Biology subjects

Paul, D.

Publications and source records attributed to Paul, D..

At least 37 records · Page 2Linked to original sources

bioRxiv2023

Activity and abundance of nitrous oxide consuming bacteria in Platismatia glauca cryptogamic lichen in boreal Finnish spruce forest.

The boreal spruce forest soil can assimilate atmospheric N2O through symbiotic relationships with mycorrhizae or with bacteria, especially during spring and autumn, when aerobic microsites to soil can form. In cold soils with large field capacity (FCD), high humidity and absence of fertilisation, a balance between absorption and emission of nitrous oxide and dinitrogen was observed to be close to zero, and even to assume negative values in some cases, thus suggesting that forest soils absorb more N2O than they emit. Furthermore, in the presence of cryptogamic coverings of mosses and lichens, the absorption value was observed to be greater than in forests with less coverage; although the main role in N2O absorption is played by soil and root system. However, the role played by epiphytic organisms in N2O absorption in the boreal forests has not been uncovered yet. We studied, N2O dynamics of the lichen, Platismatia glauca, showing that N2O is consumed especially at lower incubation temperatures. The quantitative analysis with real-time PCR of nitrous oxide reductase gene fragment nosZ, showed that enzyme is present in the lichen and the gene is more transcribed under lower incubation temperature. The presented results unveil that cryptogamic covers consume nitrous oxide (with values between 0.1 and 0.4 ng N2O-C/g (ww)/h) at the atmospheric concentration via complete dissimilatory denitrification when nitrogen is limited.

microbiology↗

bioRxiv2023

Pump-free and high-throughput generation of monodisperse hydrogel beads by microfluidic step emulsification for dLAMP-on-a-chip

Step emulsification (SE), which generates droplets by a sharp change in confinement, has emerged as a potential alternative to flow-focusing technology. Water/dispersed phase is continuously pumped through a shallow inlet channel into a deep chamber pre-filled with the oil/continuous phase. The need for one or more pumps to maintain a continuous flow for droplet generation, and the consequent use of high sample volumes, limit this technique to research labs. Here, we report a pumpfree SE technique for rapid and high-throughput generation of monodisperse hydrogel (agarose) beads using <40 {micro}l sample volume. Instead of using syringe pumps, we sequentially pipetted oil and liquid agarose into a microfluidic SE device to generate between 20000 and 80000 agarose beads in [~] 2 min. We also demonstrated the encapsulation of loop-mediated isothermal amplification mixture inside these beads at the time of their formation. Finally, using these beads as reaction chambers, we amplified nucleic acids from P. falciparum and SARS-CoV-2 inside them. The pump-free operation, tiny sample volume, and high-throughput generation of droplets by SE make our technique suitable for point-of-care diagnostics.

bioengineering↗

bioRxiv2023

Functional antagonistic interactions and genomic insights into the biosynthetic potential of human gut-derived microbiota

Concerning the biological interactions within the gut microbiome, the specialized small molecules encoded by commensal microbes mediate distinct functional aspects. However, the landscape of antagonistic interactions mediated by specialized strains and their small molecules broadly remains. Here, we sought to evaluate antimicrobial interactions as a defensive contributor to gain new insights into structure-related functions or to bring the therapeutic potential of derived molecules. We elucidated the antagonistic landscape within a collection of 330 human-gut-derived commensal microbial strains cultivated from healthy human subjects. We characterized potential antagonistic strains and found a strain-specific selective inhibition contrary to common antimicrobial drugs that wipe out a broad range of species usually found in environmental microbes. Using functional and genomic approaches for accessing biologically active natural product molecules, we identified significant biosynthetic gene clusters (BGCs) encoding the important compound families in representative gut strains which contribute to antagonistic activities and are important in host defense or maintaining homeostasis in the gut. The subsets of the BGCs were represented in metagenomics sequencing data from healthy individuals. The cell culture secretome of strains revealed potential biomarkers linked to hallmark pathways. Together, these microorganisms encode biosynthetic novelty and represent a source of biologically significant natural products important in developing new treatments for infectious diseases to cut the usage of broad-spectrum antibiotics and represent a way to combat antimicrobial resistance. Consortia of such strains can be utilized as an option for precise editing of the microbiomes or fine-tuning the microbiota-modulating therapies.

