International Journal of Genomics The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. Evidence of Divergent Amino Acid Usage in Comparative Analyses of R5- and X4-Associated HIV-1 Vpr Sequences Tue, 23 May 2017 00:00:00 +0000 Vpr is an HIV-1 accessory protein that plays numerous roles during viral replication, and some of which are cell type dependent. To test the hypothesis that HIV-1 tropism extends beyond the envelope into the vpr gene, studies were performed to identify the associations between coreceptor usage and Vpr variation in HIV-1-infected patients. Colinear HIV-1 Env-V3 and Vpr amino acid sequences were obtained from the LANL HIV-1 sequence database and from well-suppressed patients in the Drexel/Temple Medicine CNS AIDS Research and Eradication Study (CARES) Cohort. Genotypic classification of Env-V3 sequences as X4 (CXCR4-utilizing) or R5 (CCR5-utilizing) was used to group colinear Vpr sequences. To reveal the sequences associated with a specific coreceptor usage genotype, Vpr amino acid sequences were assessed for amino acid diversity and Jensen-Shannon divergence between the two groups. Five amino acid alphabets were used to comprehensively examine the impact of amino acid substitutions involving side chains with similar physiochemical properties. Positions 36, 37, 41, 89, and 96 of Vpr were characterized by statistically significant divergence across multiple alphabets when X4 and R5 sequence groups were compared. In addition, consensus amino acid switches were found at positions 37 and 41 in comparisons of the R5 and X4 sequence populations. These results suggest an evolutionary link between Vpr and gp120 in HIV-1-infected patients. Gregory C. Antell, Will Dampier, Benjamas Aiamkitsumrit, Michael R. Nonnemacher, Vanessa Pirrone, Wen Zhong, Katherine Kercher, Shendra Passic, Jean Williams, Yucheng Liu, Tony James, Jeffrey M. Jacobson, Zsofia Szep, Brian Wigdahl, and Fred C. Krebs Copyright © 2017 Gregory C. Antell et al. All rights reserved. Neurodevelopmental Disorders and Environmental Toxicants: Epigenetics as an Underlying Mechanism Mon, 08 May 2017 10:10:35 +0000 The increasing prevalence of neurodevelopmental disorders, especially autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD), calls for more research into the identification of etiologic and risk factors. The Developmental Origin of Health and Disease (DOHaD) hypothesizes that the environment during fetal and childhood development affects the risk for many chronic diseases in later stages of life, including neurodevelopmental disorders. Epigenetics, a term describing mechanisms that cause changes in the chromosome state without affecting DNA sequences, is suggested to be the underlying mechanism, according to the DOHaD hypothesis. Moreover, many neurodevelopmental disorders are also related to epigenetic abnormalities. Experimental and epidemiological studies suggest that exposure to prenatal environmental toxicants is associated with neurodevelopmental disorders. In addition, there is also evidence that environmental toxicants can result in epigenetic alterations, notably DNA methylation. In this review, we first focus on the relationship between neurodevelopmental disorders and environmental toxicants, in particular maternal smoking, plastic-derived chemicals (bisphenol A and phthalates), persistent organic pollutants, and heavy metals. We then review studies showing the epigenetic effects of those environmental factors in humans that may affect normal neurodevelopment. Nguyen Quoc Vuong Tran and Kunio Miyake Copyright © 2017 Nguyen Quoc Vuong Tran and Kunio Miyake All rights reserved. Evolution of the Apicomplexan Sugar Transporter Gene Family Repertoire Sun, 07 May 2017 00:00:00 +0000 Apicomplexan protist parasites utilize host sugars transported into the parasite by sugar transporter proteins for use as an energy source. We performed a phylum-wide phylogenetic analysis of the apicomplexan sugar transporter repertoire. Phylogenetic analyses revealed six major subfamilies of apicomplexan sugar transporters. Transporters in one subfamily have undergone expansions in Piroplasma species and Gregarina niphandrodes, while other subfamilies are highly divergent and contain genes found in only one or two species. Analyses of the divergent apicomplexan subfamilies revealed their presence in ciliates, indicating their alveolate ancestry and subsequent loss in chromerids and many apicomplexans. Ousman Mahmud and Jessica C. Kissinger Copyright © 2017 Ousman Mahmud and Jessica C. Kissinger. All rights reserved. Comparative Transcriptome Analyses of Resistant and Susceptible Near-Isogenic Wheat Lines following Inoculation with Blumeria graminis f. sp. tritici Tue, 02 May 2017 