text:
- Research
- Open Access
Genome-scale MicroRNA target prediction through clustering with Dirichlet process mixture model
© The Author(s). 2018
- Published: 24 September 2018
MicroRNA regulation is fundamentally responsible for fine-tuning the whole gene network in human and has been implicated in most physiological and pathological conditions. Studying regulatory impact of microRNA on various cellular and disease processes has resulted in numerous computational tools that investigate microRNA-mRNA interactions through the prediction of static binding site highly dependent on sequence pairing. However, what hindered the practical use of such target prediction is the interplay between competing and cooperative microRNA binding that complicates the whole regulatory process exceptionally.
We developed a new method for improved microRNA target prediction based on Dirichlet Process Gaussian Mixture Model (DPGMM) using a large collection of molecular features associated with microRNA, mRNA, and the interaction sites. Multiple validations based on microRNA-mRNA interactions reported in recent large-scale sequencing analyses and a screening test on the entire human transcriptome show that our model outperformed several state-of-the-art tools in terms of promising predictive power on binding sites specific to transcript isoforms with reduced false positive prediction. Last, we illustrated the use of predicted targets in constructing conditional microRNA-mediated gene regulation networks in human cancer.
The probability-based binding site prediction provides not only a useful tool for differentiating microRNA targets according to the estimated binding potential but also a capability highly important for exploring dynamic regulation where binding competition is involved.
- MicroRNA
- MicroRNA target prediction
- Dirichlet process Gaussian mixture
- Machine learning
- Bayesian inference
- Dynamic microRNA regulation
MicroRNAs (miRNAs) are important post-transcriptional gene regulators that silence messenger RNA (mRNA) targets via mRNA degradation or translational repression [1, 2]. They hybridize with complementary sequences in the 3′-untranslated regions of mRNA, particularly in the "seed region" (2nd-8th bases on the 5′ end), for their binding [3]. In RNA-induced silencing complex, both miRNA and mRNA are degraded if the miRNA nucleotide sequence has a high degree of complementarity to the sequence in the mRNA target [4, 5]; otherwise, the binding of miRNA to mRNA will halt mRNA translation without causing degradation [5, 6]. The large-scale miRNA-mRNA interactions detected by sequencing analyses has shown various interaction patterns, e.g., many interactions happen via complementary sequences in discontinuous regions other than seed region [7], indicating different regulatory mechanisms. In addition, compelling evidence reveals the dynamic nature of miRNA-mRNA interaction that multiple miRNAs can bind to the same mRNA sequence or different copies of the same transcript -- cooperative interactions [8], while multiple different mRNAs, possibly also with other types of RNA, e.g., long non-coding RNAs and circular RNAs [9], can compete for binding to the same miRNA -- competitive interactions [10]. Furthermore, other factors, such as genetic mutations [11–14], competition with RNA binding proteins [15, 16], and conditional expression of miRNA and mRNA can also affect the status of miRNA-mRNA interactions. All listed above indicate the complexity underlying miRNA-mediated gene regulation.
The molecular mechanisms have been partially clarified by extensive studies focusing on miRNA biogenesis and function [17, 18], which also show the participation of miRNAs in virtually every aspect of cellular activities starting with differentiation and development of cells. MiRNAs affect normal functioning of the cell including metabolism, proliferation and apoptotic cell death as well as malfunctions such as viral infection, and tumorigenesis [19–24]. In humans, it is estimated that 2500+ miRNAs can regulate over 60% of human genes [25]. Research interest in miRNA regulation has been dramatically increasing, resulting in numerous computational tools such as TargetScan [26], miRDB [27], miRanda [28], and mirSVR [29]. The miRNA targets predicted by these tools can be used to indirectly infer miRNA function, e.g., through pathway enrichment analysis [23]. However, the complexity of miRNA-mRNA binding, especially the cooperative and competitive binding modes observed with miRNAs complicates the target prediction task. Most methods that focus primarily on finding complementary sequences in the seed region fail to address this complexity.
Despite the challenges faced in computational prediction, novel sequencing techniques has facilitated experimental discovery of a large number of miRNA-mRNA interactions. For example, the crosslinking, ligation, and sequencing of hybrids (CLASH) analysis has identified 18,514 miRNA-mRNA interactions where 60% of the interactions were associated with seed region [7]. Further, the coding regions of mRNAs were shown to house ~ 60% of the binding sites. The existing algorithms are designed on the assumption of 3'-UTR centric binding, new algorithms will need to revise this assumption. Another study using covalent ligation of endogenous Argonaute–bound RNAs (CLEAR)-CLIP in human hepatoma cells corroborated the above results: ~ 26% of the interactions were associated with seed region and ~ 57% are non-3'UTR interactions [30].
In this study, we designed a new computational method for miRNA target prediction using Dirichlet Process Gaussian Mixture Model (DPGMM) [31], with integration of the large-scale sequencing-detected interactions. The main aim is to infer interactions along with indicated confidence. Given the large number of interaction patterns miRNAs and mRNAs can have (to-be-discovered) and the uncertainty about source of similarity, clustering is the tool of choice to group similar interactions with respect to either the miRNA or mRNA involved. In clustering tasks where the number of clusters are not known ahead of observing the data, the non-parametric Bayesian method DPGMM is commonly used [32–36]. DPGMM also has advantages in accommodating clusters with various sizes and structures, free specification of the number of clusters, easy computation, and interpretability [20], compared to other multi-class learning systems, such as SVM, K-means, and GMM clustering. To accomplish, we first considered a large number of molecular features related to miRNA-mRNA binding sites including sequence pairing [26], evolutionary conservation [37], free energy of the miRNA-mRNA heteroduplex [38], target site accessibility [39], and the flanking sequence of the target site on mRNA. A few novel features possibly associated with binding efficacy were also considered, such as AU-rich nucleotide composition near the binding site, proximity to sites for co-expressed miRNAs (possibly associated with cooperative action), proximity to residues pairing at miRNA nucleotides 13–16, positioning away from the center of long UTRs [2, 40]. In addition, several statistics related to binding site were also assessed, e.g., the number of complementary pairs within seed region and/or within the whole biding site. Based on these heterogeneous features, a feature vector will be constructed for each given miRNA-mRNA interaction, as input to the model.
