LncTarD is a resource that comprehensive curated functional lncRNA-target regulations in human diseases and integrated pan-cancer transcriptome data from The Cancer Genome Atlas. Currently, LncTarD documents 2822 experimentally-supported functional lncRNA-target regulations and expression associations in 177 human diseases. LncTarD provides important information about how these disease-related lncRNAs contribute to the pathogenesis, which targets are the downstream key mediators, which functions are affected, and regulatory mechanisms of lncRNAs in human diseases. LncTarD provides a user-friendly interface for conveniently browsing regulation network of functional lncRNA-target, searching and downloading the functional lncRNA-target regulations in various diseases. In addition, LncTarD provides a submission function that allows researchers to submit novel functional lncRNA-target regulations that are not documented. The detailed usage of the database is as followings:
The home page contains one schematic diagram to help users understand our database. The left figure is a conceptual graph illustrating the regulatory mechanisms of functional lncRNA-targets which affected important biological functions in human diseases (step 1 in figure below). The right text in the home page shows the summary of LncTarD database (step 2 in figure below).
User can query the LncTarD database through Quick Search and Advanced Search. Quick Search page: users can input an lncRNA or disease name or biological function to search functional lncRNA-target regulations (step 3 in figure above). In this page, only one term could be used, for combined search, please go to "Search" module. Advanced Search page: advanced search provides two panels for searching experimentally-supported functional regulation and expression association, respectively. Search panels provide multiple options for customized search of the interested contents. Users can query the interested disease-associated functional lncRNA-target regulations by combining different key words, including disease, function, drug, lncRNA, target gene and regulatory mechanism. LncTarD also offers fuzzy keyword searching capabilities, which enables easy searching by returning the closest possible matching records (see figure below). For example: 1) Input an interested disease name to query related functional lncRNA-target regulations. 2) Input an interested biological function to query related functional lncRNA-target regulations. 3) Input an interested drug. Obtaining functional lncRNA-target regulations related with drug-resistance or drug-sensitivity. 4) LncRNA-mediated regulatory mechanisms including transcriptional regulation, epigenetic regulation, chromatin looping, ceRNA or sponge, interacting with mRNA and interacting with protein could be used to obtain the results. 5) Input your interested lncRNAs or lncRNA aliases to query related regulations. 6) Input your target genes to query related regulations. Users can also input both an lncRNA and target gene to search for their regulations.
The browse page is built based on standardized classification scheme of human disease (according to Disease Ontology database) and different hierarchical classification. To browse the functional lncRNA-target regulations related a particular disease (such as Lung cancer), please click 'DiseaseCategory' (step 1 in figure below), then choose 'Cancer' and corresponding cancer type 'Lung cancer' (step 2, 3 in figure below). The lung cancer-related lncRNA-target regulations will be returned. If we are interested a particular subtype of lung cancer (such as Lung adenocarcinoma), please click 'Lung adenocarcinoma' (step 4 in figure below). The lung adenocarcinoma-related lncRNA-target regulations will show on table format on the top panel (step 5 in figure 3), as well as a functional network on the bottom panel (step 6 in figure 3). Similarly, the users can browse all entries associated with an interested event (Genes, Functions and Drugs) in a similar way.
you can click the button below the table to show the functional lncRNA-target network in lung adenocarcinoma.
In addition, browser page also provides statistics information about functional lncRNA-target regulations and human diseases.
LncTarD results are organized in a data table, with a single association record on each line that contains disease name, lncRNA name, target name, regulated direction, expression pattern of lncRNA, influenced biological functions and regulatory mechanism. For example, in Advanced Search page, experimentally-supported functional regulation panel, we input "angiogenesis" as an interested biological function. Click the "Search" button to submit. We obtained 15 experimentally-supported functional lncRNA-target regulations which are involved in angiogenesis in human diseases (see figure below).
DiseaseName: The associated disease. Regulator: The name of regulator gene, such as an lncRNA. Target: The name of target gene. RegulationDirection: The regulator negatively or positively regulated the target gene. ExpressionPattern: The differentially expressed pattern of regulators in human disease. InfluencedFunctions: The biological function positively (+) or negatively (-) affected by the lncRNA-target regulation in human disease. RegulatoryMechanism: lncRNA-mediated regulatory mechanism in human disease, including transcriptional regulation, epigenetic regulation, chromatin looping, ceRNA or sponge, interacting with mRNA and interacting with protein. More Details: Clickable links for accessing the detail information of each lncRNA-target regulation. After clicking the links, the details of the functional lncRNA-target regulation will be displayed as a table at below. Their differentially expression patterns, their pearson correlation coefficient and a scatter plot of lncRNA-target expression in TCGA pan-cancers will be also shown.