00:00:00 +0000 Powdery mildew is one of the most important diseases of wheat. In this study, the leaf RNA samples of wheat NILs carrying powdery mildew resistant and susceptible Pm2 alleles (L031 and Chancellor) and its F1 hybrid at two time points (16 h and 96 h postinoculation) were used for RNA-seq analysis. We carry comparison between similar materials at different times and between different materials at same times. The overlapping DEGs between the dominant phenotypes (L031 and F1 hybrid) and the recessive phenotype (Chancellor) were 1028 and 2214 DEGs, which were clearly lower than those between the dominant and recessive parents and thus could provide relatively accurate and valuable information. GO and KEGG enrichment analysis of DEGs revealed that other than the expected defense-related genes, differential up- and downregulation of genes from many other signaling networks were also involved. Comparative transcriptome analysis also revealed that early-stage postinoculation is important and suitable time points to study expression profiles and signaling pathways of resistance-related genes following fungal inoculation. qRT-PCR analyses showed highly consistent expression patterns of genes with RNA-seq data. The results will aid in the identification of genes and signaling pathways involved in powdery mildew response in wheat. Piyi Xing, Xueying Zhang, Yinguang Bao, Yuhai Wang, Honggang Wang, and Xingfeng Li Copyright © 2017 Piyi Xing et al. All rights reserved. Genome-Wide Identification of bZIP Family Genes Involved in Drought and Heat Stresses in Strawberry (Fragaria vesca) Tue, 11 Apr 2017 00:00:00 +0000 Basic leucine zipper (bZIP) genes are known to play a crucial role in response to various processes in plant as well as abiotic or biotic stress challenges. We have performed an identification and characterization of 50 bZIP genes across the woodland strawberry (Fragaria vesca) genome, which were divided into 10 clades according to the phylogenetic relationship of the strawberry bZIP proteins with those in Arabidopsis and rice. Five categories of intron patterns were observed within basic and hinge regions of the bZIP domains. Some additional conserved motifs have been found with the group specificity. Further, we predicted DNA-binding specificity of the basic and hinge regions as well as dimerization properties of leucine zipper regions, which was consistent with our phylogenetic clade and classified into 20 subfamilies. Across the different developmental stages of 15 organs and two types of fruits, the clade A bZIP members showed different tissue-specific expression patterns and the duplicated genes were differentially regulated, indicating a functional diversification coupled with the expansion of this gene family in strawberry. Under normal growth conditions, mrna11837 and mrna30280 of clade A showed very weak expression levels in organs and fruits, respectively; but higher expression was observed with different set of genes following drought and heat treatment, which may be caused by the separate response pathway between drought and heat treatments. Xiao-Long Wang, Xinlu Chen, Tian-Bao Yang, Qunkang Cheng, and Zong-Ming Cheng Copyright © 2017 Xiao-Long Wang et al. All rights reserved. Naturally Occurring Canine Invasive Urinary Bladder Cancer: A Complementary Animal Model to Improve the Success Rate in Human Clinical Trials of New Cancer Drugs Sun, 09 Apr 2017 00:00:00 +0000 Genomic analyses are defining numerous new targets for cancer therapy. Therapies aimed at specific genetic and epigenetic targets in cancer cells as well as expanded development of immunotherapies are placing increased demands on animal models. Traditional experimental models do not possess the collective features (cancer heterogeneity, molecular complexity, invasion, metastasis, and immune cell response) critical to predict success or failure of emerging therapies in humans. There is growing evidence, however, that dogs with specific forms of naturally occurring cancer can serve as highly relevant animal models to complement traditional models. Invasive urinary bladder cancer (invasive urothelial carcinoma (InvUC)) in dogs, for example, closely mimics the cancer in humans in pathology, molecular features, biological behavior including sites and frequency of distant metastasis, and response to chemotherapy. Genomic analyses are defining further intriguing similarities between InvUC in dogs and that in humans. Multiple canine clinical trials have been completed, and others are in progress with the aim of translating important findings into humans to increase the success rate of human trials, as well as helping pet dogs. Examples of successful targeted therapy studies and the