Biology subjects

Dar, S.

Publications and source records attributed to Dar, S..

4 recordsLinked to original sources

bioRxiv2026

TOXsiRNA: A web server to predict the toxicity of chemically modified siRNAs

Small interfering RNAs (siRNAs) are largely modified with chemical molecules to enhance their properties for use in molecular biology research and therapeutic applications. Toxicity effects may arise due to these chemical moieties as well as sequence based off-targets at cellular level. Enormous resources are required to experimentally design and test the toxicity of these chemical modifications and their combinations on siRNAs. To address this problem, we developed TOXsiRNA web server to computationally predict the toxicity of chemically modified siRNAs and their off-targets. We selected 2749 siRNAs with different permutations and combinations of 21 different chemical modifications engineered on them. Next, we used Support Vector Machine (SVM), Linear Regression (LR), K-Nearest Neighbor (KNN) and Artificial Neural Network (ANN) machine learning applications to develop models. Best performance was displayed by mononucleotide composition-based model developed with SVM, offering Pearson Correlation Coefficient (PCC) of 0.91 and 0.92 on training testing and independent validations respectively. Other sequence features like dinucleotide composition binary pattern and their combinations were also tested. Finally, three models of chemically modified siRNAs were implemented on the web server. Other algorithms that include predicting normal as well as chemically modified siRNA knockdown efficacy, off target etc. are also integrated. The resource is hosted online for scientific use freely at url: http://bioinfo.imtech.res.in/manojk/toxsirna.

bioinformatics↗

bioRxiv2026

PEPsRNA: A computational resource of experimentally tested peptide based siRNA delivery

In siRNA-based applications, cellular delivery remains one of the main hurdles. Many formulations are tested for the same and peptides came up as one of the optimal options. The latter have various advantages like natural biological presence, high specificity, and natural metabolism etc. siRNA in conjugation with peptides have exhibited enhanced mRNA silencing. Peptides aid siRNAs in condensation to smaller volumes, enhance nuclease protection, increase half-life, promote cell specific binding as well as endosomal escape and release in cytosol. Despite its prime importance, no resource is available for the peptide-based delivery of siRNAs, therefore to fill the gap we developed PEPsRNA web server. It includes 2266 entries of 270 different kinds of peptides, 106 different types of siRNAs and shRNAs along with more than 80 conjugate molecules targeting 55 different genes, experimentally tested for the delivery of the siRNAs. To provide the detailed insights of the procedure, we have incorporated analysis of the peptides (e.g. secondary structure, amino acid composition, polarity, hydrophobicity etc.), siRNAs (e.g. secondary structures with minimum free energies etc.) and associated conjugate molecules (e.g. structure, SMILES, Inchl). We have derived these values using various other tools and resources to make the web server comprehensive. We further compared various physicochemical properties with the efficacy of the peptide based on the target gene silencing, but these properties do not shown any distinct conclusive relationship. The data is available for browsing, searching and downloading freely on the web server with URL: http://bioinfo.imtech.res.in/manojk/pepsirna. Highlights PEPsRNA is the first database of experimentally tested peptides for siRNA delivery It comprised of 2266 entries with 270 peptides and about 80 conjugate molecules Analysis of peptides, siRNAs and details of conjugate molecules are provided Browse, search and various tools are incorporated for data retrieval and usage

bioinformatics↗

bioRxiv2024

Caging of membrane-to-cortex attachment proteins can trigger cellular symmetry breaking

To migrate, divide, and change shape, cells must regulate the mechanics of their periphery. The cell surface is a complex structure that consists of a thin, contractile cortical actin network tethered to the plasma membrane by specialized membrane-to-cortex attachment (MCA) proteins. This active and constantly fluctuating system maintains a delicate mechanochemical state which permits spontaneous polarization and shape change when needed. Combining in silico, in vitro, and in vivo experiments we show how membrane viscosity and MCA protein length regulate cortical dynamics. We reveal a novel mechanism whereby caging of linker proteins in the actin cortex allows for the amplification of small changes in these key parameters, leading to major alterations of cortical contractility. In cells, this mechanism alone gives rise to symmetry breaking phenomena, suggesting that local changes in lipid composition, in combination with the choice of MCA proteins, contribute to the regulation of cellular morphogenesis and function.

biophysics↗

bioRxiv2023

Gene body DNA hydroxymethylation restricts the magnitude of transcriptional changes during aging

DNA hydroxymethylation (5hmC), the most abundant oxidative derivative of DNA methylation, is typically enriched at enhancers and gene bodies of transcriptionally active and tissue-specific genes. Although aberrant genomic 5hmC has been implicated in age-related diseases, its functional role in aging remains unknown. Here, using mouse liver and cerebellum as model organs, we show that 5hmC accumulates in gene bodies associated with tissue-specific function and restricts the magnitude of gene expression changes with age. Mechanistically, 5hmC decreases the binding of splicing associated factors and correlates with age-related alternative splicing events. We found that various age-related contexts, such as prolonged quiescence and senescence, drive the accumulation of 5hmC with age. We provide evidence that this age-related transcriptionally restrictive function is conserved in mouse and human tissues. Our findings reveal that 5hmC regulates tissue-specific function and may play a role in longevity.

genomics↗