microbiology↗

bioRxiv2023

TOBF1 modulates mouse embryonic stem cell fate through co-transcriptional regulation of alternative splicing

Embryonic stem (ES) cells retain the ability to undergo lineage-specific differentiation that can eventually give rise to different cell types that constitute an organism. Although stem cell specific biological networks of transcription factors and epigenetic modifiers are well established, how the ES cell specific transcriptional and alternative splicing (AS) machinery regulate their expression has not been sufficiently explored. In this study, we show that the lncRNA associated protein TOBF1 regulates the co-transcriptional alternative splicing of transcripts necessary for maintaining stem cell identity in mouse ES cells. Overlaying information derived from TOBF1 chromatin occupancy, the distribution of its pluripotency-associated OCT-SOX binding motifs, and transcripts undergoing differential expression and alternative splicing upon its disruption unmasked local nuclear territories where these distinct events converge, ultimately leading to the maintenance of mouse ES cell identity.

developmental biology↗

bioRxiv2022

Anomalous diffusion of E. coli under microfluidic confinement and chemical gradient

We report a two-layer microfluidic device to study the combined effect of confinement and chemical gradient on the motility of wild type E. coli. We track individual E. coli in 50m and 10m wide channels, with a channel height of 2.5m, to generate quasi-2D conditions. We find that contrary to expectations, bacterial trajectories are super-diffusive even in absence of a chemical (glucose) gradient. The superdiffusive behaviour becomes more pronounced on introduction of a chemical gradient or on strengthening the lateral confinement. Runlength distributions for weak confinement in absence of chemical gradients follow an exponential distribution. Both confinement and chemoattraction induce deviations from this behaviour, with the runlength distributions approaching a power-law form under these conditions. Both confinement and chemoattraction suppress large angle tumbles as well. Our results suggest that wild-type E. coli modulates both its runs and tumbles in a similar manner under physical confinement and chemical gradient.

biophysics↗

bioRxiv2022

Meta-analysis of (single-cell method) benchmarks reveals the need for extensibility and interoperability

Computational methods represent the lifeblood of modern molecular biology. Benchmarking is important for all methods, but with a focus here on computational methods, benchmarking is critical to dissect important steps of analysis pipelines, formally assess performance across common situations as well as edge cases, and ultimately guide users on what tools to use. Benchmarking can also be important for community building and advancing methods in a principled way. We conducted a meta-analysis of recent single-cell benchmarks to summarize the scope, extensibility, neutrality, as well as technical features and whether best practices in open data and reproducible research were followed. The results highlight that while benchmarks often make code available and are in principle reproducible, they remain difficult to extend, for example, as new methods and new ways to assess methods emerge. In addition, embracing containerization and workflow systems would enhance reusability of intermediate benchmarking results, thus also driving wider adoption.

bioinformatics↗

bioRxiv2021

A Comprehensive in silico study for the Identification of Therapeutic target against Peripheral Neuropathic Pain in human

BackgroundVGF (non-acronymic) is a neuropeptide precursor or neuro-protein or neurosecretory protein which plays vital roles in the regulation of gastric contractility, mood regulation, and peripheral neuropathic pain and possibly, cancer. ObjectiveVGF may be a potential target as it has a unique contribution to the development of neuropathic pain which is a target for Oxymatrine (OMTR). MethodBased on this, we have endeavored to discover VGF inhibitors from the ChEMBL database of Oxymatrine (OMTR) analogues by employing homology modelling, molecular docking and pharmacophore analysis. ResultOur in silico investigation reveals that 13-Methoxymatrine has desired characteristics for becoming a future formulation. ConclusionTo confirm the efficacy of this compound, essential animal and clinical trials are needed to be performed. We believe that our present study will help to find an efficient and effective therapy for treating neuropathic pain in human which is modulated by VGF.

bioinformatics↗

bioRxiv2021

Oral glucose feeding enhances adherence of quiescent lymphocytes to fibronectin via non-canonical insulin signalling.