challenges to be met to fully utilize naturally occurring dog models of cancer will be reviewed. Christopher M. Fulkerson, Deepika Dhawan, Timothy L. Ratliff, Noah M. Hahn, and Deborah W. Knapp Copyright © 2017 Christopher M. Fulkerson et al. All rights reserved. Chromosome 1 Sequence Analysis of C57BL/6J-Chr1KM Mouse Strain Sun, 09 Apr 2017 00:00:00 +0000 The Chinese Kunming (KM) mouse is a widely used outbred mouse stock in China. However, its genetic structure remains unclear. In this study, we sequenced the genome of the C57BL/6J-Chr1KM (B6-Chr1KM) strain, the chromosome 1 (Chr 1) of which was derived from one KM mouse. With 36.6× average coverage of the entire genome, 0.48 million single nucleotide polymorphisms (SNPs) and 96,679 indels were detected on Chr 1 through comparison with reference strain C57BL/6J. Moreover, 46,590 of them were classified as novel mutations. Further functional annotation identified 155 genes harboring potentially functional variants, among which 27 genes have been associated with human diseases. We then performed sequence similarity and Bayesian concordance analysis using the SNPs identified on Chr 1 and their counterparts in three subspecies, Mus musculus domesticus, M. m. musculus, and M. m. castaneus. Both analyses suggested that the Chr 1 sequence of B6-Chr1KM was predominantly derived from M. m. domesticus while 9.7% of the sequence was found to be from M. m. musculus. In conclusion, our analysis provided a detailed description of the genetic variations on Chr 1 of B6-Chr1KM and a new perspective on the subspecies origin of KM mouse which can be used to guide further genetic studies with this mouse strain. Fuyi Xu, Tianzhu Chao, Yiyin Zhang, Shixian Hu, Yuxun Zhou, Hongyan Xu, Junhua Xiao, and Kai Li Copyright © 2017 Fuyi Xu et al. All rights reserved. An Integrating Approach for Genome-Wide Screening of MicroRNA Polymorphisms Mediated Drug Response Alterations Wed, 05 Apr 2017 08:07:32 +0000 MicroRNAs (miRNAs) are a class of evolutionarily conserved small noncoding RNAs, ~22 nt in length, and found in diverse organisms and play important roles in the regulation of mRNA translation and degradation. It was shown that miRNAs were involved in many key biological processes through regulating the expression of targets. Genetic polymorphisms in miRNA target sites may alter miRNA regulation and therefore result in the alterations of the drug targets. Recent studies have demonstrated that SNPs in miRNA target sites can affect drug efficiency. However, there are still a large number of specific genetic variants related to drug efficiency that are yet to be discovered. We integrated large scale of genetic variations, drug targets, gene interaction networks, biological pathways, and seeds region of miRNA to identify miRNA polymorphisms affecting drug response. In addition, harnessing the abundant high quality biological network/pathways, we evaluated the cascade distribution of tarSNP impacts. We showed that the predictions can uncover most of the known experimentally supported cases as well as provide informative candidates complementary to existing methods/tools. Although there are several existing databases predicting the gain or loss of targeting function of miRNA mediated by SNPs, such as PolymiRTS, miRNASNP, MicroSNiPer, and MirSNP, none of them evaluated the influences of tarSNPs on drug response alterations. We developed a user-friendly online database of this approach named Mir2Drug. Xianyue Wang, Hong Jiang, Wei Wu, Rongxin Zhang, Lingxiang Wu, Huan Chen, Pengping Li, Yumin Nie, Jiaofang Shao, Yan Li, Xue Lin, Sali Lv, Qh Wang, and Jie Hu Copyright © 2017 Xianyue Wang et al. All rights reserved. Transcriptome Analysis of Orange Head Chinese Cabbage (Brassica rapa L. ssp. pekinensis) and Molecular Marker Development Sun, 02 Apr 2017 00:00:00 +0000 Due to the visual appearance and high carotenoid content, orange inner leaves are a desirable trait for the Chinese cabbage. To understand the molecular mechanism underlying the formation of orange inner leaves, the BrCRTISO (Bra031539) gene, as the Br-or candidate gene, was analyzed among the white and orange varieties, and 7 single nucleotide polymorphisms (SNPs) were identified. However, only one SNP (C952 to T952) altered the amino acid sequence, resulting in a mutation from Leu318 to Phe318 in the orange varieties. Additionally, we analyzed differentially expressed genes (DEGs) between the orange and white F2 individuals (14-401 × 14-490) and found four downregulated genes were involved in the carotenoid biosynthesis pathway, which may lead to the accumulation of prolycopene and other carotenoid pigments in the orange inner leaves. In addition, we developed a novel InDel marker