Biology subjects

Tandon, D.

Publications and source records attributed to Tandon, D..

5 recordsLinked to original sources

bioRxiv2025

METRIN-KG: A knowledge graph integrating plant metabolites, traits and biotic interactions

BackgroundIn recent years, biodiversity data management has emerged as a critical pillar in global conservation efforts. Today, the ability to efficiently collect, structure, and analyze biodiversity data is central to breakthroughs in conservation, drug development, disease monitoring, ecological forecasting, and agri-tech innovation. However, due to the vastness and heterogeneity of biodiversity data, it is often confined to databases for specific research areas in isolated formats and disconnected from other relevant resources. Crucial components of such data in kingdom Plantae comprise of metabolomes - the vast array of compounds produced by plants; traits - measurable characteristics of plants that influence their growth, survival, and reproduction, and that affect ecosystem processes; and biotic interactions - relationships of plants with other living organisms, affecting the ecosystem functions. ResultsIn this work, we present METRIN-KG (MEtabolomes, TRaits, and INteractions-Knowledge Graph) a powerful data resource simplifying the integration of diverse and heterogeneous data resources such as plant metabolomes, traits, and biotic interactions. ConclusionsThe proposed knowledge graph provides an interface to interactively search for data relating plant metabolomes, traits, and interactions. This, in turn, will facilitate development of research questions in life-sciences. In this context, we provide representative case studies on how to frame queries that can be used to search for relevant data in the knowledge graph.

bioinformatics↗

bioRxiv2025

Decoupling bile acid 7α-dehydroxylation from colonization resistance to Clostridioides difficile

Secondary bile acids, generated through microbial transformation of primary bile acids secreted in bile, play a role in shaping intestinal microbial communities, modulating host immunity, and regulating energy metabolism. In vitro studies have shown that the balance between primary and secondary bile acids strongly affects spore germination, growth, and cellular physiology of Clostridioides difficile, a major nosocomial gut pathogen. In vivo correlations between microbiome composition, bile acid metabolome, and colonization resistance have led to the hypothesis that 7-dehydroxylating bacteria such as Clostridium scindens protect against C. difficile infection by producing secondary bile acids like deoxycholic acid. However, due to the genetic intractability of known 7-dehydroxylating species, direct experimental validation of this causal relationship has been challenging. In this study, we leveraged the first available 7-dehydroxylation-deficient baiH mutant to test the direct role of 7-dehydroxylated bile acid production in C. difficile colonization resistance in vivo. We colonized gnotobiotic mice with isogenic wild-type or baiH strains of the recently described 7-dehydroxylating species Faecalicatena contorta, including wild-type C. scindens-colonized mice as a positive control. Wild-type F. contorta accumulated 7-dehydroxylated bile acids at levels equivalent to C. scindens, in a strictly baiH-dependent manner. However, despite equivalent bile acid profiles, wild-type F. contorta failed to replicate the C. difficile-restrictive phenotype observed with C. scindens. These findings demonstrate that commensal clostridial 7-dehydroxylation alone is not sufficient for enhancing colonization resistance to C. difficile. Our results highlight the existence of additional, potentially bile acid-independent mechanisms by which certain commensals mediate protection, with important implications for microbiota-based therapies. Importance7-dehydroxylated secondary bile acids, including deoxycholic acid and lithocholic acid, produced by commensal clostridia are widely assumed to inhibit the important nosocomial pathogen Clostridioides difficile, yet their precise role in colonization resistance remains unresolved. Using a defined mouse microbiota and an isogenic Faecalicatena contorta strain pair differing in a single 7-dehydroxylation gene (baiH), we show that restoration of secondary bile acid production is not sufficient to delay C. difficile colonization in vivo. This contrasts with the protective effect of Clostridium scindens, which generates a similar bile acid profile. Our findings uncouple bile acid metabolism from protection and suggest that additional, strain-specific functions - such as nutrient competition or antimicrobial production - play a critical role. Understanding these mechanisms is essential for the rational design of next-generation microbiota-based therapies to prevent or treat recurrent C. difficile infection.

microbiology↗

bioRxiv2024

How clinically relevant are prostate cancer cell lines? A comprehensive characterisation and multiomics comparison.

