Motivation: Aptamers are synthetic nucleic acid molecules that can bind biological targets in virtue of both their sequence and three-dimensional structure. Aptamers are selected using SELEX, Systematic Evolution of Ligands by EXponential enrichment, a technique that exploits aptamer-target binding affinity. The SELEX procedure, coupled with high-throughput sequencing (HT-SELEX), creates billions of random sequences capable of binding different epitopes on specific targets. Since this technique produces enormous amounts of data, computational analysis represents a critical step to screen and select the most biologically relevant sequences.
Results: Here, we present APTANI, a computational tool to identify target-specific aptamers from HT-SELEX data and secondary structure information. APTANI builds on AptaMotif algorithm, originally implemented to analyze SELEX data; extends the applicability of AptaMotif to HT-SELEX data and introduces new functionalities, as the possibility to identify binding motifs, to cluster aptamer families or to compare output results from different HT-SELEX cycles. Tabular and graphical representations facilitate the downstream biological interpretation of results.
Availability And Implementation: APTANI is available at http://aptani.unimore.it.
Contact: silvio.bicciato@unimore.it
Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btv545 | DOI Listing |
bioRxiv
November 2024
Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada.
We describe an effort ("Codebook") to determine the sequence specificity of 332 putative and largely uncharacterized human transcription factors (TFs), as well as 61 control TFs. Nearly 5,000 independent experiments across multiple and assays produced motifs for just over half of the putative TFs analyzed (177, or 53%), of which most are unique to a single TF. The data highlight the extensive contribution of transposable elements to TF evolution, both in and , and identify tens of thousands of conserved, base-level binding sites in the human genome.
View Article and Find Full Text PDFbioRxiv
November 2024
Vavilov Institute of General Genetics, Russian Academy of Sciences, 119991, Moscow, Russia.
A DNA sequence pattern, or "motif", is an essential representation of DNA-binding specificity of a transcription factor (TF). Any particular motif model has potential flaws due to shortcomings of the underlying experimental data and computational motif discovery algorithm. As a part of the Codebook/GRECO-BIT initiative, here we evaluated at large scale the cross-platform recognition performance of positional weight matrices (PWMs), which remain popular motif models in many practical applications.
View Article and Find Full Text PDFNucleic Acids Res
November 2024
Neurogenomics Group, Hospital del Mar Research Institute, Parc de Recerca Biomèdica de Barcelona (PRBB), Dr. Aiguader, 88, Barcelona 08003, Catalonia, Spain.
Proneural factors of the basic helix-loop-helix family coordinate neurogenesis and neurodifferentiation. Among them, NEUROG2 and NEUROD2 subsequently act to specify neurons of the glutamatergic lineage. Disruption of these factors, their target genes and binding DNA motifs has been linked to various neuropsychiatric disorders.
View Article and Find Full Text PDFNucleic Acids Res
October 2024
Department of Surgery, Brown University, 69 Brown St Box 1822, 02912 RI, USA.
It was previously shown that DNA breathing, thermodynamic stability, as well as transcriptional activity and transcription factor (TF) bindings are functionally correlated. To ascertain the precise relationship between TF binding and DNA breathing, we developed the multi-modal deep learning model EPBDxDNABERT-2, which is based on the Extended Peyrard-Bishop-Dauxois (EPBD) nonlinear DNA dynamics model. To train our EPBDxDNABERT-2, we used chromatin immunoprecipitation sequencing (ChIP-Seq) data comprising 690 ChIP-seq experimental results encompassing 161 distinct TFs and 91 human cell types.
View Article and Find Full Text PDFBrief Bioinform
January 2024
CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, 200031, China.
Non-coding variants associated with complex traits can alter the motifs of transcription factor (TF)-deoxyribonucleic acid binding. Although many computational models have been developed to predict the effects of non-coding variants on TF binding, their predictive power lacks systematic evaluation. Here we have evaluated 14 different models built on position weight matrices (PWMs), support vector machines, ordinary least squares and deep neural networks (DNNs), using large-scale in vitro (i.
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