Identification of Hot and Cold spots in genome of Mycobacterium tuberculosis using Shewhart Control Charts

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

Draft genome sequence of Saccharopolyspora rectivirgula

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%

Quantification of stochastic noise of splicing and polyadenylation in Entamoeba histolytica

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

PENGEMBANGAN MODEL MANAJEMEN BERBASIS SEKOLAH YANG LEBIH MENGEDEPANKAN PELIBATAN PARTISIPASI MASYARAKAT UNTUK IMPLEMENTASI KURIKULUM 2013 DI BENGKULU

Penelitian ini bertujuan untuk mengembangkan model manajemen berbasis sekolah yang lebih mengedepankan pelibatan partisipasi masyarakat dalam rangka implementtasi kurikulum 2013 di Bengkulu. Penelitian tahun-1 ditujukan untuk mendeskripsikan faktor ekonomi, sosial, dan budaya masyarakat yang potensial berkontribusi terhadap pelaksanaan program sekolah. Berdasarkan data ekonomi, sosial, dan budaya tersebut maka pada tahun ke-2 peneliti akan memberikan penguatan pelibatan partisipasi masyarakat guna memberikan dukungan terhadap implementasi program sekolah, mengajak masyarakat untuk mengidentifikasi apa yang dapat mereka sumbangkan untuk kepentingan pendidikan di sekolah, dan sekolah menemukan cara yang tepat untuk meningkatkan partisipasi masyarakat. Pendekatan yang digunakan dalam mencapai tujuan tersebut antara lain dengan jalan: (1) menetapkan sekolah yang relevan dengan masalah dan bersedia menjadi subjek penelitian; (2) mengidentifikasi faktor ekonomi, sosial dan budaya masyarakat yang berpeluang memberikan kontribusi dalam pelaksanaan program sekolah; dan (3) memberikan penguatan terhadap komite sekolah agar dapat meningkatkan partisipasi masyarakat guna mendukung implementasi kurikulum 2013. Luaran penelitian tahun-1 antara lain berupa: (1) tersusun instrumen identifikasi potensi sekolah dan faktor ekonomi, sosial, dan budaya masyarakat yang potensial memberikan kontribusi pada pelaksanaan program sekolah; (2) deskripsi potensi sekolah yang dapat digunakan sebagai media pelibatan partisipasi masyarakat; (3) deskripsi faktor ekonomi, sosial, dan budaya masyarakat yang potensial memberikan kontribusi pada pelaksanaan program sekolah; dan (4) tersusun standar prosedur pelibatan partisipasi masyarakat dalam implementasi program sekolah. Semua hasil tesebut disajikan dalam (A) Laporan Penelitian; (B) Poster; (C) Makalah Seminar Internasional; (D) Proposal Penelitian Tahun-2

A Biomimetic 2D Transistor for Audiomorphic Computing

This 10-page article, published by Nature Publishing Group, discusses research related to neuromorphic computing. This research involves "... a biomimetic audiomorphic device that captures the neurobiological architecture and computational map inside the auditory cortex of barn owl..." Mimicking barn owls "super sensory neural architectures and associated algorithms through innovative solid-state devices and circuits might provide an alternative route towards energy efficient neuromorphic computing."This article includes the following sections: Abstract; Introduction; Results - Neural map and compute algorithm in barn owl, Artificial coincident detector neuron, Construction of neural auditory computational map, Artificial time delay neurons, and Neuroplasticity; Discussion; Methods; and more.Â

ABWGAT: anchor-based whole genome analysis tool

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

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

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(T) (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 tRNA(Ile)TAT 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

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

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

Comparative genome analysis of Mycobacteria focusing on tRNA and non-coding RNA

Background: The Mycobacterium genus encompasses at least 192 named species, many of which cause severe diseases such as tuberculosis. Non-tuberculosis mycobacteria (NTM) can also infect humans and animals. Some are of emerging concern because they show high resistance to commonly used antibiotics while others are used and evaluated in bioremediation or included in anticancer vaccines. Results: We provide the genome sequences for 114 mycobacterial type strains and together with 130 available mycobacterial genomes we generated a phylogenetic tree based on 387 core genes and supported by average nucleotide identity (ANI) data. The 244 genome sequences cover most of the species constituting the Mycobacterium genus. The genome sizes ranged from 3.2 to 8.1 Mb with an average of 5.7 Mb, and we identified 14 new plasmids. Moreover, mycobacterial genomes consisted of phage-like sequences ranging between 0 and 4.64% dependent on mycobacteria while the number of IS elements varied between 1 and 290. Our data also revealed that, depending on the mycobacteria, the number of tRNA and non-coding (nc) RNA genes differ and that their positions on the chromosome varied. We identified a conserved core set of 12 ncRNAs, 43 tRNAs and 18 aminoacyl-tRNA synthetases among mycobacteria. Conclusions; Phages, IS elements, tRNA and ncRNAs appear to have contributed to the evolution of the Mycobacterium genus where several tRNA and ncRNA genes have been horizontally transferred. On the basis of our phylogenetic analysis, we identified several isolates of unnamed species as new mycobacterial species or strains of known mycobacteria. The predicted number of coding sequences correlates with genome size while the number of tRNA, rRNA and ncRNA genes does not. Together these findings expand our insight into the evolution of the Mycobacterium genus and as such they establish a platform to understand mycobacterial pathogenicity, their evolution, antibiotic resistance/tolerance as well as the function and evolution of ncRNA among mycobacteria

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

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