title: Dissecting the biological relationship between TCGA miRNA and mRNA sequencing data using MMiRNA-Viewer.
abstract: BACKGROUND
  MicroRNAs (miRNA) are short nucleotides that interact with their target genes through 3' untranslated regions (UTRs). The Cancer Genome Atlas (TCGA) harbors an increasing amount of cancer genome data for both tumor and normal samples. However, there are few visualization tools focusing on concurrently displaying important relationships and attributes between miRNAs and mRNAs of both cancer tumor and normal samples. Moreover, a deep investigation of miRNA-mRNA target and biological relationships across multiple cancer types by integrating web-based analysis has not been thoroughly conducted.
  
  
  RESULTS
  We developed an interactive visualization tool called MMiRNA-Viewer that can concurrently present the co-relationships of expression between miRNA-mRNA pairs of both tumor and normal samples into a single graph. The input file of MMiRNA-Viewer contains the expression information including fold changes between normal and tumor samples for mRNAs and miRNAs, the correlation between mRNA and miRNA, and the predicted target relationship by a number of databases. Users can also load their own input data into MMiRNA-Viewer and visualize and compare detailed information about cancer-related gene expression changes, and also changes in the expression of transcription-regulating miRNAs. To validate the MMiRNA-Viewer, eight types of TCGA cancer datasets with both normal and control samples were selected in this study and three filter steps were applied subsequently. We performed Gene Ontology (GO) analysis for genes available in final selected 238 pairs and also for genes in the top 5 % (95 percentile) for each of eight cancer types to report a significant number of genes involved in various biological functions and pathways. We also calculated various centrality measurement matrices for the largest connected component(s) in each of eight cancers and reported top genes and miRNAs with high centrality measurements.
  
  
  CONCLUSIONS
  With its user-friendly interface, dynamic visualization and advanced queries, we also believe MMiRNA-Viewer offers an intuitive approach for visualizing and elucidating co-relationships between miRNAs and mRNAs of both tumor and normal samples. We suggest that miRNA and mRNA pairs with opposite fold changes of their expression and with inverted correlation values between tumor and normal samples might be most relevant for explaining the decoupling of mRNAs and their targeting miRNAs in tumor samples for certain cancer types.
authors: Department of Biology, Indiana State University, Terre Haute, IN, 47809, USA. Yongsheng.Bai@indstate.edu.|The Center for Genomic Advocacy, Indiana State University, Terre Haute, IN, 47809, USA. Yongsheng.Bai@indstate.edu.
authors: Yongsheng
authors: Y
authors: Bai
authors: Department of Biology, Indiana State University, Terre Haute, IN, 47809, USA.
authors: Lizhong
authors: L
authors: Ding
authors: Department of Mathematics and Computer Science, Indiana State University, Terre Haute, IN, 47809, USA.
authors: Steve
authors: S
authors: Baker
authors: Terre Haute South Vigo High School, Terre Haute, IN, 47809, USA.
authors: Jenny M
authors: JM
authors: Bai
authors: Department of Biology, Indiana State University, Terre Haute, IN, 47809, USA.
authors: Ethan
authors: E
authors: Rath
authors: Department of Mathematics and Computer Science, Indiana State University, Terre Haute, IN, 47809, USA.
authors: Feng
authors: F
authors: Jiang
authors: Animal Husbandry Institute, Inner Mongolia Academy of Agricultural & Animal Husbandry Sciences, Hohhot, 010031, People's Republic of China.
authors: Jianghong
authors: J
authors: Wu
authors: Department of Biostatistics, University of Michigan, Ann Arbor, MI, 48109, USA.
authors: Hui
authors: H
authors: Jiang
authors: Department of Biology, Indiana State University, Terre Haute, IN, 47809, USA.|The Center for Genomic Advocacy, Indiana State University, Terre Haute, IN, 47809, USA.
authors: Gary
authors: G
authors: Stuart
mesh_terms: D020413:3' Untranslated Regions; D019295:Computational Biology / Q000379:methods; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D017423:Sequence Analysis, RNA; D012984:Software
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D012333:RNA, Messenger
keywords: Cancer; Correlation; Expression; MMiRNA-Viewer; Regulation; TCGA; Visualization; mRNA; miRNA