For each candidate interaction, the new system can output an assignment score as posterior probability for each of the clusters. By assessing all interactions from the same cluster, one can explore new insights in interactive patterns reflected by each identified cluster. In addition, based on the sequence information of experimentally-detected interactions and aforementioned distinguishing features, this system will allow one to assess if one miRNA can bind to a specific splicing transcript, a very unique feature highly useful in practice when compared to gene-level prediction offered by existing tools. At last, we demonstrated in a breast cancer case study the application of predicted target information to infer conditional miRNA-gene interaction through modeling dynamic gene regulation while considering multiple other gene expression regulation mechanisms such as transcription factor and copy number variation (CNV).
Data preparation and feature generation
Datasets applied in this study
CLASH data [7]
17,436 interactions on Human kidney cell (HEK293), associated with Ago1
iPAR-CLIP data [8]
10,566 interactions on HEK293, human embryonic stem cell, EBV-infected lymphoblastoid cell lines, and primary effusion lymphoma cell line, associated with Ago1 and Ago2
CLEAR-CLIP data [30]
32,711 interactions on Human hepatoma cell, associated with Ago
mirTarbase [20]
11,002 interactions on Human genome, predicted by miRanda;
483 validated interactions by non-sequencing analysis
RefSeq [42]
56,000 human transcripts
Classification using mixture model
- 1)
Negative Data Generation
- 2)
Building the Classifier
The positive and negative datasets
Pos-1: Interactions reported in CLASH data
Pos-2: Interactions reported in iPAR-CLIP data
Neg-1: Interactions generated on reported miRNA and mRNA pairs
Neg-2: Interactions generated on reported miRNAs and unreported mRNAs
Neg-3: Interactions generated on unreported miRNAs and reported mRNAs
Neg-4: Interactions generated on unreported miRNAs and unreported mRNAs
In order to discover unknown binding patterns and properties, a classifier was first trained to differentiate positive interactions from negative. The rationale is as follows. After feature generation, for a given miRNA r and a set of binding sites I related to r, the ith binding site is represented with an m-dimensional feature vector xi based on a set of m features (m = 2059 in the initial analysis). Feature vectors corresponding to all the n sites in I are represented by {x1, …, xi, …, xn}. Let nc be the number of clusters observed in miRNA-mRNA interactions and zi(i = 1, …, nc) represent the cluster membership of the interaction xi. We then apply Dirichlet Process Gaussian Mixture Model (DPGMM) to obtain interaction clusters. The Dirichlet Process (DP) is the prior distribution for the mixture model specifying a distribution of probability distributions. In this setting, these distributions specify the parameters of miRNA-mRNA interaction clusters. The parameters of DP are a base distribution G0 and a positive concentration parameter α. Base distribution G0 is the expected value of the process while α determines the dispersion of the distributions around G0. A small α results in distributions that are concentrated around G0. As α increases, the dispersion of distributions increase.
- 3)
Feature Selection
- 4)
Cascade Model for MiRNA Specific Clusters
The root level clusters can be used to evaluate if a new interaction object can be correctly predicted as a real interaction or not while the lower layers can help us to evaluate if the object can be assigned to its own cluster. A certain number of mixed clusters are expected to remain in the model corresponding to different miRNAs that follow similar binding patterns.
Model evaluation and genome-scale target screening
In this study, CLASH and iPAR-CLIP data were used to train and test the model (75% of the interactions were used as training set and 25% as testing set). The final model was decided based on performance using the remaining features after feature elimination. For independent evaluation, duplicated interactions in CLEAR-CLIP data and mirTarBase data were removed and the remaining were used.
Next, the RefSeq data [43] were used to screen the whole human transcriptome for possible binding interactions with miRNAs. To determine if a position on mRNA is a candidate site for a given miRNA, we locally aligned the sequences of the candidate site and the miRNA. An extension of 30 nucleotides on both ends were considered while computing features for a given candidate binding site. A candidate binding site and a miRNA pair were tested for a possible interaction by assigning to a cluster within the clustering tree model. Leaf level clusters were considered as final cluster assignments.
An interaction confidence metric (IC) was used to rank the predicted interactions according to how reliable they are. IC for a candidate interaction i and the dominant miRNA k in i's assigned cluster is ICik = zi * ck, where zi indicates normalized assignment probability and ck is the proportion of miRNA k in the cluster.
Last, to demonstrate the use of predicted interactions under the context of studying dynamic gene regulation, we have performed a case study of inferring conditional miRNA regulation associated with cancer progression. Based on a set of genomic data on breast cancer from The Cancer Genome Atlas (TCGA) [44] including miRNA and mRNA expressions, CNVs, and DNA methylation profiles and a meta-Lasso regression model our group has been recently developed [45], miRNA regulation associated with different cancer stages were detected. Previously, the regression model evaluates the likelihood of interactions between a pair of miRNA and mRNA based on a regulatory score (RS) which is calculated through aggregation of binding probability and binding affinity [45]. In this study, we replace the RS score by the DPGMM-derived posterior probability, the highest assignment score. Along with other factors such as Transcription factor (TF)-gene regulatory potential, Lasso regression was utilized to identify the TFs and miRNAs that regulate a specific gene under a given condition.
Prediction performance on the training, testing, and independent datasets
75% of CLASH, iPAR, and negative
25% of CLASH, iPAR, and negative
Validation-1 CLEAR-CLIP
Validation-2 mirTarbase (validated)
Validation-3 mirTarbase (predicted)
Our model performs decently on the majority of data sets where the interaction discovery was sequencing-based, with the exception of mirTarBase. The sensitivity for mirTarBase data is low, 61.0% for the validated interactions and 62.0% for the predicted ones from other tools, respectively. The discrepancy can be due to two possible explanations. First, CLASH and CLIP interactions were detected by genome-wise sequencing where each miRNA-mRNA pair often involves many different interactions at different sites while the mirTarBase only reports a single binding site on a gene target. Second, predicted targets in mirTarBase were less reliable compared to the experimentally validated ones.
