Improved method for prioritization of disease associated lncRNAs based on ceRNA theory and functional genomics data

Although several computational models that predict disease-associated lncRNAs (long non-coding RNAs) exist, only a limited number of disease-associated lncRNAs are known. In this study, we mapped lncRNAs to their functional genomics context using competing endogenous RNAs (ceRNAs) theory. Based on the criteria that similar lncRNAs are likely involved in similar diseases, we proposed a disease lncRNA prioritization method, DisLncPri, to identify novel disease-lncRNA associations. Using a leave-one-out cross validation (LOOCV) strategy, DisLncPri achieved reliable area under curve (AUC) values of 0.89 and 0.87 for the LncRNADisease and Lnc2Cancer datasets that further improved to 0.90 and 0.89 by integrating a multiple rank fusion strategy. We found that DisLncPri had the highest rank enrichment score and AUC value in comparison to several other methods for case studies of alzheimer's disease, ovarian cancer, pancreatic cancer and gastric cancer. Several novel lncRNAs in the top ranks of these diseases were found to be newly verified by relevant databases or reported in recent studies. Prioritization of lncRNAs from a microarray (GSE53622) of oesophageal cancer patients highlighted ENSG00000226029 (top 2), a previously unidentified lncRNA as a potential prognostic biomarker. Our analysis thus indicates that DisLncPri is an excellent tool for identifying lncRNAs that could be novel biomarkers and therapeutic targets in a variety of human diseases.

[1]  Xing Chen,et al.  Long non-coding RNAs and complex diseases: from experimental results to computational models , 2016, Briefings Bioinform..

[2]  Xing Chen,et al.  IRWRLDA: improved random walk with restart for lncRNA-disease association prediction , 2016, Oncotarget.

[3]  K. Blennow,et al.  Alzheimer's disease , 2016, The Lancet.

[4]  Jinhuan Ding,et al.  HOTAIR overexpression correlated with worse survival in patients with solid tumors. , 2016, Minerva medica.

[5]  Peng Wang,et al.  Construction of a lncRNA-mediated feed-forward loop network reveals global topological features and prognostic motifs in human cancers , 2016, Oncotarget.

[6]  Xing Chen,et al.  FMLNCSIM: fuzzy measure-based lncRNA functional similarity calculation model , 2016, Oncotarget.

[7]  Peng Wang,et al.  Identification of prognostic biomarkers in glioblastoma using a long non-coding RNA-mediated, competitive endogenous RNA network , 2016, Oncotarget.

[8]  Rong Li,et al.  miR-675-5p enhances tumorigenesis and metastasis of esophageal squamous cell carcinoma by targeting REPS2 , 2016, Oncotarget.

[9]  Zhu-Hong You,et al.  ILNCSIM: improved lncRNA functional similarity calculation model , 2016, Oncotarget.

[10]  Jian Zhang,et al.  Construction and analysis of cardiac hypertrophy-associated lncRNA-mRNA network based on competitive endogenous RNA reveal functional lncRNAs in cardiac hypertrophy , 2016, Oncotarget.

[11]  Zheng Li,et al.  ANRIL: a pivotal tumor suppressor long non-coding RNA in human cancers , 2016, Tumor Biology.

[12]  Wei Wu,et al.  NONCODE 2016: an informative and valuable data source of long non-coding RNAs , 2015, Nucleic Acids Res..

[13]  Peng Wang,et al.  Lnc2Cancer: a manually curated database of experimentally supported lncRNAs associated with various human cancers , 2015, Nucleic Acids Res..

[14]  Rong Li,et al.  miR-675-5 p enhances tumorigenesis and metastasis of esophageal squamous cell carcinoma by targeting REPS 2 , 2016 .

[15]  Q. Guo,et al.  Comprehensive analysis of lncRNA-mRNA co-expression patterns identifies immune-associated lncRNA biomarkers in ovarian cancer malignant progression , 2015, Scientific Reports.

[16]  Daling Zhu,et al.  Long non-coding RNA growth arrest-specific transcript 5 is involved in ovarian cancer cell apoptosis through the mitochondria-mediated apoptosis pathway. , 2015, Oncology reports.

[17]  Xing Chen.  KATZLDA: KATZ measure for the lncRNA-disease association prediction , 2015, Scientific Reports.

[18]  Xiaolin Zhou,et al.  Identification of Alzheimer's disease–associated long noncoding RNAs , 2015, Neurobiology of Aging.