Cell line experiments arguably remain the most used tool in preclinical cancer research, despite their limitations. With almost 95% drugs entering human trials failing, and up to 90% preclinical research failing before even being tested in humans, we must shift the pre-clinical paradigm. A range of in silico, in vitro, in vivo and ex vivo approaches are gaining popularity, with the aim of potentially replacing cell line use. However, we cannot ignore the plethora of historical data from cell lines, nor write off their future use- especially within advanced bioengineered models. Therefore, we must question if and how cell lines hold clinical relevance. This study evaluates the clinical characteristics of 46 prostate cancer cell lines against worldwide data and investigates the biological features of seven cell lines in depth, comparing them to over 10,000 well characterised human cases from 24 studies in nine countries. Clinical features compared included age, ethnicity, Gleason grade, cancer type, treatment history and multiomics variables included mutations, copy number alterations, structural variants, microsatellite instability, mRNA and protein expression, and tumour mutational burden. We found that the most used cell lines accurately represent a minute proportion of prostate cancer patients. Furthermore, we recommend a pipeline for tailoring selection of clinically relevant cell lines with the ultimate aim of increasing the scientific methodology behind choosing a cell line.

cancer biology↗

bioRxiv2023

Pipeline for species-resolved full-length16S rRNA amplicon nanopore sequencing analysis of low-complexity bacterial microbiota

16S rRNA amplicon sequencing is a fundamental tool for characterizing prokaryotic microbial communities. While short-read 16S rRNA sequencing is a proven standard for examining complex microbiomes, it cannot achieve taxonomic classification beyond genus level. Third-generation sequencing technologies, particularly nanopore sequencing, have allowed for full-length 16S rRNA gene sequencing enabling enhanced taxonomic resolution to species and strain levels. Precise species-to-strain level classification is crucial in investigating low-complexity microbiota. This research presents an efficient pipeline using full-length 16S rRNA amplicon nanopore sequencing, spanning library prep to computational analysis for low-complexity microbiota composition analysis. We applied this pipeline to a defined intestinal bacterial community in gnotobiotic mice to evaluate different methods. Our findings revealed that the proprietary barcoded universal primers 27F-1492R from Oxford Nanopore Technologies(ONT) 16S amplicon sequencing kit did not efficiently amplify the 16S rRNA gene of Bifidobacterium species. Addressing this constraint, we designed degenerate primers and employed ONTs native barcoding kit for library preparation. We developed a customized wet lab and bioinformatics pipeline for processing and classifying amplicon reads at the species level. Validation of the protocol using a mock community DNA sample with known composition confirmed a reduced analytical bias. Additionally, our method surpassed Illumina short-read V3-V4 amplicon sequencing, achieving accurate species-level classification compared to Illuminas genus-level accuracy. This pipeline is tailored for analyzing the composition of low-complexity microbiota from natural ecosystems and synthetic/gnotobiotic communities. It is cost- and time-effective and therefore accessible for small-scale studies that would otherwise be hindered by the typically long turnaround times of NGS services. Importance16S rRNA amplicon sequencing is conventionally used to identify microbes and determine their composition in microbial communities. Deep amplicon sequencing of complex microbiomes is well established using short-read sequencing targeting variable regions of the 16S rRNA gene. Short reads enable the classification of bacteria until the genus level in the taxa hierarchy, whereas long reads provide better chances of identifying bacteria to species and even strain levels. This study introduces a streamlined approach for analyzing simple microbial communities using full-length 16S rRNA amplicon nanopore long read sequencing. This approach surpasses Illumina sequencing in species accuracy, is cost-effective and time-efficient. Tailored for low-complexity microbiota, it facilitates studies in natural or synthetic communities, especially beneficial for smaller-scale projects with limited resources.

bioinformatics↗

bioRxiv2022

The stationary phase-specific sRNA fimR2 is a multifunctional regulator of bacterial motility, biofilm formation and virulence

Bacterial pathogens employ a plethora of virulence factors for host invasion, and their use is tightly regulated to maximize infection efficiency and manage resources in a nutrient-limited environment. Here we show that during Escherichia coli stationary phase the small non-coding RNA fimR2 regulates fimbrial and flagellar biosynthesis at the post-transcriptional level, leading to biofilm formation as the dominant mode of survival under conditions of nutrient depletion. fimR2 interacts with the translational regulator CsrA, antagonizing its functions and firmly tightening control over motility and biofilm formation. Generated through RNase E cleavage, fimR2 regulates stationary phase biology independently of the chaperones Hfq and ProQ. The Salmonella enterica version of fimR2 induces effector protein secretion by the type III secretion system and stimulates infection, thus linking the sRNA to virulence. This work reveals the importance of bacterial sRNAs in modulating various aspects of bacterial physiology including stationary phase and virulence. HighlightsO_LIfimR2 expression causes biofilm formation and alters bacterial outer membrane architecture C_LIO_LIfimR2 modulates CsrA activity and sequesters it from its targets C_LIO_LIThe Salmonella fimR2 variant is functional in E. coli C_LIO_LIfimR2 is generated through RNase E processing and enhances infectivity C_LI

molecular biology↗