Publications by authors named "Sarbashis Das"

17 Publications

  • Page 1 of 1

A biomimetic neural encoder for spiking neural network.

Nat Commun 2021 04 9;12(1):2143. Epub 2021 Apr 9.

Department of Engineering Science and Mechanics, Pennsylvania State University, University Park, PA, USA.

Spiking neural networks (SNNs) promise to bridge the gap between artificial neural networks (ANNs) and biological neural networks (BNNs) by exploiting biologically plausible neurons that offer faster inference, lower energy expenditure, and event-driven information processing capabilities. However, implementation of SNNs in future neuromorphic hardware requires hardware encoders analogous to the sensory neurons, which convert external/internal stimulus into spike trains based on specific neural algorithm along with inherent stochasticity. Unfortunately, conventional solid-state transducers are inadequate for this purpose necessitating the development of neural encoders to serve the growing need of neuromorphic computing. Here, we demonstrate a biomimetic device based on a dual gated MoS field effect transistor (FET) capable of encoding analog signals into stochastic spike trains following various neural encoding algorithms such as rate-based encoding, spike timing-based encoding, and spike count-based encoding. Two important aspects of neural encoding, namely, dynamic range and encoding precision are also captured in our demonstration. Furthermore, the encoding energy was found to be as frugal as ≈1-5 pJ/spike. Finally, we show fast (≈200 timesteps) encoding of the MNIST data set using our biomimetic device followed by more than 91% accurate inference using a trained SNN.
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http://dx.doi.org/10.1038/s41467-021-22332-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035177PMC
April 2021

Author Correction: Extensive genomic diversity among Mycobacterium marinum strains revealed by whole genome sequencing.

Sci Rep 2020 Mar 18;10(1):5246. Epub 2020 Mar 18.

Department of Cell and Molecular Biology, Box 596, Biomedical Centre, SE-751 24, Uppsala, Sweden.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41598-020-61218-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078255PMC
March 2020

A biomimetic 2D transistor for audiomorphic computing.

Nat Commun 2019 08 1;10(1):3450. Epub 2019 Aug 1.

Engineering Science and Mechanics, Pennsylvania State University, University Park, PA, 16802, USA.

In this article, we introduce a biomimetic audiomorphic device that captures the neurobiological architecture and computational map inside the auditory cortex of barn owl known for its exceptional hunting ability in complete darkness using auditory cues. The device consists of multiple split-gates with nanogaps on a semiconducting MoS channel connected to the source/drain contacts for imitating the spatial map of coincidence detector neurons and tunable RC circuits for imitating the interaural time delay neurons following the Jeffress model of sound localization. Furthermore, we use global back-gating capability to demonstrate neuroplasticity to capture behavioral and/or adaptation related changes in the barn owl. Finally, the virtual source model for current transport is combined with finite element COMSOL multiphysics simulations to explain and project the performance of the biomimetic audiomorphic device. We find that the precision of the biomimetic device can supersede the barn owl by orders of magnitude.
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http://dx.doi.org/10.1038/s41467-019-11381-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6673702PMC
August 2019

Comparative genomics of Mycobacterium mucogenicum and Mycobacterium neoaurum clade members emphasizing tRNA and non-coding RNA.

BMC Evol Biol 2019 06 18;19(1):124. Epub 2019 Jun 18.

Department of Cell and Molecular Biology, Biomedical Centre, Box 596, SE-751 24, Uppsala, Sweden.

Background: Mycobacteria occupy various ecological niches and can be isolated from soil, tap water and ground water. Several cause diseases in humans and animals. To get deeper insight into our understanding of mycobacterial evolution focusing on tRNA and non-coding (nc)RNA, we conducted a comparative genome analysis of Mycobacterium mucogenicum (Mmuc) and Mycobacterium neoaurum (Mneo) clade members.

