Biological Factor Regulatory Neural Network

Genes are fundamental for analyzing biological systems and many recent works proposed to utilize gene expression for various biological tasks by deep learning models. Despite their promising performance, it is hard for deep neural networks to provide biological insights for humans due to their black-box nature. Recently, some works integrated biological knowledge with neural networks to improve the transparency and performance of their models. However, these methods can only incorporate partial biological knowledge, leading to suboptimal performance. In this paper, we propose the Biological Factor Regulatory Neural Network (BFReg-NN), a generic framework to model relations among biological factors in cell systems. BFReg-NN starts from gene expression data and is capable of merging most existing biological knowledge into the model, including the regulatory relations among genes or proteins (e.g., gene regulatory networks (GRN), protein-protein interaction networks (PPI)) and the hierarchical relations among genes, proteins and pathways (e.g., several genes/proteins are contained in a pathway). Moreover, BFReg-NN also has the ability to provide new biologically meaningful insights because of its white-box characteristics. Experimental results on different gene expression-based tasks verify the superiority of BFReg-NN compared with baselines. Our case studies also show that the key insights found by BFReg-NN are consistent with the biological literature

Single Cells Are Spatial Tokens: Transformers for Spatial Transcriptomic Data Imputation

Spatially resolved transcriptomics brings exciting breakthroughs to single-cell analysis by providing physical locations along with gene expression. However, as a cost of the extremely high spatial resolution, the cellular level spatial transcriptomic data suffer significantly from missing values. While a standard solution is to perform imputation on the missing values, most existing methods either overlook spatial information or only incorporate localized spatial context without the ability to capture long-range spatial information. Using multi-head self-attention mechanisms and positional encoding, transformer models can readily grasp the relationship between tokens and encode location information. In this paper, by treating single cells as spatial tokens, we study how to leverage transformers to facilitate spatial tanscriptomics imputation. In particular, investigate the following two key questions: (1) $\textit{how to encode spatial information of cells in transformers}$, and (2) $\textit{ how to train a transformer for transcriptomic imputation}$. By answering these two questions, we present a transformer-based imputation framework, SpaFormer, for cellular-level spatial transcriptomic data. Extensive experiments demonstrate that SpaFormer outperforms existing state-of-the-art imputation algorithms on three large-scale datasets while maintaining superior computational efficiency

Prediction of High-Risk Types of Human Papillomaviruses Using Reduced Amino Acid Modes

A human papillomavirus type plays an important role in the early diagnosis of cervical cancer. Most of the prediction methods use protein sequence and structure information, but the reduced amino acid modes have not been used until now. In this paper, we introduced the modes of reduced amino acids to predict high-risk HPV. We first reduced 20 amino acids into several nonoverlapping groups and calculated their structure and physicochemical modes for high-risk HPV prediction, which was tested and compared with the existing methods on 68 samples of known HPV types. The experiment result indicates that the proposed method achieved better performance with an accuracy of 96.49%, indicating that the reduced amino acid modes might be used to improve the prediction of high-risk HPV types

Unveiling the influence of surrounding materials and realization of multi-level storage in resistive switching memory

Considerable efforts have been made to obtain better control of the switching behavior of resistive random access memory (RRAM) devices, such as using modified or multilayer switching materials. Although considerable progress has been made, the reliability and stability of the devices greatly deteriorate due to dispersed electric field caused by low permittivity surrounding materials. By introducing surrounding materials with a relatively higher dielectric constant, the RRAM devices become promising for cost-effective applications by achieving multilevel storage functionality and improved scalability. A device designed by this principle exhibits multiple distinct and non-volatile conductance states. Moreover, the issue of the increasing forming voltage during device scaling is also solved, improving the capacity of the chips and reducing the power dissipation in the process of the device miniaturization. The COMSOL simulation helps to reveal that the enhanced performance is correlated with a more concentrated electric field around the conductive filament, which is favorable for controlling the connection and rupture of the resistive filament

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field