Biology subjects

Singh, A. K.

Publications and source records attributed to Singh, A. K..

At least 127 records · Page 7Linked to original sources

bioRxiv2020

The Impact of Hand Movement Velocity on Cognitive Conflict Processing in a 3D Object Selection Task

Detecting and correcting incorrect body movements is an essential part of everyday interaction with ones environment. The human brain provides a monitoring system that constantly controls and adjusts our actions according to our surroundings. However, when our brains predictions about a planned action do not match the sensory inputs resulting from that action, cognitive conflict occurs. Much is known about cognitive conflict in 1D/2D environments; however, less is known about the role of movement characteristics associated with cognitive conflict in 3D environment. Hence, we devised an object selection task in a virtual reality (VR) environment to test how the velocity of hand movements impacts human brain responses. From a series of analyses of EEG recordings synchronized with motion capture, we found that the velocity of the participants hand movements modulated the brains response to proprioceptive feedback during the task and induced a prediction error negativity (PEN). Additionally, the PEN originates in the anterior cingulate cortex and is itself modulated by the ballistic phase of the hands movement. These findings suggest that velocity is an essential component of integrating hand movements with visual and proprioceptive information during interactions with real and virtual objects.

neuroscience↗

bioRxiv2020

Exome sequencing identifies ARID2 as a novel tumor suppressor in early-onset sporadic rectal cancer

Early-onset sporadic rectal cancer (EOSRC) is a unique and predominant colorectal cancer (CRC) subtype in India. In order to understand the tumorigenic process in EOSRC, we performed whole exome sequencing of 47 microsatellite stable EOSRC samples. Signature 1 was the predominant mutational signature in EOSRC, as previously shown in other CRC exome studies. More importantly, we identified TP53, KRAS, APC, PIK3R1 and SMAD4 as significantly mutated (q<0.1) and ARID1A and ARID2 as near-significantly mutated (restricted hypothesis testing; q<0.1) candidate drivers. Unlike the other candidates, the tumorigenic potential of ARID2, encoding a component of the SWI/SNF chromatin remodeling complex, is largely unexplored in CRC. shRNA mediated ARID2 knockdown performed in two different CRC cell lines resulted in significant alterations in transcript levels of cancer-related target genes. More importantly, ARID2 knockdown promoted several tumorigenic features including cell viability, proliferation, ability to override contact inhibition of growth, and migration besides significantly increasing tumor formation ability in nude mice. The observed gain in tumorigenic features were rescued upon ectopic expression of ARID2. Analyses of the TCGA CRC dataset revealed poorer survival in patients with ARID2 alterations. We therefore propose ARID2 as a novel tumor suppressor in CRC.

cancer biology↗

bioRxiv2020

Sex-specific crossover rates did not change with parental age in Arabidopsis

Crossing over, the exchange of DNA between the chromosomes during meiosis, contributes significantly to genetic variation. The rate of crossovers (CO) varies depending upon the taxon, population, age, external conditions, and also, sometimes, between the sexes, a phenomenon called heterochiasmy. In the model plant Arabidopsis thaliana, the male rate of crossovers (mCO) is typically nearly double the female rate (fCO). With increasing parental age, it has been reported that the disparity decreases, because fCO rises while mCO remains stable. That finding, however, is based on chromosome-based averaging, and it is unclear whether all parts of the genome respond similarly. We addressed this point by examining how the level of heterochiasmy responded to parental age in eight genomic intervals distributed across the five chromosomes of Arabidopsis. Unlike the previous work, in each of the eight intervals, the level of heterochiasmy did not change with age, that is, the ratio mCO:fCO remained stable. As expected, though, amongst the intervals, the levels of heterochiasmy at any of the four ages examined, did vary. We propose that while the levels of heterochiasmy in Arabidopis might decrease with age on a chromosomal basis, as reported earlier, this is not true for all locations within each chromosome. This has practical implications for plant breeding research, a major aim of which is identifying ways to induce local increases in CO rates.

