An Event-Driven Approach to Genotype Imputation on a Custom RISC-V Cluster.

This article proposes an event-driven solution to genotype imputation, a technique used to statistically infer missing genetic markers in DNA. The work implements the widely accepted Li and Stephens model, primary contributor to the computational complexity of modern x86 solutions, in an attempt to determine whether further investigation of the application is warranted in the event-driven domain. The model is implemented using graph-based Hidden Markov Modeling and executed as a customized forward/backward dynamic programming algorithm. The solution uses an event-driven paradigm to map the algorithm to thousands of concurrent cores, where events are small messages that carry both control and data within the algorithm. The design of a single processing element is discussed. This is then extended across multiple cores and executed on a custom RISC-V NoC cluster called POETS. Results demonstrate how the algorithm scales over increasing hardware resources and a multi-core run demonstrates a 270X reduction in wall-clock processing time when compared to a single-threaded x86 solution. Optimisation of the algorithm via linear interpolation is then introduced and tested, with results demonstrating a wall-clock reduction time of  âˆ¼ 5 orders of magnitude when compared to a similarly optimised x86 solution.

Coupling Bulk Phase Separation of Disordered Proteins to Membrane Domain Formation in Molecular Simulations on a Bespoke Compute Fabric.

Phospholipid membranes surround the cell and its internal organelles, and their multicomponent nature allows the formation of domains that are important in cellular signalling, the immune system, and bacterial infection. Cytoplasmic compartments are also created by the phase separation of intrinsically disordered proteins into biomolecular condensates. The ubiquity of lipid membranes and protein condensates raises the question of how three-dimensional droplets might interact with two-dimensional domains, and whether this coupling has physiological or pathological importance. Here, we explore the equilibrium morphologies of a dilute phase of a model disordered protein interacting with an ideal-mixing, two-component lipid membrane using coarse-grained molecular simulations. We find that the proteins can wet the membrane with and without domain formation, and form phase separated droplets bound to membrane domains. Results from much larger simulations performed on a novel non-von-Neumann compute architecture called POETS, which greatly accelerates their execution compared to conventional hardware, confirm the observations. Reducing the wall clock time for such simulations requires new architectures and computational techniques. We demonstrate here an inter-disciplinary approach that uses real-world biophysical questions to drive the development of new computing hardware and simulation algorithms.