Mitochondrial (MT) mutations serve as natural genetic markers for inferring clonal relationships using single cell sequencing data. However, the fundamental challenge of MT mutation-based lineage tracing is automated identification of informative MT mutations. Here, we introduced an open-source computational algorithm called "MitoTracer", which accurately identified clonally informative MT mutations and inferred evolutionary lineage from scRNA-seq or scATAC-seq samples. We benchmarked MitoTracer using the ground-truth experimental lineage sequencing data and demonstrated its superior performance over the existing methods measured by high sensitivity and specificity. MitoTracer is compatible with multiple single cell sequencing platforms. Its application to a cancer evolution dataset revealed the genes related to primary BRAF-inhibitor resistance from scRNA-seq data of BRAF-mutated cancer cells. Overall, our work provided a valuable tool for capturing real informative MT mutations and tracing the lineages among cells.

The Industrial Internet of Things (IIoT) is emerging as a promising technology that can accelerate the application of industrial intelligence to smart factories. Because of the sensitive nature of user data, federated learning (FL) which performs distributed machine learning while preserving data privacy, is leveraged to meet the accuracy and privacy requirements of IIoT end devices/clients. However, the unreliable communications in IIoT may result in possible single-point failures in the typical single-server FL framework, thereby negatively affecting the training efficiency. In this paper, we study on the client scheduling problem in a multi-server FL framework for the communication reliability and training efficiency improvement. Specifically, we focus on a semi-decentralized FL (SD-FL) framework, where edge servers and clients collaborate to train a shared global model through unreliable intra-cluster model aggregation and inter-cluster model consensus because of the model transmission error in client-server and server-server communication. Then, a client-server association optimization problem is formulated, with the objective of minimizing the global training loss. Resorting to the convergence analysis of SD-FL, the original problem is simplified and transformed into an integer nonlinear programming problem to guide us to design a high-efficiency client scheduling scheme. Finally, experimental results show that the proposed scheme significantly outperforms the baselines in terms of the test accuracy and training loss.

Designing biological sequences is an important challenge that requires satisfying complex constraints and thus is a natural problem to address with deep generative modeling. Diffusion generative models have achieved considerable success in many applications. Score-based generative stochastic differential equations (SDE) model is a continuous-time diffusion model framework that enjoys many benefits, but the originally proposed SDEs are not naturally designed for modeling discrete data. To develop generative SDE models for discrete data such as biological sequences, here we introduce a diffusion process defined in the probability simplex space with stationary distribution being the Dirichlet distribution. This makes diffusion in continuous space natural for modeling discrete data. We refer to this approach as Dirchlet diffusion score model. We demonstrate that this technique can generate samples that satisfy hard constraints using a Sudoku generation task. This generative model can also solve Sudoku, including hard puzzles, without additional training. Finally, we applied this approach to develop the first human promoter DNA sequence design model and showed that designed sequences share similar properties with natural promoter sequences.

Abstract With the development of mobile edge computing technology, edge caching provides a feasible solution for low‐latency and high‐reliability data forwarding in the Internet of Vehicles (IoV). Due to the limited number and storage capacity of the edge servers, and the limited communication range of a single vehicle, the delay and connection requirements are hard to be satisfied. A vehicle clustering based edge caching scheme is proposed in this paper, aiming at minimizing the content acquisition delay of the requesting vehicles (RVs) within the communication range of the edge servers. After getting the optimal vehicle association results, the minimization of content acquisition delay is transformed into a knapsack problem, which is then solved by a dynamic programming algorithm to obtain the optimal cache decisions. Simulation results show that the proposed scheme reduces task acquisition delay by at least about 100 s and increases the cache hit rate by about 50%, compared with the random cache scheme.