in the first intron, which cosegregates with the phenotypes of orange color inner leaves. In conclusion, these findings enhance our understanding of the underlying mechanism of pigment accumulation in the inner leaves of the Chinese cabbage. Additionally, the SNP (C952 to T952) and the InDel marker will facilitate the marker-assisted selection during Chinese cabbage breeding. Jingjuan Li, Yihui Zhang, Qian Ding, Huayin Li, Lifeng Liu, Fengde Wang, and Jianwei Gao Copyright © 2017 Jingjuan Li et al. All rights reserved. The Promise of Genomic Studies on Human Diseases: From Basic Science to Clinical Application Wed, 29 Mar 2017 00:00:00 +0000 Lam C. Tsoi, Bethany Wolf, and Y. Ann Chen Copyright © 2017 Lam C. Tsoi et al. All rights reserved. Application of Genomic In Situ Hybridization in Horticultural Science Tue, 28 Mar 2017 10:30:14 +0000 Molecular cytogenetic techniques, such as in situ hybridization methods, are admirable tools to analyze the genomic structure and function, chromosome constituents, recombination patterns, alien gene introgression, genome evolution, aneuploidy, and polyploidy and also genome constitution visualization and chromosome discrimination from different genomes in allopolyploids of various horticultural crops. Using GISH advancement as multicolor detection is a significant approach to analyze the small and numerous chromosomes in fruit species, for example, Diospyros hybrids. This analytical technique has proved to be the most exact and effective way for hybrid status confirmation and helps remarkably to distinguish donor parental genomes in hybrids such as Clivia, Rhododendron, and Lycoris ornamental hybrids. The genome characterization facilitates in hybrid selection having potential desirable characteristics during the early hybridization breeding, as this technique expedites to detect introgressed sequence chromosomes. This review study epitomizes applications and advancements of genomic in situ hybridization (GISH) techniques in horticultural plants. Fahad Ramzan, Adnan Younis, and Ki-Byung Lim Copyright © 2017 Fahad Ramzan et al. All rights reserved. Temporal Changes in Gene Expression Profile during Mature Adipocyte Dedifferentiation Sun, 19 Mar 2017 00:00:00 +0000 Objective. To characterize changes in gene expression profile during human mature adipocyte dedifferentiation in ceiling culture. Methods. Subcutaneous (SC) and omental (OM) adipose tissue samples were obtained from 4 participants paired for age and BMI. Isolated adipocytes were dedifferentiated in ceiling culture. Gene expression analysis at days 0, 4, 7, and 12 of the cultures was performed using Affymetrix Human Gene 2.0 STvi arrays. Hierarchical clustering according to similarity of expression changes was used to identify overrepresented functions. Results. Four clusters gathered genes with similar expression between day 4 to day 7 but decreasing expression from day 7 to day 12. Most of these genes coded for proteins involved in adipocyte functions (LIPE, PLIN1, DGAT2, PNPLA2, ADIPOQ, CEBPA, LPL, FABP4, SCD, INSR, and LEP). Expression of several genes coding for proteins implicated in cellular proliferation and growth or cell cycle increased significantly from day 7 to day 12 (WNT5A, KITLG, and FGF5). Genes coding for extracellular matrix proteins were differentially expressed between days 0, 4, 7, and 12 (COL1A1, COL1A2, and COL6A3, MMP1, and TGFB1). Conclusion. Dedifferentiation is associated with downregulation of transcripts encoding proteins involved in mature adipocyte functions and upregulation of genes involved in matrix remodeling, cellular development, and cell cycle. Julie Anne Côté, Frédéric Guénard, Julie Lessard, Marc Lapointe, Simon Biron, Marie-Claude Vohl, and André Tchernof Copyright © 2017 Julie Anne Côté et al. All rights reserved. The Promise of Agriculture Genomics Sun, 05 Mar 2017 00:00:00 +0000 Wenqin Wang, Xuan H. Cao, Mihai Miclăuș, Jianhong Xu, and Wenwei Xiong Copyright © 2017 Wenqin Wang et al. All rights reserved. Racial Differences in Expression Levels of miRNA Machinery-Related Genes, Dicer, Drosha, DGCR8, and AGO2, in Asian Korean Papillary Thyroid Carcinoma and Comparative Validation Using the Cancer Genome Atlas Thu, 02 Mar 2017 08:26:25 +0000 Aberrant regulation of microRNA (miRNA) machinery components is associated with various human cancers, including papillary thyroid carcinoma (PTC), which is the most common type of thyroid cancer, and a higher prevalent female malignancy. The purpose of this study is to investigate racial differences in mRNA expression levels of four miRNA machinery components, Dicer, Drosha, DGCR8, and AGO2, and their correlations with clinicopathological characteristics. Forty PTC samples from female