Intra-relation reconstruction from inter-relation: miRNA to gene expression

BackgroundIn computational biology, a novel knowledge has been obtained mostly by identifying 'intra-relation,' the relation between entities on a specific biological level such as from gene expression or from microRNA (miRNA) and many such researches have been successful. However, intra-relations are not fully explaining complex cancer mechanisms because the inter-relation information between different levels of genomic data is missing, e.g. miRNA and its target genes. The 'inter-relation' between different levels of genomic data can be constructed from biological experimental data as well as genomic knowledge.MethodsPreviously, we have proposed a graph-based framework that integrates with multi-layers of genomic data, copy number alteration, DNA methylation, gene expression, and miRNA expression, for the cancer clinical outcome prediction. However, the limitation of previous work was that we integrated with multi-layers of genomic data without considering of inter-relationship information between genomic features. In this paper, we propose a new integrative framework that combines genomic dataset from gene expression and genomic knowledge from inter-relation between miRNA and gene expression for the clinical outcome prediction as a pilot study.ResultsIn order to demonstrate the validity of the proposed method, the prediction of short-term/long-term survival for 82 patients in glioblastoma multiforme (GBM) was adopted as a base task. Based on our results, the accuracy of our predictive model increases because of incorporation of information fused over genomic dataset from gene expression and genomic knowledge from inter-relation between miRNA and gene expression.ConclusionsIn the present study, the intra-relation of gene expression was reconstructed from inter-relation between miRNA and gene expression for prediction of short-term/long-term survival of GBM patients. Our finding suggests that the utilization of external knowledge representing miRNA-mediated regulation of gene expression is substantially useful for elucidating the cancer phenotype.

[1]  Robert Weil,et al.  Genomic expression patterns distinguish long-term from short-term glioblastoma survivors: a preliminary feasibility study. , 2008, Genomics.

[2]  L. Chin,et al.  Malignant astrocytic glioma: genetics, biology, and paths to treatment. , 2007, Genes & development.

[3]  Bernhard Schölkopf,et al.  Cluster Kernels for Semi-Supervised Learning , 2002, NIPS.

[4]  Michael Ruogu Zhang,et al.  Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization. , 1998, Molecular biology of the cell.

[5]  A. Saxena,et al.  Abnormalities of p16, p15 and CDK4 genes in recurrent malignant astrocytomas. , 1996, Oncogene.

[6]  S. Knuutila,et al.  Classification of human cancers based on DNA copy number amplification modeling , 2008, BMC Medical Genomics.

[7]  Karl T Kelsey,et al.  MicroRNA responses to cellular stress. , 2006, Cancer research.

[8]  P. Rothberg,et al.  Oncogenes and cancer. , 1983, Cancer investigation.

[9]  M. West,et al.  Patterns of Gene Expression That Characterize Long-term Survival in Advanced Stage Serous Ovarian Cancers , 2005, Clinical Cancer Research.

[10]  Irmtraud M. Meyer,et al.  The clonal and mutational evolution spectrum of primary triple-negative breast cancers , 2012, Nature.

[11]  M. West,et al.  Gene expression predictors of breast cancer outcomes , 2003, The Lancet.

[12]  Zev A. Binder,et al.  The Genetic Landscape of the Childhood Cancer Medulloblastoma , 2011, Science.

[13]  D. Pe’er,et al.  Module networks: identifying regulatory modules and their condition-specific regulators from gene expression data , 2003, Nature Genetics.

[14]  Derek Y. Chiang,et al.  The landscape of somatic copy-number alteration across human cancers , 2010, Nature.

[15]  Andreas Martin Lisewski,et al.  Graph sharpening plus graph integration: a synergy that improves protein functional classification , 2007, Bioinform..

[16]  Ugo Pastorino,et al.  MicroRNA signatures in tissues and plasma predict development and prognosis of computed tomography detected lung cancer , 2011, Proceedings of the National Academy of Sciences.

[17]  Thomas D. Schmittgen,et al.  Regulation of microRNA processing in development, differentiation and cancer , 2008, Journal of cellular and molecular medicine.

[18]  Bernhard Schölkopf,et al.  Fast protein classification with multiple networks , 2005, ECCB/JBI.

[19]  K. Skullerud,et al.  [Intracranial tumors in adults]. , 2003, Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke.

[20]  Philip Lijnzaad,et al.  An expression profile for diagnosis of lymph node metastases from primary head and neck squamous cell carcinomas , 2005, Nature Genetics.

[21]  J. Mesirov,et al.  Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. , 1999, Science.

[22]  Tongbin Li,et al.  miRecords: an integrated resource for microRNA–target interactions , 2008, Nucleic Acids Res..