Impaired glucose metabolism is associated with chronic inflammation, aberrant immunity and anomalous leukocyte trafficking. Conversely, infusion of functional immune cells restores glucose metabolism. Despite being exposed to periodic alterations in blood insulin levels upon fasting and feeding, studies exploring the physiological effects of these hormonal changes on quiescent circulating lymphocytes are missing. Here we find that oral glucose load in healthy men and mice enhance adherence of circulating peripheral blood mononuclear cells (PBMCs) to fibronectin. This led to increased homing of post-load PBMCs to injured blood vessels. Cell culture based experiments on Jurkat-T cells and PBMCs demonstrated that insulin elicits these adhesive effects through a non-canonical signalling involving insulin growth factor-1 receptor (IGF-1R) and phospholipase C gamma-1 (PLC{gamma}-1) mediated activation of integrin {beta}1. Our findings point to the relevance of post-prandial insulin spikes in regulating homing of circulating T-cells to various organs for tissue repair and immunity. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=123 SRC="FIGDIR/small/464163v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@11edce6org.highwire.dtl.DTLVardef@1389835org.highwire.dtl.DTLVardef@90c96eorg.highwire.dtl.DTLVardef@1988a63_HPS_FORMAT_FIGEXP M_FIG Insulin mediates fibronectin adherence of lymphocytes through non-canonical signalling. Insulin mediates auto-phosphorylation of IGF-1 receptor at Tyr1135 leading to activation of PLC-{gamma}1 through Tyr783 phosphorylation, which in turn leads to the activation of integrin 1 through intracellular calcium to ultimately enhance adhesion of quiescent lymphocytes to fibronectin. C_FIG

physiology↗

bioRxiv2021

Convergent use of phosphatidic acid for Hepatitis C virus and SARS-CoV-2 replication organelle formation

Double membrane vesicles (DMVs) are used as replication organelles by phylogenetically and biologically distant pathogenic RNA viruses such as hepatitis C virus (HCV) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Viral DMVs are morphologically analogous to DMVs formed during autophagy, and although the proteins required for DMV formation are extensively studied, the lipids driving their biogenesis are largely unknown. Here we show that production of the lipid phosphatidic acid (PA) by acylglycerolphosphate acyltransferase (AGPAT) 1 and 2 in the ER is important for DMV biogenesis in viral replication and autophagy. Using DMVs in HCV-replicating cells as model, we found that AGPATs are recruited to and critically contribute to HCV replication and DMV formation. AGPAT1/2 double knockout also impaired SARS-CoV-2 replication and the formation of autophagosome-like structures. By using correlative light and electron microscopy, we observed the relocalization of AGPAT proteins to HCV and SARS-CoV-2 induced DMVs. In addition, an intracellular PA sensor accumulated at viral DMV formation sites, consistent with elevated levels of PA in fractions of purified DMVs analyzed by lipidomics. Apart from AGPATs, PA is generated by alternative pathways via phosphotidylcholine (PC) and diacylglycerol (DAG). Pharmacological inhibition of these synthesis pathways also impaired HCV and SARS-CoV-2 replication as well as formation of autophagosome-like DMVs. These data identify PA as an important lipid used for replication organelle formation by HCV and SARS-CoV-2, two phylogenetically disparate viruses causing very different diseases, i.e. chronic liver disease and COVID-19, respectively. In addition, our data argue that host-targeting therapy aiming at PA synthesis pathways might be suitable to attenuate replication of these viruses. One Sentence SummaryPhosphatidic acid is important for the formation of double membrane vesicles, serving as replication organelles of hepatitis C virus and SARS-CoV-2, and offering a possible host-targeting strategy to treat SARS-CoV-2 infection.

microbiology↗

bioRxiv2021

Analysis of variability of functionals of recombinant protein production trajectories based on limited data

We propose a method for analyzing the variability in smooth, possibly nonlinear, functionals associated with a set of product production trajectories measured under different experimental conditions. The key challenge is to make meaningful inference on these parameters across different experimental conditions when only a limited number of measurements in time are collected for each treatment, and when there are only a few, or no, replicates available. For this purpose we adopt a modeling approach by representing the production trajectories in a B-spline basis, and develop a bootstrap-based inference procedure for the parameters of interest, also accounting for multiple comparisons. The methodology is applied to study two types of quantities of interest - "time to harvest" and "maximal productivity" in the context of an experiment on the production of certain recombinant proteins under laboratory conditions. We complement the findings by extensive numerical experiments that look into the effects of different types of bootstrap procedures and associated schemes for computing p-values for tests of hypotheses.

