Dataset Information

Interpreting genomic data via entropic dissection.

ABSTRACT: Since the emergence of high-throughput genome sequencing platforms and more recently the next-generation platforms, the genome databases are growing at an astronomical rate. Tremendous efforts have been invested in recent years in understanding intriguing complexities beneath the vast ocean of genomic data. This is apparent in the spurt of computational methods for interpreting these data in the past few years. Genomic data interpretation is notoriously difficult, partly owing to the inherent heterogeneities appearing at different scales. Methods developed to interpret these data often suffer from their inability to adequately measure the underlying heterogeneities and thus lead to confounding results. Here, we present an information entropy-based approach that unravels the distinctive patterns underlying genomic data efficiently and thus is applicable in addressing a variety of biological problems. We show the robustness and consistency of the proposed methodology in addressing three different biological problems of significance--identification of alien DNAs in bacterial genomes, detection of structural variants in cancer cell lines and alignment-free genome comparison.

SUBMITTER: Azad RK

PROVIDER: S-EPMC3592408 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Interpreting genomic data via entropic dissection.

Azad Rajeev K RK Li Jing J

Nucleic acids research 20121003 1

Since the emergence of high-throughput genome sequencing platforms and more recently the next-generation platforms, the genome databases are growing at an astronomical rate. Tremendous efforts have been invested in recent years in understanding intriguing complexities beneath the vast ocean of genomic data. This is apparent in the spurt of computational methods for interpreting these data in the past few years. Genomic data interpretation is notoriously difficult, partly owing to the inherent he ...[more]

PMID: 23036836

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Project description:BACKGROUND: There are many methods for analyzing microarray data that group together genes having similar patterns of expression over all conditions tested. However, in many instances the biologically important goal is to identify relatively small sets of genes that share coherent expression across only some conditions, rather than all or most conditions as required in traditional clustering; e.g. genes that are highly up-regulated and/or down-regulated similarly across only a subset of conditions. Equally important is the need to learn which conditions are the decisive ones in forming such gene sets of interest, and how they relate to diverse conditional covariates, such as disease diagnosis or prognosis. RESULTS: We present a method for automatically identifying such candidate sets of biologically relevant genes using a combination of principal components analysis and information theoretic metrics. To enable easy use of our methods, we have developed a data analysis package that facilitates visualization and subsequent data mining of the independent sources of significant variation present in gene microarray expression datasets (or in any other similarly structured high-dimensional dataset). We applied these tools to two public datasets, and highlight sets of genes most affected by specific subsets of conditions (e.g. tissues, treatments, samples, etc.). Statistically significant associations for highlighted gene sets were shown via global analysis for Gene Ontology term enrichment. Together with covariate associations, the tool provides a basis for building testable hypotheses about the biological or experimental causes of observed variation. CONCLUSION: We provide an unsupervised data mining technique for diverse microarray expression datasets that is distinct from major methods now in routine use. In test uses, this method, based on publicly available gene annotations, appears to identify numerous sets of biologically relevant genes. It has proven especially valuable in instances where there are many diverse conditions (10's to hundreds of different tissues or cell types), a situation in which many clustering and ordering algorithms become problematic. This approach also shows promise in other topic domains such as multi-spectral imaging datasets.

Dataset Information

Interpreting genomic data via entropic dissection.

Publications

Interpreting genomic data via entropic dissection.

Similar Datasets

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