computational genomics teams

Abstract: Unsigned linear unichromosomal genomes with genes labeled 1, . . . , n are represented by permutations of these labels, whose adjacencies are the unordered pairs of genes occurring consecutively. The breakpoint distance counts the adjacencies of one genome that are absent from the other, and a breakpoint median minimizes the total breakpoint distance to a given set of genomes. Deciding whether a permutation is a median often requires a minimization over the whole symmetric group, which makes the median set resistant to exact counting. We replace this global condition by a local one: a c-approximate median is a genome having at most c adjacencies absent from all the input genomes. For a fixed genome we introduce its approximate median inverse, the set of ordered k-tuples of genomes ad- mitting it as a c-approximate median, and we construct and count this set explicitly. For k genomes chosen uniformly and independently at random, this gives the probability that a given genome is a c-approximate median and the expected number of such approximate medians. The relaxation is not only technical: approximate medians and near-optimal genomes co- incide up to a shift of the tolerance that remains bounded in probability as the number of genes grows. Finally, we derive an explicit upper bound on the probability that a given genome is an exact median, and on the expected number of exact breakpoint medians.

Abstract: Scientific measurements such as single-cell RNA (scRNA) sequencing often take the form of nonnegative integer counts, whereas continuous-state diffusion models approximate this discrete structure using continuous coordinates. Building on stochastic chemical reaction networks (CRNs), a class of count-native Markov jump processes, we introduce CRNDiff, a structured framework that combines count-space diffusion with inference-time conditioning on rare subpopulations. An independent birth--death instantiation yields a closed-form transition kernel for forward noising. This kernel enables reverse sampling via forward-filtering backward-sampling (FFBS) and supports data-driven selection of the terminal noising time, eliminating the need for a validation sweep. This tractability also lets us introduce tilted Feynman--Kac (FK) steering, a method for sampling target subpopulations from a frozen generator without retraining. By tilting posterior marginals before FK particle correction, steering mitigates importance-weight concentration when the target population is rare. Using scRNA-seq data from the human heart cell atlas, we test the ability of CRNDiff to generate cell-type-specific distributions. Across the three evaluated target populations, CRNDiff achieves the highest conditional fidelity among the evaluated generative models, with larger mean purity margins for rarer target populations. Generated cells preserve marker-level differential-expression structure. Replacing real training cells for the target classes with generated cells yields downstream classification performance approaching that of the real-data reference.