Asian Korean PTC patients were enrolled. Using qPCR, we examined mRNA expression levels of the components and next validated our results by comparison with results of female white American in the TCGA PTC project. Interestingly, mRNA expression levels of the selected factors were altered in the TCGA PTC samples. However, only Drosha showed a significantly lower expression level in Asian Korean PTC samples. Furthermore, the mRNA expression levels of the four components showed no association with clinicopathological characteristics in both groups. On the other hand, positive correlations were observed between altered mRNA expression levels of Dicer and Drosha and DGCR8 and Drosha in TCGA PTC samples. These findings collectively revealed that altered mRNA expression levels of miRNA machinery components might be responsible for racial differences in the carcinogenesis of PTC. Jaegil Kim, Woo-Jae Park, Kwang-Joon Jeong, Sun Hee Kang, Sun Young Kwon, Shin Kim, and Jong-Wook Park Copyright © 2017 Jaegil Kim et al. All rights reserved. A Review of Recent Advancement in Integrating Omics Data with Literature Mining towards Biomedical Discoveries Sun, 26 Feb 2017 07:10:14 +0000 In the past decade, the volume of “omics” data generated by the different high-throughput technologies has expanded exponentially. The managing, storing, and analyzing of this big data have been a great challenge for the researchers, especially when moving towards the goal of generating testable data-driven hypotheses, which has been the promise of the high-throughput experimental techniques. Different bioinformatics approaches have been developed to streamline the downstream analyzes by providing independent information to interpret and provide biological inference. Text mining (also known as literature mining) is one of the commonly used approaches for automated generation of biological knowledge from the huge number of published articles. In this review paper, we discuss the recent advancement in approaches that integrate results from omics data and information generated from text mining approaches to uncover novel biomedical information. Kalpana Raja, Matthew Patrick, Yilin Gao, Desmond Madu, Yuyang Yang, and Lam C. Tsoi Copyright © 2017 Kalpana Raja et al. All rights reserved. Case Study of Somaclonal Variation in Resistance Genes Mlo and Pme3 in Flaxseed (Linum usitatissimum L.) Induced by Nanoparticles Thu, 23 Feb 2017 08:20:23 +0000 Nanoparticles influence on genome is investigated worldwide. The appearance of somaclonal variation is a cause of great concern for any micropropagation system. Somaclonal variation describes the tissue-culture-induced phenotypic and genotypic variations. This paper shows the results of somaclonal variation in two resistance genes pectin methylesterase and Mlo-like protein in all tissue culture development stages, as donor plant, calluses, and regenerants of Linum usitatissimum induced by gold and silver nanoparticles. In this paper, it was essential to obtain DNA material from all tissue culture development stages from one donor plant to record changes in each nucleotide sequence. Gene region specific primers were developed for resistance genes such as Mlo and Pme3 to define the genetic variability in tissue culture of L. usitatissimum. In recent years, utilization of gold and silver nanoparticles in tissue culture is increased and the mechanisms of changes in genome induced by nanoparticles still remain unclear. Obtained data show the somaclonal variation increase in calluses obtained from one donor plant and grown on medium supplemented by gold nanoparticles (Mlo ; Pme3 ) or silver nanoparticles (Mlo ; Pme3 ) and decrease in regenerants. Morphological parameters of calluses showed a number of differences between each investigated culture group. Inese Kokina, Ilona Mickeviča, Marija Jermaļonoka, Linda Bankovska, Vjačeslavs Gerbreders, Andrejs Ogurcovs, and Inese Jahundoviča Copyright © 2017 Inese Kokina et al. All rights reserved. Genomewide Expression and Functional Interactions of Genes under Drought Stress in Maize Thu, 23 Feb 2017 00:00:00 +0000 A genomewide transcriptome assay of two subtropical genotypes of maize was used to observe the expression of genes at seedling stage of drought stress. The number of genes expressed differentially was greater in HKI1532 (a drought tolerant genotype) than in PC3 (a drought sensitive genotype), indicating primary differences at the transcriptional level in stress tolerance. The global coexpression networks of the two genotypes differed significantly with respect to the number of modules and the coexpression pattern within the modules. A total of 174 drought-responsive genes were selected from HKI1532, and their