bioengineering↗

bioRxiv2021

Modelling Human Gait using a Nonlinear Differential Equation

We introduce an innovative method for the investigation of human gait, which is based on the visualisation of the vertical component of the movement of the centre of mass during walking or running, in the space of the coordinates position, velocity, and acceleration of the centre of mass. Collected data has been numerically approximated by the best fitting curve for a non-linear model. The resulting equation for the best fitting plane or curve in this space is a differential equation of second order. The model that we suggest is a Duffing equation with coefficients that depend on the height of a walker or runner and on the angular frequency of the oscillation. Statistics about the distribution of the Duffing stiffness depending on the speed is presented. 1 Author SummaryWe study the human gait modelled by the movement of the centre of mass of the test person. This is an example of a biological process which can be considered as a periodical dynamic system. Roughly, this movement behaves in a similar way to a vibrating mass suspended on a spring, but it is more complex. The vertical component of the movement during walking or running can be visualised as an oscillogram: a graph of the position as a function of time. We suggest a visualisation of the data in 3D space, where the coordinates describe position, velocity, and acceleration. Our new visualisation method allows us to model the movement of a persons centre of mass by a nonlinear differential equation. The resulting curve for an ideal spring-mass movement, without viscosity or external force, is an ellipse in the suggested 3D space. The shape of the data curve shows at which position an additional force was applied, or the movement slowed down. Some deviations are common for all test persons and others are different. In the future we plan to investigate the reasons for these deviations, such as different running techniques or the presence of injuries.

bioengineering↗

bioRxiv2021

Temperature-dependent Self assembly of biofilaments during red blood cell sickling

Molecular self-assembly plays vital role in various biological functions. However, when aberrant molecules self-assemble to form large aggregates, it can give rise to various diseases. For example, the sickle cell disease and Alzheimers disease are caused by self-assembled hemoglobin fibers and amyloid plaques, respectively. Here we study the assembly kinetics of such fibers using kinetic Monte-Carlo simulation. We focus on the initial lag time of these highly stochastic processes, during which self-assembly is very slow. The lag time distributions turn out to be similar for two very different regimes of polymerization, namely, a) when polymerization is slow and depolymerization is fast, and b) the opposite case, when polymerization is fast and depolymerization is slow. Using temperature dependent on- and off-rates for hemoglobin fiber growth, reported in recent in-vitro experiments, we show that the mean lag time can exhibit non-monotonic behaviour with respect to change of temperature.

biophysics↗

bioRxiv2020

Tethering-facilitated DNA 'opening' and complementary roles of β-hairpin motifs in the Rad4/XPC DNA damage sensor protein

XPC/Rad4 initiates eukaryotic nucleotide excision repair on structurally diverse helix-destabilizing/distorting DNA lesions by selectively opening these sites while rapidly diffusing along undamaged DNA. Previous structural studies showed that Rad4, when tethered to DNA, could also open undamaged DNA, suggesting a kinetic gating mechanism whereby lesion discrimination relied on efficient opening versus diffusion. However, solution studies in support of such a mechanism were lacking and how opening is brought about remained unclear. Here, we present crystal structures and fluorescence-based conformational analyses on tethered complexes, showing that Rad4 can indeed open undamaged DNA in solution and that such opening can largely occur without one or the other of the {beta}-hairpin motifs in the BHD2 or BHD3 domains. Notably, the Rad4-bound open DNA adopts multiple conformations in solution notwithstanding the DNAs original structure or the {beta}-hairpins. Molecular dynamics simulations reveal compensatory roles of the {beta}-hairpins, which may render robustness in dealing with and opening diverse lesions. Our study showcases how fluorescence-based studies can be used to obtain information complementary to ensemble structural studies. The tethering-facilitated DNA opening of undamaged sites and the dynamic nature of open DNA may shed light on how the protein functions within and beyond NER in cells.

biochemistry↗

bioRxiv2020

Light-induced modulation of DNA recognition by the Rad4/XPC damage sensor protein

