Xeno-miRNet: a comprehensive database and analytics platform to explore xeno-miRNAs and their potential targets

Xeno-miRNAs are microRNAs originating from exogenous species detected in host biofluids. A growing number of studies have suggested that many of these xeno-miRNAs may be involved in cross-species interactions and manipulations. To date, hundreds of xeno-miRNAs have been reported in different hosts at various abundance levels. Based on computational predictions, many more miRNAs could be potentially transferred to human circulation system. There is a clear need for bioinformatics resources and tools dedicated to xeno-miRNA annotations and their potential functions. To address this need, we have systematically curated xeno-miRNAs from multiple sources, performed target predictions using well-established algorithms, and developed a user-friendly web-based tool—Xeno-miRNet—to allow researchers to search and explore xeno-miRNAs and their potential targets within different host species. Xeno-miRNet currently contains 1,702 (including both detected and predicted) xeno-miRNAs from 54 species and 98,053 potential gene targets in six hosts. The web application is freely available at http://xeno.mirnet.ca.

[1]  Hugo Naya,et al.  Mining of public sequencing databases supports a non-dietary origin for putative foreign miRNAs: underestimated effects of contamination in NGS , 2014, RNA.

[2]  Michal Ziv-Ukelson,et al.  Gene bi-targeting by viral and human miRNAs , 2010, BMC Bioinformatics.

[3]  Xia Li,et al.  Functional dissection of virus-human crosstalk mediated by miRNAs based on the VmiReg database. , 2015, Molecular bioSystems.

[4]  M. Zamanian,et al.  Release of Small RNA-containing Exosome-like Vesicles from the Human Filarial Parasite Brugia malayi , 2015, PLoS neglected tropical diseases.

[5]  Sam Griffiths-Jones,et al.  Bias in microRNA functional enrichment analysis , 2015, Bioinform..

[6]  X. Chen,et al.  Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA , 2011, Cell Research.

[7]  S. Kundu,et al.  IIKmTA: Inter and Intra Kingdom miRNA-Target Analyzer , 2018, Interdisciplinary Sciences: Computational Life Sciences.

[8]  E. Gottwein Kaposi’s Sarcoma-Associated Herpesvirus microRNAs , 2012, Front. Microbio..

[9]  Xiwei Wu,et al.  Cross-kingdom inhibition of breast cancer growth by plant miR159 , 2016, Cell Research.

[10]  L. Qu,et al.  Exo-miRExplorer: A Comprehensive Resource for Exploring and Comparatively Analyzing Exogenous MicroRNAs , 2017, Front. Microbiol..

[11]  H. Weiner,et al.  The Host Shapes the Gut Microbiota via Fecal MicroRNA. , 2016, Cell host & microbe.

[12]  Yvonne Tay,et al.  MicroRNAs to Nanog, Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation , 2008, Nature.

[13]  Anjali J. Koppal,et al.  Supplementary data: Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites , 2010 .

[14]  Sai Wang,et al.  Release of extracellular vesicles containing small RNAs from the eggs of Schistosoma japonicum , 2016, Parasites & Vectors.

[15]  Paula Ribeiro,et al.  miRNet - dissecting miRNA-target interactions and functional associations through network-based visual analysis , 2016, Nucleic Acids Res..

[16]  J. Zempleni,et al.  Computational Characterization of Exogenous MicroRNAs that Can Be Transferred into Human Circulation , 2015, PloS one.

[17]  S. Tavazoie,et al.  A microRNA regulon that mediates endothelial recruitment and metastasis by cancer cells , 2011, Nature.

[18]  Hsien-Da Huang,et al.  ViTa: prediction of host microRNAs targets on viruses , 2006, Nucleic Acids Res..

[19]  Seunghyun Park,et al.  vHoT: a database for predicting interspecies interactions between viral microRNA and host genomes , 2011, Archives of Virology.

[20]  Jun Ding,et al.  TarPmiR: a new approach for microRNA target site prediction , 2016, Bioinform..

[21]  Jens Allmer,et al.  One Step Forward, Two Steps Back; Xeno-MicroRNAs Reported in Breast Milk Are Artifacts , 2016, PloS one.

[22]  C. K. Hsiao,et al.  miRSystem: An Integrated System for Characterizing Enriched Functions and Pathways of MicroRNA Targets , 2012, PloS one.