The network visualization aims to intuitively display the lncRNA-target regulation in human disease, their influenced biological functions, the regulatory mechanisms and related drugs. This network is illustrated with ECharts plugins. Three layout presentations are available: 'Radial Tree' (by default), 'Horizontal Tree' (i.e. Left to Right Tree) and 'Vertical Tree' (i.e. Top to Bottom Tree). For example, the figure below using 'Radial Tree' layout shows the functional lncRNA-target regulations which are involved in angiogenesis in human diseases.
Now we change the layout. The figure below using 'Horizontal Tree' layout shows the functional lncRNA-target regulations which are involved in angiogenesis in human diseases.
To further learn and explore the interested functional lncRNA-target regulation in human disease, user can click "More Details" in the result table to obtain the corresponding metadata. 1) Basic information
Experimental method for lncRNA-target: the method of experimental validation for each lncRNA-target regulation. Experimental method for lncRNA expression: method of experimental validation for lncRNA expression dysregulation. Data Accession: lncRNA microarray or lncRNA sequence data, which used to validate the dysregulation of lncRNA expression.Click the link to download the relevant data. Regulatory Type: There are three regulatory types including association, binding/interaction and regulation. The lncRNA-target relationships obtained based on knockdown or overexpression of a specific lncRNA (association). There are molecular interaction or binding sites between lncRNA and targets (binding/interaction). Other lncRNA-target relationships are regarded to regulation. Level of Regulation: If regulatory type of lncRNA-target is binding/interaction, we recorded the molecular level of interaction. For example, RNA-RNA represents the lncRNA interacting with mRNA or miRNA. Drugs: The lncRNA-target regulation contribute to chemoresistance or chemosensitivity of the drug. Cancer Stem Cell: The association between the functional lncRNA-target regulation and cancer stem cell. Hallmark: The cancer hallmarks influenced by the functional lncRNA-target regulation. Disease Category: The category of diseases based on Disease Ontology. Regulator Type: The gene type of the regulator. Target Type: The gene type of the target. Regulatory EnsembleID: The Ensemble ID of the regulator. Target EnsembleID: The Ensemble ID of the target. Regulator EntrezID: The Entrez ID of the regulator. Target EntrezID: The Entrez ID of the target. Regulator Aliases: The aliases of lncRNAs or TFs. Target Aliases: The aliases of genes. Target Aliases: The aliases of genes. Regulator Location: The genomic location of the regulator. Target Location: The genomic location of the target. Evidence: The detailed descriptions of the functional lncRNA-target regulation in human disease according to the reference. PubMed: The pubmed ID of the reference.
2) Differentially expressed patterns of the functional lncRNA-target regulation based on TCGA/GEO dataset was shown if available. Table: the table shows differential expression pattern of lncRNAs and targets. FC: A base-2 logarithm to fold changes of genes expression between tumor samples and normal samples. FDR: False discovery rate of genes expression between tumor samples and normal samples using DEseq2/limma.
The boxplot shows the expression distribution of genes (TPM value). * Fold change>2 and FDR < 0.05, Statistical analyses were using DEseq2/limma.
3) Expression correlation of functional lncRNA-target regulation based on TCGA/GEO dataset was also shown if available. In addition, to show the dynamic expression correlation of functional lncRNA-target regulations in human disease, pearson correlation coefficients between lncRNA and key target in each of 33 TCGA cancer types are shown. After clicking interested cancer type in heatmap, a scatter plot of lncRNA-target expression will be shown if available (as figure below shows).
Similar visualization results for lncRNA microarray or sequence data used in the original article showed in "GEO" panel.
To download data in the LncTarD, select the menu 'Download'. LncTarD provides downloadable file in TEXT format. This file contains key targets and important biological functions driven by disease-related lncRNAs and lncRNA-mediated regulatory mechanisms in human diseases. Additionally, lncRNA microarray or sequence data used in the original articles, differentially expressed patterns of lncRNAs and targets, expression correlation and significance level between lncRNA and key target in 33 TCGA cancer types are also provided.
LncTarD offers a submission page that enables other researchers to submit novel functional lncRNA-target regulation data in human diseases. Once approved by the submission review committee, the submitted record will be included in the LncTarD database and made available to the public in the update release.