Motivation: Gene regulatory networks (GRNs) encode gene regulation in living organisms, and have become a critical tool to understand complex biological processes. However, due to the dynamic and complex nature of gene regulation, inferring GRNs from scRNA-seq data is still a challenging task. Existing computational methods usually focus on the close connections between genes, and ignore the global structure and distal regulatory relationships.
View Article and Find Full Text PDFDrug combination therapy has gradually become a promising treatment strategy for complex or co-existing diseases. As drug-drug interactions (DDIs) may cause unexpected adverse drug reactions, DDI prediction is an important task in pharmacology and clinical applications. Recently, researchers have proposed several deep learning methods to predict DDIs.
View Article and Find Full Text PDFMotivation: Drug combination therapy has exhibited remarkable therapeutic efficacy and has gradually become a promising clinical treatment strategy of complex diseases such as cancers. As the related databases keep expanding, computational methods based on deep learning model have become powerful tools to predict synergistic drug combinations. However, predicting effective synergistic drug combinations is still a challenge due to the high complexity of drug combinations, the lack of biological interpretability, and the large discrepancy in the response of drug combinations in vivo and in vitro biological systems.
View Article and Find Full Text PDFSingle-cell RNA sequencing (scRNA-seq) measures transcriptome-wide gene expression at single-cell resolution. Clustering analysis of scRNA-seq data enables researchers to characterize cell types and states, shedding new light on cell-to-cell heterogeneity in complex tissues. Recently, self-supervised contrastive learning has become a prominent technique for underlying feature representation learning.
View Article and Find Full Text PDFNetwork data analysis is a crucial method for mining complicated object interactions. In recent years, random walk and neural-language-model-based network representation learning (NRL) approaches have been widely used for network data analysis. However, these NRL approaches suffer from the following deficiencies: firstly, because the random walk procedure is based on symmetric node similarity and fixed probability distribution, the sampled vertices' sequences may lose local community structure information; secondly, because the feature extraction capacity of the shallow neural language model is limited, they can only extract the local structural features of networks; and thirdly, these approaches require specially designed mechanisms for different downstream tasks to integrate vertex attributes of various types.
View Article and Find Full Text PDFDomain adaptation aims to learn a classifier for a target domain task by using related labeled data from the source domain. Because source domain data and target domain task may be mismatched, there is an uncertainty of source domain data with respect to the target domain task. Ignoring the uncertainty may lead to models with unreliable and suboptimal classification results for the target domain task.
View Article and Find Full Text PDFThe development of single-cell RNA-seq (scRNA-seq) technology allows researchers to characterize the cell types, states and transitions during dynamic biological processes at single-cell resolution. One of the critical tasks is to infer pseudo-time trajectory. However, the existence of transition cells in the intermediate state of complex biological processes poses a challenge for the trajectory inference.
View Article and Find Full Text PDFAccurate inference of gene regulatory rules is critical to understanding cellular processes. Existing computational methods usually decompose the inference of gene regulatory networks (GRNs) into multiple subproblems, rather than detecting potential causal relationships simultaneously, which limits the application to data with a small number of genes. Here, we propose BiRGRN, a novel computational algorithm for inferring GRNs from time-series single-cell RNA-seq (scRNA-seq) data.
View Article and Find Full Text PDFGene regulatory network models the interactions between transcription factors and target genes. Reconstructing gene regulation network is critically important to understand gene function in a particular cellular context, providing key insights into complex biological systems. We develop a new computational method, named iMPRN, which integrates multiple prior networks to infer regulatory network.
View Article and Find Full Text PDFIEEE/ACM Trans Comput Biol Bioinform
August 2022
Cellular programs often exhibit strong heterogeneity and asynchrony in the timing of program execution. Single-cell RNA-seq technology has provided an unprecedented opportunity for characterizing these cellular processes by simultaneously quantifying many parameters at single-cell resolution. Robust trajectory inference is a critical step in the analysis of dynamic temporal gene expression, which can shed light on the mechanisms of normal development and diseases.
View Article and Find Full Text PDFA complex tissue contains a variety of cells with distinct molecular signatures. Single-cell RNA sequencing has characterized the transcriptomes of different cell types and enables researchers to discover the underlying mechanisms of cellular heterogeneity. A critical task in single-cell transcriptome studies is to uncover transcriptional differences among specific cell types.
View Article and Find Full Text PDFEpigenetic alteration is a fundamental characteristic of nearly all human cancers. Tumor cells not only harbor genetic alterations, but also are regulated by diverse epigenetic modifications. Identification of epigenetic similarities across different cancer types is beneficial for the discovery of treatments that can be extended to different cancers.
View Article and Find Full Text PDFBackground: Epigenome is highly dynamic during the early stages of embryonic development. Epigenetic modifications provide the necessary regulation for lineage specification and enable the maintenance of cellular identity. Given the rapid accumulation of genome-wide epigenomic modification maps across cellular differentiation process, there is an urgent need to characterize epigenetic dynamics and reveal their impacts on differential gene regulation.
View Article and Find Full Text PDFBackground: Human cancers are complex ecosystems composed of cells with distinct molecular signatures. Such intratumoral heterogeneity poses a major challenge to cancer diagnosis and treatment. Recent advancements of single-cell techniques such as scRNA-seq have brought unprecedented insights into cellular heterogeneity.
View Article and Find Full Text PDFBMC Bioinformatics
December 2016
Background: Differentiation of human embryonic stem cells requires precise control of gene expression that depends on specific spatial and temporal epigenetic regulation. Recently available temporal epigenomic data derived from cellular differentiation processes provides an unprecedented opportunity for characterizing fundamental properties of epigenomic dynamics and revealing regulatory roles of epigenetic modifications.
Results: This paper presents a spatial temporal clustering approach, named STCluster, which exploits the temporal variation information of epigenomes to characterize dynamic epigenetic mode during cellular differentiation.
IEEE/ACM Trans Comput Biol Bioinform
March 2016
Nucleosomes are basic elements of chromatin structure. The positioning of nucleosomes along a genome is very important to dictate eukaryotic DNA compaction and access. Current computational methods have focused on the analysis of nucleosome occupancy and the positioning of well-positioned nucleosomes.
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