Biomolecular structural changes upon binding/unbinding are key to their functions. However, characterization of such dynamical processes with high spatial and temporal resolutions is difficult as it requires ways to rapidly trigger the assembly/disassembly as well as ways to monitor the structural changes over time. Recently, various chemical strategies have been developed to use light to trigger changes in oligonucleotide structures, thereby their activities. Here we report that photoswitchable DNA can be used to modulate the DNA binding of the Rad4/XPC DNA repair complex using light. Rad4/XPC specifically binds to diverse helix-destabilizing/distorting lesions including bulky organic adducts and functions as a key initiator for the eukaryotic nucleotide excision repair (NER) pathway. We show that the 6-nitropiperonyloxymethyl (NPOM)-modified DNA is recognized by the Rad4 protein as a specific substrate and that the specific binding can be abolished by light-induced cleavage of the NPOM group from DNA in a dose-dependent manner. Fluorescence lifetime-based analyses of the DNA conformations suggest that free NPOM-DNA retains B-DNA-like conformations despite its bulky NPOM adduct, but Rad4-binding renders it to be heterogeneously distorted. Subsequent extensive conformational searches and molecular dynamics simulations demonstrate that NPOM in DNA can be housed in the major groove of the DNA, with stacking interactions among the nucleotide pairs remaining largely unperturbed and thus retaining overall B-DNA conformation. Our work suggests that photoactivable DNA can be used as a DNA lesion surrogate to study DNA repair mechanisms such as nucleotide excision repair. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=103 SRC="FIGDIR/small/313114v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@1f31fc7org.highwire.dtl.DTLVardef@ab512dorg.highwire.dtl.DTLVardef@15e8493org.highwire.dtl.DTLVardef@51f58d_HPS_FORMAT_FIGEXP M_FIG Graphical Summary This work shows that a photolabile 6-nitropiperonyloxymethyl (NPOM)-modified DNA is specifically recognized by the Rad4/XPC damage sensor protein complex that initiates the nucleotide excision repair pathway; light-induced cleavage of NPOM abolishes the specific binding to Rad4/XPC. C_FIG

biochemistry↗

bioRxiv2020

SARS-CoV-2 infects brain choroid plexus and disrupts the blood-CSF-barrier

Coronavirus disease-19 (COVID-19), caused by the SARS-CoV-2 virus, leads primarily to respiratory symptoms that can be fatal, particularly in at risk individuals. However, neurological symptoms have also been observed in patients, including headache, seizures, stroke, and fatigue. The cause of these complications is not yet known, and whether they are due to a direct infection of neural cells, such as neurons and astrocytes, or through indirect effects on supportive brain cells, is unknown. Here, we use brain organoids to examine SARS-CoV-2 neurotropism. We examine expression of the key viral receptor ACE2 in single-cell RNA sequencing (scRNA-seq) revealing that only a subset of choroid plexus cells but not neurons or neural progenitors express this entry factor. We then challenge organoids with both SARS-CoV-2 spike protein pseudovirus and live virus to demonstrate high viral tropism for choroid plexus epithelial cells but not stromal cells, and little to no infection of neurons or glia. We find that infected cells of the choroid plexus are an apolipoprotein and ACE2 expressing subset of epithelial barrier cells. Finally, we show that infection with live SARS-CoV-2 leads to barrier breakdown of the choroid plexus. These findings suggest that neurological complications may result from effects on the choroid plexus, an important barrier that normally prevents entry of immune cells and cytokines into the cerebrospinal fluid (CSF) and brain.

neuroscience↗

bioRxiv2020

Furin cleavage of SARS-CoV-2 Spike promotes but is not essential for infection and cell-cell fusion

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects cells by binding to the host cell receptor Ace2 and undergoing virus-host membrane fusion. Fusion is triggered by the protease TMPRSS2, which processes the viral Spike (S) protein to reveal the fusion peptide. SARS-CoV-2 has evolved a multibasic site at the S1-S2 boundary, which is thought to be cleaved by furin in order to prime S protein for TMPRSS2 processing. Here we show that CRISPR-Cas9 knockout of furin reduces, but does not prevent, the production of infectious SARS-CoV-2 virus. Comparing S processing in furin knockout cells to multibasic site mutants reveals that while loss of furin substantially reduces S1-S2 cleavage it does not prevent it. SARS-CoV-2 S protein also mediates cell-cell fusion, potentially allowing virus to spread virion-independently. We show that loss of furin in either donor or acceptor cells reduces, but does not prevent, TMPRSS2-dependent cell-cell fusion, unlike mutation of the multibasic site that completely prevents syncytia formation. Our results show that while furin promotes both SARS-CoV-2 infectivity and cell-cell spread it is not essential, suggesting furin inhibitors will not prevent viral spread.

