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

Concurrent Geometric Multicasting

We present MCFR, a multicasting concurrent face routing algorithm that uses geometric routing to deliver a message from source to multiple targets. We describe the algorithm's operation, prove it correct, estimate its performance bounds and evaluate its performance using simulation. Our estimate shows that MCFR is the first geometric multicast routing algorithm whose message delivery latency is independent of network size and only proportional to the distance between the source and the targets. Our simulation indicates that MCFR has significantly better reliability than existing algorithms

Robust and MaxMin Optimization under Matroid and Knapsack Uncertainty Sets

Consider the following problem: given a set system (U,I) and an edge-weighted graph G = (U, E) on the same universe U, find the set A in I such that the Steiner tree cost with terminals A is as large as possible: "which set in I is the most difficult to connect up?" This is an example of a max-min problem: find the set A in I such that the value of some minimization (covering) problem is as large as possible. In this paper, we show that for certain covering problems which admit good deterministic online algorithms, we can give good algorithms for max-min optimization when the set system I is given by a p-system or q-knapsacks or both. This result is similar to results for constrained maximization of submodular functions. Although many natural covering problems are not even approximately submodular, we show that one can use properties of the online algorithm as a surrogate for submodularity. Moreover, we give stronger connections between max-min optimization and two-stage robust optimization, and hence give improved algorithms for robust versions of various covering problems, for cases where the uncertainty sets are given by p-systems and q-knapsacks.Comment: 17 pages. Preliminary version combining this paper and http://arxiv.org/abs/0912.1045 appeared in ICALP 201

A note on the data-driven capacity of P2P networks

We consider two capacity problems in P2P networks. In the first one, the nodes have an infinite amount of data to send and the goal is to optimally allocate their uplink bandwidths such that the demands of every peer in terms of receiving data rate are met. We solve this problem through a mapping from a node-weighted graph featuring two labels per node to a max flow problem on an edge-weighted bipartite graph. In the second problem under consideration, the resource allocation is driven by the availability of the data resource that the peers are interested in sharing. That is a node cannot allocate its uplink resources unless it has data to transmit first. The problem of uplink bandwidth allocation is then equivalent to constructing a set of directed trees in the overlay such that the number of nodes receiving the data is maximized while the uplink capacities of the peers are not exceeded. We show that the problem is NP-complete, and provide a linear programming decomposition decoupling it into a master problem and multiple slave subproblems that can be resolved in polynomial time. We also design a heuristic algorithm in order to compute a suboptimal solution in a reasonable time. This algorithm requires only a local knowledge from nodes, so it should support distributed implementations. We analyze both problems through a series of simulation experiments featuring different network sizes and network densities. On large networks, we compare our heuristic and its variants with a genetic algorithm and show that our heuristic computes the better resource allocation. On smaller networks, we contrast these performances to that of the exact algorithm and show that resource allocation fulfilling a large part of the peer can be found, even for hard configuration where no resources are in excess.Comment: 10 pages, technical report assisting a submissio