plant biology↗

bioRxiv2020

Salinomycin inhibits epigenetic modulator EZH2 to enhance Death Receptors in Colon Cancer Stem Cells

Drug resistance is one of the trademark features of Cancer Stem Cells (CSCs). We and others have recently shown that paucity of functional death receptors (DR4/5) on the cell surface of tumor cells is one of the major reasons for drug resistance, but their involvement in the context of in CSCs is poorly understood. By harnessing CSC specific cytotoxic function of salinomycin, we discovered a critical role of epigenetic modulator EZH2 in regulating the expression of DRs in colon CSCs. Our unbiased proteome profiler array approach followed by ChIP analysis of salinomycin treated cells indicated that the expression of DRs, especially DR4 is epigenetically repressed in colon CSCs. Concurrently, EZH2 knockdown demonstrated increased expression of DR4/DR5, significant reduction of CSC phenotype such as spheroid formation in-vitro and tumorigenic potential in-vivo in colon cancer. TCGA data analysis of human colon cancer clinical samples shows strong inverse correlation between EZH2 and DR4. Taken together, this study provides an insight about epigenetic regulation of DR4 in colon CSCs and advocates that drug resistant colon cancer can be therapeutically targeted by combining TRAIL and small molecule EZH2 inhibitors.

cancer biology↗

bioRxiv2020

Semecarpus anacardium Linn. leaf extract exhibits activities against breast cancer and prolongs the survival of tumor bearing mice

Semecarpus anacardium Linn. is commonly used in various traditional medicines from ancient times. The nuts have been described in Ayurveda medication systems to treat numerous clinical ailments. However, isolating phytochemical constituents from nuts remains challenging and exhibits cytotoxic effects on other cells. In this study, we have standardized procedures for isolating phytochemicals from the leaf extract. The ethyl acetate leaf extract selectively affects cancer cells in a dose-dependent manner (IC50: 0.57 g/ml in MCF-7 cells) in various cancer cell lines. Next, we examined if the extract incubation could induce cell cycle arrest and suppress cell migration in the cell culture model. Consistent with this idea, the leaf extract could potentially affect the aggressive migration nature of cancer cells. Moreover, oral administration of extract significantly restored tumor growth in mice. Together, these observations suggest the anti-cancer activities of S. anacardium leaf potential for both in vitro and in vivo models. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=90 SRC="FIGDIR/small/898940v3_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@3fefborg.highwire.dtl.DTLVardef@594510org.highwire.dtl.DTLVardef@c525d2org.highwire.dtl.DTLVardef@1362978_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

bioRxiv2020

Virtaul screening of MAP-Tau protein inhibitors from Semecarpus anacardium Linn. leaf extract for cancer prevention

Semecarpus anacardium is a well known Indian medicinal plant with various medicinal properties like hypoglycemic, antioxidant, anticancer, anti-inflammatory, anti-geriatric, antimicrobial and hair growth promoter, etc. The molecular mechanism of metabolites from fruiting bodies of S. anacardium against cancer has been described but anticancerous properties in its leaves are still unknown. The leaves were extracted in petroleum ether, ethyl acetate and methanol and assayed for anticancer activity using MTT assay. The active extract was evaluated for mode of cell death induction using EtBr-AO double staining and analyzed for phytochemical constituents using GC-MS, followed by molecular docking studies for exploration of possibility for anticancer agents and Drugability. In this study, ethyl acetate extract of leaf was found potent cytotoxic in MCF-7 cells and also induced apoptosis. It has also found the SLE is safe for normal cells. The molecular docking studies were done to explore the probable mechanism of action of the extract which showed 9 compounds are targeting the microtubule-associated protein tau (MAPT). MAPT promotes assembling and prevents disassembling to arrest the cell cycle. The overexpression of MAPT induces chemoresistance to cancerous cells against conventional drugs like paclitaxel. We have identified 17 compounds from ethyl acetate extract of S. anacardium leaves and drawn its chemical structure by using chembiodraw software to transform into pdb format. Further, the compounds have been subjected for molecular docking study to investigate its interactive efficiency with MAPT protein. The compound 13 had higher interactive potential to MAPT with binding energy -31.75 kcal/mol and lowest binding energy (-15.44 kcal/mol) was observed in compound 6. The present study suggested that the compounds from leaves of S. anacardium could be alternative approach of conventional drug for cancer treatment with cost effective and less side effect.

