TFLink: an integrated gateway to access transcription factor–target gene interactions for multiple species

Abstract

Analysis of transcriptional regulatory interactions and their comparisons across multiple species are crucial for progress in various fields in biology, from functional genomics to the evolution of signal transduction pathways. However, despite the rapidly growing body of data on regulatory interactions in several eukaryotes, no databases exist to provide curated high-quality information on transcription factor–target gene interactions for multiple species. Here, we address this gap by introducing the TFLink gateway, which uniquely provides experimentally explored and highly accurate information on transcription factor–target gene interactions (∼12 million), nucleotide sequences and genomic locations of transcription factor binding sites (∼9 million) for human and six model organisms: mouse, rat, zebrafish, fruit fly, worm and yeast by integrating 10 resources. TFLink provides user-friendly access to data on transcription factor–target gene interactions, interactive network visualizations and transcription factor binding sites, with cross-links to several other databases. Besides containing accurate information on transcription factors, with a clear labelling of the type/volume of the experiments (small-scale or high-throughput), the source database and the original publications, TFLink also provides a wealth of standardized regulatory data available for download in multiple formats. The database offers easy access to high-quality data for wet-lab researchers, supplies data for gene set enrichment analyses and facilitates systems biology and comparative gene regulation studies. Database URL https://tflink.net/

Learning gene networks under SNP perturbation using SNP and allele-specific expression data

“…S14 HIP). For the trans -acting eQTLs from Type II blocks, we looked for TFs in the genome neighborhood and the targets of the TF in the TFLink database 24 that overlap with the eGenes. We focused on Type II blocks, as these eQTLs were in relatively small linked regions.…”

AutophagyNet: High-resolution data source for the analysis of autophagy and its regulation

“…Although the knowledge on autophagy regulation has been expanded significantly, data on post-translational and (post-)transcriptional regulations are scattered across many resources -making it difficult to find and integrate highquality and relevant data. Currently, there are large-scale databases such as BioGrid [68] TFLink [19] and TarBase [30] to describe these regulatory interactions. However, these resources do not provide autophagy regulation-related information, therefore filtering to autophagy-related data can be challenging and time consuming.…”

“…The dataset behind AutophagyNet was made up-to-date by downloading the most recent datasets of sources used previously in the ARN resource. We have also added four further, large resources (e.g., OmniPath [24] and TFLink [19]), resulting in a total of 23 high quality resources (Supplementary Table 2). Compared to the ARN, in AutophagyNet, we have nearly doubled the number of transcription factors (from 413 to 829) and miRNAs (from 386 to 609) involved in the regulation of autophagy.…”

“…Information on the type of interaction (i.e. phosphorylation, co-localization), interaction detection methods and other annotations were also imported from the integrated resources (e.g., InnateDB [29], TFlink [19] and TarBase [30]) where available.…”

“…However, current data on transcriptional regulation of autophagy genes is scattered across many resources (e.g., DoRothEA [17] and GTRD [18]), which makes it challenging to find and integrate high-quality and relevant data. To bridge this gap, TFLink [19] was developed, collecting and integrating transcription factor -target gene interactions from major databases. However, even TFLink does not provide a way to investigate direct and indirect autophagyregulating transcription factors.…”