[19]  Peng Wang,et al.  miRSponge: a manually curated database for experimentally supported miRNA sponges and ceRNAs , 2015, Database J. Biol. Databases Curation.

[20]  Xing Chen,et al.  Predicting lncRNA-disease associations and constructing lncRNA functional similarity network based on the information of miRNA , 2015, Scientific Reports.

[21]  Jia Yu,et al.  Long non-coding RNA MEG3 functions as a competing endogenous RNA to regulate gastric cancer progression , 2015, Journal of experimental & clinical cancer research : CR.

[22]  Qionghai Dai,et al.  Constructing lncRNA functional similarity network based on lncRNA-disease associations and disease semantic similarity , 2015, Scientific Reports.

[23]  H. Cai,et al.  LncRNA-AP001631.9 promotes cell migration in gastric cancer. , 2015, International journal of clinical and experimental pathology.

[24]  Xia Li,et al.  Identification of lncRNA-associated competing triplets reveals global patterns and prognostic markers for cancer , 2015, Nucleic acids research.

[25]  Dapeng Hao,et al.  Prioritizing candidate disease-related long non-coding RNAs by walking on the heterogeneous lncRNA and disease network. , 2015, Molecular bioSystems.

[26]  Min Li,et al.  Heterogeneous Network Model to Infer Human Disease-Long Intergenic Non-Coding RNA Associations , 2015, IEEE Transactions on NanoBioscience.

[27]  Ming Zhou,et al.  Genomic analysis of drug resistant pancreatic cancer cell line by combining long non-coding RNA and mRNA expression profling. , 2015, International journal of clinical and experimental pathology.

[28]  J. Fadista,et al.  RNA sequencing: current and prospective uses in metabolic research. , 2014, Journal of molecular endocrinology.

[29]  K. Hua,et al.  Overexpression of long non-coding RNA HOTAIR predicts poor patient prognosis and promotes tumor metastasis in epithelial ovarian cancer. , 2014, Gynecologic oncology.

[30]  Lei Yang,et al.  Promoter hypermethylation influences the suppressive role of maternally expressed 3, a long non-coding RNA, in the development of epithelial ovarian cancer. , 2014, Oncology reports.

[31]  Shaoli Das,et al.  lnCeDB: Database of Human Long Noncoding RNA Acting as Competing Endogenous RNA , 2014, PloS one.

[32]  Liping Su,et al.  MALAT1 promotes cell proliferation in gastric cancer by recruiting SF2/ASF. , 2014, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[33]  Xinghua Shi,et al.  A Network Based Method for Analysis of lncRNA-Disease Associations and Prediction of lncRNAs Implicated in Diseases , 2014, PloS one.

[34]  Xing Chen,et al.  A Computational Framework to Infer Human Disease-Associated Long Noncoding RNAs , 2014, PloS one.

[35]  Hui Zhou,et al.  starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein–RNA interaction networks from large-scale CLIP-Seq data , 2013, Nucleic Acids Res..

[36]  Bart De Moor,et al.  eXtasy: variant prioritization by genomic data fusion , 2013, Nature Methods.

[37]  Xing Chen,et al.  Novel human lncRNA-disease association inference based on lncRNA expression profiles , 2013, Bioinform..

[38]  Xiang Li,et al.  Identification of active transcription factor and miRNA regulatory pathways in Alzheimer's disease , 2013, Bioinform..

[39]  C. Peng,et al.  Downregulation of gas5 increases pancreatic cancer cell proliferation by regulating CDK6 , 2013, Cell and Tissue Research.

[40]  Shi-ping Liu,et al.  Identification of differentially expressed long non-coding RNAs in human ovarian cancer cells with different metastatic potentials , 2013, Cancer biology & medicine.

[41]  Ke Liu,et al.  Linc2GO: a human LincRNA function annotation resource based on ceRNA hypothesis , 2013, Bioinform..

[42]  Xia Li,et al.  mirTarPri: Improved Prioritization of MicroRNA Targets through Incorporation of Functional Genomics Data , 2013, PloS one.

[43]  Xing Chen,et al.  LncRNADisease: a database for long-non-coding RNA-associated diseases , 2012, Nucleic Acids Res..

[44]  Xiaoke Ma,et al.  Long non-coding RNAs function annotation: a global prediction method based on bi-colored networks , 2012, Nucleic acids research.

