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Bhattacharyya, M.

Publications and source records attributed to Bhattacharyya, M..

At least 19 recordsLinked to original sources

South Asian Maternal Lineage haplogroup R30 Provides Phylogenetic Evidence of human dispersal across South Asia

South Asia is central to debates on early human dispersals, particularly the Out of Africa model and Eurasian colonization. Studies of M haplogroups have been used to support both Northern and Southern route hypotheses, but current archaeological and genetic evidence in the region remains contradictory. In the present work, we find that in addition to haplogroup M lineages, a few R lineages exhibit ancient, locally rooted variation, with R30 being one of the widespread haplogroup of R lineages across South Asia. To better understand South Asian demographic history, we investigated the phylogeographic distribution of haplogroup R30, an indigenous lineage. We used 190 complete modern and ancient sequences from diverse mainland and island populations including incorporation of 44 newly generated sequences which enabled the refinement of the R30 phylogeny and the identification of a novel basal lineage, R30c. Bayesian and {rho}-based age estimates suggest that R30 originated in the Indian subcontinent ~50 kya. Early diversification likely occurred in Northern India, giving rise to R30b (~44 kya), while R30a and R30c differentiated primarily in Southern India. Several subclades of haplogroup R30 exhibit strong signatures of founder effects, particularly among the language isolate Vedda of Sri Lanka, Uru Kurumban of Southern India, and the populations of the Lakshadweep archipelago. Bayesian skyline analyses indicate long-term demographic stability followed by rapid lineage expansion ~20 kya and more recent declines consistent with localised drift and relatively recent founder events. The presence of early-diverging R30 lineages in Thailand and Indonesia further supports long-term connections between South and Southeast Asia. Overall, archaeological and genetic evidence point towards the multiple migrations for South Asia colonizations.

evolutionary biology↗

A painless nerve growth factor variant uncouples nociceptive and neurotrophic TrkA signaling

Nerve growth factor (NGF) binding to the receptor tyrosine kinase, TrkA, drives neurotrophic signaling essential for neuronal development and survival. This interaction simultaneously drives peripheral pain, making this pathway an attractive but complicated therapeutic target for chronic pain. By integrating single-molecule microscopy, structural and electrophysiology analyses, with a human NGF variant, NGFpainless, which retains neurotrophic effects but abolishes pain, we delineate the molecular mechanisms that bias TrkA signaling towards neurotrophic functions without triggering nociception. We show that, unlike wild-type NGF, NGFpainless fails to sensitize TRPV1 channels to capsaicin, thus disengaging TrkA from the nociceptive pathway. We further show that this selective loss of nociceptive TrkA signaling by NGFpainless results from its reduced ability to activate PLC{gamma}1 and trigger calcium release compared to NGF, while still preserving the ERK and AKT signaling essential for neurotrophic functions. This biased signaling arises from reduced electrostatic complementarity at the TrkA:NGFpainless complex interface, which shortens the lifetime of this functional complex on native membranes. Mutations in TrkA that restore the electrostatic complementarity at the TrkA:NGFpainless interface eliminate biased signaling. This mechanistic understanding of TrkA binding by NGFpainless, and how it differs from NGF, will spur the development of two therapeutic classes of molecules - one that selectively suppresses nociceptive signaling while preserving neurotrophic functions in chronic pain, and another that enhances neurotrophic activity without evoking peripheral pain in neurodegenerative conditions.

neuroscience↗

Two-Step Mechanism of Bruton's Tyrosine Kinase MembraneRecruitment and Activation