microbiology↗

bioRxiv2020

PAN-INDIA 1000 SARS-CoV-2 RNA Genome Sequencing Reveals Important Insights into the Outbreak

The PAN-INDIA 1000 SARS-CoV-2 RNA Genome Sequencing Consortium has achieved its initial goal of completing the sequencing of 1000 SARS-CoV-2 genomes from nasopharyngeal and oropharyngeal swabs collected from individuals testing positive for COVID-19 by Real Time PCR. The samples were collected across 10 states covering different zones within India. Given the importance of this information for public health response initiatives investigating transmission of COVID-19, the sequence data is being released in GISAID database. This information will improve our understanding on how the virus is spreading, ultimately helping to interrupt the transmission chains, prevent new cases of infection, and provide impetus to research on intervention measures. This will also provide us with information on evolution of the virus, genetic predisposition (if any) and adaptation to human hosts. One thousand and fifty two sequences were used for phylodynamic, temporal and geographic mutation patterns and haplotype network analyses. Initial results indicate that multiple lineages of SARS-CoV-2 are circulating in India, probably introduced by travel from Europe, USA and East Asia. A2a (20A/B/C) was found to be predominant, along with few parental haplotypes 19A/B. In particular, there is a predominance of the D614G mutation, which is found to be emerging in almost all regions of the country. Additionally, mutations in important regions of the viral genome with significant geographical clustering have also been observed. The temporal haplotype diversities landscape in each region appears to be similar pan India, with haplotype diversities peaking between March-May, while by June A2a (20A/B/C) emerged as the predominant one. Within haplotypes, different states appear to have different proportions. Temporal and geographic patterns in the sequences obtained reveal interesting clustering of mutations. Some mutations are present at particularly high frequencies in one state as compared to others. The negative estimate Tajimas D (D = -2.26817) is consistent with the rapid expansion of SARS-CoV-2 population in India. Detailed mutational analysis across India to understand the gradual emergence of mutants at different regions of the country and its possible implication will help in better disease management.

genomics↗

bioRxiv2020

Phylogenomic analysis of SARS-CoV-2 genomes from western India reveals unique linked mutations

India has become the third worst-hit nation by the COVID-19 pandemic caused by the SARS-CoV-2 virus. Here, we investigated the molecular, phylogenomic, and evolutionary dynamics of SARS-CoV-2 in western India, the most affected region of the country. A total of 90 genomes were sequenced. Four nucleotide variants, namely C241T, C3037T, C14408T (Pro4715Leu), and A23403G (Asp614Gly), located at 5UTR, Orf1a, Orf1b, and Spike protein regions of the genome, respectively, were predominant and ubiquitous (90%). Phylogenetic analysis of the genomes revealed four distinct clusters, formed owing to different variants. The major cluster (cluster 4) is distinguished by mutations C313T, C5700A, G28881A are unique patterns and observed in 45% of samples. We thus report a newly emerging pattern of linked mutations. The predominance of these linked mutations suggests that they are likely a part of the viral fitness landscape. A novel and distinct pattern of mutations in the viral strains of each of the districts was observed. The Satara district viral strains showed mutations primarily at the 3' end of the genome, while Nashik district viral strains displayed mutations at the 5' end of the genome. Characterization of Pune strains showed that a novel variant has overtaken the other strains. Examination of the frequency of three mutations i.e., C313T, C5700A, G28881A in symptomatic versus asymptomatic patients indicated an increased occurrence in symptomatic cases, which is more prominent in females. The age-wise specific pattern of mutation is observed. Mutations C18877T, G20326A, G24794T, G25563T, G26152T, and C26735T are found in more than 30% study samples in the age group of 10-25. Intriguingly, these mutations are not detected in the higher age range 61-80. These findings portray the prevalence of unique linked mutations in SARS-CoV-2 in western India and their prevalence in symptomatic patients. ImportanceElucidation of the SARS-CoV-2 mutational landscape within a specific geographical location, and its relationship with age and symptoms, is essential to understand its local transmission dynamics and control. Here we present the first comprehensive study on genome and mutation pattern analysis of SARS-CoV-2 from the western part of India, the worst affected region by the pandemic. Our analysis revealed three unique linked mutations, which are prevalent in most of the sequences studied. These may serve as a molecular marker to track the spread of this viral variant to different places.

genomics↗