Dataset Information

MeShClust: an intelligent tool for clustering DNA sequences.

ABSTRACT: Sequence clustering is a fundamental step in analyzing DNA sequences. Widely-used software tools for sequence clustering utilize greedy approaches that are not guaranteed to produce the best results. These tools are sensitive to one parameter that determines the similarity among sequences in a cluster. Often times, a biologist may not know the exact sequence similarity. Therefore, clusters produced by these tools do not likely match the real clusters comprising the data if the provided parameter is inaccurate. To overcome this limitation, we adapted the mean shift algorithm, an unsupervised machine-learning algorithm, which has been used successfully thousands of times in fields such as image processing and computer vision. The theory behind the mean shift algorithm, unlike the greedy approaches, guarantees convergence to the modes, e.g. cluster centers. Here we describe the first application of the mean shift algorithm to clustering DNA sequences. MeShClust is one of few applications of the mean shift algorithm in bioinformatics. Further, we applied supervised machine learning to predict the identity score produced by global alignment using alignment-free methods. We demonstrate MeShClust's ability to cluster DNA sequences with high accuracy even when the sequence similarity parameter provided by the user is not very accurate.

SUBMITTER: James BT

PROVIDER: S-EPMC6101578 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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MeShClust: an intelligent tool for clustering DNA sequences.

James Benjamin T BT Luczak Brian B BB Girgis Hani Z HZ

Nucleic acids research 20180801 14

Sequence clustering is a fundamental step in analyzing DNA sequences. Widely-used software tools for sequence clustering utilize greedy approaches that are not guaranteed to produce the best results. These tools are sensitive to one parameter that determines the similarity among sequences in a cluster. Often times, a biologist may not know the exact sequence similarity. Therefore, clusters produced by these tools do not likely match the real clusters comprising the data if the provided parameter ...[more]

PMID: 29718317

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Project description:BackgroundHistone modifications play important roles in gene regulation, heredity, imprinting, and many human diseases. The histone code is complex and consists of more than 100 marks. Therefore, biologists need computational tools to characterize general signatures representing the distributions of tens of chromatin marks around thousands of regions.ResultsTo this end, we developed a software tool, HebbPlot, which utilizes a Hebbian neural network in learning a general chromatin signature from regions with a common function. Hebbian networks can learn the associations between tens of marks and thousands of regions. HebbPlot presents a signature as a digital image, which can be easily interpreted. Moreover, signatures produced by HebbPlot can be compared quantitatively. We validated HebbPlot in six case studies. The results of these case studies are novel or validating results already reported in the literature, indicating the accuracy of HebbPlot. Our results indicate that promoters have a directional chromatin signature; several marks tend to stretch downstream or upstream. H3K4me3 and H3K79me2 have clear directional distributions around active promoters. In addition, the signatures of high- and low-CpG promoters are different; H3K4me3, H3K9ac, and H3K27ac are the most different marks. When we studied the signatures of enhancers active in eight tissues, we observed that these signatures are similar, but not identical. Further, we identified some histone modifications - H3K36me3, H3K79me1, H3K79me2, and H4K8ac - that are associated with coding regions of active genes. Other marks - H4K12ac, H3K14ac, H3K27me3, and H2AK5ac - were found to be weakly associated with coding regions of inactive genes.ConclusionsThis study resulted in a novel software tool, HebbPlot, for learning and visualizing the chromatin signature of a genetic element. Using HebbPlot, we produced a visual catalog of the signatures of multiple genetic elements in 57 cell types available through the Roadmap Epigenomics Project. Furthermore, we made a progress toward a functional catalog consisting of 22 histone marks. In sum, HebbPlot is applicable to a wide array of studies, facilitating the deciphering of the histone code.

Dataset Information

MeShClust: an intelligent tool for clustering DNA sequences.

Publications

MeShClust: an intelligent tool for clustering DNA sequences.

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