Peripheral membrane proteins (PMPs) are critical mediators of signaling cascades initiated via activation of cell-surface receptors. Their functions rely on their innate ability to interact with membranes dynamically in response to rapidly changing cellular conditions. This membrane recruitment may occur via high-affinity interactions with specific lipids or transient, low-affinity membrane interactions. These weak and dynamic interactions that are critical regulators of protein function are challenging to capture. Taking Brutons Tyrosine Kinase (BTK), a non-receptor tyrosine kinase essential for B cell activation, as an example, we demonstrate a native mass spectrometry (nMS) platform to understand the recruitment of PMPs by directly studying it from lipid bilayers customized to target membranes. Our data demonstrates that BTK recognizes phosphatidylserine (PS) through sites distinct from phosphatidylinositol (3,4,5) phosphate (PIP3) binding. We show PS-bound BTK retains PIP3 binding simultaneously via high-affinity sites, exhibiting PIP3-independent basal membrane recruitment of BTK. Biochemical assays show that this PS-mediated recruitment sensitizes BTK to PIP3-mediated activation under near-physiological concentrations of PIP3. Thus, we propose a two-step model for BTK membrane recruitment and activation. A low-affinity interaction with high-copy number PS enables plasma membrane recruitment of BTK and increases its membrane-bound concentration. Upon B-cell activation, this pre-recruited, membrane-bound BTK population localizes to PIP3-rich domains through electrostatic gliding along the membrane driven by low-affinity PS and high-affinity PIP3 binding. This indicates a cooperative mechanism where PS can amplify B-cell signaling through increased membrane-bound BTK concentration. Our work demonstrates a general model of PH-domain-containing protein regulation by weak protein-lipid interactions, which can be extended to many other PMPs.

biophysics↗

Phosphoinositide 3-kinase regulates wild-type RAS signaling to confer resistance to KRAS inhibition

Despite the availability of RAS inhibitors and the dependence of >90% of pancreatic ductal adenocarcinomas (PDAC) on oncogenic KRAS mutations, resistance to KRAS inhibition remains a serious obstacle. We show here that phosphoinositide 3-kinase (PI3K) plays a major role in this resistance through upstream activation of wild-type RAS signaling - beyond its known KRAS effector function. Combining proximity labeling, CRISPR screens, live-cell imaging, and functional assays we found that PI3K orchestrates phosphoinositide-mediated GAB1 recruitment to the plasma membrane, nucleating assembly of RAS signaling complexes that activate mitogen-activated protein kinase (MAPK) in an EGFR/SHP2/SOS1-dependent manner. We further demonstrate that inhibiting PI3K enhances sensitivity to mutant-specific KRAS inhibitors in PDAC cells, including cells with clinically identified PIK3CA mutations. Our findings refine RAS-PI3K signaling paradigms, reveal that PI3K-driven wild-type RAS activation drives resistance to KRAS inhibition, and illuminate new avenues for augmenting KRAS-targeted therapies in PDAC.

cancer biology↗

STUDIES ON INTERACTION OF MORIN WITH CURLI TO IDENTIFY AGGREGATION NATURE

Morin (3,5,7,2',4'-pentahydroxyflavone) is a flavonoid compound exhibited a range of biological functions, including anti-inflammatory, antioxidant, antiviral, and anti-allergic activities. It has the ability to disaggregate amyloid fibrils, making it a potential inhibitor of diseases caused by amyloid protein fibrillation. This study focuses on the interaction between Morin and Curli amyloid fibrils, which are produced by some Enterobacteriaceae, including Salmonella sp. And E. coli, as a major component of their biofilms. The Curli amyloid fibrils can lead to neurodegenerative diseases through a signalling cascade causing various human diseases, such as Alzheimers and Huntingtons diseases. Thioflavin T (ThT) fluorescence assays to purified Curli, and molecular docking between Morin and Curli indicates nature of binding at molecular level. The results showed that Morin quenched Curli fluorescence in a concentration-dependent manner, indicating dynamic quenching. Stern-Volmer analysis revealed that Morin binds to Curli with a binding constant of approximately 102 L/mol. This binding was found to be spontaneous, with hydrophobic interactions playing a significant role. ThT fluorescence assays confirmed that Morin inhibited Curli fibrillation, suggesting a potential therapeutic application. Molecular docking analysis revealed specific interactions between Morin and Curli, providing insights into their binding at the molecular level. In conclusion, this study demonstrates the dynamic quenching of Curli fluorescence by Morin and suggested that Morin may inhibit Curli fibrillation, making it a valuable candidate for the development of therapeutic drugs.

biochemistry↗

A proteome-wide quantitative guide for nanoscale spatially resolved extraction of membrane proteins into native nanodiscs