bioinformatics↗

bioRxiv2019

Global redistribution and local migration in semi-discrete host-parasitoid population dynamic models.

Host-parasitoid population dynamics is often probed using a semi-discrete/hybrid modeling framework. Here, the update functions in the discrete-time model connecting year-to-year changes in the population densities are obtained by solving ordinary differential equations that mechanistically describe interactions when hosts become vulnerable to parasitoid attacks. We use this semi-discrete formalism to study two key spatial effects: local movement (migration) of parasitoids between patches during the vulnerable period; and yearly redistribution of populations across patches outside the vulnerable period. Our results show that in the absence of any redistribution, constant density-independent migration and parasitoid attack rates are unable to stabilize an otherwise unstable host-parasitoid population dynamics. Interestingly, inclusion of host redistribution (but not parasitoid redistribution) before the start of the vulnerable period can lead to stable coexistence of both species. Next, we consider a Type-III functional response (parasitoid attack rate increases with host density), where the absence of any spatial effects leads to a neutrally stable host-parasitoid equilibrium. As before, density-independent parasitoid migration by itself is again insufficient to stabilize the population dynamics and host redistribution provides a stabilizing influence. Finally, we show that a Type-III functional response combined with density-dependent parasitoid migration leads to stable coexistence, even in the absence of population redistributions. In summary, we have systematically characterized parameter regimes leading to stable/unstable population dynamics with different forms of spatial heterogeneity coupled to the parasitoids functional response using mechanistically formulated semi-discrete models.

ecology↗

bioRxiv2019

CXCR4 intracellular protein regulates drug resistance and tumorigenic potential via modulating the expression of Death Receptor 5

CXCR4 overexpression in solid tumors has been strongly associated with poor prognosis and adverse clinical outcome. However, CXCR4 signaling inhibitor drug Plerixafor has shown limited clinical success in cancer treatment. Therefore, CXCR4 signaling may not be the exclusive contributor to its pro-tumorigenic functions. In our continuous effort to understand the chemokine receptor signaling inhibition as cancer therapy, here we unexpectedly discovered that instead of its signaling, intracellular CXCR4 protein augments therapy resistance and pro-tumorigenic functions. Unbiased proteome profiler apoptosis array followed by immunoblot, FACS, real-time PCR and ChIP analyses demonstrate that CXCR4 promotes DR5 downregulation via modulating differential recruitment of transcription factors p53 and YY1 to its promoter. Surprisingly, inhibiting CXCR4 mediated signals failed to block the above phenotype. Irrespective of CXCR4 surface expression, its loss compromised colon tumor growth in vivo. Finally, TCGA data mining and human patient sample data analysis showed CXCR4 and DR5 are inversely regulated in human cancers. Together, we showed evidence for the first time that targeting CXCR4 intracellular protein may be critical to dampen the pro-tumorigenic functions of CXCR4.

cancer biology↗

bioRxiv2019

Genome-wide analysis of polymorphisms identified domestication-associated polymorphism desert carrying important rice grain size/weight QTL

