The TTSMI database: a catalog of triplex target DNA sites associated with genes and regulatory elements in the human genome

Abstract

A triplex target DNA site (TTS), a stretch of DNA that is composed of polypurines, is able to form a triple-helix (triplex) structure with triplex-forming oligonucleotides (TFOs) and is able to influence the site-specific modulation of gene expression and/or the modification of genomic DNA. The co-localization of a genomic TTS with gene regulatory signals and functional genome structures suggests that TFOs could potentially be exploited in antigene strategies for the therapy of cancers and other genetic diseases. Here, we present the TTS Mapping and Integration (TTSMI; http://ttsmi.bii.a-star.edu.sg) database, which provides a catalog of unique TTS locations in the human genome and tools for analyzing the co-localization of TTSs with genomic regulatory sequences and signals that were identified using next-generation sequencing techniques and/or predicted by computational models. TTSMI was designed as a user-friendly tool that facilitates (i) fast searching/filtering of TTSs using several search terms and criteria associated with sequence stability and specificity, (ii) interactive filtering of TTSs that co-localize with gene regulatory signals and non-B DNA structures, (iii) exploration of dynamic combinations of the biological signals of specific TTSs and (iv) visualization of a TTS simultaneously with diverse annotation tracks via the UCSC genome browser.

Figure 1.

A screenshot of the TTSMI database and the search results. (A) TTS search terms and basic search criteria (e.g. Gene ID 4609). (B) TTS filtering options, which are categorized into four groups: ‘Sequence context’ (sequence content of the TTS), ‘Gene region annotation’ (the TTS is located in a specific gene annotation regions), ‘Annotation tracks’ (the TTS shares a common nucleotide with the annotation tracks) and ‘Other options’ (other helpful options). (C) A close-up screenshot of TTS search results showing the current active filtering options, including gene regions and annotation tracks, as well as the paging, genome visualization and downloading buttons at the bottom. (D) Chromosome view of TTS locations (Watson strand in blue and Crick strand in red) in the human genome via the UCSC genome browser. (E) TTS information page of TTS.8.23.128748414 (the detailed information is available in Supplementary Figure S3).

Figure 2.

The TTS locations of anti-TNF-α targets in the mouse chromosome and two TTS candidates in the human chromosome.