The intricate molecular environment of the native membrane profoundly influences every aspect of membrane protein (MP) biology. Despite this, the most prevalent method of studying MPs uses detergent-like molecules that disrupt and remove this vital local membrane context. This severely impedes our ability to quantitatively decipher the local molecular context and comprehend its regulatory role in the structure, function, and biogenesis of MPs. Using a library of membrane-active polymers we have developed a platform for the high-throughput analysis of the membrane proteome. The platform enables near-complete spatially resolved extraction of target MPs directly from their endogenous membranes into native nanodiscs that maintain the local membrane context. We accompany this advancement with an open-access database that quantifies the polymer-specific extraction variability for 2065 unique mammalian MPs and provides the most optimized condition for each of them. Our method enables rapid and near-complete extraction and purification of target MPs directly from their endogenous organellar membranes at physiological expression levels while maintaining the nanoscale local membrane environment. Going beyond the plasma membrane proteome, our platform enables extraction from any target organellar membrane including the endoplasmic reticulum, mitochondria, lysosome, Golgi, and even transient organelles such as the autophagosome. To further validate this platform, we took several independent MPs and demonstrated how our resource can enable rapid extraction and purification of target MPs from different organellar membranes with high efficiency and purity. Further, taking two synaptic vesicle MPs, we show how the database can be extended to capture multiprotein complexes between overexpressed MPs. We expect these publicly available resources to empower researchers across disciplines to efficiently capture membrane nano-scoops containing a target MP and interface with structural, functional, and other bioanalytical approaches. We demonstrate an example of this by combining our extraction platform with single-molecule TIRF imaging to demonstrate how it can enable rapid determination of homo-oligomeric states of target MPs in native cell membranes.

biophysics↗

RAPID HEMATOCRIT ESTIMATION USING A FOLD-CREASE INDUCED FAST FLOWING PAPER SENSOR

Increased evaporative losses and flow obstructions can present substantial impediments to current paper analytical devices ({micro}PADs) for efficient on-site testing of biological fluids. Strategic enhancements in wicking rates of paper may thereby counter these limitations and enable on-demand healthcare monitoring. Therefore, herein we have leveraged the features of paper fold-crease regions, for the very first time, and developed a novel fast-flowing platform using laser printing to accelerate fluid flow through paper. A series of extensive experiments have been conducted to optimize the design and maximize wicking rates of {micro}PADs for smaller liquid volumes, making it well-suited for analysing biofluids. The investigation delves into structural alterations within the creased regions, employing both static and dynamic force application strategies. A first-generation Washburn type model in excellent agreement with the experimental findings is developed, providing a comprehensive insight into the fundamental physics involved. Finally, the folded channels are utilized for a distance-based hematocrit sensor employing grade-1 filter paper at very low-cost, simplified fabrication, lesser sample volume and faster analysis. The findings of this work unveil a plethora of potentialities for employing paper and paper folds to develop affordable medical devices with advanced analytical functionalities, specifically tailored for the resource-constrained settings. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/577541v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@4ba7e4org.highwire.dtl.DTLVardef@fb7945org.highwire.dtl.DTLVardef@1d6df10org.highwire.dtl.DTLVardef@1ceb742_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

Determination of oligomeric organization of membrane proteins from native membranes at nanoscale-spatial and single-molecule resolution

The oligomeric organization of membrane proteins in native cell membranes is a critical regulator of their function. High-resolution quantitative measurements of oligomeric assemblies and how they change under different conditions are indispensable to the understanding of membrane protein biology. We report a single-molecule imaging technique (Native-nanoBleach) to determine the oligomeric distribution of membrane proteins directly from native membranes at an effective spatial resolution of [~]10 nm. We achieved this by capturing target membrane proteins in "native nanodiscs" with their proximal native membrane environment using amphipathic copolymers. We established this method using structurally and functionally diverse membrane proteins with well-established stoichiometries. We then applied Native-nanoBleach to quantify the oligomerization status of a receptor tyrosine kinase (TrkA) and a small GTPase (KRas) under conditions of growth-factor binding or oncogenic mutations, respectively. Native-nanoBleach provides a sensitive, single-molecule platform to quantify membrane protein oligomeric distributions in native membranes at an unprecedented spatial resolution.

biophysics↗

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↗

Overexpression of Interleukin-8 and Interleukin-13 as potent immune markers associated with survival and dietary habits in esophageal squamous cell carcinoma.