Rice grain size and weight are major determinant of grain quality and yield and so have been under rigorous selection since domestication. However, genetic basis for contrasting grain size/weight trait among indian germplasm, and their association with domestication shaped evolutionary region is not studied before. To identify genetic basis of grain size/weight two long (LGG) and two short grain genotypes (SGG) were resequenced. LGG (LGR and Pusa Basmati 1121) differentiated from SGG (Sonasal and Bindli) by 504439 SNPs and 78166 InDels. The LRK gene cluster was significantly affected and a truncation mutation in the LRK8 kinase domain was uniquely associated with LGG. Phylogeny with 3000 diverse rice accessions revealed four sequenced genotypes belonged to japonica group and were at the edge of clades indicating source of genetic diversity available in Asian rice population. Five SNPs significantly were associated with grain size/weight and top three SNPs were validated in RIL mapping populations, suggesting this study as a valuable resource for high-throughput genotyping. A contiguous [~]6 Mb polymorphism desert region carrying a major grain weight QTL was identified on chromosome 5 in four sequenced genotypes. Further, among 3000, this region was identified as evolutionary important site with significant positive selection, elevated LD, and multiple selection sweeps, stabilising many domestication-related traits including grain size/weight. The aus group genotype retained more allelic variations in the desert region than japonica and indica, and likely to be one of the differentiation point for aus group. We suggest this desert region as an important evolutionary node that can be selected in breeding programs for improvement of grain yield and quality. All data and analysis can be accessed from RiceSzWtBase database.\n\nSignificance statementBeing an important trait, rice grain size/weight has been under rigorous selection since domestication. However, a link between this trait and domestication is not so directly established. In addition to characterization of novel grain size/weight-associated SNPs, in this study, [~] 6 Mb polymorphism desert region harboring major grain weight QTL was identified on chromosome 5, which turned out to be an evolutionary important site with multiple selection sweeps and introgression events, significantly correlated with domestication-related traits.

plant biology↗

bioRxiv2019

Visualisation of ribosomes in Drosophila axons using Ribo-BiFC

Rates of protein synthesis and the number of translating ribosomes vary greatly between different cells in various cell states. The distribution of assembled, and potentially translating, ribosomes within cells can be visualised in Drosophila by using Bimolecular Fluorescence Complementation (BiFC) to monitor the interaction between tagged pairs of 40S and 60S ribosomal proteins (RPs) that are close neighbours across inter-subunit junctions in the assembled 80S ribosome. Here we describe transgenes that express two novel RP pairs tagged with Venus-based BiFC fragments that considerably increase the sensitivity of this technique that we termed Ribo-BiFC. This improved method should provide a convenient way of monitoring the local distribution of ribosomes in most Drosophila cells and we suggest that could be implemented in other organisms. We visualized 80S ribosomes in larval photoreceptors and in other neurons. Assembled ribosomes are most abundant in the various neuronal cell bodies, but they are also present along the lengths of axons and are concentrated in growth cones of larval and pupal photoreceptors. Surprisingly, there is relatively less puromycin incorporation in the distal portion of axons in the optic stalk, suggesting that some of the ribosomes that have started translation may not be engaged in elongation in axons that are still growing.

cell biology↗

bioRxiv2019

Ligand dependent gene regulation by transient ER clustered enhancers

Unliganded nuclear receptors have been implicated in ligand-dependent gene regulation. However, the underlying mechanisms are not fully understood. Here we demonstrate that unliganded ER binds to specific sites in the genome thereby pre-marking them as future functional enhancers. Upon ligand exposure, ER binds to several EREs relatively proximal to the pre-marked, or persistent, ER-bound sites. Interestingly, the persistent sites interact extensively, via chromatin looping, with the proximal transiently bound sites forming ER clustered enhancers in 3D. CRISPR-based deletion of TFF1 persistent site disrupts the formation of its clustered enhancer resulting in the loss of E2-dependent induced expression of TFF1 and its neighboring genes within the same cluster. The clustered enhancers overlap with nuclear ER puncta that coalesce in a ligand-dependent manner. Furthermore, formation of clustered enhancers, as well as puncta, coincide with the active phase of signaling and their later disappearance results in the loss of gene expression even though persistent sites remain bound by ER. Our results establish the role of persistent unliganded ER binding in priming enhancer clusters in 3D that drive transient, but robust, gene expression in a ligand-dependent fashion.