Selected features
A subset of the initial 2059 features (Methods) that optimized the performance of the model was selected using 5-fold cross validation. A minimal set of discriminative features were kept that optimized the model by eliminating the noisy features (Fig. 1B). Feature selection was based on minimum information loss which represents the loss of the predictive power. We observed a slight increase in the overall accuracy on mirTarBase data from 61 to 62% to 64% accuracy after the least important features were eliminated recursively (with 377 remaining features).
During feature elimination, we observed that sensitivity and specificity were complementary while the accuracy and MCC were relatively consistent. The model containing 377 features resulted in the highest accuracy and MCC (see Additional file 1). We used these features in our final model. An additional table lists the top 30 selected features, ranked by AUC value that reflects the discerning power (see Additional file 2). For example, the alignment score on the binding site, the open degree of the mRNA sequence, and 'T' counts in both miRNA and mRNA sequences are highly distinguishing for miRNA-mRNA interaction (Fig. 1B).
Final classification model
The final model was trained using the selected 377 features and the optimal parameters. The performance of our method was evaluated in terms of classification performance and clustering coherence as follows.
Classification performance
Performance based on the 1st and leaf layer clusters
75% of CLASH, iPAR, negative
25% of CLASH, iPAR, negative
Validation-2 mirTarbase (val.)
Validation-3 mirTarbase (pre.)
MiRNA/mRNA specific clusters
Validation study
Our method was compared with other state-of-the-art miRNA target prediction tools including TargetScan [26], miRDB [27], microT [46], and microT-CDS [47], based on the predicted positive interactions (Additional file 2). While our method only predicted 22,215 interactions among 550 miRNAs and 7529 mRNAs, others show significantly higher numbers that are beyond the census estimation. For example, TargetScan, microT and microT-CDS all predicted over millions of interactions among these miRNAs and mRNAs, which implies higher levels of false positives. When comparing the average targets per miRNA and average miRNA regulators per mRNA, our results are closer to reality. On the other hand, all four exisitng tools reported greater number of targets for one miRNA. We used the 37,539 positive examples in our test data to compare the sensitivity of our method with these tools. Our method achieves considerably higher sensitivity (see Additional file 2).
Transcriptome screening
A case study of conditional miRNA regulation in Cancer
Emerging sequencing technologies has changed the landscape of research on miRNA target identification. Availability of data pertaining to genome-scale miRNA interactome facilitated bioinformatics research immensely. Particularly, use of transcript-level interaction data combined with mRNA specific features in this study allows confidence in our model for transcript-level target prediction. To the best of our knowledge, splicing transcript specific miRNA binding site prediction is a novel feature that is lacking in many existing tools.
Moreover, a considerable amount of miRNA-mRNA interactions via complementary sequences have been discovered in gapped regions [11]. These findings suggest that prediction solely depending on sequence and/or contextual features such as binding energy, seed match, and conservation is not sufficient. As such the static target prediction tools that utilize only that information have received critical skepticism. We addressed this challenge in our model by incorporating data about various types of molecular features that differentiate distinct interaction patterns. Meanwhile, high false prediction miRNA target prediction rates are still a big concern.
There are several technical challenges that we encountered during the course of this work. We have used publicly available sequencing data. In compiling the data derived from different sequencing technologies, the raw sequence data needed to be reprocessed and a consolidated annotation had to be produced. Another challenge we faced is a common one in miRNA target prediction research, i.e., the negative set is huge compared to the positive set 10 times more in our case. To make our negative set more representative, we devised a new method and maintained a comparable size with the positive set.
The ambiguity around cooperative and competitive binding mechanisms adds to the complexity and semi-stochasticity associated with miRNA-mediated gene regulation. Our method can be used to infer competitive binding, since it assigns likelihoods to the numerous potential binding sites of a gene to the same miRNA which can be used to evaluate the binding potential. Our recent study shows that several miRNAs can affect a given pathway by regulating the same or different genes involved in the pathway [45]. For example, miR-18a-3p, −320a, −193b-3p, and -92b-3p co-regulate the glycolysis/gluconeogenesis and focal adhesion in cancers of kidney, liver, lung, and uterus. Similar applications shed light on miRNA regulatory mechanisms and novel roles and meanwhile, the functional studies all highlight the importance and challenges of reliable miRNA-mRNA interaction prediction.
In this study we developed a new method for predicting human miRNA-mRNA interactions reliably. This statistical approach has improved prediction performance compared to similar existing tools and includes several unique features. Importantly, this tool can address practical questions such as common binding properties across miRNAs. Also, the interactions are predicted at transcript level which gives a more detailed view of interaction than the existing tools that predict gene-level binding sites. In our future work, we plan to identify miRNA co-binding module by use of conditional mRNA and miRNA genomic data, which will take the stochastic nature of miRNA-mRNA interaction into consideration. As such, we believe this study lay out the groundwork for future research on cooperative miRNA module and dynamic gene regulation.
The authors would like to thank all SBBI members who have been involved in this work for providing helpful discussions and technical assistance.
This research is support by the NIH funded COBRE grant (1P20GM104320), Food for health seed grant, the Tobacco Settlement Fund and the NIH&USDA/NIFA (1 R01 DK107264/NIFA 2016–67001-25301; publication cost was funded by this grant).
Availability of data and materials
All data analyzed during this study are publicly available. CLASH data are available in the Gene Expression Omnibus (GEO) repository under accession number GSE46039, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE46039. iPAR-CLIP and CLEAR-CLIP data are included in the supplementary information of [8, 30], respectively. miRTarBase data are available from http://mirtarbase.mbc.nctu.edu.tw/php/index.php. The RefSeq data are available from resources at NCBI, http://www.ncbi.nlm.nih.gov.
About this supplement
This article has been published as part of BMC Genomics Volume 19 Supplement 7, 2018: Selected articles from the IEEE BIBM International Conference on Bioinformatics & Biomedicine (BIBM) 2017: genomics. The full contents of the supplement are available online at https://bmcgenomics.biomedcentral.com/articles/supplements/volume-19-supplement-7.
Authors' contributions
JC conceived this study. ZH and CL implemented the model and performed the analysis. JS and KP conducted part of the validation. ZH, CL, and JC wrote the manuscript. All authors read and approved the final manuscript.
