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International Journal of Genomics publishes papers in all areas of genome-scale analysis, including bioinformatics, clinical and disease genomics, epigenomics, evolutionary and functional genomics, genome engineering, and synthetic genomics.
Chief Editor, Professor Nislow, is currently based at the University of British Columbia as a Tier 1 Canada Research Chair in Translational Genomics, with a background in yeast genetics and genomics.
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Long Noncoding RNA HOTTIP Serves as an Independent Predictive Biomarker for the Prognosis of Patients with Clear Cell Renal Cell Carcinoma
Several studies have indicated that HOXA transcript at the distal tip (HOTTIP) play important roles in the tumorigenesis and development of various cancers. We aim to investigate the expression and prognostic value of HOTTIP in clear cell renal cell carcinoma (ccRCC). A systematic review of PubMed, Embase, Medline, and Web of Science databases was performed to select eligible literatures relevant to the correlation between HOTTIP expression and clinical outcome of different cancers. The association between the HOTTIP level and overall survival (OS), lymph node metastasis (LNM), or clinical stage was subsequently analyzed. Survival analyses were performed in a large cohort of more than 500 patients with ccRCC from The Cancer Genome Atlas (TCGA) using bioinformatic methods. Seventeen studies with a total of 1594 patients with thirteen kinds of carcinomas were included in this analysis. The result showed that high HOTTIP expression could predict worse outcome in cancer patients, with the pooled hazard ratio (HR) of 2.34 (95% confidence interval (CI) 1.96–2.79, ). The result also showed that elevated HOTTIP expression was correlated with more LNM (, 95% CI 1.91-3.58, ) and advanced clinical stage (, 95% CI 2.58-4.93, ). We further validated that ccRCC patients with higher HOTTIP expression tend to have unsatisfactory outcomes both in the entire TCGA dataset and different clinical stratums, like age, grade, and stage. The tumor of those patients was associated with a larger size, easier to metastasis, advanced clinical stage, and a higher pathological grade. These findings suggested that increased HOTTIP expression might act as a novel prognostic marker for ccRCC patients.
Mining the Prognostic Value of HNRNPAB and Its Function in Breast Carcinoma
Heterogeneous nuclear ribonucleoproteins (HNRNPs) are crucial members in the pathogenesis and progression of numerous cancers. However, the expression pattern and clinical significance of HNRNPs in breast carcinoma (BC) remain to be investigated. In the present study, bioinformatic analysis identified HNRNPAB as the only commonly upregulated HNRNP in BC. Elevated expression of HNRNPAB was positively associated with more aggressive diseases and poorer survival rates in BC. Pathway analysis revealed that HNRNPAB coexpressed genes were enriched in the pathway of G2/M phase transition, and the expression level of HNRNPAB was strongly correlated with those of CCNB1, CDK1, CDC25A, and CDC25C. Experiments in vitro demonstrated that HNRNPAB knockdown suppressed cell proliferation and blocked the G2/M phase transition in BC. Taken together, this study provides the initial evidence that HNRNPAB may be employed as an innovative therapeutic target as well as a prognostic biomarker in BC patients.
Diagnostic Value of miR-103 in Patients with Sepsis and Noninfectious SIRS and Its Regulatory Role in LPS-Induced Inflammatory Response by Targeting TLR4
Background. Sepsis is a life-threatening condition and a systemic inflammatory response syndrome (SIRS) driven by infection. This study aimed at investigating the expression of microRNA-103 (miR-103) in sepsis patients, evaluating its diagnostic value, and exploring the regulatory effect of miR-103 on LPS-induced inflammation in monocytes. Methods. Expression of miR-103 was measured using quantitative real-time PCR. A receiver operating characteristics curve was plotted to evaluate the diagnostic vale of miR-103. Serum and cell supernatant levels of proinflammatory cytokines were analyzed using ELISA. The interaction between miR-103 and Toll-like receptors 4 (TLR4) was analyzed using luciferase reporter assay. The effect of miR-103 on inflammation was examined in LPS-treated monocytes. Results. Serum expression of miR-103 was decreased in noninfectious SIRS and sepsis patients compared with healthy controls, and the lowest expression value was observed in sepsis patients (all ). Serum levels of miR-103 have considerable diagnostic accuracy in distinguishing sepsis patients from SIRS patients and healthy controls. A negative correlation was found between miR-103 and inflammatory responses in sepsis patients. TLR4 was demonstrated to be a direct target of miR-103 and was negatively regulated by miR-103 in monocytes. The promoted inflammatory responses by LPS in monocytes were reversed by the overexpression of miR-103. Conclusion. All the data revealed that serum decreased miR-103 in sepsis patients serves as a promising noninvasive diagnostic biomarker and may be involved in the pathogenesis of sepsis by regulating inflammatory responses via targeting TLR4.
