The study of drug-target interaction plays an important role in the process of drug development. The subject of DTI forecasting has advanced significantly in the last several years, yielding numerous significant research findings and methodologies. Heterogeneous data sources provide richer information and comprehensive perspectives for drug-target interaction prediction, so many existing methods rely on heterogeneous networks, and graph embedding technology becomes an important technology to extract information from heterogeneous networks. These approaches, however, are less concerned with potential noisy information in heterogeneous networks and more focused on the extent of information extraction in those networks. Based on this, a potential DTI predictive network model called FBRWPC is proposed in this paper. It uses a fine-grained similarity selection program to first integrate similarity on similar networks and then a bidirectional random walk graph embedding learning method with restart to obtain an updated drug target interaction matrix. Through the use of similarity selection and fine-grained selection similarity integration, the framework can effectively filter out the noise present in heterogeneous networks and enhance the model\'s prediction performance. The experimental findings demonstrate that, even after being split up into four distinct types of data sets, FBRWPC can still retain great prediction performance, a sign of the model\'s resilience and good generalization.

Mathematical models describing the spatial spreading and invasion of populations of biological cells are often developed in a continuum modelling framework using reaction-diffusion equations. While continuum models based on linear diffusion are routinely employed and known to capture key experimental observations, linear diffusion fails to predict well-defined sharp fronts that are often observed experimentally. This observation has motivated the use of nonlinear degenerate diffusion; however, these nonlinear models and the associated parameters lack a clear biological motivation and interpretation. Here, we take a different approach by developing a stochastic discrete lattice-based model incorporating biologically inspired mechanisms and then deriving the reaction-diffusion continuum limit. Inspired by experimental observations, agents in the simulation deposit extracellular material, which we call a substrate, locally onto the lattice, and the motility of agents is taken to be proportional to the substrate density. Discrete simulations that mimic a two-dimensional circular barrier assay illustrate how the discrete model supports both smooth and sharp-fronted density profiles depending on the rate of substrate deposition. Coarse-graining the discrete model leads to a novel partial differential equation (PDE) model whose solution accurately approximates averaged data from the discrete model. The new discrete model and PDE approximation provide a simple, biologically motivated framework for modelling the spreading, growth and invasion of cell populations with well-defined sharp fronts. Open-source Julia code to replicate all results in this work is available on GitHub.

The discovery of novel therapeutic targets, defined as proteins which drugs can interact with to induce therapeutic benefits, typically represent the first and most important step of drug discovery. One solution for target discovery is target repositioning, a strategy which relies on the repurposing of known targets for new diseases, leading to new treatments, less side effects and potential drug synergies. Biological networks have emerged as powerful tools for integrating heterogeneous data and facilitating the prediction of biological or therapeutic properties. Consequently, they are widely employed to predict new therapeutic targets by characterizing potential candidates, often based on their interactions within a Protein-Protein Interaction (PPI) network, and their proximity to genes associated with the disease. However, over-reliance on PPI networks and the assumption that potential targets are necessarily near known genes can introduce biases that may limit the effectiveness of these methods. This study addresses these limitations in two ways. First, by exploiting a multi-layer network which incorporates additional information such as gene regulation, metabolite interactions, metabolic pathways, and several disease signatures such as Differentially Expressed Genes, mutated genes, Copy Number Alteration, and structural variants. Second, by extracting relevant features from the network using several approaches including proximity to disease-associated genes, but also unbiased approaches such as propagation-based methods, topological metrics, and module detection algorithms. Using prostate cancer as a case study, the best features were identified and utilized to train machine learning algorithms to predict 5 novel promising therapeutic targets for prostate cancer: IGF2R, C5AR, RAB7, SETD2 and NPBWR1.

This paper deals with a reliability system hit by three types of shocks ranked as harmless, critical, or extreme, depending on their magnitudes, being below H1, between H1 and H2, and above H2, respectively. The system\'s failure is caused by a single extreme shock or by a total of N critical shocks. In addition, the system fails under occurrences of M pairs of shocks with lags less than some δ (δ-shocks) in any order. Thus, the system fails when one of the three named cumulative damages occurs first. Thus, it fails due to the competition of the three associated shock processes. We obtain a closed-form joint distribution of the time-to-failure, shock count upon failure, δ-shock count, and cumulative damage to the system on failure, to name a few. In particular, the reliability function directly follows from the marginal distribution of the failure time. In a modified system, we restrict δ-shocks to those with small lags between consecutive harmful shocks. We treat the system as a generalized random walk process and use an embellished variant of discrete operational calculus developed in our earlier work. We demonstrate analytical tractability of our formulas which are also validated, through Monte Carlo simulation.

Swarm robots are frequently preferred for the exploration of harsh environments and search and rescue operations. This study explores the factors that influence the movement strategies of autonomous robot swarms and their impact on swarm distribution in the field, employing simulation-based analysis. The research consists of two parts: initially, robots undergo free-fall as passive entities, followed by a phase where they employ predefined movement strategies from their fall positions. The study aims to investigate how the initial position and related parameters affect movement characteristics and the ultimate swarm distribution. To achieve this objective, four parameters-radius, height, mass, and the Coefficient of Restitution-were identified, each assigned three different values. The study observes the effects of these parameters on robot motion, considering motion strategies such as Random Walk, Levy Walk, Markov Process, and Brownian Motion. Results indicate that increasing parameter values induce changes in the position values of the free-falling swarm in the first part, which is the initial position for the second part, influencing movement strategies in diverse ways. The outcomes are analyzed concerning the radial and angular spread of the robots. Radial spread measures how far swarm elements spread from their initial positions, while angular spread indicates how homogeneously the robots are distributed according to the polar angle. The study comprehensively investigates how the movement strategies of autonomous robot swarms are impacted by parameters and how these effects manifest in the results. The findings are anticipated to enhance the effective utilization of autonomous robot swarms in exploration missions.