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
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Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Authors' Affiliations
- Chen K, Rajewsky N. The evolution of gene regulation by transcription factors and microRNAs. Nat Rev Genet. 2007;8:93–103.View ArticleGoogle Scholar
- Jing Q, Huang S, Guth S, Zarubin T, Motoyama A, Chen J, et al. Involvement of microRNA in AU-rich element-mediated mRNA instability. Cell. 2005;120:623–34.View ArticleGoogle Scholar
- Schirle NT, Sheu-Gruttadauria J, MacRae IJ. Structural basis for microRNA targeting. Science. 2014;346:608–13.View ArticleGoogle Scholar
- Rana TM. Illuminating the silence: understanding the structure and function of small RNAs. Nat Rev Mol Cell Biol. 2007;8:23–36.View ArticleGoogle Scholar
- Ameres SL, Zamore PD. Diversifying microRNA sequence and function. Nat Rev Mol Cell Biol. 2013;14:475–88.View ArticleGoogle Scholar
- Ebert MS, Neilson JR, Sharp PA. MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nat Methods. 2007;4:721–6.View ArticleGoogle Scholar
- Helwak A, Kudla G, Dudnakova T, Tollervey D. Mapping the human miRNA interactome by CLASH reveals frequent noncanonical binding. Cell. 2013;153:654–65.View ArticleGoogle Scholar
- Chi SW, Zang JB, Mele A, Darnell RB. Argonaute HITS-CLIP decodes microRNA-mRNA interaction maps. Nature. 2009;460:479–86.View ArticleGoogle Scholar
- Yamamura S, Imai-Sumida M, Tanaka Y, Dahiya R. Interaction and cross-talk between non-coding RNAs. Cell Mol Life Sci. 2018;75:467–84.View ArticleGoogle Scholar
- Guil S, Esteller M. RNA-RNA interactions in gene regulation: the coding and noncoding players. Trends Biochem Sci. 2015;40:248–56.View ArticleGoogle Scholar
- Chin LJ, Ratner E, Leng S, Zhai R, Nallur S, Babar I, et al. A SNP in a let-7 microRNA complementary site in the KRAS 3′UTR increases non-small cell lung Cancer risk. Cancer Res. 2008;68:8535–40.View ArticleGoogle Scholar
- Jiang S, Zhang H-W, Lu M-H, He X-H, Li Y, Gu H, et al. MicroRNA-155 functions as an OncomiR in breast cancer by targeting the suppressor of cytokine signaling 1 gene. Cancer Res. 2010;70:3119–27.View ArticleGoogle Scholar
- Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H, Endoh H, et al. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res. 2004;64:3753–6.View ArticleGoogle Scholar
- Mayr C, Hemann MT, Bartel DP. Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation. Science. 2007;315:1576–9.View ArticleGoogle Scholar
- Poliseno L, Salmena L, Zhang J, Carver B, Haveman WJ, Pandolfi PP. A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature. 2010;465:1033–8.View ArticleGoogle Scholar
- Mayr C, Bartel DP. Widespread shortening of 3'UTRs by alternative cleavage and polyadenylation activates oncogenes in cancer cells. Cell. 2009;138:673–84.View ArticleGoogle Scholar
- Claycomb J, Abreu-Goodger C, Buck AH. RNA-mediated communication between helminths and their hosts: the missing links. RNA Biol. 2017;14:436–41.View ArticleGoogle Scholar
- Treiber T, Treiber N, Meister G. Regulation of microRNA biogenesis and function. Thromb Haemost. 2012;107:605–10.View ArticleGoogle Scholar
- Xu J, Li C-X, Li Y-S, Lv J-Y, Ma Y, Shao T-T, et al. MiRNA-miRNA synergistic network: construction via co-regulating functional modules and disease miRNA topological features. Nucleic Acids Res. 2011;39:825–36.View ArticleGoogle Scholar
- Hsu SD, Tseng YT, Shrestha S, Lin YL, Khaleel A, Chou CH, et al. miRTarBase update 2014: an information resource for experimentally validated miRNA-target interactions. Nucleic Acids Res. 2014;42(Database issue):D78–85.View ArticleGoogle Scholar
- Friedman RC. Farh KK-H, Burge CB, Bartel DP. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 2009;19:92–105.View ArticleGoogle Scholar
- Bao W, Fu H-J, Xie Q-S, Wang L, Zhang R, Guo Z-Y, et al. HER2 interacts with CD44 to up-regulate CXCR4 via epigenetic silencing of microRNA-139 in gastric cancer cells. Gastroenterology. 2011;141:2076–2087.e6.View ArticleGoogle Scholar
- Iliopoulos D. MicroRNA circuits regulate the Cancer-inflammation link. Sci Signal 2014;7:pe8–pe8.View ArticleGoogle Scholar
- Yang D, Sun Y, Hu L, Zheng H, Ji P, Pecot CV, et al. Integrated analyses identify a master microRNA regulatory network for the mesenchymal subtype in serous ovarian cancer. Cancer Cell. 2013;23:186–99.View ArticleGoogle Scholar
- Acunzo M, Romano G, Wernicke D, Croce CM. MicroRNA and cancer--a brief overview. Adv Biol Regul. 2015;57:1–9.View ArticleGoogle Scholar
- Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005;120:15–20.View ArticleGoogle Scholar
- Wong N, Wang X. miRDB: an online resource for microRNA target prediction and functional annotations. Nucleic Acids Res. 2015;43(Database issue):D146–52.View ArticleGoogle Scholar
- Enright AJ, John B, Gaul U, Tuschl T, Sander C, Marks DS. MicroRNA targets in drosophila. Genome Biol. 2003;5:R1.View ArticleGoogle Scholar
- Betel D, Koppal A, Agius P, Sander C, Leslie C. Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites. Genome Biol. 2010;11:R90.View ArticleGoogle Scholar
- Moore MJ, Scheel TKH, Luna JM, Park CY, Fak JJ, Nishiuchi E, et al. miRNA–target chimeras reveal miRNA 3′-end pairing as a major determinant of Argonaute target specificity. Nat Commun. 2015;6:8864.View ArticleGoogle Scholar
- Teh YW, Jordan MI, Beal MJ, Blei DM. Hierarchical Dirichlet processes. J Am Stat Assoc. 2006;101:1566–81.View ArticleGoogle Scholar
- Escobar MD. Estimating normal means with a Dirichlet process prior. J Am Stat Assoc. 1994;89:268–77.View ArticleGoogle Scholar
- Escobar MD, West M. Bayesian density estimation and inference using mixtures. J Am Stat Assoc. 1995;90:577–88.View ArticleGoogle Scholar
- Müller P, Erkanli A, West M. Bayesian curve fitting using multivariate normal mixtures. Biometrika. 1996;83:67–79.View ArticleGoogle Scholar
- Rasmussen CE. The infinite Gaussian mixture model. In: In advances in neural information processing systems 12: MIT Press; 2000. p. 554–60.Google Scholar
- Antoniak CE. Mixtures of Dirichlet processes with applications to Bayesian nonparametric problems. Ann Stat. 1974;2:1152–74.View ArticleGoogle Scholar
- Loh Y-HE, Yi SV, Streelman JT. Evolution of microRNAs and the diversification of species. Genome Biol Evol. 2011;3:55–65.View ArticleGoogle Scholar