coexpression network revealed key correlations between different adaptive pathways, each cluster of the network representing a specific biological function. Transcription factors related to ABA-dependent stomatal closure, signalling, and phosphoprotein cascades work in concert to compensate for reduced photosynthesis. Under stress, water balance was maintained by coexpression of the genes involved in osmotic adjustments and transporter proteins. Metabolism was maintained by the coexpression of genes involved in cell wall modification and protein and lipid metabolism. The interaction of genes involved in crucial biological functions during stress was identified and the results will be useful in targeting important gene interactions to understand drought tolerance in greater detail. Nepolean Thirunavukkarasu, Rinku Sharma, Nidhi Singh, Kaliyugam Shiriga, Sweta Mohan, Swati Mittal, Shikha Mittal, Mallana Gowdra Mallikarjuna, Atmakuri Ramakrishna Rao, Prasanta Kumar Dash, Firoz Hossain, and Hari Shanker Gupta Copyright © 2017 Nepolean Thirunavukkarasu et al. All rights reserved. Exploration of Nitrate Reductase Metabolic Pathway in Corynebacterium pseudotuberculosis Mon, 20 Feb 2017 11:44:33 +0000 Based on the ability of nitrate reductase synthesis, Corynebacterium pseudotuberculosis is classified into two biovars: Ovis and Equi. Due to the presence of nitrate reductase, the Equi biovar can survive in absence of oxygen. On the other hand, Ovis biovar that does not have nitrate reductase is able to adapt to various ecological niches and can grow on certain carbon sources. Apart from these two biovars, some other strains are also able to carry out the reduction of nitrate. The enzymes that are involved in electron transport chain are also identified by in silico methods. Findings about pathogen metabolism can contribute to the identification of relationship between nitrate reductase and the C. pseudotuberculosis pathogenicity, virulence factors, and discovery of drug targets. Sintia Almeida, Cassiana Sousa, Vinícius Abreu, Carlos Diniz, Elaine M. S. Dorneles, Andrey P. Lage, Debmalya Barh, and Vasco Azevedo Copyright © 2017 Sintia Almeida et al. All rights reserved. Integrating Biological Covariates into Gene Expression-Based Predictors of Radiation Sensitivity Wed, 08 Feb 2017 12:44:50 +0000 The use of gene expression-based classifiers has resulted in a number of promising potential signatures of patient diagnosis, prognosis, and response to therapy. However, these approaches have also created difficulties in trying to use gene expression alone to predict a complex trait. A practical approach to this problem is to integrate existing biological knowledge with gene expression to build a composite predictor. We studied the problem of predicting radiation sensitivity within human cancer cell lines from gene expression. First, we present evidence for the need to integrate known biological conditions (tissue of origin, RAS, and p53 mutational status) into a gene expression prediction problem involving radiation sensitivity. Next, we demonstrate using linear regression, a technique for incorporating this knowledge. The resulting correlations between gene expression and radiation sensitivity improved through the use of this technique (best-fit adjusted increased from 0.3 to 0.84). Overfitting of data was examined through the use of simulation. The results reinforce the concept that radiation sensitivity is not driven solely by gene expression, but rather by a combination of distinct parameters. We show that accounting for biological heterogeneity significantly improves the ability of the model to identify genes that are associated with radiosensitivity. Vidya P. Kamath, Javier F. Torres-Roca, and Steven A. Eschrich Copyright © 2017 Vidya P. Kamath et al. All rights reserved. Whole-Genome Characteristics and Polymorphic Analysis of Vietnamese Rice Landraces as a Comprehensive Information Resource for Marker-Assisted Selection Tue, 07 Feb 2017 08:32:54 +0000 Next generation sequencing technologies have provided numerous opportunities for application in the study of whole plant genomes. In this study, we present the sequencing and bioinformatic analyses of five typical rice landraces including three indica and two japonica with potential blast resistance. A total of 688.4 million 100 bp paired-end reads have yielded approximately 30-fold coverage to compare with the Nipponbare reference genome. Among them, a small number of reads were mapped to both chromosomes and organellar genomes. Over two million and eight hundred thousand single nucleotide polymorphisms (SNPs) and insertions and deletions (InDels) in indica and japonica lines have been determined, which potentially