[23]  E. Olson,et al.  A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure , 2006, Proceedings of the National Academy of Sciences.

[24]  Fan Chung,et al.  Spectral Graph Theory , 1996 .

[25]  Ju Han Kim,et al.  Synergistic effect of different levels of genomic data for cancer clinical outcome prediction , 2012, J. Biomed. Informatics.

[26]  D. Busam,et al.  An Integrated Genomic Analysis of Human Glioblastoma Multiforme , 2008, Science.

[27]  Joe W. Gray,et al.  Translating insights from the cancer genome into clinical practice , 2008, Nature.

[28]  Stefanie Dimmeler,et al.  The microRNA-17~92 cluster: Still a miRacle? , 2009, Cell cycle.

[29]  Xi Chen,et al.  The use of hsa-miR-21, hsa-miR-181b and hsa-miR-106a as prognostic indicators of astrocytoma. , 2010, European journal of cancer.

[30]  D. Bartel MicroRNAs Genomics, Biogenesis, Mechanism, and Function , 2004, Cell.

[31]  Ju Han Kim,et al.  Genomic characterization of perturbation sensitivity , 2007, ISMB/ECCB.

[32]  S. Hanash,et al.  Integrated global profiling of cancer , 2004, Nature Reviews Cancer.

[33]  H. Horvitz,et al.  MicroRNA expression profiles classify human cancers , 2005, Nature.

[34]  Weida Tong,et al.  DNA Microarrays Are Predictive of Cancer Prognosis: A Re-evaluation , 2010, Clinical Cancer Research.

[35]  A. Sparks,et al.  The Genomic Landscapes of Human Breast and Colorectal Cancers , 2007, Science.

[36]  Michael Gribskov,et al.  Use of Receiver Operating Characteristic (ROC) Analysis to Evaluate Sequence Matching , 1996, Comput. Chem..

[37]  J.,et al.  The New England Journal of Medicine , 2012 .

[38]  Sujaya Srinivasan,et al.  A Ten-microRNA Expression Signature Predicts Survival in Glioblastoma , 2011, PloS one.

[39]  Francisco Azuaje,et al.  An assessment of recently published gene expression data analyses: reporting experimental design and statistical factors , 2006, BMC Medical Informatics Decis. Mak..

[40]  D. Bartel MicroRNAs: Target Recognition and Regulatory Functions , 2009, Cell.

[41]  Yudong D. He,et al.  Gene expression profiling predicts clinical outcome of breast cancer , 2002, Nature.

[42]  Yves A. Lussier,et al.  Breakthroughs in genomics data integration for predicting clinical outcome , 2012, J. Biomed. Informatics.

[43]  Wei Liu,et al.  S100B attenuates microglia activation in gliomas: Possible role of STAT3 pathway , 2011, Glia.

[44]  Jian Li,et al.  Temporal dissection of tumorigenesis in primary cancers. , 2011, Cancer discovery.

[45]  D. Rousseau,et al.  ATAD 3A and ATAD 3B are distal 1p-located genes differentially expressed in human glioma cell lines and present in vitro anti-oncogenic and chemoresistant properties. , 2008, Experimental cell research.

[46]  Zoubin Ghahramani,et al.  Combining active learning and semi-supervised learning using Gaussian fields and harmonic functions , 2003, ICML 2003.

[47]  Bernhard Schölkopf,et al.  Learning with Local and Global Consistency , 2003, NIPS.

[48]  U. Feige,et al.  Spectral Graph Theory , 2015 .

[49]  Moshe Oren,et al.  Transcriptional activation of miR-34a contributes to p53-mediated apoptosis. , 2007, Molecular cell.

[50]  Janez Demsar,et al.  Statistical Comparisons of Classifiers over Multiple Data Sets , 2006, J. Mach. Learn. Res..

[51]  Mikhail Belkin,et al.  Regularization and Semi-supervised Learning on Large Graphs , 2004, COLT.

[52]  Benjamin J. Raphael,et al.  Integrated Genomic Analyses of Ovarian Carcinoma , 2011, Nature.

[53]  Sohail Asghar,et al.  A REVIEW OF FEATURE SELECTION TECHNIQUES IN STRUCTURE LEARNING , 2013 .

[54]  Raquel Díaz,et al.  Deregulated expression of miR‐106a predicts survival in human colon cancer patients , 2008, Genes, chromosomes & cancer.

[55]  Hyunjung Shin,et al.  Prediction of Protein Function from Networks , 2006, Semi-Supervised Learning.

[56]  D. Bartel,et al.  MicroRNAs Modulate Hematopoietic Lineage Differentiation , 2004, Science.