Biology subjects

Shukla, G.

Publications and source records attributed to Shukla, G..

4 recordsLinked to original sources

bioRxiv2026

novelBGC: An interactive dual-score framework for biosynthetic gene cluster novelty assessment and candidate prioritisation

Genome mining now yields tens of thousands of putative biosynthetic gene clusters (BGCs) per project, yet, separating genuinely novel candidates from rediscoveries of known compounds remains the rate-limiting step before experimental validation. Single-axis prioritisation tools, antiSMASH similarity, BiG-FAM GCF distance, and self-resistance-enzyme (SRE) filters such as ARTS, each surface a different facet of evidence, yet their isolated use systematically over-ranks rediscovery-prone BGCs and overlooks genuinely orphan clusters. We present novelBGC, a web-hosted framework that converts these disparate outputs into two deliberately non-inverse continuous metrics per BGC, a Novelty (N) and a Reference Similarity (RS) score which together define a 2D decision plane that resolves rediscoveries, divergent family members, contig-edge artefacts, and uncharted chemistry with interactive visualisations, with all component weights user-tuneable at submission. Retrospective validation across three independent experimental datasets demonstrates the utility of the framework for candidate prioritization. Within the first 186-BGC SRE-guided cloning study, every confirmed bioactive product fell within the low-to-mid N band whereas 55 high-N (N [≥] 0.50) BGCs were never selected. Moreover, in the other two studies, it correctly prioritised the fully orphan lariocidin BGC of Paenibacillus sp. M2 and the divergent within-family indanopyrrole-A idp BGC of Streptomyces sp. CNX-425. Together, these case studies demonstrate that the joint (N, RS) space facilitates prioritization decisions that are difficult to achieve using any single criterion alone. from identical input data. novelBGC requires no command-line expertise, no local tool installation, and no manual integration of intermediate output formats, addressing a well-documented accessibility barrier for wet-laboratory researchers engaging with genome-mining workflows. novelBGC is freely available at https://project.iith.ac.in/sharmaglab/novelbgc/.

bioinformatics↗

bioRxiv2025

16S-23S-5S rRNA Database: a comprehensive integrated database of archaeal and bacterial rRNA sequences, alignments, intragenomic heterogeneity, and secondary structures

The 16S-23S-5S ribosomal RNA (rRNA) gene operon is a cornerstone of ribosomal architecture and function, making it an indispensable molecular marker for microbial taxonomy and phylogenetics. Despite the extensive development of 16S rRNA gene databases, a significant void persists in comprehensive resources that integrate all three rRNA genes (16S, 23S, and 5S), their precise alignments, intragenomic heterogeneity, and intricate structural details. To address this critical research gap, we introduce the 16S-23S-5S rRNA Database, a meticulously curated and intuitive platform encompassing around 5000 complete bacterial and archaeal genomes. This database provides granular operon-level annotations, robust alignment data, quantitative copy number statistics, percent identity matrices, and predicted secondary structures for each rRNA component. Our rigorous methodology integrates covariance models from RFAM with BLAST-based analyses for sequence comparisons, Clustal Omega for multiple sequence alignment, and Circos for genomic visualization, thereby elucidating the genomic architecture, sequence diversity, and structural conservation of rRNA genes. Crucially, the database systematically accounts for intragenomic heterogeneity, a factor paramount for accurate microbial classification and the inference of evolutionary trajectories. Our analysis reveals prevalent phyla such as Pseudomonadota (1,891 genomes), Actinomycetota (846 genomes), and Bacillota (773 genomes), with Bacillota exhibiting the highest average rRNA gene copy numbers (e.g., 16S = 6.64 {+/-} 3.3, 23S = 6.63 {+/-} 3.3, and 5S = 6.8 {+/-} 3.3). Across all bacterial genomes, the 16S, 23S, and 5S rRNA genes exhibited average copy numbers of 4.25 {+/-} 2.88, 4.24 {+/-} 2.89, and 4.44 {+/-} 3.08, respectively. The responsive web interface, engineered with HTML5, JavaScript, and Flask, incorporates user feedback mechanisms to enhance usability. By integrating these comprehensive elements, the 16S-23S-5S rRNA Database not only fills a substantial lacuna in the field of rRNA data analysis but also establishes a foundational resource for large-scale investigations in microbial systematics, genome evolution, and ribosomal biology, benefiting taxonomists, microbial genomics, and microbiome researchers alike. Availability and implementation: The 16S-23S-5S rRNA Database is available as an open-access database at https://project.iith.ac.in/sharmaglab/rrnadatabase/. ImportanceUnderstanding the diversity of microbes is essential for research in health, environment, and biotechnology. Ribosomal RNA (rRNA) genes, especially the 16S gene, are commonly used to classify microbes, but studies often ignore the full set of rRNA genes (16S, 23S, and 5S) together. Our work bridges this gap by creating the first comprehensive database that includes all three rRNA genes from around 5,000 microbial genomes. It offers detailed annotations, sequence alignments, intragenomic heterogeneity, and structural insights, helping scientists more accurately classify microbes and trace their evolution. This resource is designed to be easy to use and will support a wide range of microbiological research.

genomics↗

bioRxiv2024

A unique bacterial family strikes again!

In a recent study, Rolf Muller and colleagues identified a novel myxobacterial family Pendulisporaceae, encompassing four new strains with biosynthetic gene clusters (BGCs) largely distinct from known families. These strains, sourced from 1980s soil samples, display unique genomic and chemical features, suggesting significant biotechnological and pharmaceutical potential. This study underscores the value of exploring underrepresented microbial taxa for novel natural products, highlighting the potential of the family Pendulisporaceae as a source of new antimicrobial and therapeutic agents.

microbiology↗

bioRxiv2019

Phosphorimidate Derivatives of Acyclovir; Antiviral Activity Against Canine Parvovirus In Vitro

Canine parvovirosis is a very transmissible, severe and often deadly infectious disease of dogs caused by Type II canine parvovirus (CPV-2). Recently shows that Parvoviruses are very resistant to Acyclovir which is often used for HSV Chemotherapy in humans and various virucidal purposes in animal diseases in veterinary clinics and animal housing facilities. If acquiescence with vaccination programs and with appropriate decontamination plans is guaranteed, there should be no continuous, nor common, CPV-2 outbreaks. However, a continuous spread of CPV-2 infections is observed, even in shelters where an appropriate vaccination program is applied, and this is reason to provide an antiviral drug therapy. The aim of the present study was to Development of antiviral drugs with determination the effect of concentration of new chemical entity and analyze Acyclovir analogous against CPV-2 strains. A sensitive in vitro assay capable of measuring the infectivity of CPV-2 was employed to determine the efficacy of three different concentrations of 9-(2-hydroxyethomethyl)guanine phosphoromonomorpholidate. We successfully show that new compounds inhibit CPV-2 replication with exhibiting 50% inhibitory concentrations (IC50s) in the low-micromolar range (50M).

pharmacology and toxicology↗