Dataset Information

Data mining of functional RNA structures in genomic sequences.

ABSTRACT: The normal functions of genomes depend on the precise expression of messenger RNAs and noncoding RNAs (ncRNAs) such as transfer RNAs and microRNAs in eukaryotes. These ncRNAs and functional RNA structures (FRSs) act as regulators or response elements for cellular factors and participate in transcription, posttranscriptional processing, and translation. Knowledge discovery of these FRSs in huge DNA/RNA sequence databases is a very important step to reach our goal of going from genomic sequence data to biological knowledge for understanding RNA-based regulation. Analyses of a large number of FRSs have indicated that the FRS can be well characterized by some quantitative measures such as significance and well-ordered scores of the local segment. Various data mining tools have been developed and successfully applied to FRS discovery in genomic sequence databases. Here, we summarize our efforts in the computational discovery of structured features of ncRNAs and FRSs within complex genomes by EDscan and SigED.

SUBMITTER: Le SY

PROVIDER: S-EPMC8301259 | biostudies-literature | 2011 Jan-Feb

REPOSITORIES: biostudies-literature

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Data mining of functional RNA structures in genomic sequences.

Le Shu-Yun SY Shapiro Bruce A BA

Wiley interdisciplinary reviews. Data mining and knowledge discovery 20110110 1

The normal functions of genomes depend on the precise expression of messenger RNAs and noncoding RNAs (ncRNAs) such as transfer RNAs and microRNAs in eukaryotes. These ncRNAs and functional RNA structures (FRSs) act as regulators or response elements for cellular factors and participate in transcription, posttranscriptional processing, and translation. Knowledge discovery of these FRSs in huge DNA/RNA sequence databases is a very important step to reach our goal of going from genomic sequence da ...[more]

PMID: 34306322

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Project description:BackgroundThe highly dimensional data produced by functional genomic (FG) studies makes it difficult to visualize relationships between gene products and experimental conditions (i.e., assays). Although dimensionality reduction methods such as principal component analysis (PCA) have been very useful, their application to identify assay-specific signatures has been limited by the lack of appropriate methodologies. This article proposes a new and powerful PCA-based method for the identification of assay-specific gene signatures in FG studies.ResultsThe proposed method (PM) is unique for several reasons. First, it is the only one, to our knowledge, that uses gene contribution, a product of the loading and expression level, to obtain assay signatures. The PM develops and exploits two types of assay-specific contribution plots, which are new to the application of PCA in the FG area. The first type plots the assay-specific gene contribution against the given order of the genes and reveals variations in distribution between assay-specific gene signatures as well as outliers within assay groups indicating the degree of importance of the most dominant genes. The second type plots the contribution of each gene in ascending or descending order against a constantly increasing index. This type of plots reveals assay-specific gene signatures defined by the inflection points in the curve. In addition, sharp regions within the signature define the genes that contribute the most to the signature. We proposed and used the curvature as an appropriate metric to characterize these sharp regions, thus identifying the subset of genes contributing the most to the signature. Finally, the PM uses the full dataset to determine the final gene signature, thus eliminating the chance of gene exclusion by poor screening in earlier steps. The strengths of the PM are demonstrated using a simulation study, and two studies of real DNA microarray data--a study of classification of human tissue samples and a study of E. coli cultures with different medium formulations.ConclusionWe have developed a PCA-based method that effectively identifies assay-specific signatures in ranked groups of genes from the full data set in a more efficient and simplistic procedure than current approaches. Although this work demonstrates the ability of the PM to identify assay-specific signatures in DNA microarray experiments, this approach could be useful in areas such as proteomics and metabolomics.

Project description:Viruses of microbes impact all ecosystems where microbes drive key energy and substrate transformations including the oceans, humans and industrial fermenters. However, despite this recognized importance, our understanding of viral diversity and impacts remains limited by too few model systems and reference genomes. One way to fill these gaps in our knowledge of viral diversity is through the detection of viral signal in microbial genomic data. While multiple approaches have been developed and applied for the detection of prophages (viral genomes integrated in a microbial genome), new types of microbial genomic data are emerging that are more fragmented and larger scale, such as Single-cell Amplified Genomes (SAGs) of uncultivated organisms or genomic fragments assembled from metagenomic sequencing. Here, we present VirSorter, a tool designed to detect viral signal in these different types of microbial sequence data in both a reference-dependent and reference-independent manner, leveraging probabilistic models and extensive virome data to maximize detection of novel viruses. Performance testing shows that VirSorter's prophage prediction capability compares to that of available prophage predictors for complete genomes, but is superior in predicting viral sequences outside of a host genome (i.e., from extrachromosomal prophages, lytic infections, or partially assembled prophages). Furthermore, VirSorter outperforms existing tools for fragmented genomic and metagenomic datasets, and can identify viral signal in assembled sequence (contigs) as short as 3kb, while providing near-perfect identification (>95% Recall and 100% Precision) on contigs of at least 10kb. Because VirSorter scales to large datasets, it can also be used in "reverse" to more confidently identify viral sequence in viral metagenomes by sorting away cellular DNA whether derived from gene transfer agents, generalized transduction or contamination. Finally, VirSorter is made available through the iPlant Cyberinfrastructure that provides a web-based user interface interconnected with the required computing resources. VirSorter thus complements existing prophage prediction softwares to better leverage fragmented, SAG and metagenomic datasets in a way that will scale to modern sequencing. Given these features, VirSorter should enable the discovery of new viruses in microbial datasets, and further our understanding of uncultivated viral communities across diverse ecosystems.

Dataset Information

Data mining of functional RNA structures in genomic sequences.

Publications

Data mining of functional RNA structures in genomic sequences.

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