A Novel Convex Relaxation for Non-Binary Discrete Tomography

We present a novel convex relaxation and a corresponding inference algorithm for the non-binary discrete tomography problem, that is, reconstructing discrete-valued images from few linear measurements. In contrast to state of the art approaches that split the problem into a continuous reconstruction problem for the linear measurement constraints and a discrete labeling problem to enforce discrete-valued reconstructions, we propose a joint formulation that addresses both problems simultaneously, resulting in a tighter convex relaxation. For this purpose a constrained graphical model is set up and evaluated using a novel relaxation optimized by dual decomposition. We evaluate our approach experimentally and show superior solutions both mathematically (tighter relaxation) and experimentally in comparison to previously proposed relaxations

A Practical Algorithm for Reconstructing Level-1 Phylogenetic Networks

Recently much attention has been devoted to the construction of phylogenetic networks which generalize phylogenetic trees in order to accommodate complex evolutionary processes. Here we present an efficient, practical algorithm for reconstructing level-1 phylogenetic networks - a type of network slightly more general than a phylogenetic tree - from triplets. Our algorithm has been made publicly available as the program LEV1ATHAN. It combines ideas from several known theoretical algorithms for phylogenetic tree and network reconstruction with two novel subroutines. Namely, an exponential-time exact and a greedy algorithm both of which are of independent theoretical interest. Most importantly, LEV1ATHAN runs in polynomial time and always constructs a level-1 network. If the data is consistent with a phylogenetic tree, then the algorithm constructs such a tree. Moreover, if the input triplet set is dense and, in addition, is fully consistent with some level-1 network, it will find such a network. The potential of LEV1ATHAN is explored by means of an extensive simulation study and a biological data set. One of our conclusions is that LEV1ATHAN is able to construct networks consistent with a high percentage of input triplets, even when these input triplets are affected by a low to moderate level of noise

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

A simple fixed parameter tractable algorithm for computing the hybridization number of two (not necessarily binary) trees

Here we present a new fixed parameter tractable algorithm to compute the hybridization number r of two rooted, not necessarily binary phylogenetic trees on taxon set X in time (6^r.r!).poly(n)$, where n=|X|. The novelty of this approach is its use of terminals, which are maximal elements of a natural partial order on X, and several insights from the softwired clusters literature. This yields a surprisingly simple and practical bounded-search algorithm and offers an alternative perspective on the underlying combinatorial structure of the hybridization number problem

A Max-Product EM Algorithm for Reconstructing Markov-tree Sparse Signals from Compressive Samples

We propose a Bayesian expectation-maximization (EM) algorithm for reconstructing Markov-tree sparse signals via belief propagation. The measurements follow an underdetermined linear model where the regression-coefficient vector is the sum of an unknown approximately sparse signal and a zero-mean white Gaussian noise with an unknown variance. The signal is composed of large- and small-magnitude components identified by binary state variables whose probabilistic dependence structure is described by a Markov tree. Gaussian priors are assigned to the signal coefficients given their state variables and the Jeffreys' noninformative prior is assigned to the noise variance. Our signal reconstruction scheme is based on an EM iteration that aims at maximizing the posterior distribution of the signal and its state variables given the noise variance. We construct the missing data for the EM iteration so that the complete-data posterior distribution corresponds to a hidden Markov tree (HMT) probabilistic graphical model that contains no loops and implement its maximization (M) step via a max-product algorithm. This EM algorithm estimates the vector of state variables as well as solves iteratively a linear system of equations to obtain the corresponding signal estimate. We select the noise variance so that the corresponding estimated signal and state variables obtained upon convergence of the EM iteration have the largest marginal posterior distribution. We compare the proposed and existing state-of-the-art reconstruction methods via signal and image reconstruction experiments.Comment: To appear in IEEE Transactions on Signal Processin