[23]  Jun-Hu Chen,et al.  Identification and characterization of microRNAs in Trichinella spiralis by comparison with Brugia malayi and Caenorhabditis elegans , 2011, Parasitology Research.

[24]  L. Lim,et al.  MicroRNA targeting specificity in mammals: determinants beyond seed pairing. , 2007, Molecular cell.

[25]  R. Weinberg,et al.  Tumour invasion and metastasis initiated by microRNA-10b in breast cancer , 2007, Nature.

[26]  Ana Kozomara,et al.  miRBase: annotating high confidence microRNAs using deep sequencing data , 2013, Nucleic Acids Res..

[27]  T. Geary,et al.  Detection of Circulating Parasite-Derived MicroRNAs in Filarial Infections , 2014, PLoS neglected tropical diseases.

[28]  Juan Cui,et al.  miRDis: a Web tool for endogenous and exogenous microRNA discovery based on deep-sequencing data analysis , 2017, Briefings Bioinform..

[29]  X. Estivill,et al.  Survey of 800+ data sets from human tissue and body fluid reveals xenomiRs are likely artifacts. , 2017, RNA.

[30]  A. Marcilla,et al.  The revised microRNA complement of Fasciola hepatica reveals a plethora of overlooked microRNAs and evidence for enrichment of immuno-regulatory microRNAs in extracellular vesicles. , 2015, International journal for parasitology.

[31]  Russell Bowler,et al.  The multiMiR R package and database: integration of microRNA–target interactions along with their disease and drug associations , 2014, Nucleic acids research.

[32]  Artemis G. Hatzigeorgiou,et al.  DIANA-miRPath v3.0: deciphering microRNA function with experimental support , 2015, Nucleic Acids Res..

[33]  Marc K Halushka,et al.  Toward the promise of microRNAs – Enhancing reproducibility and rigor in microRNA research , 2016, RNA biology.

[34]  Hanah Margalit,et al.  RepTar: a database of predicted cellular targets of host and viral miRNAs , 2010, Nucleic Acids Res..

[35]  Youxin Jin,et al.  Deep sequencing-based identification of pathogen-specific microRNAs in the plasma of rabbits infected with Schistosoma japonicum , 2013, Parasitology.

[36]  Pengfei Cai,et al.  Identification and characterization of microRNAs and endogenous siRNAs in Schistosoma japonicum , 2010, BMC Genomics.

[37]  Nectarios Koziris,et al.  DIANA-microT web server: elucidating microRNA functions through target prediction , 2009, Nucleic Acids Res..

[38]  K. Zen,et al.  Reply to Lack of detectable oral bioavailability of plant microRNAs after feeding in mice , 2013, Nature Biotechnology.

[39]  Andrea J. O'Hara,et al.  EBV microRNAs in primary lymphomas and targeting of CXCL-11 by ebv-mir-BHRF1-3. , 2008, Cancer research.

[40]  Wen-chang Lin,et al.  Vir-Mir db: prediction of viral microRNA candidate hairpins , 2007, Nucleic Acids Res..

[41]  Michael Hackenberg,et al.  Surface analysis of Dicrocoelium dendriticum. The molecular characterization of exosomes reveals the presence of miRNAs. , 2014, Journal of proteomics.

[42]  J. Qin,et al.  Kaposi's sarcoma‐associated herpesvirus (KSHV)‐encoded microRNAs promote matrix metalloproteinases (MMPs) expression and pro‐angiogenic cytokine secretion in endothelial cells , 2017, Journal of medical virology.

[43]  Manoj Kumar,et al.  VIRmiRNA: a comprehensive resource for experimentally validated viral miRNAs and their targets , 2014, Database J. Biol. Databases Curation.

[44]  K. Gunsalus,et al.  Combinatorial microRNA target predictions , 2005, Nature Genetics.

[45]  Rick M. Maizels,et al.  Exosomes secreted by nematode parasites transfer small RNAs to mammalian cells and modulate innate immunity , 2014, Nature Communications.

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

[47]  Yuanji Zhang,et al.  Lack of detectable oral bioavailability of plant microRNAs after feeding in mice , 2013, Nature Biotechnology.

[48]  G. Cheng,et al.  Molecular characterization of S. japonicum exosome-like vesicles reveals their regulatory roles in parasite-host interactions , 2016, Scientific Reports.