computational biology teams

Abstract: Exact optimization of synonymous coding sequences under a joint folding-energy and codon-usage objective is limited by expensive dynamic-programming splits and large working sets. \textsc{SparseDesign} applies candidate sparsification to the multiloop recurrence of a Turner~2004 dangle-0 solver over a weighted codon automaton. A direct branch is retained only when it strictly improves on every partitionable or endpoint-unpaired realization of the same endpoint states. We prove equivalence to the dense recurrence in real arithmetic, under an explicit scalar branch-interface assumption. With $N$ automaton states, edge set $E$ and $Z$ retained candidates, multiloop work is $O(N^2+N|E|+NZ)$; worst-case time remains cubic for bounded-width automata and total memory remains quadratic. Endpoint ownership permits parallel candidate construction without locks. While synthetic stress families can benefit little from sparsification and exhibit near-quadratic candidate growth, natural proteins show substantial candidate-count reductions. In our 7,600-task campaign, the 2,000-protein human-table panel has median retention of only 3.53\% at $λ=0$ and 2.15\% at $λ=4$, corresponding to approximately 28.3-fold and 46.4-fold reductions relative to all feasible direct intervals. The primary performance experiments use an AMD EPYC 7313 server. For human Dp427c (11,031 nt, $λ=0$), 16-thread packed \textsc{SparseDesign} achieves five-run medians of 236.54 seconds wall-clock time and 14.43 GiB peak RSS. Compared with the single-thread local dense LinearDesign fork on the same server (4,912 seconds, 402.10 GiB RSS), this gives a 20.8-fold wall-clock speedup and a 27.9-fold peak-memory reduction. On a Core i9-14900KF commodity PC with 64 GiB RAM, the same input, layout and thread count achieve 126.42 seconds and 14.43 GiB RSS.

Abstract: Many deep learning approaches to RNA secondary structure prediction have recently been proposed. They typically output a weight matrix $W$ where $W_{ij}$ is an arbitrary weight for base $i$ pairing with base $j$. Converting this matrix to a predicted secondary structure or base-pairing probability matrix typically involves ad hoc and problematic downstream algorithms. Despite the importance of this conversion step, which we refer to as structure extraction, it has received relatively little attention in the literature. In this work, we analyze how the congruence between training and extraction methods affects prediction performance. To do this, we compare four extraction algorithms: a Nussinov-like dynamic programming method, maximum-weight graph matching and the greedy extraction algorithms used by SPOT-RNA and RiNALMo. These are evaluated on outputs from the pretrained RiNALMo model and three toy models trained in this paper: a differentiable Nussinov-like model, a binary cross-entropy (BCE) baseline, and a model that incorporates a novel symmetric doubly stochastic matrix (SDSM) normalization algorithm during training which allows it to output base-pairing probability matrices directly, without a separate extraction step. This SDSM normalization algorithm is differentiable and can be added inline to any deep learning model during training and evaluation. We find that the performance of each extraction method depends strongly on how the corresponding model was trained. Considering the toy models themselves, the SDSM model showed the strongest overall performance: it outperformed the BCE baseline under all four extraction algorithms and produced pre-extraction outputs closest to the ground truth. These results suggest that SDSM normalization is a tractable alternative to traditional structure extraction.

Abstract: A cell's identity depends on where it sits in tissue: for example, a macrophage behaves differently in a tumor core than at its edge. Spatial transcriptomics has transformed how we study this by recovering that lost coordinate, but it does so by producing data that is simultaneously high-dimensional, multimodal, and uncertain. Visualizing this combination is a hard problem in its own right, and one that warrants an assessment of how the field currently represents it, what has worked, and what is still missing. We surveyed 148 papers and 1,824 figure panels using a What-Why-How coding framework grounded in Munzner's nested model, connecting the data represented, the biological tasks motivating each visualization, and the design choices through which they are expressed; a subset of the surveyed work also contributed dedicated interactive visualization software that was not necessarily reflected in the static figures, and we looked at what interaction capabilities those tools supported as well. We close by outlining where the field stands and the challenges ahead for bioinformatics and visualization researchers to tackle together.

Abstract: We study the recovery of forward and reverse quadratic optimal-transport maps from unpaired samples in high dimensions. We introduce a bidirectional neural framework in which the learned maps induce forward and backward displacement interpolants, while the training objective combines bidirectional quadratic action, discriminator-restricted Jensen-Shannon endpoint objectives, and two-sided cycle consistency. The construction requires neither precomputed sample pairings nor an explicit convex-potential parameterization. For absolutely continuous probability measures supported on a compact convex set, and under the stated generator-approximation, discriminator-richness, and minimizer-attainment conditions, we prove a population recovery theorem: for every prescribed accuracy, the sum of the corresponding \(L^2\) errors between any global minimizer and the forward and reverse quadratic Brenier maps is below that accuracy, provided the discriminator level is sufficiently large and the annealing action weight becomes sufficiently small. Moreover, the cycle loss is bounded above by \(λW_2^2(μ_0,μ_1)\). Complementary results quantify approximate invertibility and show that exact endpoint Jensen-Shannon divergence and cycle consistency control missing target mass and many-to-one map collapse, respectively. Experiments on Swiss roll, MNIST, CelebA, single-cell perturbation data, and chest X-ray images evaluate endpoint fidelity, transport cost, inverse consistency, and the geometry of the induced interpolations.