Results: Genome sizes for Mmuc- and Mneo-clade members vary between 5.4 and 6.5 Mbps with the complete Mmuc (type strain) genome encompassing 6.1 Mbp. The number of tRNA genes range between 46 and 79 (including one pseudo tRNA gene) with 39 tRNA genes common among the members of these clades, while additional tRNA genes were probably acquired through horizontal gene transfer. Selected tRNAs and ncRNAs (RNase P RNA, tmRNA, 4.5S RNA, Ms1 RNA and 6C RNA) are expressed, and the levels for several of these are higher in stationary phase compared to exponentially growing cells. The rare tRNATAT isoacceptor and two for mycobacteria novel ncRNAs: the Lactobacillales-derived GOLLD RNA and a homolog to the antisense Salmonella typhimurium phage Sar RNA, were shown to be present and expressed in certain Mmuc-clade members.

Conclusions: Phages, IS elements, horizontally transferred tRNA gene clusters, and phage-derived ncRNAs appears to have influenced the evolution of the Mmuc- and Mneo-clades. While the number of predicted coding sequences correlates with genome size, the number of tRNA coding genes does not. The majority of the tRNA genes in mycobacteria are transcribed mainly from single genes and the levels of certain ncRNAs, including RNase P RNA (essential for the processing of tRNAs), are higher at stationary phase compared to exponentially growing cells. We provide supporting evidence that Ms1 RNA represents a mycobacterial 6S RNA variant. The evolutionary routes for the ncRNAs RNase P RNA, tmRNA and Ms1 RNA are different from that of the core genes.
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http://dx.doi.org/10.1186/s12862-019-1447-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6582537PMC
June 2019

Extended insight into the Mycobacterium chelonae-abscessus complex through whole genome sequencing of Mycobacterium salmoniphilum outbreak and Mycobacterium salmoniphilum-like strains.

Sci Rep 2019 03 14;9(1):4603. Epub 2019 Mar 14.

Department of Cell and Molecular Biology, Box 596, Biomedical Centre, SE-751 24, Uppsala, Sweden.

Members of the Mycobacterium chelonae-abscessus complex (MCAC) are close to the mycobacterial ancestor and includes both human, animal and fish pathogens. We present the genomes of 14 members of this complex: the complete genomes of Mycobacterium salmoniphilum and Mycobacterium chelonae type strains, seven M. salmoniphilum isolates, and five M. salmoniphilum-like strains including strains isolated during an outbreak in an animal facility at Uppsala University. Average nucleotide identity (ANI) analysis and core gene phylogeny revealed that the M. salmoniphilum-like strains are variants of the human pathogen Mycobacterium franklinii and phylogenetically close to Mycobacterium abscessus. Our data further suggested that M. salmoniphilum separates into three branches named group I, II and III with the M. salmoniphilum type strain belonging to group II. Among predicted virulence factors, the presence of phospholipase C (plcC), which is a major virulence factor that makes M. abscessus highly cytotoxic to mouse macrophages, and that M. franklinii originally was isolated from infected humans make it plausible that the outbreak in the animal facility was caused by a M. salmoniphilum-like strain. Interestingly, M. salmoniphilum-like was isolated from tap water suggesting that it can be present in the environment. Moreover, we predicted the presence of mutational hotspots in the M. salmoniphilum isolates and 26% of these hotspots overlap with genes categorized as having roles in virulence, disease and defense. We also provide data about key genes involved in transcription and translation such as sigma factor, ribosomal protein and tRNA genes.
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http://dx.doi.org/10.1038/s41598-019-40922-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418233PMC
March 2019

Transcriptomics of cardiac biopsies reveals differences in patients with or without diagnostic parameters for heart failure with preserved ejection fraction.

Sci Rep 2019 02 28;9(1):3179. Epub 2019 Feb 28.

Department of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, S-751 24, Uppsala, Sweden.