- Yue D, Liu H, Huang Y. Survey of computational algorithms for MicroRNA target prediction. Curr Genomics. 2009;10:478–92.View ArticleGoogle Scholar
- Kertesz M, Iovino N, Unnerstall U, Gaul U, Segal E. The role of site accessibility in microRNA target recognition. Nat Genet. 2007;39:1278–84.View ArticleGoogle Scholar
- Peterson SM, Thompson JA, Ufkin ML, Sathyanarayana P, Liaw L, Congdon CB. Common features of microRNA target prediction tools. Front Genet. 2014;5:23.View ArticleGoogle Scholar
- Hakguder Z, Liao C, Shu J, Cui J. A new statistical model for genome-scale MicroRNA target prediction. IEEE International Conference on Bioinformatics and Biomedicine (BIBM) 2017 p. 2017:101–7.Google Scholar
- Raftery AE. Bayes factors and BIC: comment on "a critique of the Bayesian information criterion for model selection". Sociol Methods Res. 1999;27:411–27.View ArticleGoogle Scholar
- O'Leary NA, Wright MW, Brister JR, Ciufo S, Haddad D, McVeigh R, et al. Reference sequence (RefSeq) database at NCBI: current status, taxonomic expansion, and functional annotation. Nucleic Acids Res. 2016;44(Database issue):D733–45.View ArticleGoogle Scholar
- Weinstein JN, Collisson EA, Mills GB, Shaw KM, Ozenberger BA, Ellrott K, et al. The Cancer genome atlas pan-Cancer analysis project. Nat Genet. 2013;45:1113–20.View ArticleGoogle Scholar
- Shu J, Silva BVRE, Gao T, Xu Z, Cui J. Dynamic and modularized MicroRNA regulation and its implication in human cancers. Sci Rep. 2017;7:13356.View ArticleGoogle Scholar
- Maragkakis M, Reczko M, Simossis VA, Alexiou P, Papadopoulos GL, Dalamagas T, et al. DIANA-microT web server: elucidating microRNA functions through target prediction. Nucleic Acids Res. 2009;37(Web Server):W273–6.View ArticleGoogle Scholar
- Reczko M, Maragkakis M, Alexiou P, Grosse I, Hatzigeorgiou AG. Functional microRNA targets in protein coding sequences. Bioinformatics. 2012;28:771–6.View ArticleGoogle Scholar


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Added: 2019-02-01
Category: plumbers


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DJEVEL - Blant Svarte Graner LP **
Blazing through the underground, Norwegian black metallers Djevel continues to lead their way through the old-school format as the traditionally-minded group heads out into the same fields and patterns normally reserved to the old-school ways which befit the band members collective experience.
While the ravenous old-school tendency carried throughout here is the main problem associated with it, there's little else that really strikes as being detrimental enough to allow this one to be of quite significant interest to any fan or interested party in second-wave Norwegian black metal.
Ltd. white vinyl in gatefold sleeve.


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Amelia Liana Easy Sculpting Tutorial
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Selected publications
Journal Articles
- A comparison of joint species distribution models for presence-absence data. Methods in Ecology and Evolution. 10. 2019
- A review of evidence about use and performance of species distribution modelling ensembles like BIOMOD. Diversity and Distributions. 2019
- Inferring species richness using multispecies occupancy modeling: Estimation performance and interpretation. Ecology and Evolution. 9. 2019
- Towards meaningful monitoring: A case study of a threatened rodent. Austral Ecology. 44. 2019
- blockCV: An r package for generating spatially or environmentally separated folds for k-fold cross-validation of species distribution models. Methods in Ecology and Evolution. 10. 2019
Journal Articles
- 20th Anniversary Editorial: Animal Conservation 1998-2018. Animal Conservation. 21. 2018
- A spatially integrated framework for assessing socioecological drivers of carnivore decline. Journal of Applied Ecology. 55. 2018
- High Carbon Stock forests provide co-benefits for tropical biodiversity. Journal of Applied Ecology. 55. 2018
- Model averaging in ecology: a review of Bayesian, information-theoretic, and tactical approaches for predictive inference. Ecological Monographs. 88. 2018
- Traits influence detection of exotic plant species in tropical forests. PLoS One. 13. 2018
- blockCV: an R package for generating spatially or environmentally separated folds for k-fold cross-validation of species distribution models 2018
Journal Articles
- Graphical diagnostics for occupancy models with imperfect detection. Methods in Ecology and Evolution. 8. 2017
- Model-based approaches to deal with detectability: a comment on Hutto (2016a). Ecological Applications. 27. 2017
- Modelling of species distributions, range dynamics and communities under imperfect detection: advances, challenges and opportunities. Ecography. 40. 2017
Journal Articles Refereed
- Cross-validation strategies for data with temporal, spatial, hierarchical, or phylogenetic structure. Ecography. 40. 2017
- Dealing with false-positive and false-negative errors about species occurrence at multiple levels. Methods in Ecology and Evolution. 8. 2017
- Species occupancy estimation and imperfect detection: shall surveys continue after the first detection?. A St A - Advances in Statistical Analysis. 101. 2017
Journal Articles Refereed
- Adaptive management for improving species conservation across the captive-wild spectrum. Biological Conservation. 199. 2016
- Cost-efficient effort allocation for camera-trap occupancy surveys of mammals. Biological Conservation. 204. 2016
- Deep-sea diversity patterns are shaped by energy availability. Nature. 533. 2016
- Statistical approaches to account for false-positive errors in environmental DNA samples. Molecular Ecology Resources. 16. 2016
Other Refereed Contribution to Refereed Journals
- Incorporating Imperfect Detection into Joint Models of Communities: A response to Warton et al.. Trends in Ecology & Evolution. 31. 2016
Journal Articles Refereed
- Accounting for detectability when surveying for rare or declining reptiles: Turning rocks to find the Grassland Earless Dragon in Australia. Biological Conservation. 182. 2015
- Is my species distribution model fit for purpose? Matching data and models to applications. Global Ecology and Biogeography. 24. 2015
