An Efficient Algorithm for Computing High-Quality Paths amid Polygonal Obstacles

We study a path-planning problem amid a set $\mathcal{O}$ of obstacles in $\mathbb{R}^2$, in which we wish to compute a short path between two points while also maintaining a high clearance from $\mathcal{O}$; the clearance of a point is its distance from a nearest obstacle in $\mathcal{O}$. Specifically, the problem asks for a path minimizing the reciprocal of the clearance integrated over the length of the path. We present the first polynomial-time approximation scheme for this problem. Let $n$ be the total number of obstacle vertices and let $\varepsilon \in (0,1]$. Our algorithm computes in time $O(\frac{n^2}{\varepsilon ^2} \log \frac{n}{\varepsilon})$ a path of total cost at most $(1+\varepsilon)$ times the cost of the optimal path.Comment: A preliminary version of this work appear in the Proceedings of the 27th Annual ACM-SIAM Symposium on Discrete Algorithm

Path Similarity Analysis: a Method for Quantifying Macromolecular Pathways

Diverse classes of proteins function through large-scale conformational changes; sophisticated enhanced sampling methods have been proposed to generate these macromolecular transition paths. As such paths are curves in a high-dimensional space, they have been difficult to compare quantitatively, a prerequisite to, for instance, assess the quality of different sampling algorithms. The Path Similarity Analysis (PSA) approach alleviates these difficulties by utilizing the full information in 3N-dimensional trajectories in configuration space. PSA employs the Hausdorff or Fr\'echet path metrics---adopted from computational geometry---enabling us to quantify path (dis)similarity, while the new concept of a Hausdorff-pair map permits the extraction of atomic-scale determinants responsible for path differences. Combined with clustering techniques, PSA facilitates the comparison of many paths, including collections of transition ensembles. We use the closed-to-open transition of the enzyme adenylate kinase (AdK)---a commonly used testbed for the assessment enhanced sampling algorithms---to examine multiple microsecond equilibrium molecular dynamics (MD) transitions of AdK in its substrate-free form alongside transition ensembles from the MD-based dynamic importance sampling (DIMS-MD) and targeted MD (TMD) methods, and a geometrical targeting algorithm (FRODA). A Hausdorff pairs analysis of these ensembles revealed, for instance, that differences in DIMS-MD and FRODA paths were mediated by a set of conserved salt bridges whose charge-charge interactions are fully modeled in DIMS-MD but not in FRODA. We also demonstrate how existing trajectory analysis methods relying on pre-defined collective variables, such as native contacts or geometric quantities, can be used synergistically with PSA, as well as the application of PSA to more complex systems such as membrane transporter proteins.Comment: 9 figures, 3 tables in the main manuscript; supplementary information includes 7 texts (S1 Text - S7 Text) and 11 figures (S1 Fig - S11 Fig) (also available from journal site

The Role of Problem Representation in Producing Near-Optimal TSP Tours

Gestalt psychologists pointed out about 100 years ago that a key to solving difficult insight problems is to change the mental representation of the problem, as is the case, for example, with solving the six matches problem in 2D vs. 3D space. In this study we ask a different question, namely what representation is used when subjects solve search, rather than insight problems. Some search problems, such as the traveling salesman problem (TSP), are defined in the Euclidean plane on the computer monitor or on a piece of paper, and it seems natural to assume that subjects who solve a Euclidean TSP do so using a Euclidean representation. It is natural to make this assumption because the TSP task is defined in that space. We provide evidence that, on the contrary, subjects may produce TSP tours in the complex-log representation of the TSP city map. The complex-log map is a reasonable assumption here, because there is evidence suggesting that the retinal image is represented in the primary visual cortex as a complex-log transformation of the retina. It follows that the subject’s brain may be “solving” the TSP using complex-log maps. We conclude by pointing out that solving a Euclidean problem in a complex-log representation may be acceptable, even desirable, if the subject is looking for near-optimal, rather than optimal solutions

Reconstructing complex lineage trees from scRNA-seq data using MERLoT

Advances in single-cell transcriptomics techniques are revolutionizing studies of cellular differentiation and heterogeneity. It has become possible to track the trajectory of thousands of genes across the cellular lineage trees that represent the temporal emergence of cell types during dynamic processes. However, reconstruction of cellular lineage trees with more than a few cell fates has proved challenging. We present MERLoT (https://github.com/soedinglab/merlot), a flexible and user-friendly tool to reconstruct complex lineage trees from single-cell transcriptomics data. It can impute temporal gene expression profiles along the reconstructed tree. We show MERLoT’s capabilities on various real cases and hundreds of simulated datasets