent with a maximum number of input triplets, even when the input is dense. As a response to this intractability we give an exact algorithm for constructing level-1 networks consistent with a maximum number of input triplets