Since scientific investigations have demonstrated that aberrant expression of miRNAs brings about the incidence of numerous intricate diseases, precise determination of miRNA-disease relationships greatly contributes to the advancement of human medical progress. To tackle the issue of inefficient conventional experimental approaches, numerous computational methods have been proposed to predict miRNA-disease association with enhanced accuracy. However, constructing miRNA-gene-disease heterogeneous network by incorporating gene information has been relatively under-explored in existing computational techniques. Accordingly, this paper puts forward a technique to predict miRNA-disease association by applying autoencoder and implementing random walk on miRNA-gene-disease heterogeneous network(AE-RW). Firstly, we integrate association information and similarities between miRNAs, genes, and diseases to construct a miRNA-gene-disease heterogeneous network. Subsequently, we consolidate two network feature representations extracted independently via an autoencoder and a random walk procedure. Finally, deep neural network(DNN) are utilized to conduct association prediction. The experimental results demonstrate that the AE-RW model achieved an AUC of 0.9478 through 5-fold CV on the HMDD v3.2 dataset, outperforming the five most advanced existing models. Additionally, case studies were implemented for breast and lung cancer, further validated the superior predictive capabilities of our model.

Gastrulation is the first major differentiation process in animal embryos. However, the dynamics of human gastrulation remain mostly unknown owing to the ethical limitations. We studied the dynamics of the mesoderm and endoderm cell differentiation from human pluripotent stem cells for insight into the cellular dynamics of human gastrulation. Human pluripotent stem cells have properties similar to those of the epiblast, which gives rise to the three germ layers. The mesoderm and endoderm were induced with more than 75% purity from human induced pluripotent stem cells. Single-cell dynamics of pluripotent stem cell-derived mesoderm and endoderm cells were traced using time-lapse imaging. Both mesoderm and endoderm cells migrate randomly, accompanied by short-term directional persistence. No substantial differences were detected between mesoderm and endoderm migration. Computer simulations created using the measured parameters revealed that random movement and external force, such as the spread out of cells from the primitive streak area, mimicked the homogeneous discoidal germ layer formation. These results were consistent with the development of amniotes, which suggests the effectiveness of human pluripotent stem cells as a good model for studying human embryogenesis.

The inferred rate of default (IRD) was first introduced as an indicator of default risk computable from information publicly reported by the Bulgarian National Bank. We have provided a more detailed justification for the suggested methodology for forecasting the IRD on the bank-group- and bank-system-level based on macroeconomic factors. Furthermore, we supply additional empirical evidence in the time-series analysis. Additionally, we demonstrate that IRD provides a new perspective for comparing credit risk across bank groups. The estimation methods and model assumptions agree with current Bulgarian regulations and the IFRS 9 accounting standard. The suggested models could be used by practitioners in monthly forecasting the point-in-time probability of default in the context of accounting reporting and in monitoring and managing credit risk.

BACKGROUND: The rapid devolvement of single cell RNA sequencing (scRNA-seq) technology leads to huge amounts of scRNA-seq data, which greatly advance the research of many biomedical fields involving tissue heterogeneity, pathogenesis of disease and drug resistance etc. One major task in scRNA-seq data analysis is to cluster cells in terms of their expression characteristics. Up to now, a number of methods have been proposed to infer cell clusters, yet there is still much space to improve their performance.
RESULTS: In this paper, we develop a new two-step clustering approach to effectively cluster scRNA-seq data, which is called TSC - the abbreviation of Two-Step Clustering. Particularly, by dividing all cells into two types: core cells (those possibly lying around the centers of clusters) and non-core cells (those locating in the boundary areas of clusters), we first clusters the core cells by hierarchical clustering (the first step) and then assigns the non-core cells to the corresponding nearest clusters (the second step). Extensive experiments on 12 real scRNA-seq datasets show that TSC outperforms the state of the art methods.
CONCLUSIONS: TSC is an effective clustering method due to its two-steps clustering strategy, and it is a useful tool for scRNA-seq data analysis.

The type six secretion system (T6SS) is a transmembrane protein complex that mediates bacterial cell killing. The T6SS comprises three main components (transmembrane, baseplate and sheath/tube complexes) that are sequentially assembled in order to enable an attacking cell to transport payloads into neighbouring cells. A T6SS attack disrupts the function of essential cellular components of target cells, typically resulting in their death. While the assembled T6SS adopts a fixed position in the cell membrane of the attacking cell, the location of the firing site varies between firing events. In Serratia marcescens, a post-translational regulatory network regulates the assembly and firing kinetics of the T6SS in a manner that affects the attacking cell\'s ability to kill target cells. Moreover, when the ability of membrane complexes to reorient is reduced, an attacking cell\'s competitiveness is also reduced. In this study, we will develop a mathematical model that describes both the spatial motion and assembly/disassembly of a firing T6SS. The model represents the motion of a T6SS on the cell membrane as a state-dependent random walk. Using the model, we will explore how both spatial and temporal effects can combine to give rise to different firing phenotypes. Using parameters inferred from the available literature, we show that variation in estimated diffusion coefficients is sufficient to give rise to either spatially local or global firers.