Dataset Information

CAMUR: Knowledge extraction from RNA-seq cancer data through equivalent classification rules.

ABSTRACT: Nowadays, knowledge extraction methods from Next Generation Sequencing data are highly requested. In this work, we focus on RNA-seq gene expression analysis and specifically on case-control studies with rule-based supervised classification algorithms that build a model able to discriminate cases from controls. State of the art algorithms compute a single classification model that contains few features (genes). On the contrary, our goal is to elicit a higher amount of knowledge by computing many classification models, and therefore to identify most of the genes related to the predicted class.We propose CAMUR, a new method that extracts multiple and equivalent classification models. CAMUR iteratively computes a rule-based classification model, calculates the power set of the genes present in the rules, iteratively eliminates those combinations from the data set, and performs again the classification procedure until a stopping criterion is verified. CAMUR includes an ad-hoc knowledge repository (database) and a querying tool.We analyze three different types of RNA-seq data sets (Breast, Head and Neck, and Stomach Cancer) from The Cancer Genome Atlas (TCGA) and we validate CAMUR and its models also on non-TCGA data. Our experimental results show the efficacy of CAMUR: we obtain several reliable equivalent classification models, from which the most frequent genes, their relationships, and the relation with a particular cancer are deduced.dmb.iasi.cnr.it/camur.phpemanuel@iasi.cnr.itSupplementary data are available at Bioinformatics online.

SUBMITTER: Cestarelli V

PROVIDER: S-EPMC4795614 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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CAMUR: Knowledge extraction from RNA-seq cancer data through equivalent classification rules.

Cestarelli Valerio V Fiscon Giulia G Felici Giovanni G Bertolazzi Paola P Weitschek Emanuel E

Bioinformatics (Oxford, England) 20151030 5

<h4>Motivation</h4>Nowadays, knowledge extraction methods from Next Generation Sequencing data are highly requested. In this work, we focus on RNA-seq gene expression analysis and specifically on case-control studies with rule-based supervised classification algorithms that build a model able to discriminate cases from controls. State of the art algorithms compute a single classification model that contains few features (genes). On the contrary, our goal is to elicit a higher amount of knowledge ...[more]

PMID: 26519501

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Project description:Background:In the Next Generation Sequencing (NGS) era a large amount of biological data is being sequenced, analyzed, and stored in many public databases, whose interoperability is often required to allow an enhanced accessibility. The combination of heterogeneous NGS genomic data is an open challenge: the analysis of data from different experiments is a fundamental practice for the study of diseases. In this work, we propose to combine DNA methylation and RNA sequencing NGS experiments at gene level for supervised knowledge extraction in cancer. Methods:We retrieve DNA methylation and RNA sequencing datasets from The Cancer Genome Atlas (TCGA), focusing on the Breast Invasive Carcinoma (BRCA), the Thyroid Carcinoma (THCA), and the Kidney Renal Papillary Cell Carcinoma (KIRP). We combine the RNA sequencing gene expression values with the gene methylation quantity, as a new measure that we define for representing the methylation quantity associated to a gene. Additionally, we propose to analyze the combined data through tree- and rule-based classification algorithms (C4.5, Random Forest, RIPPER, and CAMUR). Results:We extract more than 15,000 classification models (composed of gene sets), which allow to distinguish the tumoral samples from the normal ones with an average accuracy of 95%. From the integrated experiments we obtain about 5000 classification models that consider both the gene measures related to the RNA sequencing and the DNA methylation experiments. Conclusions:We compare the sets of genes obtained from the classifications on RNA sequencing and DNA methylation data with the genes obtained from the integration of the two experiments. The comparison results in several genes that are in common among the single experiments and the integrated ones (733 for BRCA, 35 for KIRP, and 861 for THCA) and 509 genes that are in common among the different experiments. Finally, we investigate the possible relationships among the different analyzed tumors by extracting a core set of 13 genes that appear in all tumors. A preliminary functional analysis confirms the relation of part of those genes (5 out of 13 and 279 out of 509) with cancer, suggesting to focus further studies on the new individuated ones.

Project description:RNA sequencing (RNA-Seq) is a powerful technique for the gene-expression profiling of organisms that uses the capabilities of next-generation sequencing technologies. Developing gene-expression-based classification algorithms is an emerging powerful method for diagnosis, disease classification and monitoring at molecular level, as well as providing potential markers of diseases. Most of the statistical methods proposed for the classification of gene-expression data are either based on a continuous scale (eg. microarray data) or require a normal distribution assumption. Hence, these methods cannot be directly applied to RNA-Seq data since they violate both data structure and distributional assumptions. However, it is possible to apply these algorithms with appropriate modifications to RNA-Seq data. One way is to develop count-based classifiers, such as Poisson linear discriminant analysis and negative binomial linear discriminant analysis. Another way is to bring the data closer to microarrays and apply microarray-based classifiers. In this study, we compared several classifiers including PLDA with and without power transformation, NBLDA, single SVM, bagging SVM (bagSVM), classification and regression trees (CART), and random forests (RF). We also examined the effect of several parameters such as overdispersion, sample size, number of genes, number of classes, differential-expression rate, and the transformation method on model performances. A comprehensive simulation study is conducted and the results are compared with the results of two miRNA and two mRNA experimental datasets. The results revealed that increasing the sample size, differential-expression rate and decreasing the dispersion parameter and number of groups lead to an increase in classification accuracy. Similar with differential-expression studies, the classification of RNA-Seq data requires careful attention when handling data overdispersion. We conclude that, as a count-based classifier, the power transformed PLDA and, as a microarray-based classifier, vst or rlog transformed RF and SVM classifiers may be a good choice for classification. An R/BIOCONDUCTOR package, MLSeq, is freely available at https://www.bioconductor.org/packages/release/bioc/html/MLSeq.html.

Dataset Information

CAMUR: Knowledge extraction from RNA-seq cancer data through equivalent classification rules.

Publications

CAMUR: Knowledge extraction from RNA-seq cancer data through equivalent classification rules.

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