BackgroundInterleukin-8 (IL8), Interleukin-12 (IL12) and Interleukin-13 (IL13) are cytokines that play regulatory role in cancer pathogenesis. We analysed their expression profile to evaluate as molecular biomarkers of esophageal squamous cell carcinoma (ESCC) and their association with different parameters. MethodsExpression analysis of IL8, IL12 and IL13 were performed by Real time qPCR in blood and tumor tissue of 120 ESCC patients. The expression profiles were associated with different clinicopathological and dietary factors. Survival and hazard analysis were also performed. ResultsWhen compared to normal controls, IL8 expression showed upregulation in 83% tissue samples (p=0.000) and 62% blood samples (p=0.388), IL12 expression showed upregulation in 62% tissue samples (p=0.435) and 57% blood samples (p=0.222) and IL13 expression showed upregulation in 83% tissue samples (p=0.001) and 68% blood samples (p=0.312). Significant positive correlation (p<0.05) was observed between tissue and blood level expression of IL8, IL12 and IL13. Different clinicopathological factors and dietary habits showed significant association (p<0.05) with IL8, IL12 and IL13 expression.. Statistically significant positive correlation were observed for IL8 and IL13 expression in tissue as well as IL13 and IL12 expression in both tissue and blood. Also significant negative correlation of IL8 and IL12 expression in blood and tissue were also observed. Tumor stage, node stage, metastasis, consumption of betel nut, tobacco, alcohol, hot food, smoked food, spices, IL8 expression in blood, IL13 expression in tissue and IL12 expression in blood and tissue showed significant association (p<0.05) with survival of ESCC patients. ConclusionsAltered expression of IL8, IL12 and IL13 may be associated with ESCC progression. Overexpression of IL8 and IL13 in tissue samples may be potential biomarkers for ECSS screening. Additionally, results from both survival and hazard analysis data indicate the effects of various parameters on the survival and mortality rate of ESCC patients.

immunology↗

Supervised Machine Learning Enables Geospatial Microbial Provenance

The recent increase in publicly available metagenomic datasets with geospatial metadata has made it possible to determine location-specific, microbial fingerprints from around the world. Such fingerprints can be useful for comparing microbial niches for environmental research, as well as for applications within forensic science and public health. To determine the regional specificity for environmental metagenomes, we examined 4305 shotgun-sequenced samples from the MetaSUB Consortium dataset - the most extensive public collection of urban microbiomes, spanning 60 different cities, 30 countries, and 6 continents. We were able to identify city-specific microbial fingerprints using supervised machine learning (SML) on the taxonomic classifications, and we also compared the performance of ten SML classifiers. We then further evaluated the five algorithms with the highest accuracy, with the city and continental accuracy ranging from 85-89% to 90-94%, respectively. We then used these results to develop Cassandra, a random-forest-based classifier that identifies indicator species to aid in fingerprinting and can infer higher-order microbial interactions at each site. We further tested the Cassandra algorithm on the Tara Oceans dataset, the largest collection of marine-based microbial genomes, where it classified the oceanic sample locations with 83% accuracy. These results and code show the utility of SML methods and Cassandra to identify bioindicator species across both oceanic and urban environments, which can help guide ongoing efforts in biotracing, environmental monitoring, and microbial forensics (MF).

microbiology↗

Accountable Prediction of Drug ADMET Properties with Molecular Descriptors

Drugs are chemical substances of low molecular weights that require to travel from the site of administration to the site of action. For safety and effective permeability, drugs are required to exhibit ideal absorption, distribution, metabolism, excretion and toxicity (ADMET) properties. Given the Simplified Molecular Input Line Entry System (SMILES) representation of drugs, we aim to predict their ADMET properties. By feeding molecular descriptors (as global features) to traditional machine learning models, we show that ADMET properties of drug molecules can be predicted with an accuracy competitive with the state-of-the-art deep learning models. We demonstrate that the proposed approach with only 31 molecular descriptors beats the state-of-the-art for 3 datasets. Moreover, it stands the second best for 2 other datasets, where none of the best provides a statistically significant improvement. We also demonstrate that two-dimensional descriptors can better represent absorption, distribution and excretion properties than the fingerprints widely used in the literature. However, they fail to distinguish metabolism and toxicity properties.

bioinformatics↗

Efflux-linked Accelerated Evolution of Antibiotic Resistance at a Population Edge