- Threatened species impact assessments: survey effort requirements based on criteria for cumulative impacts. Diversity and Distributions. 21. 2015
- Valid auto-models for spatially autocorrelated occupancy and abundance data. Methods in Ecology and Evolution. 6. 2015
- When do we need more data? A primer on calculating the value of information for applied ecologists. Methods in Ecology and Evolution. 6. 2015
Journal Articles Refereed
- From planning to implementation: explaining connections between adaptive management and population models. Frontiers in Ecology and Evolution. 2. 2014
- Ignoring Imperfect Detection in Biological Surveys Is Dangerous: A Response to 'Fitting and Interpreting Occupancy Models'. PLoS One. 9. 2014
- Imperfect detection impacts the performance of species distribution models. Global Ecology and Biogeography. 23. 2014
- Maxent is not a presence-absence method: a comment on Thibaud et al.. Methods in Ecology and Evolution. 5. 2014
- Optimal surveillance strategy for invasive species management when surveys stop after detection. Ecology and Evolution. 4. 2014
- Two-Stage Bayesian Study Design for Species Occupancy Estimation. Journal of Agricultural, Biological, and Environmental Statistics. 19. 2014
Journal Articles Refereed
- Analysing and mapping species range dynamics using occupancy models. Journal of Biogeography. 40. 2013
- Cryptic mammals caught on camera: Assessing the utility of range wide camera trap data for conserving the endangered Asian tapir. Biological Conservation. 162. 2013
Journal Articles Refereed
- Designing studies to detect differences in species occupancy: power analysis under imperfect detection. Methods in Ecology and Evolution. 3. 2012
- Models for species-detection data collected along transects in the presence of abundance-induced heterogeneity and clustering in the detection process. Methods in Ecology and Evolution. 3. 2012
- When Is a Species Declining? Optimizing Survey Effort to Detect Population Changes in Reptiles. PLoS One. 7. 2012
Journal Articles
- Erratum to: Species Occupancy Modeling for Detection Data Collected Along a Transect(J. Agric. Biol. Environ. Stat, 10.1007/s13253-010-0053-3). Journal of Agricultural, Biological, and Environmental Statistics. 16. 2011
Journal Articles Refereed
- Impact of sampling with replacement in occupancy studies with spatial replication. Methods in Ecology and Evolution. 2. 2011
- Population Status of a Cryptic Top Predator: An Island-Wide Assessment of Tigers in Sumatran Rainforests. PLoS One. 6. 2011
- Species Occupancy Modeling for Detection Data Collected Along a Transect. Journal of Agricultural, Biological, and Environmental Statistics. 16. 2011
Journal Articles Refereed
- Design of occupancy studies with imperfect detection. Methods in Ecology and Evolution. 1. 2010
- Monitoring tigers with confidence. Integrative Zoology. 5. 2010
- Satellite imagery as a single source of predictor variables for habitat suitability modelling: how Landsat can inform the conservation of a critically endangered lemur. Journal of Applied Ecology. 47. 2010
- Using occupancy as a state variable for monitoring the Critically Endangered Alaotran gentle lemur Hapalemur alaotrensis. Endangered Species Research. 11. 2010


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Microsoft Azure Online Training
Course Brief
We are one of the few Microsoft Azure online training courses in Hyderabad that offer this course. Before getting into details, let us understand a few things about azure. Azure is a cloud computing program that was created by Microsoft. This program is mostly used to build, manage and deploy services and applications through various data managed centers.
Our Microsoft Azure online training offers a wide knowledge on the various cloud services ranging from storage, analytics, computing and networking among others. Our Microsoft Azure online training classes are uniquely structured to help people choose the services to develop new applications or run existing ones in public clouds.
This course will also equip you with skills on how to develop and manage, mobile, web and your line of business applications. Our Microsoft Azure online training courses also teach people on how to manage accounts access and user identify. A person can gain this and many more by enrolling for this course. Contact us today and stand out from your fellow competitors.
Our Azure certification training course covers the following topic:
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- An introduction to the cloud services. We will look at its concept, what it offers and how it can be used.
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Getting Started with Windows Azure
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Windows Azure Features
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Azure Media Services
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- Introduction to Identity and fundamentals of ACS
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Access Control Service
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Do you talk about what is Microsoft Azure and what it comprises of ?
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Does this course talk about how to integrate on premises core infrastructure ?
The Microsoft Azure course is complete and it covers most aspects of Azure. We have set aside an entire chapter that talks on how to integrate on premises and identity infrastructure using Microsoft Azure.
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We have many years of experience when it comes to offering online courses, including Microsoft Azure.Secondly; our course is designed in a manner everyone can understand what is being conveyed.
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Thank you for asking this important question.Yes, our certificates are globally recognized. We have met all the required standards set.Secondly; we have acquired all the necessary licenses that allow us to operate. They are always up to date.
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You can always organize for a makeup class with your course instructor.Alternatively; you can request a copy of the recorded class you go through it.
How long will it take for me to design an Azure application and run it on public cloud ?