molecular biology↗

bioRxiv2018

Physicochemical and microbiological profile of the potable water of Eastern Himalayan State Sikkim: An Indication of Severe Fecal Contamination and Immediate Health Risk

Increasing population, rapid urbanization and climate change have immensely affected the freshwater sources around the world. The continuous decline in the number of natural potable water sources raises serious concern about the overall health of the human population. Developing countries are the most affected in this regard due to lack of proper hygienic maintenance protocols. Sikkim an Eastern Himalayan state with mountains as predominant topological features, harbors several natural spring water (SW). These spring waters are the primary source of potable water for the population in the four districts of the state viz. East (E), West (W), South (S) and North (N). Several incidences of water-borne diseases and the relative lack of scientific evaluation reports on the water quality of the area have educed this study. Lack of any standard filtration and purification practice among the population is one of the prime factors for the outspread of different waterborne pathogen in the state. The people of the state mostly use boiling as a dominant method of water purification, while only a small percentage of people in the West district were found to use modern standard purification system (W = 30%). The rainy season was found to be the major contributor of different diseases (E = 86%; W=100%; S=100%; N=80%) and statistical analysis of the fecal coliforms of the different season also indicated a significant difference at p < 0.05. There was no statistical significance among the physicochemical parameter of the SW but surprisingly the water from the four districts was recorded with traces of highly toxic heavy metals like mercury/WHO limit (0.001-0.007mg/l/0.001) as well as lead/WHO limit (0.001-0.007mg/l/0.05) and selenium/WHO limit (0.526-0.644 mg/l/0.01) which was above the WHO permissible limit. Piper analysis showed that water was dominated by cation sodium ion (Na+) and bicarbonate (HCO3-) anion and the water can be categorized as Mg-HCO3- type. Pairwise Pearson correlation showed a significant correlation between Electrical conductivity and TDS (r = 0.998/1.00) as well as alkalinity and turbidity (0.993/1.00). The microbial confirmatory test showed severity in fecal contamination with high counts of Total Coliform (TC), Escherichia coli (EC) and Enterococcus (EN). Highest TC was recorded from W (37.26/ml) and lowest in N (22.13/ ml) in spring water. Highest contamination of Escherichia coli and Enterococcus was found in E (EC = 8.7/ml; EN = 2.08/ml) followed by S (EC = 8.4/ml and EN = 2.05/ml). It was found that community reservoir (CR) tank was more contaminated than SP, which indicates the negligence in maintenance and fecal contamination during transportation to the reservoir. Though household water was least contaminated compared to CR and SP, but it fails in WHO standard criteria for drinking water. These results indicate an immediate health risk of the resident of the state and which needs to be taken care of sooner as possible by protecting the important potable sources with required policies and regulations.

microbiology↗

bioRxiv2018

Effect of light intensity and nutritional value of food resources on flight response of adult parasitoid, Cotesia plutellae (Kurdjumov) (Hymenoptera: Braconidae)

Cotesia plutellae (Kurdjumov) (Hymenoptera: Braconidae) is the major larval parasitoid of Plutella xylostella (L) (Lepidoptera: Plutellidae), which is a serious pest of cruciferous plants throughout the world. We evaluated the influence of light intensities and feeding conditions on the vertical angle of flight in freshly emerged wasps in a cylinder having diameter 15cm and height 30cm. Light intensity was found to directly affects the flight activity. Increase in light intensity causes increase in vertical flight of the female wasps. However, Increase in light intensity did not influence the inclination of vertical flight in males. Feeding condition was also found to affect the vertical flight of the wasps. Honey odour, from below the flight chamber, arrested the flight of unfed or sucrose fed wasps. However, flight of honey fed wasps was not affected by honey odour. Male flight response was also influenced by feeding condition and light intensity but the response was not as higher as shown by females. The present study is useful for selecting suitable food prior to inundative release of parasitoid in the field at suitable time period of the day.