Efflux is a common mechanism of resistance to antibiotics. We show that efflux itself promotes accumulation of antibiotic-resistance mutations (ARM). This phenomenon was initially discovered in a bacterial swarm where the linked phenotypes of high efflux and high mutation frequencies spatially segregated to the swarm edge, driven there by motility. We uncovered and validated a global regulatory network that connects high efflux to downregulation of specific DNA repair pathways even in non-swarming states. The efflux-DNA repair link was corroborated in a clinical resistome database: genomes with mutations that increase efflux exhibit a significant increase in ARMs. Accordingly, efflux inhibitors decreased evolvability to antibiotic resistance. Swarms also revealed how bacterial populations serve as reservoir of ARMs even in absence of antibiotic selection pressure. High efflux at the edge births mutants that, despite compromised fitness, survive there because of reduced competition. This finding is relevant to biofilms where efflux activity is high.

microbiology↗

CDK1 and HSP90AA1 appears as novel regulatory gene in Non-Small Cell Lung Cancer: A Bioinformatics Approach

Lung cancer is one of the most invasive cancer affecting over a million of population. Non-small cell lung cancer constitutes up to 85% of all lung cancer cases. Therefore, it is important to identify prognostic biomarkers of NSCLC for therapeutic purpose. The complex behaviour of the NSCLC gene-regulatory network interaction is investigated using a network theoretical approach. We used eight NSCLC microarray datasets GSE19188, GSE118370, GSE10072, GSE101929, GSE7670, GSE33532, GSE31547, GSE31210 and meta analyse them to find differentially expressed genes (DEGs), construct protein-protein interaction (PPI) network, analysed its topological properties, significant modules using network analyser with MCODE, construct a PPI-MCODE network using the genes of the significant modules. We used topological properties such as Maximal Clique Centrality (MCC) and bottleneck from the PPI-MCODE network. We compare them with hub genes (those with highest degrees) to find key regulator (KR) gene. This result is also validated by finding of common genes among top twenty hub genes, genes with highest betweenness, closeness centrality and eigenvector values. It was found that two genes, CDK1 and HSP90AA1 were common in PPI-MCODE combined analysis, and it was also found that CDK1, HSP90AA1 and HSPA8 were common among hub and bottle neck properties and suggesting significant regulatory role of CDK1 in non-small cell lung cancer. After validation, the common genes among top twenty hubs and centrality values like Betweenness Centrality, Closeness Centrality and eigen vector properties, CDK1 again appeared as the common gene. Our study as a summary suggested CDK1 as key regulator gene in complex NSCLC network interaction using network theoretical approach and described the complex topological properties of the network.

systems biology↗

Redox Nanomedicine Cures Chronic Kidney Disease (CKD) by Mitochondrial Reconditioning

Targeting reactive oxygen species (ROS) while maintaining cellular redox signaling is crucial in the development of redox medicine for the therapeutic benefit as the origin of several prevailing diseases including chronic kidney disease (CKD) is linked to ROS imbalance and associated mitochondrial dysfunction. Here, we have shown that an indigenously developed nanomedicine comprising of Mn3O4 nanoparticles duly functionalized by biocompatible ligand citrate (C-Mn3O4 NPs) can maintain cellular redox balance in an animal model. We developed a cisplatin-induced CKD model in C57BL/6j mice where severe mitochondrial dysfunction resulting in oxidative distress lead to the pathogenesis. Four weeks of treatment with C-Mn3O4 NPs restored renal function, preserved normal kidney architecture, ameliorated overexpression of pro-inflammatory cytokines, and arrested glomerulosclerosis and interstitial fibrosis in CKD mice. A detailed study involving human embryonic kidney (HEK 293) cells and isolated mitochondria from experimental animals revealed that the molecular mechanism behind the pharmacological action of the nanomedicine involves protection of structural and functional integrity of mitochondria from oxidative damage, the subsequent reduction in intracellular ROS, and maintenance of cellular redox homeostasis. To the best of our knowledge, such studies that efficiently treated a multifaceted disease like CKD using a biocompatible redox nanomedicine are sparse in the literature. Successful clinical translation of this nanomedicine may open a new avenue in redox-mediated therapeutics of several other diseases (e.g., diabetic nephropathy, neurodegeneration, and cardiovascular disease) where oxidative distress plays a central role in pathogenesis.

pharmacology and toxicology↗

Nanotube mediated cell-to-cell communication and cannibalism in Halobacillus sp. GSS1 isolated from Sundarbans, India: A cryptic story of survival under nutrient-limiting condition

