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CRISPR technology has enabled large-scale cell lineage tracing for complex multicellular organisms by mutating synthetic genomic barcodes during organismal development. However, these sophisticated biological tools currently use ad-hoc and outmoded computational methods to reconstruct the cell lineage tree from the mutated barcodes. Because these methods are agnostic to the biological mechanism, they are unable to take full advantage of the datas structure. We propose a statistical model for the mutation process and develop a procedure to estimate the tree topology, branch lengths, and mutation parameters by iteratively applying penalized maximum likelihood estimation. In contrast to existing techniques, our method estimates time along each branch, rather than number of mutation events, thus providing a detailed account of tissue-type differentiation. Via simulations, we demonstrate that our method is substantially more accurate than existing approaches. Our reconstructed trees also better recapitulate known aspects of zebrafish development and reproduce similar results across fish replicates.
Tuffley and Steel (1997) proved that Maximum Likelihood and Maximum Parsimony methods in phylogenetics are equivalent for sequences of characters under a simple symmetric model of substitution with no common mechanism. This result has been widely cit
The random coefficients model $Y_i={beta_0}_i+{beta_1}_i {X_1}_i+{beta_2}_i {X_2}_i+ldots+{beta_d}_i {X_d}_i$, with $mathbf{X}_i$, $Y_i$, $mathbf{beta}_i$ i.i.d, and $mathbf{beta}_i$ independent of $X_i$ is often used to capture unobserved heterogene
We consider the problem of estimating parameters of stochastic differential equations (SDEs) with discrete-time observations that are either completely or partially observed. The transition density between two observations is generally unknown. We pr
In this paper we present a novel method for estimating the parameters of a parametric diffusion processes. Our approach is based on a closed-form Maximum Likelihood estimator for an approximating Continuous Time Markov Chain (CTMC) of the diffusion p
We are frequently faced with a large collection of antibodies, and want to select those with highest affinity for their cognate antigen. When developing a first-line therapeutic for a novel pathogen, for instance, we might look for such antibodies in