There is no specific answer to this question. It depends on a person's understanding capacity. Our instructions are easy to understand.
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It will be better if you pay the entire fees. You can come to the office we discuss if you are planning to pay in installments.
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You can start class anytime a quorum has been attained. Register with us today to start with the next lot of students.
Here are some of the reviews we have received from students who enrolled for our Azure live online training course:
I was spending a lot of money hiring experts to design applications for me or run them using public clouds. The Microsoft Azure online training course has impacted me with enough knowledge to create and manage my various applications. Venktesh prasad
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I was really worried that my business was slowly collapsing. This is because my main competitors were ahead of me. I enrolled for this course as a last resort. This course taught me valuable things that made me effectively compete with my fellow competitors. Mohit gupta
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In the past few years, it seems that entertainment apps have taken over the mobile app landscape. Entertainment apps allow us to be entertained on-the-go, no matter where we are. Ten or so years ago, the only way to watch your favorite show or keep up with the latest entertainment news was at home with your TV or computer.
These days, you can access different forms of entertainment from your mobile devices, making it easy to stay in the loop wherever you are! Here are some of the best apps for entertainment.
There's a reason why Netflix is one of the most popular entertainment apps out there. The Netflix app allows users to watch their favorite movies and TV shows wherever they have a Wifi connection, as well as customize their recommendations towards programs they would be interested in.
The platform also features a variety of Netflix original movies, shows, and even stand-up comedy specials, so there is always something new to discover. If you don't already have a Netflix subscription, the platform offers a one-month free trial before you sign up.
Spotify is the go-to music streaming app for millions of people for its free basic services, easy-to-use layout, and huge music collection. Spotify allows users to build custom playlists that can be accessed wherever you have Wifi (a premium membership lets you listen to music offline, too) and quickly and easily search for artists and songs on the platform.
Spotify also features a "Discover Weekly" playlist, a playlist of songs curated to your unique tastes. Spotify is one of the best apps to quickly and seamlessly stream the music you want to listen to!
Special Guest
The Special Guest app has seriously been changing the landscape of entertainment apps. Special Guest is a talent app that allows users to hire talent to perform at various parties and events. The app, founded by actor and comedian Damon Wayans Jr. and entrepreneur and bestselling author Kris Jones, serves as a mutually beneficial platform that lets talented performers get paid for doing what they love.
Actors, comedians, musicians, and even celebrity impersonators are available for booking through the app, and people looking to hire talent can check out past performances to get a feel for a performer before booking them. Special Guest is currently available exclusively in the Apple App Store.
SoundCloud is sort of a cross between a music streaming service and a social media platform. SoundCloud allows anyone to upload original music to the platform, as well as podcasts and audiobooks. For aspiring musicians who just want to be heard, SoundCloud provides a free way to upload original work and build an audience. Many now-famous artists once got their start on SoundCloud, and the platform continues to be the go-to for up-and-coming talent to this day.
Dating Apps
If you are single then you would enjoy talking to some people online and why not make friends and even more in real life. We live in an era where there is an app for almost everything so why not for talking with others too. You may even find women for marriage on this sites. Just because they are designed for flirts and causal dates, it doesn't mean you can't find your soul mate there.


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· U5 Series Firmware Update [2018.12.01]
I'm DinoBot Supporters.
· Update contents
1. Fixed problem where LPCM 5.1 / 7.7 channel audio is played in 2 channels when playing Blu-ray file
· U5Mimi ATV8 Beta Update Instructions
With this update, ATV8 (Android 8) beta version of U5Mini can be used.
Because it is still in beta, it only supports OTA update via update server.
U5PVR users will receive ATV8 version support after the official version update of U5Mini product.
ATV8 version is in beta, so there are many things to improve.
The media center was not included in the update, especially because the media center was not working properly.
ATV8 non-implementation details are as follows.
1. CEC function not implemented.
2. AOL (Android Over Linux) function not implemented.
3. Backup / Restore function not implemented.
4. Media center function not implemented.
ATV7 <==> ATV8 is supported by OTA but all user data will be erased, so please be aware that you can use it only if you want to test the beta version.
· Firmware manual download link
· Full Version : Update after device initialization.(all installed apps and all settings are initialized.)
· Normal Version : Update without device initialization.(Existing apps and settings are available.)
# U5PVR:Deluxe
· Full Version : http://U4Quad.iptime.org/firmware/atv7/deluxe/U5Quad_BADA/full/update.zip
· Normal Version : http://U4Quad.iptime.org/firmware/atv7/deluxe/U5Quad_BADA/default/update.zip
# U5PVR:Slim
· Full Version : http://U4Quad.iptime.org/firmware/atv7/slim/U5Quad_BADA/full/update.zip
· Normal Version : http://U4Quad.iptime.org/firmware/atv7/slim/U5Quad_BADA/default/update.zip
# U5Mini (PVR&OTT Integrated firmware)
· Full Version : http://U4Quad.iptime.org/firmware/atv7/mini/full/update.zip
· Normal Version : http://U4Quad.iptime.org/firmware/atv7/mini/default/update.zip
· Previous version firmware download link
# U5Mini Firmware download : https://drive.google.com/drive/folders/1ZriruzYss2jWLegG8lkSNA46MN2LmaUY?ogsrc=32


text:
Trump on Taking Syrian Refugees: 'They Could Be ISIS, It Could Be a Plot'
On "Hannity" tonight, Donald Trump stood by his statement that as president, he would ship out all the Syrian refugees who are brought into America.
Trump pointed out that the U.S. already has too many problems, including a multi-trillion dollar deficit.
"Now, we're going to start taking 200,000 people. We have no idea where they come from. They could be ISIS. It could be a plot," Trump said, adding he notices a lot of "young, strong men" among the refugees but not a lot of women.
Trump explained that during a speech in New Hampshire, he said that he would notify any refugee coming to the U.S. that he will ship them out. He said that some critics have responded to that statement by asking how he plans to do that.
"Well, they're shipping them in, why can't we ship them out?" Trump said. "If we take 200,000 people - and they could very well be ISIS, we have no idea who they are - we are absolutely insane. This country is going insane."
