Dataset Information

Identifying functional miRNA-mRNA regulatory modules with correspondence latent dirichlet allocation.

ABSTRACT: MicroRNAs (miRNAs) are small non-coding RNAs that cause mRNA degradation and translational inhibition. They are important regulators of development and cellular homeostasis through their control of diverse processes. Recently, great efforts have been made to elucidate their regulatory mechanism, but the functions of most miRNAs and their precise regulatory mechanisms remain elusive. With more and more matched expression profiles of miRNAs and mRNAs having been made available, it is of great interest to utilize both expression profiles to discover the functional regulatory networks of miRNAs and their target mRNAs for potential biological processes that they may participate in.We present a probabilistic graphical model to discover functional miRNA regulatory modules at potential biological levels by integrating heterogeneous datasets, including expression profiles of miRNAs and mRNAs, with or without the prior target binding information. We applied this model to a mouse mammary dataset. It effectively captured several biological process specific modules involving miRNAs and their target mRNAs. Furthermore, without using prior target binding information, the identified miRNAs and mRNAs in each module show a large proportion of overlap with predicted miRNA target relationships, suggesting that expression profiles are crucial for both target identification and discovery of regulatory modules.

SUBMITTER: Liu B

PROVIDER: S-EPMC2995118 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Identifying functional miRNA-mRNA regulatory modules with correspondence latent dirichlet allocation.

Liu Bing B Liu Lin L Tsykin Anna A Goodall Gregory J GJ Green Jeffrey E JE Zhu Min M Kim Chang Hee CH Li Jiuyong J

Bioinformatics (Oxford, England) 20101017 24

<h4>Motivation</h4>MicroRNAs (miRNAs) are small non-coding RNAs that cause mRNA degradation and translational inhibition. They are important regulators of development and cellular homeostasis through their control of diverse processes. Recently, great efforts have been made to elucidate their regulatory mechanism, but the functions of most miRNAs and their precise regulatory mechanisms remain elusive. With more and more matched expression profiles of miRNAs and mRNAs having been made available, ...[more]

PMID: 20956247

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Project description:Interactions between stressed organisms and their microbiome environments may provide new routes for understanding and controlling biological systems. However, microbiomes are a form of high-dimensional data, with thousands of taxa present in any given sample, which makes untangling the interaction between an organism and its microbial environment a challenge. Here we apply Latent Dirichlet Allocation (LDA), a technique for language modeling, which decomposes the microbial communities into a set of topics (non-mutually-exclusive sub-communities) that compactly represent the distribution of full communities. LDA provides a lens into the microbiome at broad and fine-grained taxonomic levels, which we show on two datasets. In the first dataset, from the literature, we show how LDA topics succinctly recapitulate many results from a previous study on diseased coral species. We then apply LDA to a new dataset of maize soil microbiomes under drought, and find a large number of significant associations between the microbiome topics and plant traits as well as associations between the microbiome and the experimental factors, e.g. watering level. This yields new information on the plant-microbial interactions in maize and shows that LDA technique is useful for studying the coupling between microbiomes and stressed organisms. Author summary Host-microbe interaction may be an important factor determining the performance and survival of an organism under stress. Understanding how microbiomes influence organisms under stress is a challenging new area of research because microbiomes are complex with the potential for complex responses and adaptations to stress that influence their interactions with the other stressed organisms. We show the use of LDA, a data-science technique in the context of environmental microbial datasets to break down the thousands of microbes present in samples into groups called topics; each topic is a group of organisms that occur together as a common pattern in the dataset. We show that this technique, combined with correlation analyses, provides a way to view a very large set of microbes in a sample as a smaller, more manageable set of communities of microbial taxa related to experimental conditions and plant traits. In this way, LDA helps to unravel complex interactions between organisms and their microbiome, which could help to better predict the behavior of real-world ecological systems, and perhaps support them through many challenges brought by changing climate and environment.

Project description:BackgroundMicroRNA (miRNA) sponges with multiple tandem miRNA binding sequences can sequester miRNAs from their endogenous target mRNAs. Therefore, miRNA sponge acting as a decoy is extremely important for long-term loss-of-function studies both in vivo and in silico. Recently, a growing number of in silico methods have been used as an effective technique to generate hypotheses for in vivo methods for studying the biological functions and regulatory mechanisms of miRNA sponges. However, most existing in silico methods only focus on studying miRNA sponge interactions or networks in cancer, the module-level properties of miRNA sponges in cancer is still largely unknown.ResultsWe propose a novel in silico method, called miRSM (miRNA Sponge Module) to infer miRNA sponge modules in breast cancer. We apply miRSM to the breast invasive carcinoma (BRCA) dataset provided by The Cancer Genome Altas (TCGA), and make functional validation of the computational results. We discover that most miRNA sponge interactions are module-conserved across two modules, and a minority of miRNA sponge interactions are module-specific, existing only in a single module. Through functional annotation and differential expression analysis, we also find that the modules discovered using miRSM are functional miRNA sponge modules associated with BRCA. Moreover, the module-specific miRNA sponge interactions among miRNA sponge modules may be involved in the progression and development of BRCA. Our experimental results show that miRSM is comparable to the benchmark methods in recovering experimentally confirmed miRNA sponge interactions, and miRSM outperforms the benchmark methods in identifying interactions that are related to breast cancer.ConclusionsAltogether, the functional validation results demonstrate that miRSM is a promising method to identify miRNA sponge modules and interactions, and may provide new insights for understanding the roles of miRNA sponges in cancer progression and development.

Dataset Information

Identifying functional miRNA-mRNA regulatory modules with correspondence latent dirichlet allocation.

Publications

Identifying functional miRNA-mRNA regulatory modules with correspondence latent dirichlet allocation.

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