Publications by authors named "Thuc Duy Le"

Article Synopsis
  • RNA-sequencing technology aids in understanding miRNA regulation in diseases like cancer, but existing methods often struggle with sample-specific inference due to sample heterogeneity.
  • A new framework called Scan has been developed, integrating 27 network inference methods to effectively analyze tissue and cell-specific miRNA regulation from both bulk and single-cell RNA-sequencing data.
  • Scan enhances prediction accuracy by using prior miRNA target information and allows the construction of correlation networks, ultimately improving our understanding of miRNA regulation on an individual sample level.
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  • Acute myeloid leukemia (AML) displays a variety of genetic mutations and DNA methylation changes, with a study focusing on FLT3 mutant versus wild-type cases to explore the causes behind differentiation blockage in AML.
  • The analysis utilized TCGA-LAML data, employing tools like cBioPortal and ChAMP to assess gene expression and methylation, revealing significant correlations and biological processes associated with altered gene activity in AML.
  • Key findings included a global hypo-methylated status in certain genes linked to critical transcription pathways, particularly the homeobox gene superfamily, and the overexpression of WT1 in FLT3 mutants, suggesting a mechanism for regulating methylation and advancing understanding of AML's biology for potential therapy development.
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Complex multi-omics effects drive the clustering of cardiometabolic risk factors, underscoring the imperative to comprehend how individual and combined omics shape phenotypic variation. Our study partitions phenotypic variance in metabolic syndrome (MetS), blood glucose (GLU), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and blood pressure through genome, transcriptome, metabolome, and exposome (i.e.

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  • * The SCOM framework identifies and analyzes the competition among ncRNAs, highlighting that malignant tumors commonly share key ncRNAs rather than specific interactions, including their roles in drug resistance and immune regulation.
  • * SCOM and its accompanying web-based database, SCOMdb, serve as valuable tools for researchers to explore ncRNA regulation and identify potential biomarkers for cancer diagnostics and prognostics.
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  • Instrumental variable (IV) methods are crucial for understanding causal effects from observational data, especially in the presence of hidden confounders, but selecting a valid IV is essential to avoid bias.
  • This article introduces a data-driven algorithm designed to identify valid IVs by leveraging partial ancestral graphs (PAGs) and determining candidate ancestral IVs (AIVs) along with their conditioning sets.
  • Experimental results demonstrate that this new IV discovery algorithm produces more accurate causal effect estimates than existing state-of-the-art IV methods when applied to both synthetic and real-world datasets.
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Summary: MicroRNA (miRNA) sponges influence the capability of miRNA-mediated gene silencing by competing for shared miRNA response elements and play significant roles in many physiological and pathological processes. It has been proved that computational or dry-lab approaches are useful to guide wet-lab experiments for uncovering miRNA sponge regulation. However, all of the existing tools only allow the analysis of miRNA sponge regulation regarding a group of samples, rather than the miRNA sponge regulation unique to individual samples.

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The traditional way for discovering genes which drive cancer (namely cancer drivers) neglects the dynamic information of cancer development, even though it is well known that cancer progresses dynamically. To enhance cancer driver discovery, we expand cancer driver concept to dynamic cancer driver as a gene driving one or more bio-pathological transitions during cancer progression. Our method refers to the fact that cancer should not be considered as a single process but a compendium of altered biological processes causing the disease to develop over time.

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Causal effect estimation from observational data is a crucial but challenging task. Currently, only a limited number of data-driven causal effect estimation methods are available. These methods either provide only a bound estimation of causal effects of treatment on the outcome or generate a unique estimation of the causal effect but making strong assumptions on data and having low efficiency.

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Background: Existing computational methods for studying miRNA regulation are mostly based on bulk miRNA and mRNA expression data. However, bulk data only allows the analysis of miRNA regulation regarding a group of cells, rather than the miRNA regulation unique to individual cells. Recent advance in single-cell miRNA-mRNA co-sequencing technology has opened a way for investigating miRNA regulation at single-cell level.

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Article Synopsis
  • The article explores the complex interactions of competing endogenous RNA (ceRNA) and microRNA (miRNA) sponges, which are groups that compete with each other to influence biological processes, particularly in cancer.* -
  • It reviews current methods and databases for identifying miRNA sponge modules, highlighting their significance in understanding cancer mechanisms and the competitive effects of these interactions.* -
  • The authors evaluate the effectiveness of these methods using pan-cancer datasets and discuss future challenges and directions for improving the computational inference of miRNA sponge modules.*
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The classification of clinical samples based on gene expression data is an important part of precision medicine. In this manuscript, we show how transforming gene expression data into a set of personalized (sample-specific) networks can allow us to harness existing graph-based methods to improve classifier performance. Existing approaches to personalized gene networks have the limitation that they depend on other samples in the data and must get re-computed whenever a new sample is introduced.