Genome-Wide Analysis, Characterization, and Expression Profile of the Basic Leucine Zipper Transcription Factor Family in Pineapple
This study identified 57 basic leucine zipper (bZIP) genes from the pineapple genome, and the analysis of these bZIP genes was focused on the evolution and divergence after multiple duplication events in relation to the pineapple genome fusion. According to bioinformatics analysis of a phylogenetic tree, the bZIP gene family was divided into 11 subgroups in pineapple, Arabidopsis, and rice; gene structure and conserved motif analyses showed that bZIP genes within the same subgroup shared similar intron-exon organizations and motif composition. Further synteny analysis showed 17 segmental duplication events with 27 bZIP genes. The study also analyzed the pineapple gene expression of bZIP genes in different tissues, organs, and developmental stages, as well as in abiotic stress responses. The RNA-sequencing data showed that AcobZIP57 was upregulated in all tissues, including vegetative and reproductive tissues. AcobZIP28 and AcobZIP43 together with the other 25 bZIP genes did not show high expression levels in any tissue. Six bZIP genes were exposed to abiotic stress, and the relative expression levels were detected by quantitative real-time PCR. A significant response was observed for AcobZIP24 against all kinds of abiotic stresses at 24 and 48 h in pineapple root tissues. Our study provides a perspective for the evolutionary history and general biological involvement of the bZIP gene family of pineapple, which laid the foundation for future functional characterization of the bZIP genes in pineapple.
Statistical Method Based on Bayes-Type Empirical Score Test for Assessing Genetic Association with Multilocus Genotype Data
Simultaneous testing of multiple genetic variants for association is widely recognized as a valuable complementary approach to single-marker tests. As such, principal component regression (PCR) has been found to have competitive power. We focus on exploring a robust test for an unknown genetic mode of all SNPs, an unknown Hardy-Weinberg equilibrium (HWE) in a population, and a large number of all SNPs. First, we propose a new global test by means of the use of codominant codes for all markers and PCR. The new global test is built on an empirical Bayes-type score statistic for testing marginal associations with each single marker. The new global test gains power by robustly exploiting the Hardy-Weinberg equilibrium in the control population and effectively using linkage disequilibrium among test markers. The new global test reduces to PCR when the genotype for each marker is coded as the number of minor alleles. This connection lends insight into the power of the new global test relative to PCR and some other popular multimarker test methods. Second, we propose a robust test method based on the new global test and the ordinary PCR test built on a prospective score statistic for testing marginal associations with each single marker when the genotype for each marker is coded as the number of minor alleles by taking the minimum value of these two tests. Finally, through extensive simulation studies and analysis of the association between pancreatic cancer and some genes of interest, we show that the proposed robust test method has desirable power and can often identify association signals that may be missed by existing methods.
Transcriptional Sequencing and Gene Expression Analysis of Various Genes in Fruit Development of Three Different Black Pepper (Piper nigrum L.) Varieties
Black pepper (Piper nigrum) is a vital spice crop with uses ranging from culinary to pharmacological applications. However, limited genetic information has constrained the understanding of the molecular regulation of flower and fruit development in black pepper. In this study, a comparison among three different black pepper varieties, Semengok Aman (SA), Kuching (KC), and Semengok 1 (S1), with varying fruit characteristics was used to provide insight on the genetic regulation of flower and fruit development. Next-generation sequencing (NGS) technology was used to determine the flower and fruit transcriptomes by sequencing on an Illumina HiSeq 2500 platform followed by de novo assembly using SOAPdenovo-Trans. The high-quality assembly of 66,906 of unigenes included 64.4% of gene sequences (43,115) with similarity to one or more protein sequences from the GenBank database. Annotation with Blast2Go assigned 37,377 genes to one or more Gene Ontology terms. Of these genes, 5,874 genes were further associated with the biological pathways recorded in the KEGG database. Comparison of flower and fruit transcriptome data from the three different black pepper varieties revealed a large number of DEGs between flower and fruit of the SA variety. Gene Ontology (GO) enrichment analysis further supports functions of DEGs between flower and fruit in the categories of carbohydrate metabolic processes, embryo development, and DNA metabolic processes while the DEGs in fruit relate to biosynthetic process, secondary metabolic process, and catabolic process. The enrichment of DEGs in KEGG pathways was also investigated, and a large number of genes were found to belong to the nucleotide metabolism and carbohydrate metabolism categories. Gene expression profiling of flower formation-related genes reveals that other than regulating the flowering in black pepper, the flowering genes might also be implicated in the fruit development process. Transcriptional analysis of sugar transporter and carbohydrate metabolism genes in different fruit varieties suggested that the carbohydrate metabolism in black pepper fruit is developmentally regulated, and some genes might serve as potential genes for future crop quality improvement. Study on the piperine-related gene expression analysis suggested that lysine-derived products might present in all stages of fruit development, but the transportation was only active at the early stage of fruit development. These results indicate several candidate genes related to the development of flower and fruit in black pepper and provide a resource for future functional analysis and potentially for future crop improvement.