[45]  J. Jia,et al.  Combination of p53(ser15) and p21/p21(thr145) in peripheral blood lymphocytes as potential Alzheimer's disease biomarkers , 2012, Neuroscience Letters.

[46]  Rafael C. Jimenez,et al.  The IntAct molecular interaction database in 2012 , 2011, Nucleic Acids Res..

[47]  Shangwei Ning,et al.  Prioritizing human cancer microRNAs based on genes’ functional consistency between microRNA and cancer , 2011, Nucleic acids research.

[48]  P. Pandolfi,et al.  A ceRNA Hypothesis: The Rosetta Stone of a Hidden RNA Language? , 2011, Cell.

[49]  J. Mattick,et al.  The melanoma-upregulated long noncoding RNA SPRY4-IT1 modulates apoptosis and invasion. , 2011, Cancer research.

[50]  G. Leuba,et al.  The role of the ubiquitin proteasome system in Alzheimer's disease , 2011, Experimental biology and medicine.

[51]  Shuli Kang,et al.  Large-scale prediction of long non-coding RNA functions in a coding–non-coding gene co-expression network , 2011, Nucleic acids research.

[52]  Chi-Ying F. Huang,et al.  miRTarBase: a database curates experimentally validated microRNA–target interactions , 2010, Nucleic Acids Res..

[53]  Ana Kozomara,et al.  miRBase: integrating microRNA annotation and deep-sequencing data , 2010, Nucleic Acids Res..

[54]  Phillip A. Sharp,et al.  Emerging Roles for Natural MicroRNA Sponges , 2010, Current Biology.

[55]  Yadong Wang,et al.  Prioritization of disease microRNAs through a human phenome-microRNAome network , 2010, BMC Systems Biology.

[56]  C. Sander,et al.  Target mRNA abundance dilutes microRNA and siRNA activity , 2010, Molecular systems biology.

[57]  Gautier Koscielny,et al.  Ensembl Genomes: Extending Ensembl across the taxonomic space , 2009, Nucleic Acids Res..

[58]  Geoffrey S. Tobias,et al.  Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer , 2009, Nature Genetics.

[59]  Phillip W. Lord,et al.  Semantic Similarity in Biomedical Ontologies , 2009, PLoS Comput. Biol..

[60]  Robert C. Bast,et al.  The biology of ovarian cancer: new opportunities for translation , 2009, Nature Reviews Cancer.

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

[62]  Sandhya Rani,et al.  Human Protein Reference Database—2009 update , 2008, Nucleic Acids Res..

[63]  Martin Reczko,et al.  The database of experimentally supported targets: a functional update of TarBase , 2008, Nucleic Acids Res..

[64]  J. Komorowski,et al.  Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation. , 2008, Molecular cell.

[65]  Letizia Carramusa,et al.  The PVT‐1 oncogene is a Myc protein target that is overexpressed in transformed cells , 2007, Journal of cellular physiology.

[66]  Thomas D. Schmittgen,et al.  Ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas. , 2007, Cancer cell.

[67]  Jing Zhao,et al.  Activation of p53 by MEG3 Non-coding RNA* , 2007, Journal of Biological Chemistry.

[68]  Maria Victoria Schneider,et al.  MINT: a Molecular INTeraction database. , 2002, FEBS letters.

[69]  Igor Jurisica,et al.  The c-Myc oncogene directly induces the H19 noncoding RNA by allele-specific binding to potentiate tumorigenesis. , 2006, Cancer research.

[70]  Bassem A. Hassan,et al.  Gene prioritization through genomic data fusion , 2006, Nature Biotechnology.

[71]  Mike Tyers,et al.  BioGRID: a general repository for interaction datasets , 2005, Nucleic Acids Res..

[72]  Emily Bernstein,et al.  RNA meets chromatin. , 2005, Genes & development.

[73]  Igor Jurisica,et al.  Online Predicted Human Interaction Database , 2005, Bioinform..

[74]  Jacques Ferlay,et al.  Estimates of cancer incidence in China for 2000 and projections for 2005. , 2005, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[75]  Gary D. Bader,et al.  BIND-a data specification for storing and describing biomolecular interactions, molecular complexes and pathways , 2000, Bioinform..

[76]  Philip Resnik,et al.  Using Information Content to Evaluate Semantic Similarity in a Taxonomy , 1995, IJCAI.

[77]  J. Voltas,et al.  [Treatment of gastric cancer]. , 1982, Revista de medicina de la Universidad de Navarra.