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Identifying the genes responsible for driving cancer is of critical importance for directing treatment. Accordingly, multiple computational tools have been developed to facilitate this task. Due to the different methods employed by these tools, different data considered by the tools, and the rapidly evolving nature of the field, the selection of an appropriate tool for cancer driver discovery is not straightforward.

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In molecular biology, microRNA (miRNA) sponges are RNA transcripts which compete with other RNA transcripts for binding with miRNAs. Research has shown that miRNA sponges have a fundamental impact on tissue development and disease progression. Generally, to achieve a specific biological function, miRNA sponges tend to form modules or communities in a biological system.

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Summary: The development of new drugs is costly, time consuming and often accompanied with safety issues. Drug repurposing can avoid the expensive and lengthy process of drug development by finding new uses for already approved drugs. In order to repurpose drugs effectively, it is useful to know which proteins are targeted by which drugs.

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Motivation: microRNAs (miRNAs) are important gene regulators and they are involved in many biological processes, including cancer progression. Therefore, correctly identifying miRNA-mRNA interactions is a crucial task. To this end, a huge number of computational methods has been developed, but they mainly use the data at one snapshot and ignore the dynamics of a biological process.

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Until now, existing methods for identifying lncRNA related miRNA sponge modules mainly rely on lncRNA related miRNA sponge interaction networks, which may not provide a full picture of miRNA sponging activities in biological conditions. Hence there is a strong need of new computational methods to identify lncRNA related miRNA sponge modules. In this work, we propose a framework, LMSM, to identify LncRNA related MiRNA Sponge Modules from heterogeneous data.

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After publication of this supplement article [1], it was brought to our attention that the Fig. 3 was incorrect. The correct Fig.

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Background: Studying multiple microRNAs (miRNAs) synergism in gene regulation could help to understand the regulatory mechanisms of complicated human diseases caused by miRNAs. Several existing methods have been presented to infer miRNA synergism. Most of the current methods assume that miRNAs with shared targets at the sequence level are working synergistically.

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Background: A microRNA (miRNA) sponge is an RNA molecule with multiple tandem miRNA response elements that can sequester miRNAs from their target mRNAs. Despite growing appreciation of the importance of miRNA sponges, our knowledge of their complex functions remains limited. Moreover, there is still a lack of miRNA sponge research tools that help researchers to quickly compare their proposed methods with other methods, apply existing methods to new datasets, or select appropriate methods for assisting in subsequent experimental design.

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Multi-Source Causal Feature Selection.

IEEE Trans Pattern Anal Mach Intell

September 2020

Causal feature selection has attracted much attention in recent years, as the causal features selected imply the causal mechanism related to the class attribute, leading to more reliable prediction models built using them. Currently there is a need of developing multi-source feature selection methods, since in many applications data for studying the same problem has been collected from various sources, such as multiple gene expression datasets obtained from different experiments for studying the causes of the same disease. However, the state-of-the-art causal feature selection methods generally tackle a single dataset, and a direct application of the methods to multiple datasets will result in unreliable results as the datasets may have different distributions.

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Background: miRBase is the primary repository for published miRNA sequence and annotation data, and serves as the "go-to" place for miRNA research. However, the definition and annotation of miRNAs have been changed significantly across different versions of miRBase. The changes cause inconsistency in miRNA related data between different databases and articles published at different times.

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Background: Estimating heterogeneous treatment effect is a fundamental problem in biological and medical applications. Recently, several recursive partitioning methods have been proposed to identify the subgroups that respond differently towards a treatment, and they rely on a fitness criterion to minimize the error between the estimated treatment effects and the unobservable ground truths.

Results: In this paper, we propose that a heterogeneity criterion, which maximizes the differences of treatment effects among the subgroups, also needs to be considered.

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Motivation: MicroRNAs (miRNAs) are small non-coding RNAs with the length of ∼22 nucleotides. miRNAs are involved in many biological processes including cancers. Recent studies show that long non-coding RNAs (lncRNAs) are emerging as miRNA sponges, playing important roles in cancer physiology and development.

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It is known that noncoding RNAs (ncRNAs) cover ∼98% of the transcriptome, but do not encode proteins. Among ncRNAs, long noncoding RNAs (lncRNAs) are a large and diverse class of RNA molecules, and are thought to be a gold mine of potential oncogenes, anti-oncogenes and new biomarkers. Although only a minority of lncRNAs is functionally characterized, it is clear that they are important regulators to modulate gene expression and involve in many biological functions.

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Summary: Identifying molecular cancer subtypes from multi-omics data is an important step in the personalized medicine. We introduce CancerSubtypes, an R package for identifying cancer subtypes using multi-omics data, including gene expression, miRNA expression and DNA methylation data. CancerSubtypes integrates four main computational methods which are highly cited for cancer subtype identification and provides a standardized framework for data pre-processing, feature selection, and result follow-up analyses, including results computing, biology validation and visualization.

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