Heart failure affects 2-3% of adult Western population. Prevalence of heart failure with preserved left ventricular (LV) ejection fraction (HFpEF) increases. Studies suggest HFpEF patients to have altered myocardial structure and functional changes such as incomplete relaxation and increased cardiac stiffness. We hypothesised that patients undergoing elective coronary bypass surgery (CABG) with HFpEF characteristics would show distinctive gene expression compared to patients with normal LV physiology. Myocardial biopsies for mRNA expression analysis were obtained from sixteen patients with LV ejection fraction ≥45%. Five out of 16 patients (31%) had echocardiographic characteristics and increased NTproBNP levels indicative of HFpEF and this group was used as HFpEF proxy, while 11 patients had Normal LV physiology. Utilising principal component analysis, the gene expression data clustered into two groups, corresponding to HFpEF proxy and Normal physiology, and 743 differentially expressed genes were identified. The associated top biological functions were cardiac muscle contraction, oxidative phosphorylation, cellular remodelling and matrix organisation. Our results also indicate that upstream regulatory events, including inhibition of transcription factors STAT4, SRF and TP53, and activation of transcription repressors HEY2 and KDM5A, could provide explanatory mechanisms to observed gene expression differences and ultimately cardiac dysfunction in the HFpEF proxy group.
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http://dx.doi.org/10.1038/s41598-019-39445-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6395693PMC
February 2019

Extensive genomic diversity among Mycobacterium marinum strains revealed by whole genome sequencing.

Sci Rep 2018 08 13;8(1):12040. Epub 2018 Aug 13.

Department of Cell and Molecular Biology, Box 596, Biomedical Centre, SE-751 24, Uppsala, Sweden.

Mycobacterium marinum is the causative agent for the tuberculosis-like disease mycobacteriosis in fish and skin lesions in humans. Ubiquitous in its geographical distribution, M. marinum is known to occupy diverse fish as hosts. However, information about its genomic diversity is limited. Here, we provide the genome sequences for 15 M. marinum strains isolated from infected humans and fish. Comparative genomic analysis of these and four available genomes of the M. marinum strains M, E11, MB2 and Europe reveal high genomic diversity among the strains, leading to the conclusion that M. marinum should be divided into two different clusters, the "M"- and the "Aronson"-type. We suggest that these two clusters should be considered to represent two M. marinum subspecies. Our data also show that the M. marinum pan-genome for both groups is open and expanding and we provide data showing high number of mutational hotspots in M. marinum relative to other mycobacteria such as Mycobacterium tuberculosis. This high genomic diversity might be related to the ability of M. marinum to occupy different ecological niches.
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http://dx.doi.org/10.1038/s41598-018-30152-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6089878PMC
August 2018

The Mycobacterium phlei Genome: Expectations and Surprises.

Genome Biol Evol 2016 Apr 8;8(4):975-85. Epub 2016 Apr 8.

Department of Cell and Molecular Biology, Box 596, Biomedical Centre, Uppsala, Sweden

Mycobacterium phlei, a nontuberculosis mycobacterial species, was first described in 1898-1899. We present the complete genome sequence for theM. phlei CCUG21000(T)type strain and the draft genomes for four additional strains. The genome size for all five is 5.3 Mb with 69.4% Guanine-Cytosine content. This is ≈0.35 Mbp smaller than the previously reported M. phlei RIVM draft genome. The size difference is attributed partly to large bacteriophage sequence fragments in theM. phlei RIVM genome. Comparative analysis revealed the following: 1) A CRISPR system similar to Type 1E (cas3) in M. phlei RIVM; 2) genes involved in polyamine metabolism and transport (potAD,potF) that are absent in other mycobacteria, and 3) strain-specific variations in the number of σ-factor genes. Moreover,M. phlei has as many as 82 mce(mammalian cell entry) homologs and many of the horizontally acquired genes in M. phlei are present in other environmental bacteria including mycobacteria that share similar habitat. Phylogenetic analysis based on 693 Mycobacterium core genes present in all complete mycobacterial genomes suggested that its closest neighbor is Mycobacterium smegmatis JS623 and Mycobacterium rhodesiae NBB3, while it is more distant toM. smegmatis mc2 155.
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http://dx.doi.org/10.1093/gbe/evw049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4860684PMC
April 2016

Comparative Sigma Factor-mRNA Levels in Mycobacterium marinum under Stress Conditions and during Host Infection.

