Biology subjects

Dey, U.

Publications and source records attributed to Dey, U..

3 recordsLinked to original sources

bioRxiv2026

Regions of genome plasticity are systematically organized into recurrent integration spots that shape accessory-genome functional architecture: insights from a complete genome of strain F1C1 and pangenomic analysis of the Ralstonia solanacearum species complex

1The Ralstonia solanacearum species complex (RSSC) is a highly diverse plant pathogen whose evolution is shaped by horizontal gene transfer. We generated a complete, gap-free hybrid genome assembly of F1C1, a South Asian Phylotype I strain classified as R. pseudosolanacearum. The closed assembly resolves a bipartite genome (3.73 Mb chromosome; 2.03 Mb megaplasmid), enabling precise localization of mobile genetic elements. Using F1C1 together with 142 complete RSSC genomes, we implemented a lineage-stratified pangenome framework that reveals a hierarchically structured gene repertoire and shows that accessory gene content can discriminate host-associated lineages beyond core-genome. Pangenome-informed mapping of genome plasticity identified 651 conserved integration spots that concentrate accessory turnover and are enriched for adaptive functions, including type III secretion system effectors and antiviral defense systems (e.g., Wadjet and CRISPR-Cas). Genes within these spots display elevated Ka/Ks relative to housekeeping functions, consistent with conflict-driven diversification and/or relaxed constraint. Together, these results link RSSC genome architecture to adaptive potential and provide a spot-based framework for genomic surveillance and resistance breeding in bacterial wilt pathosystems.

genomics↗

bioRxiv2025

DNA Conformational Flexibility Descriptors Improve Transcription Factor Binding Prediction Across the Protein Families

Precise binding of transcription factors (TFs) to specific DNA sequences is fundamental to gene regulation, yet the molecular principles underpinning TF-DNA specificity remain incompletely understood. While nucleotide sequence and DNA shape are known determinants of TF binding, the role of DNA flexibility encompassing axial, torsional, and stretching dynamics-- remains largely unexplored, particularly across diverse TF families. Here, we systematically integrate experimentally and computationally derived DNA flexibility descriptors into predictive models of TF-DNA binding specificity. Through extensive analyses of large-scale in vitro datasets from HT-SELEX, SELEX-Seq, protein binding microarrays encompassing mam-malian and Drosophila TFs, we demonstrate that flexibility-augmented models consistently outperform sequence based models, and DNA shape augmented models to an extent. These improvements are robust across diverse experimental platforms, and scale of the datasets, underscoring the importance of DNA conformational dynamics in indirect readout. Quantitative analyses of position-specific flexibility contributions reveal distinct "flexibility hotspots" within transcription factor binding sites and their flanking regions. This is exemplified by structural insights into the homeodomain TF MSX1, where localized DNA bendability directly correlates with enhanced binding affinity and precise recognition specificity. Finally, leveraging in vivo ChIP-Seq and DNase-Seq data from ENCODE, we further validate that DNA flexibility substantially enhances the identification of functional TF binding sites across various TF families and cellular contexts. Collectively, current findings substantiate DNA flexibility as a fundamental element of the cis-regulatory code and significantly advancing predictive frameworks of gene regulatory networks.

bioinformatics↗

bioRxiv2025

DNA sequence encoded conformational flexibility orchestrates pioneer transcription factor nucleosome interaction landscape

BackgroundEukaryotic gene regulation depends on transcription factors (TFs) recognizing short DNA motifs within chromatin. Many of these motifs lie within nucleosomes, where DNA is sharply bent, rotationally phased, and constrained by histone-DNA contacts. Yet only a subset is occupied in any cellular context. Motif identity alone, therefore, cannot fully explain selective TF engagement with nucleosomal DNA. We asked whether sequence-derived DNA conformational flexibility provides an interpretable representation of sequence context relevant to TF recognition on nucleosomes. ResultsWe compiled five DNA flexibility descriptors in the Python package DNAflexpy, representing bendability, torsional deformation, backbone conformational variability, and stiffness. We built quantitative models of TF binding affinity across 226 datasets from a high-throughput in vitro TF-nucleosome binding assay. Flexibility-augmented models improved prediction over mononucleotide baselines in most datasets, with smaller but reproducible gains over trinucleotide baselines. The gains were not uniform: they varied across TF families and were concordant with DNA shape-fluctuation features, suggesting that DNAflexpy descriptors capture a sequence-encoded structural signal. In PIONEAR-seq data, model performance generalized across nucleosomal templates in a TF- and sequence-dependent manner. Beyond prediction, position-resolved flexibility footprints revealed deformation signatures at cognate motifs and flanking regions across diverse TF families. For SOX11, model-derived footprints aligned with DNA shape fluctuations from nanosecond-to-microsecond molecular dynamics trajectories of SOX11-bound nucleosomes, consistent with independently observed DNA conformational dynamics and bound-state stabilization. The in vivo data showed a similar but more context-dependent pattern. OCT4 occupancy tended to correlate with local flexibility, whereas GATA3-pioneered regions showed flexibility coupled with altered rotational positioning of cognate motifs. Flexibility-augmented classifiers further improved discrimination of occupied nucleosomal motifs across ENCODE datasets. Torsional flexibility features, particularly twist dispersion and trx, were most informative for classification. ConclusionsSequence-derived DNA conformational flexibility provides a quantitative and interpretable representation of sequence context in TF recognition on nucleosomes. By augmenting sequence with structural information, these models help quantify and interpret an indirect-readout contribution in which DNA deformation tendencies may complement motif sequence and DNA shape. This framework may help explain why only selected motif instances are engaged in chromatin, without treating flexibility as independent of primary sequence.

bioinformatics↗