animal behavior and cognition↗

bioRxiv2018

The RNA helicase UPF1 associates with mRNAs co-transcriptionally and is required in nuclear processes of gene expression

UPF1 is an RNA helicase that is required for efficient nonsense-mediated mRNA decay (NMD) in eukaryotes, and the predominant view is that UPF1 mainly operates on the 3UTRs of mRNAs that are directed for NMD in the cytoplasm. Here we offer evidence, obtained from Drosophila, that UPF1 constantly moves between the nucleus and cytoplasm and that it has multiple functions in the nucleus. It is associated, genome-wide, with nascent RNAs at most of the active Pol II transcription sites and at some Pol III-transcribed genes, as demonstrated microscopically on the polytene chromosomes of salivary gland and by ChIP-seq analysis in S2 cells. Intron recognition seems to interfere with association and translocation of UPF1 on nascent pre-mRNA transcripts, and cells depleted of UPF1 show defects in several nuclear processes essential to correct gene expression - most strikingly, the release of mRNAs from transcription sites and mRNA export from the nucleus.

cell biology↗

bioRxiv2018

Emergence of Multidrug-Resistant Uropathogens harboring ESBL, Carbapenem, Aminoglycosides and AmpC resistant genes from Northern India

Extended-spectrum {beta}-lactamase (ESBL) producing bacteria acts as a serious threat, and its co-existence with other antibiotic resistant gene makes the clinical scenario worse nowadays. Therefore in this study, we investigated the occurrence of ESBL genes coexisting with carbapenem, AmpC and aminoglycoside resistance gene in uropathogens. Out of 1516 urine samples, 454 showed significant bacteriuria with a prevalence rate of 29.94 %. Escherichia coli (n=340) were found to be the most predominant uropathogen followed by Klebsiella pneumoniae (n=92), Pseudomonas aeruginosa (n=10) and Proteus mirabilis (n=9). Among the total uropathogens, sixty-three ESBL-producers were identified which included blaCTX-M-15 (n=32), followed by blaCTX-M-15 + blaOXA-2 (n=15), blaCTX-M-15 + blaOXA-2 + blaTEM (n=6), blaOXA-2 (n=5), bla OXA-2 + bla SHV-76 (n=1), bla TEM+SHV-76 (n= 1) and bla TEM (n=1). All ESBL genes were found on plasmid incompatibility types: HI1, I1, FIA+FIB, FIA and Y and were horizontally transferable. Among 63 ESBL-producers, 59 isolates harboured carbapenem-resistant genes which included blaNDM-5 (n=48), blaNDM-5 + blaOXA-48 (n=5), blaNDM-5 + blaIMP (n=5) and blaNDM-5 + blaIMP + blaVIM (n=1). The ESBL producing uropathogens also harbored 16S rRNA methylase genes which included rmtB (n=9), rmtA (n=4), rmtC (n=1) and ArmA (n=1) followed by AmpC genes which includes CIT (n=8) and DHA-1 (n=1) genes. Imipenem and gentamicin were found to be more effective. We speculating, this is the first report showing the prevalence of multidrug-resistant uropathogens in this area demanding regular surveillance for such resistance mechanisms which will be useful for health personnel to treat ESBL infection and its co-existence with another antibiotic resistance gene.

microbiology↗

bioRxiv2018

BCG overexpressing an endogenous STING agonist provides enhanced protection against pulmonary tuberculosis