PLoS One 2015 7;10(10):e0139823. Epub 2015 Oct 7.

Department of Cell and Molecular Biology, Uppsala University Biomedical Centre, Uppsala, Sweden.

We have used RNASeq and qRT-PCR to study mRNA levels for all σ-factors in different Mycobacterium marinum strains under various growth and stress conditions. We also studied their levels in M. marinum from infected fish and mosquito larvae. The annotated σ-factors were expressed and transcripts varied in relation to growth and stress conditions. Some were highly abundant such as sigA, sigB, sigC, sigD, sigE and sigH while others were not. The σ-factor mRNA profiles were similar after heat stress, during infection of fish and mosquito larvae. The similarity also applies to some of the known heat shock genes such as the α-crystallin gene. Therefore, it seems probable that the physiological state of M. marinum is similar when exposed to these different conditions. Moreover, the mosquito larvae data suggest that this is the state that the fish encounter when infected, at least with respect to σ-factor mRNA levels. Comparative genomic analysis of σ-factor gene localizations in three M. marinum strains and Mycobacterium tuberculosis H37Rv revealed chromosomal rearrangements that changed the localization of especially sigA, sigB, sigD, sigE, sigF and sigJ after the divergence of these two species. This may explain the variation in species-specific expression upon exposure to different growth conditions.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0139823PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4596819PMC
June 2016

Characterization of Three Mycobacterium spp. with Potential Use in Bioremediation by Genome Sequencing and Comparative Genomics.

Genome Biol Evol 2015 Jun 16;7(7):1871-86. Epub 2015 Jun 16.

Department of Cell and Molecular Biology, Uppsala University, Sweden

We provide the genome sequences of the type strains of the polychlorophenol-degrading Mycobacterium chlorophenolicum (DSM43826), the degrader of chlorinated aliphatics Mycobacterium chubuense (DSM44219) and Mycobacterium obuense (DSM44075) that has been tested for use in cancer immunotherapy. The genome sizes of M. chlorophenolicum, M. chubuense, and M. obuense are 6.93, 5.95, and 5.58 Mb with GC-contents of 68.4%, 69.2%, and 67.9%, respectively. Comparative genomic analysis revealed that 3,254 genes are common and we predicted approximately 250 genes acquired through horizontal gene transfer from different sources including proteobacteria. The data also showed that the biodegrading Mycobacterium spp. NBB4, also referred to as M. chubuense NBB4, is distantly related to the M. chubuense type strain and should be considered as a separate species, we suggest it to be named Mycobacterium ethylenense NBB4. Among different categories we identified genes with potential roles in: biodegradation of aromatic compounds and copper homeostasis. These are the first nonpathogenic Mycobacterium spp. found harboring genes involved in copper homeostasis. These findings would therefore provide insight into the role of this group of Mycobacterium spp. in bioremediation as well as the evolution of copper homeostasis within the Mycobacterium genus.
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http://dx.doi.org/10.1093/gbe/evv111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4524478PMC
June 2015

Draft Genome Sequence of Saccharopolyspora rectivirgula.

Genome Announc 2014 Jan 9;2(1). Epub 2014 Jan 9.

Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.

We have sequenced the genome of Saccharopolyspora rectivirgula, the causative agent of farmer's lung disease. The draft genome consists of 182 contigs totaling 3,977,051 bp, with a GC content of 68.9%.
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http://dx.doi.org/10.1128/genomeA.01117-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3886947PMC
January 2014

Genetic heterogeneity revealed by sequence analysis of Mycobacterium tuberculosis isolates from extra-pulmonary tuberculosis patients.

BMC Genomics 2013 Jun 17;14:404. Epub 2013 Jun 17.

School of Computational and Integrative Sciences, Jawaharlal Nehru University, New Delhi, India.

