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      Subtype-WESLR: identifying cancer subtype with weighted ensemble sparse latent representation of multi-view data

      1 , 1 , 1
      Briefings in Bioinformatics
      Oxford University Press (OUP)

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          Abstract

          The discovery of cancer subtypes has become much-researched topic in oncology. Dividing cancer patients into subtypes can provide personalized treatments for heterogeneous patients. High-throughput technologies provide multiple omics data for cancer subtyping. Integration of multi-view data is used to identify cancer subtypes in many computational methods, which obtain different subtypes for the same cancer, even using the same multi-omics data. To a certain extent, these subtypes from distinct methods are related, which may have certain guiding significance for cancer subtyping. It is a challenge to effectively utilize the valuable information of distinct subtypes to produce more accurate and reliable subtypes. A weighted ensemble sparse latent representation (subtype-WESLR) is proposed to detect cancer subtypes on heterogeneous omics data. Using a weighted ensemble strategy to fuse base clustering obtained by distinct methods as prior knowledge, subtype-WESLR projects each sample feature profile from each data type to a common latent subspace while maintaining the local structure of the original sample feature space and consistency with the weighted ensemble and optimizes the common subspace by an iterative method to identify cancer subtypes. We conduct experiments on various synthetic datasets and eight public multi-view datasets from The Cancer Genome Atlas. The results demonstrate that subtype-WESLR is better than competing methods by utilizing the integration of base clustering of exist methods for more precise subtypes.

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          Most cited references41

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          Is Open Access

          edgeR: a Bioconductor package for differential expression analysis of digital gene expression data

          Summary: It is expected that emerging digital gene expression (DGE) technologies will overtake microarray technologies in the near future for many functional genomics applications. One of the fundamental data analysis tasks, especially for gene expression studies, involves determining whether there is evidence that counts for a transcript or exon are significantly different across experimental conditions. edgeR is a Bioconductor software package for examining differential expression of replicated count data. An overdispersed Poisson model is used to account for both biological and technical variability. Empirical Bayes methods are used to moderate the degree of overdispersion across transcripts, improving the reliability of inference. The methodology can be used even with the most minimal levels of replication, provided at least one phenotype or experimental condition is replicated. The software may have other applications beyond sequencing data, such as proteome peptide count data. Availability: The package is freely available under the LGPL licence from the Bioconductor web site (http://bioconductor.org). Contact: mrobinson@wehi.edu.au
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            COMPREHENSIVE MOLECULAR CHARACTERIZATION OF CLEAR CELL RENAL CELL CARCINOMA

            Genetic changes underlying clear cell renal cell carcinoma (ccRCC) include alterations in genes controlling cellular oxygen sensing (e.g. VHL) and the maintenance of chromatin states (e.g. PBRM1). We surveyed more than 400 tumors using different genomic platforms and identified 19 significantly mutated genes. The PI3K/Akt pathway was recurrently mutated, suggesting this pathway as a potential therapeutic target. Widespread DNA hypomethylation was associated with mutation of the H3K36 methyltransferase SETD2, and integrative analysis suggested that mutations involving the SWI/SNF chromatin remodeling complex (PBRM1, ARID1A, SMARCA4) could have far-reaching effects on other pathways. Aggressive cancers demonstrated evidence of a metabolic shift, involving down-regulation of genes involved in the TCA cycle, decreased AMPK and PTEN protein levels, up-regulation of the pentose phosphate pathway and the glutamine transporter genes, increased acetyl-CoA carboxylase protein, and altered promoter methylation of miR-21 and GRB10. Remodeling cellular metabolism thus constitutes a recurrent pattern in ccRCC that correlates with tumor stage and severity and offers new views on the opportunities for disease treatment.
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              DIANA-miRPath v3.0: deciphering microRNA function with experimental support

              The functional characterization of miRNAs is still an open challenge. Here, we present DIANA-miRPath v3.0 (http://www.microrna.gr/miRPathv3) an online software suite dedicated to the assessment of miRNA regulatory roles and the identification of controlled pathways. The new miRPath web server renders possible the functional annotation of one or more miRNAs using standard (hypergeometric distributions), unbiased empirical distributions and/or meta-analysis statistics. DIANA-miRPath v3.0 database and functionality have been significantly extended to support all analyses for KEGG molecular pathways, as well as multiple slices of Gene Ontology (GO) in seven species (Homo sapiens, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Caenorhabditis elegans, Gallus gallus and Danio rerio). Importantly, more than 600 000 experimentally supported miRNA targets from DIANA-TarBase v7.0 have been incorporated into the new schema. Users of DIANA-miRPath v3.0 can harness this wealth of information and substitute or combine the available in silico predicted targets from DIANA-microT-CDS and/or TargetScan v6.2 with high quality experimentally supported interactions. A unique feature of DIANA-miRPath v3.0 is its redesigned Reverse Search module, which enables users to identify and visualize miRNAs significantly controlling selected pathways or belonging to specific GO categories based on in silico or experimental data. DIANA-miRPath v3.0 is freely available to all users without any login requirement.
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                Author and article information

                Journal
                Briefings in Bioinformatics
                Oxford University Press (OUP)
                1467-5463
                1477-4054
                January 2022
                January 17 2022
                January 2022
                January 17 2022
                October 05 2021
                : 23
                : 1
                Affiliations
                [1 ]Intelligent Data Center, School of Mathematics, Sun Yat-Sen University, Guangzhou, 510275, China
                Article
                10.1093/bib/bbab398
                34607358
                cb451ddb-1f43-45b7-be45-913fbce746c6
                © 2021

                https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model

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