Trump also weighed in on the increasing Russian aggression in Syria. Earlier this week, Trump urged caution by the U.S. and argued that it's a "wonderful thing" that Russia wants to fight ISIS in Syria.
Trump told "Hannity" that the U.S. doesn't aim for victory anymore in its military engagements, whether it's Iraq, Afghanistan or fighting ISIS.
"We used to be the country that never lost a war. Now, we never win a war," Trump said. "We haven't had the right leaders. We haven't had the right thinking or thought process. Hopefully, if I win, that will change and it'll change quickly."
The GOP contender stood by his stance that he doesn't want the U.S. to be bogged down in Syria, which he said could now happen to Russia.
Watch the interview above, and hear more from Trump on "Cashin In" with Eric Bolling, Saturday at 11:30a ET.
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text: GALLEGOS RUIZ, Roberto, CHINKULTIC: una cuidad Maya, Intro. By Roman Pina Chan, 126 p. with lots of illustrations, includes ceramics (Jaguar God of the Underworld incensarios) and architecture. Probably has more pictures of Chinkultic than any prior or subsequent book. Tells the story of draining and dredging the cenote at Chinkultic hoping to find a treasure comparable to that of Chichen Itza.


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Last summer, I attended an event at Raised Bar in the Renaissance Hotel Chicago with Tour Texas courtesy of Windy City Bloggers. I was able to chat with representatives from several cities around Texas from San Antonio to Houston to Irving. While visiting Texas on my annual trip last fall, I reconnected with the rep from Irving and had the opportunity to join other members of the media on a weekend press trip. It was an incredible experience where I got to meet several wonderful people and we all had a ton of fun. Honestly, it was a blast. I was overfed, over-entertained and I have so many great memories from that trip. Not to mention my to-do list for the DFW area which has since expanded by about five times what it started at.
We visited several restaurants, toured many sites and met quite a few people. I can only hope that they invite me on another trip in the future because let me tell you, no one does it like Texas does. They pulled out all the stops and made sure we all had a great time but more importantly, felt like we were at home. I have a lot of posts coming up on Irving and the DFW area in general over the next few months but today, we're kicking it off with five things you should do in Irving. It's short and sweet, a great way to kick start your adventure of a new destination.
Big Beat Dallas (grand opening March 29 - Apr. 2nd)
During our tour of the city, we got a behind the scenes look at Big Beat Dallas while it was still under construction. Almost three months later the location has come a long way with opening weekend set for March 29th through April 2nd. I'm so excited for this entertainment giant to open that I may even take a quick trip back to Irving just to experience the opening events!
The space will include an indoor/outdoor farmers and ranchers market serving everything from seasonal produce to fresh meats, cheeses and retail items. Restaurant concepts include a Latin-style bar, walk-up barbecue joint, wine and scotch bars, outdoor food stations, Texas-style restaurant concept, martini bar, ice cream, and much more. Free music performances will happen every single day of the year and properties throughout the center will also include live blues, American-style jazz, piano bars and more. The Facebook page for Big Beat Dallas is a great source of updates and information and they're getting a lot of great local media attention at the moment as well. Next time I make it to the DFW area, I'll definitely be checking out Big Beat which you can expect to see on here as well.
Big State Fountain Grill
Would you believe me if I said I'd never tried any kind of soda float before my most recent visit to Irving? Well, you're not alone. Several of the people in the group of the press trip I went on couldn't believe it either. Let's back it up for a second. The Big State Fountain Grill was one of the stops on our Tour of Irving Day and boy am I glad it was. What has to be one of the few remaining old-school diners, Big State Fountain Grill is run by family and feels like family. The staff are so friendly and the food is SO good. The owner's daughter, who runs the joint, actually came out from working on the line in the kitchen to chat with us. It was a unique experience in the best kind of way. Big State has an enormous menu with anything you could think of but what you really need to visit for is their Fountain Favorites. Get a Big State Root Beer or Cream Soda. If you prefer ice cream, you'll never see larger scoops! It was at Big State I had my first ever soda float. I don't like Root Beer but that was no problem. They came out with a gigantic Dr. Pepper float and I think my mind is still blown.
Irving Heritage District (Downtown)
The Irving Heritage District is the downtown area of the city of Irving. It's main goal is to preserve the history of the city and display it for locals and visitors to experience. Heritage Park features "The Caster Cabin built in 1887, a replication of the Rock Island Depot built in 1903, and Irving's first water tower, windmill, and library" (source: Visit Irving). Visit one of Irving's oldest homes at the Heritage House which has period antiques and items to take you back in time. The Heritage District additionally includes the Texas Musicians Museum, Big State Diner, and more.
Texas Musicians Museum
Music lovers are going to enjoy this one. The Texas Musicians Museum celebrates local talent with memorabilia and artifacts. From Selena to Buddy Holly, the Dixie Chicks to Destiny's Child, and Tonya Tucker to ZZ Top, this museum has a little bit from every corner of the music industry. Even Barney! Listen to original records, see musical instruments and outfits from the artists. Anyone would find at least one artist they admire or love in this museum. Tours are available for those interested in a more informed experience. They also have live entertainment on weekends! Grab some grub at Smokin' Joe's Cafe with a margarita and watch a Texas-born musician perform.
The Mustangs of Las Colinas & Museum
A sculpture created by African wildlife artist Robert Glen, the Mustangs of Las Colinas depict "nine bronze mustangs galloping across a granite prairie stream." It's a gorgeous piece with an odd setting. The "stream" and waterfall is peaceful. Since we visited on the weekend, it was quiet but on any other weekday, the square would be bustling with people. It almost seemed like an oxymoron but in a beautiful kind of way. Across the street from the Mustangs of Las Colinas is the museum which showcases the life and story of Robert Glen, especially the eight years of work it took to create this sculpture in particular.


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Used to integrate Android apps with Facebook Platform. - facebook/facebook- android-sdk. Samples - 84 releases - Facebook - facebook-android-sdk/NOTICE. Used to integrate Android apps with Facebook Platform. - facebook/facebook- android-sdk. View code and samples on Github. Component SDKs. The Facebook SDK for Android contains six component SDKs that you can connect to individually.
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