Genomics and Informatics最新文献

Brugada syndrome (BS) is an autosomal dominant inheritance cardiac arrhythmia disorder associated with sudden death in young adults. Thailand has the highest prevalence of BS worldwide, and over 60% of patients with BS still have unclear disease etiology. Here, we performeda new viral metagenome analysis pipeline called VIRIN and validated it with whole genome sequencing (WGS) data of HeLa cell lines and hepatocellular carcinoma. Then the VIRIN pipelinewas applied to identify viral integration positions from unmapped WGS data of Thai males, including 100 BS patients (case) and 100 controls. Even though the sample preparation had noviral enrichment step, we can identify several virus genes from our analysis pipeline. The predominance of human endogenous retrovirus K (HERV-K) viruses was found in both cases andcontrols by blastn and blastx analysis. This study is the first report on the full-length HERV-Kassembled genomes in the Thai population. Furthermore, the HERV-K integration breakpointpositions were validated and compared between the case and control datasets. Interestingly,Brugada cases contained HERV-K integration breakpoints at promoters five times more oftenthan controls. Overall, the highlight of this study is the BS-specific HERV-K breakpoint positionsthat were found at the gene coding region "NBPF11" (n = 9), "NBPF12" (n = 8) and longnon-coding RNA (lncRNA) "PCAT14" (n = 4) region. The genes and the lncRNA have been reported to be associated with congenital heart and arterial diseases. These findings provide another aspect of the BS etiology associated with viral genome integrations within the humangenome.

Penalized regression has been widely used in genome-wide association studies for jointanalyses to find genetic associations. Among penalized regression models, the least absolute shrinkage and selection operator (Lasso) method effectively removes some coefficientsfrom the model by shrinking them to zero. To handle group structures, such as genes andpathways, several modified Lasso penalties have been proposed, including group Lasso andsparse group Lasso. Group Lasso ensures sparsity at the level of pre-defined groups, eliminating unimportant groups. Sparse group Lasso performs group selection as in group Lasso,but also performs individual selection as in Lasso. While these sparse methods are useful inhigh-dimensional genetic studies, interpreting the results with many groups and coefficients is not straightforward. Lasso's results are often expressed as trace plots of regressioncoefficients. However, few studies have explored the systematic visualization of group information. In this study, we propose a multi-level polar Lasso (MP-Lasso) chart, which caneffectively represent the results from group Lasso and sparse group Lasso analyses. An Rpackage to draw MP-Lasso charts was developed. Through a real-world genetic data application, we demonstrated that our MP-Lasso chart package effectively visualizes the resultsof Lasso, group Lasso, and sparse group Lasso.

Atropa belladonna is a valuable medicinal plant and a commercial source of tropane alkaloids, which are frequently utilized in therapeutic practice. In this study, bioinformaticmethodologies were used to examine the pattern of coding sequences and the factors thatmight influence codon usage bias in the chloroplast genome of Atropa belladonna andother nightshade genomes. The chloroplast engineering being a promising field in modernbiotechnology, the characterization of chloroplast genome is very important. The resultsrevealed that the chloroplast genomes of Nicotiana tabacum, Solanum lycopersicum, Capsicum frutescens, Datura stramonium, Lyciumbarbarum, Solanum melongena, and Solanumtuberosum exhibited comparable codon usage patterns. In these chloroplast genomes, weobserved a weak codon usage bias. According to the correspondence analysis, the genesisof the codon use bias in these chloroplast genes might be explained by natural selection,directed mutational pressure, and other factors. GC12 and GC3S were shown to have nomeaningful relationship. Further research revealed that natural selection primarily shapedthe codon usage in A. belladonna and other nightshade genomes for translational efficiency. The sequencing properties of these chloroplast genomes were also investigated by investing the occurrences of palindromes and inverted repeats, which would be useful forfuture research on medicinal plants.