Background: Tuberculosis remains a major public health problem. Clinical tuberculosis manifests often as pulmonary and occasionally as extra-pulmonary tuberculosis. The emergence of drug resistant tubercle bacilli and its association with HIV is a formidable challenge to curb the spread of tuberculosis. There have been concerted efforts by whole genome sequencing and bioinformatics analysis to identify genomic patterns and to establish a relationship between the genotype of the organism and clinical manifestation of tuberculosis. Extra-pulmonary TB constitutes 15-20 percent of the total clinical cases of tuberculosis reported among immunocompetent patients, whereas among HIV patients the incidence is more than 50 percent. Genomic analysis of M. tuberculosis isolates from extra pulmonary patients has not been explored.

Results: The genomic DNA of 5 extra-pulmonary clinical isolates of M. tuberculosis derived from cerebrospinal fluid, lymph node fine needle aspirates (FNAC) / biopsies, were sequenced. Next generation sequencing approach (NGS) was employed to identify Single Nucleotide Variations (SNVs) and computational methods used to predict their consequence on functional genes. Analysis of distribution of SNVs led to the finding that there are mixed genotypes in patient isolates and that many SNVs are likely to influence either gene function or their expression. Phylogenetic relationship between the isolates correlated with the origin of the isolates. In addition, insertion sites of IS elements were identified and their distribution revealed a variation in number and position of the element in the 5 extra-pulmonary isolates compared to the reference M. tuberculosis H37Rv strain.

Conclusions: The results suggest that NGS sequencing is able to identify small variations in genomes of M. tuberculosis isolates including changes in IS element insertion sites. Moreover, variations in isolates of M. tuberculosis from non-pulmonary sites were documented. The analysis of our results indicates genomic heterogeneity in the clinical isolates.
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http://dx.doi.org/10.1186/1471-2164-14-404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3699378PMC
June 2013

Identification and expression of stressosomal proteins in Mycobacterium marinum under various growth and stress conditions.

FEMS Microbiol Lett 2013 May 2;342(2):98-105. Epub 2013 Apr 2.

Department of Cell and Molecular Biology, Biomedical Centre, Uppsala University, SE-751 24 Uppsala, Sweden.

Like other bacteria, Mycobacterium spp. have developed different strategies in response to environmental changes such as nutrient limitations and other different stress situations. We have identified candidate genes (rsb genes) from Mycobacterium marinum involved in the regulation of the activity of the alternative sigma factor, σ(F) . This is a homolog of the master regulator of general stress response, σ(B) , and the sporulation-specific sigma factor, σ(F) , in Bacillus subtilis. The organization of these genes in M. marinum and B. subtilis is similar. Transcriptome and qRT-PCR data show that these genes are indeed expressed in M. marinum and that the levels of expression vary with growth phase and exposure to stress. In particular, cold stress caused a significant rise in the expression of all identified rsb and sigF genes. We discuss these data in relation to what is currently known for other Mycobacterium spp.
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http://dx.doi.org/10.1111/1574-6968.12118DOI Listing
May 2013

Quantification of stochastic noise of splicing and polyadenylation in Entamoeba histolytica.

Nucleic Acids Res 2013 Feb 20;41(3):1936-52. Epub 2012 Dec 20.

Institut Pasteur, Unité Biologie Cellulaire du Parasitisme, Département Biologie cellulaire et infection, F-75015 Paris, France, INSERM U786, F-75015 Paris, France.

Alternative splicing and polyadenylation were observed pervasively in eukaryotic messenger RNAs. These alternative isoforms could either be consequences of physiological regulation or stochastic noise of RNA processing. To quantify the extent of stochastic noise in splicing and polyadenylation, we analyzed the alternative usage of splicing and polyadenylation sites in Entamoeba histolytica using RNA-Seq. First, we identified a large number of rarely spliced alternative junctions and then showed that the occurrence of these alternative splicing events is correlated with splicing site sequence, occurrence of constitutive splicing events and messenger RNA abundance. Our results implied the majority of these alternative splicing events are likely to be stochastic error of splicing machineries, and we estimated the corresponding error rates. Second, we observed extensive microheterogeneity of polyadenylation cleavage sites, and the extent of such microheterogeneity is correlated with the occurrence of constitutive cleavage events, suggesting most of such microheterogeneity is likely to be stochastic. Overall, we only observed a small fraction of alternative splicing and polyadenylation isoforms that are unlikely to be solely stochastic, implying the functional relevance of alternative splicing and polyadenylation in E. histolytica is limited. Lastly, we revised the gene models and annotated their 3'UTR in AmoebaDB, providing valuable resources to the community.
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http://dx.doi.org/10.1093/nar/gks1271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3561952PMC
February 2013

Identification of hot and cold spots in genome of Mycobacterium tuberculosis using Shewhart Control Charts.

