Search term box facilitates a search of TTSs by TTS ID, Entrez gene ID, NCBI reference sequence (refSeq) ID, chromosome location, gene symbol or gene description keywords.
In addition, to speed up the search, TTSs were categorized into groups based on basic search criteria of TTS including:
(the search engine will automatically find start and end position of chromosome 1 and search TTS belonging entire the chromosome)
(The search engine will list TTS which are located in chromosome 1 starting from position 1,971,769 to position 2,106,694)
(The search engine will list TTS which are located in genomic vicinity of Entrez Gene identifier 5590)
(The search engine will list TTS which are located in genomic vicinity of RefSeq identifer NM_001033581)
(The search engine will search TTS with TTS identifer TTS.1.24.2027361)
(The search engine will list genes with HUGO Gene Nomenclature Committee identifier PRKCZ)
(The search engine will list genes containing "oncogene" in gene description)
(The search engine will list genes containing "oncogene" and "kinase" in gene description)
(The search engine will list genes containing "oncogene" but not "viral" and "virus" in gene description)
(The search engine will list genes containing "proto-oncogene" in gene description)
(The search engine will list all TTS found in the human genome; hg18)
Too many TTS came out from the search term? "Filtering options" (FO) panel provides optional filtration for more specific TTS(s) based on genome co-localization of TTSs with annotated gene region and several other structural and functional annotation tracks. It helps the user focus on the structural and functional features of TTS of interest. In addition, FO allows the user to choose combination of TTS with some specific TTS search criteria (e.g. TTS length, off-targets, %G, and di-nucleotide content), specific gene regions, gene regulatory regions, etc. FO tools are useful to select biologically meaningful TTS(s) that could be used as the targets for TFO-based molecular biology techniques, drug discovery and anti-gene therapy. In addition, it also provides TTS search criteria optimization for GA and GT motifs of TFO reported by Vekhoff, Ceccaldi et al. (2008), as well as exclusion of TTS containing repeat element and/or non-B DNA structures.
These options allow users to filter TTS results by incorporating a range of nucleotide properties as follow:
In addition, number of potential off-target TTSs with one base mismatch could be adjust based on acceptable off-target risk defined by user. Although, TTSMI database provides only unique location of TTSs in the human genome, TTS sequences with single mismatch could be found in other genomic locations (called TTS off-target sites) and could potentially form triplex structure with TFO with much less triplex stability. Therefore, the less number of off-targets that the TTS has, the more specific it is.
We provide co-localization of TTS with gene function-associated annotation tracks including Chromatin accessibility, Chromatin state, TFBS by ChIP-Seq experiment, CpG Island, G-quadruplex, Non-B DNA structures, TFBS by conserved motifs, evolutionary conserved region, repeat element, and SNPs build 138,
This option allows user to extract lists of TTS that co-localize with annotation track of interest or combination of annotation tracks. Furthermore, it provides logical operator "AND" and "OR" to input combination of annotation tracks. The logical "AND" will list the TTS that co-localize with all selected annotation tracks while the logical "OR" will list the TTS that co-localize with at least one of selected annotation tracks.
It has been known that triplex structure have different biological roles in different gene regions. The co-localization of TTS with specific gene region can help user to limit the list of TTS in the particular regions of interest (e.g. promoter or 5'UTR).
To do that the user can check box for the specific gene regions as listed here.
The knowledge based filtering option is provided for the user who looks for the prospective
DNA targets for the designing specific TFO. The filtering criteria are
described in Vekhoff, Ceccaldi et al. (2008)
.
The search criteria will be set as below when the option was checked.
Furthermore, users can filter out the sequences which could potentially compete with triplex-forming structure by forming alternative DNA structures such as G-quadruplex and non-B DNA.