Stimulator of interferon genes (STING) has emerged as a key signaling receptor that induces proinflammatory cytokines, and small molecule STING agonists are being developed as anticancer and antiviral agents. Here we report a strategy of delivering a STING agonist from within live BCG. We generated a recombinant BCG (BCG-disA-OE) that overexpresses the endogenous mycobacterial diadenylate cyclase gene and releases high levels of the STING agonist c-di-AMP. In macrophages BCG-disA-OE elicited statistically significantly stronger TNF-, IL-6, IL-1{beta}, IRF3, and IFN-{beta} levels than BCG-WT. In a 24-week guinea pig vaccination-Mtb challenge model, BCG-disA-OE reduced lung weights, pathology scores, and Mtb CFU counts in lungs by 28% (p<0.05), 34%, and 2.0 log10 CFU units (p < 0.5) compared with BCG-WT, respectively. Overproduction of the STING agonist c-di-AMP significantly enhanced the protective efficacy of BCG against pulmonary and extrapulmonary tuberculosis. Our findings support the development of BCG-vectored STING agonists as a TB vaccine strategy.

microbiology↗

bioRxiv2018

Integrating genotype and weather variables for soybean yield prediction using deep learning

Realized performance of complex traits is dependent on both genetic and environmental factors, which can be difficult to dissect due to the requirement for multiple replications of many genotypes in diverse environmental conditions. To mediate these problems, we present a machine learning framework in soybean (Glycine max (L.) Merr.) to analyze historical performance records from Uniform Soybean Tests (UST) in North America, with an aim to dissect and predict genotype response in multiple envrionments leveraging pedigree and genomic relatedness measures along with weekly weather parameters. The ML framework of Long Short Term Memory - Recurrent Neural Networks works by isolating key weather events and genetic interactions which affect yield, seed oil, seed protein and maturity enabling prediction of genotypic responses in unseen environments. This approach presents an exciting avenue for genotype x environment studies and enables prediction based systems. Our approaches can be applied in plant breeding programs with multi-environment and multi-genotype data, to identify superior genotypes through selection for commercial release as well as for determining ideal locations for efficient performance testing.

bioinformatics↗

bioRxiv2018

First report on Bacterial Diversity of Potable Spring water of Indian Himalayan Region

Water quality of a region directly corroborates with the health index of people. People in the Himalayan hills mainly depend upon the spring water for potability. To determine the microbial ecology of the spring waters of Sikkim, the variable region of 16S rRNA has been sequenced using Illumina MiSeq. Phylum wise annotation showed the East and North district are mostly dominated by Proteobacteria (41% and 35.80%), whereas West and South district is dominated by Planctomycetes (38.46%) and Verrucomicrobia (33%). The consistent dominance phyla in the all the four districts were Bacteriodetes (34-24%) which was highest dominancy in North district and lowest in wets district. Genus wise distribution showed the abundance of Brevifolis, Flavobacterium, Verrucomicrobia subdivision3, Emticica, Cytophaga, Prosthecobacter, Planctomycetes, Varivorax, Arcicella, Isosphera, Sedimunibacterium etc. The East district showed highest dominancy of genus Emticicia whereas Planctomycetes in the West district. The North district was mainly dominated by genus Arcicella and Brevifollis in the South district. North on the antonymous showed totally different sets of microbial diversity. North district showed an abundance of Arcicella, Planctomycetes, Schlerensia and Azohydromonas. The heat map produced by Bray Curtis distance method produced three clusters which showed the close relationship between West and East district microbiome that further related to South district. The sample of North district formed out group that showed different community structure from other three districts. The principle component analysis was showed that the east and South district samples are closely related and distantly correlated to the west Sikkim, but the North district showed completely different microbial community. The canonical correspondence analysis showed correlation between bacterial diversity and hydrochemistry and it was found that the bacterial diversity was influenced by the concentration of different metallic ions like sodium, calcium, barium and iron. This is a first report from the Eastern Himalayan region of India and it largely enhances our knowledge about the microbial structure of potable spring water of Eastern Himalayan. This study is useful for Government of India as well as the state government to adopt the different strategic treatment procedures to improve the quality of water that is supplied to the community resides in the Himalayan regions and solely dependent on this untreated spring water.

microbiology↗