Microorganisms play a self-protective role by evolving their genetic and metabolic machinery to thrive in extreme environmental habitats. Halophiles are such salt-loving extremophilic microorganisms able to adapt, survive, and tend to grow at high salt concentrations. In this study, we have isolated Halobacillus sp. GSS1 from Sundarbans mangrove, India having a strong salt-tolerant ability (up to 4M) in Zobell Marine 2216 medium. The salt adaptation mechanism of Halobacillus sp. was investigated by Confocal microscopy using [Na+] specific dye, Sodium Green indicating the salt-in strategy for their osmoadaptation. Electron microscopic studies revealed that a contact-dependent cell-to-cell communication was profound among the Halobacillus sp. under nutrient limiting condition. This communication is mediated by nanotube, which is highly recommended for the exchange of molecular information between the two individual bacteria. The existence of the ymdB gene strongly supports our claim for nanotube formation by Halobacillus sp. GSS1. Surprisingly, Halobacillus sp. not only utilizing the nanotubes for communication, rather they desperately use nanotubes as a survival weapon under nutrient limiting conditions by triggering cannibalism. This is the first-ever report on the existence of nanotube mediated cell-to-cell communication and cannibalism in any halophilic bacteria, isolated from Sundarbans mangrove forest, India. HighlightsO_LIThe existence of nanotube mediated cell-to-cell communication was discovered in Halobacillus sp. GSS1, isolated from Sundarbans mangrove, India. C_LIO_LIThe communication of Halobacillus sp. GSS1 was established through single or multiple nanotubes with the neighboring cells. C_LIO_LIIntercellular nanotube communication was possible only after the participation of two individual bacteria. C_LIO_LIHalobacillus sp. GSS1 also uses these nanotubes as a survival weapon by triggering the cannibalism to kill their genetically identical siblings. C_LIO_LIThe presence of the ymdB gene in Halobacillus sp. GSS1 strongly confers the evidence of nanotube formation. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=191 SRC="FIGDIR/small/340307v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@1491155org.highwire.dtl.DTLVardef@1123b5org.highwire.dtl.DTLVardef@13f6509org.highwire.dtl.DTLVardef@10261b2_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

Motif Analysis in k-mer Networks: An Approach towards Understanding SARS-CoV-2 Geographical Shifts

With an increasing number of SARS-CoV-2 sequences available day by day, new genomic information is getting revealed to us. As SARS-CoV-2 sequences highlight wide changes across the samples, we aim to explore whether these changes reveal the geographical origin of the corresponding samples. The k-mer distributions, denoting normalized frequency counts of all possible combinations of nucleotide of size upto k, are often helpful to explore sequence level patterns. Given the SARS-CoV-2 sequences are highly imbalanced by its geographical origin (relatively with a higher number samples collected from the USA), we observe that with proper under-sampling k-mer distributions in the SARS-CoV-2 sequences predict its geographical origin with more than 90% accuracy. The experiments are performed on the samples collected from six countries with maximum number of sequences available till July 07, 2020. This comprises SARS-CoV-2 sequences from Australia, USA, China, India, Greece and France. Moreover, we demonstrate that the changes of genomic sequences characterize the continents as a whole. We also highlight that the network motifs present in the sequence similarity networks have a significant difference across the said countries. This, as a whole, is capable of predicting the geographical shift of SARS-CoV-2.

bioinformatics↗

Tracing Back the Temporal Change of SARS-Cov-2 with Genomic Signatures

The coronavirus disease (COVID-19) outbreak starting from China at the end of 2019 and its subsequent spread in many countries have given rise to thousands of coronavirus samples being collected and sequenced till date. To trace back the initial temporal change of SARS-CoV-2, the coronavirus implicated in COVID-19, we study the limited genomic sequences that were available within the first couple of months of its spread. These samples were collected under varying circumstances and highlight wide variations in their genomic compositions. In this paper, we explore whether these variations characterize the initial temporal change of SARS-CoV-2 sequences. We observe that n-mer distributions in the SARS-CoV-2 samples, which were collected at an earlier period of time, predict its collection timeline with approximately 78% accuracy. However, such a distinctive pattern disappears with the inclusion of samples collected at a later time. We further observe that isolation sources (e.g., oronasopharynx, saliva, feces, etc.) could not be predicted by the n-mer patterns in these sequences. Finally, the phylogenetic and protein-alignment analyses highlight interesting associations between SARS-CoV-2 and other coronaviruses.

bioinformatics↗