Breast cancer (BC) is a significant threat to female health, with both modifiable andnon-modifiable risk factors. It is essential to monitor patients regularly and to raise population awareness. Increasing research also suggests that E-selectin (SELE) may increase tumor angiogenesis and the development of cancer. This study investigated SELE single-nucleotide polymorphisms (SNPs) in the following positions: rs5367T/C, rs5368C/T, rs5362T/G,and rs5362T/C. Using polymerase chain reaction, significant differences in allele and genotype frequencies were found between BC patients and controls. Position rs5368 was associated with an increased risk of BC for the CT and TT genotypes, with odds ratios (ORs) of16.3 and 6.90 (Fisher probability = 0.0001, p = 0.005). Women with the T allele had a 19.3-fold higher incidence of BC, while allele C may be a protective allele against BC (OR, 0.05).Heterozygous genotypes at rs5367, rs5362, and rs5362 were significantly more common inBC patients, with ORs of 5.70, 4.50, and 3.80, respectively. These SNPs may be associatedwith the risk of BC, because the frequency of mutant alleles was significantly higher in patients (OR: 4.26, 3.83, and 4.30, respectively) than in controls (OR: 0.23, 0.30, and 0.20, respectively). These SNPs may be considered a common genotype in the Iraqi population,with the wild-type allele having a protective fraction and the mutant allele having an environmental fraction. The results also revealed a 2-fold increase in gene expression in BCpatients compared to controls, with a significant effect (p = 0.017). This study's findingsconfirm the importance of SELE polymorphisms in cancer risk prediction.

Klebsiella pneumoniae is a gram-negative bacterium that is known for causing infection innosocomial settings. As reported by the World Health Organization, carbapenem-resistantEnterobacteriaceae, a category that includes K. pneumoniae, are classified as an urgentthreat, and the greatest concern is that these bacterial pathogens may acquire genetictraits that make them resistant towards antibiotics. The last class of antibiotics, carbapenems, are not able to combat these bacterial pathogens, allowing them to clonally expandantibiotic-resistant strains. Most antibiotics target essential pathways of bacterial cells;however, these targets are no longer susceptible to antibiotics. Hence, in our study, we focused on a hypothetical protein in K. pneumoniae that contains a DNA methylation proteindomain, suggesting a new potential site as a drug target. DNA methylation regulates theattenuation of bacterial virulence. We integrated computational-aided drug design by using a bioinformatics approach to perform subtractive genomics, virtual screening, and fingerprint similarity search. We identified a new potential drug, koenimbine, which could bea novel antibiotic.

Food security will be affected by climate change worldwide, particularly in the developingworld, where the most important food products originate from plants. Plants are often exposed to environmental stresses that may affect their growth, development, yield, and foodquality. Auxin is a hormone that plays a critical role in improving plants' tolerance of environmental conditions. Auxin controls the expression of many stress-responsive genes inplants by interacting with specific cis-regulatory elements called auxin-responsive elements (AuxREs). In this work, we performed an in silico prediction of AuxREs in promotersof five auxin-responsive genes in Zea mays. We applied a data fusion approach based onthe combined use of Dempster-Shafer evidence theory and fuzzy sets. Auxin has a directimpact on cell membrane proteins. The short-term auxin response may be represented bythe regulation of transmembrane gene expression. The detection of an AuxRE in the promoter of prolyl oligopeptidase (POP) in Z. mays and the 3-fold overexpression of this geneunder auxin treatment for 30 min indicated the role of POP in maize auxin response. POP isregulated by auxin to perform stress adaptation. In addition, the detection of two AuxRETGTCTC motifs in the upstream sequence of the bx1 gene suggests that bx1 can be regulated by auxin. Auxin may also be involved in the regulation of dehydration-responsive element-binding and some members of the protein kinase superfamily.

Various methods of frequent pattern mining have been applied to genetic problems, specifically, to the combined association of two genotypes (a genotype pattern, or diplotype) at different DNA variants with disease. These methods have the ability to come up with a selection of genotype patterns that are more common in affected than unaffected individuals, and the assessment of statistical significance for these selected patterns poses some unique problems, which are briefly outlined here.

BLAST, a basic bioinformatics tool for searching local sequence similarity, has been one of the most widely used bioinformatics programs since its introduction in 1990. Users generally use the web-based NCBI-BLAST program for BLAST analysis. However, users with large sequence data are often faced with a problem of upload size limitation while using the web-based BLAST program. This proves inconvenient as scientists often want to run BLAST on their own data, such as transcriptome or whole genome sequences. To overcome this issue, we developed NBLAST, a graphical user interface-based BLAST program that employs a two-way system, allowing the use of input sequences either as "query" or "target" in the BLAST analysis. NBLAST is also equipped with a dot plot viewer, thus allowing researchers to create custom database for BLAST and run a dot plot similarity analysis within a single program. It is available to access to the NBLAST with http://nbitglobal.com/nblast.