Sci Rep 2012 2;2:297. Epub 2012 Mar 2.

School of Computational and Integrative Sciences, JawaharlalNehru University, New Delhi, India.

The organization of genomic sequences is dynamic and undergoes change during the process of evolution. Many of the variations arise spontaneously and the observed genomic changes can either be distributed uniformly throughout the genome or be preferentially localized to some regions (hot spots) compared to others. Conversely cold spots may tend to accumulate very few variations or none at all. In order to identify such regions statistically, we have developed a method based on Shewhart Control Chart. The method was used for identification of hot and cold spots of single-nucleotide variations (SNVs) in Mycobacterium tuberculosis genomes. The predictions have been validated by sequencing some of these regions derived from clinical isolates. This method can be used for analysis of other genome sequences particularly infectious microbes.
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http://dx.doi.org/10.1038/srep00297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291883PMC
April 2013

ABWGAT: anchor-based whole genome analysis tool.

Bioinformatics 2009 Dec 14;25(24):3319-20. Epub 2009 Oct 14.

Center for Computational Biology and Bioinformatics, School of Information Technology, Jawaharlal Nehru University, New Delhi, 110067, India.

Summary: Large numbers of genomes are being sequenced regularly and the rate will go up in future due to availability of new genome sequencing techniques. In order to understand genotype to phenotype relationships, it is necessary to identify sequence variations at the genomic level. Alignment of a pair of genomes and parsing the alignment data is an accepted approach for identification of variations. Though there are a number of tools available for whole-genome alignment, none of these allows automatic parsing of the alignment and identification of different kinds of genomic variants with high degree of sensitivity. Here we present a simple web-based interface for whole genome comparison named ABWGAT (Anchor-Based Whole Genome Analysis Tool) that is simple to use. The output is a list of variations such as SNVs, indels, repeat expansion and inversion.

Availability: The web server is freely available to non-commercial users at the following address http://abwgc.jnu.ac.in/_sarba. Supplementary data are available at http://abwgc.jnu.ac.in/_sarba/cgi-bin/abwgc_retrival.cgi using job id 524, 526 and 528.

Contact: [email protected]; [email protected]
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http://dx.doi.org/10.1093/bioinformatics/btp587DOI Listing
December 2009

Single-nucleotide variations associated with Mycobacterium tuberculosis KwaZulu-Natal strains.

J Biosci 2009 Sep;34(3):397-404

Center for Computational Biology and Bioinformatics, School of Information Technology, Jawaharlal Nehru University, New Delhi 110 067, India.

The occurrence of drug resistance in Mycobacterium tuberculosis, the aetiological agent of tuberculosis (TB), is hampering the management and control of TB in the world. Here we present a computational analysis of recently sequenced drug-sensitive (DS), multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of M. tuberculosis. Single-nucleotide variations (SNVs) were identified in a pair-wise manner using the anchor-based whole genome comparison (ABWGC) tool and its modified version. For this analysis, four fully sequenced genomes of different strains of M. tuberculosis were taken along with three KwaZulu-Natal (KZN) strains isolated from South Africa including one XDR and one MDR strain. KZN strains were compared with other fully sequenced strains and also among each other. The variations were analysed with respect to their biological influence as a result of either altered structure or synthesis. The results suggest that the DR phenotype may be due to changes in a number of genes. The database on KZN strains can be accessed through the website http://mirna.jnu.ac.in/mgdd/.
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http://dx.doi.org/10.1007/s12038-009-0046-yDOI Listing
September 2009
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