have significant impacts on multiple transcripts of genes. SNP deserts, contiguous SNP-low regions, were found on chromosomes 1, 4, and 5 of all genomes of rice examined. Based on the distribution of SNPs per 100 kilobase pairs, the phylogenetic relationships among the landraces have been constructed. This is the first step towards revealing several salient features of rice genomes in Vietnam and providing significant information resources to further marker-assisted selection (MAS) in rice breeding programs. Hien Trinh, Khoa Truong Nguyen, Lam Van Nguyen, Huy Quang Pham, Can Thu Huong, Tran Dang Xuan, La Hoang Anh, Mario Caccamo, Sarah Ayling, Nguyen Thuy Diep, Cuong Nguyen, Khuat Huu Trung, and Tran Dang Khanh Copyright © 2017 Hien Trinh et al. All rights reserved. The Draft Genome and Transcriptome of the Atlantic Horseshoe Crab, Limulus polyphemus Mon, 06 Feb 2017 13:20:51 +0000 The horseshoe crab, Limulus polyphemus, exhibits robust circadian and circatidal rhythms, but little is known about the molecular mechanisms underlying those rhythms. In this study, horseshoe crabs were collected during the day and night as well as high and low tides, and their muscle and central nervous system tissues were processed for genome and transcriptome sequencing, respectively. The genome assembly resulted in contigs with N50 of 4,736, while the transcriptome assembly resulted in contigs and N50 of 3,497. Analysis of functional completeness by the identification of putative universal orthologs suggests that the transcriptome has three times more total expected orthologs than the genome. Interestingly, RNA-Seq analysis indicated no statistically significant changes in expression level for any circadian core or accessory gene, but there was significant cycling of several noncircadian transcripts. Overall, these assemblies provide a resource to investigate the Limulus clock systems and provide a large dataset for further exploration into the taxonomy and biology of the Atlantic horseshoe crab. Stephen D. Simpson, Jordan S. Ramsdell, Winsor H. Watson III, and Christopher C. Chabot Copyright © 2017 Stephen D. Simpson et al. All rights reserved. The Numerical Predominance and Large Transcriptome Differences of Neutrophils in Peripheral Blood Together Inevitably Account for a Reported Pulmonary Tuberculosis Signature Mon, 06 Feb 2017 11:48:06 +0000 Previous transcriptomic analysis revealed a 393-transcript signature (PTBsig), which is dominated by interferon inducible genes, in whole blood of pulmonary tuberculosis (PTB) patients. Comparisons with a limited set of interferon-driven genes among separated monocytes, CD4+ T cells, CD8+ T cells, and neutrophils indicated that the signature is due to changes in neutrophils, the overwhelmingly predominant cell type. By extending the analysis to the entire 393 transcripts of PTBsig and by switching the cell proportions between separated monocytes, CD4+ T cells, CD8+ T cells, and neutrophils, we create putative PTBsig for whole blood (pPTBsig) in which CD4+ or CD8+ T cells or monocytes predominated or in which the cell proportions were unchanged. These putative signatures are then compared to the actual reported PTBsig. We show that, because of their predominance in peripheral blood and their larger transcriptional responses, neutrophils were indeed almost exclusively responsible for PTBsig. We caution that the functional significance of changes in other cell types might escape notice in transcriptome analysis that is based upon whole blood. Kang Wu, Ka-Wing Wong, Wang-Long Deng, Hao Zhang, Jing Li, Douglas B. Lowrie, and Xiao-Yong Fan Copyright © 2017 Kang Wu et al. All rights reserved. Characteristics and Validation Techniques for PCA-Based Gene-Expression Signatures Mon, 06 Feb 2017 09:57:36 +0000 Background. Many gene-expression signatures exist for describing the biological state of profiled tumors. Principal Component Analysis (PCA) can be used to summarize a gene signature into a single score. Our hypothesis is that gene signatures can be validated when applied to new datasets, using inherent properties of PCA. Results. This validation is based on four key concepts. Coherence: elements of a gene signature should be correlated beyond chance. Uniqueness: the general direction of the data being examined can drive most of the observed signal. Robustness: if a gene signature is designed to measure a single biological effect, then this signal should be sufficiently strong and distinct compared to other signals within the signature. Transferability: the derived PCA gene signature score should describe the same biology in the target dataset as it does in the training dataset. Conclusions. The proposed validation procedure ensures that PCA-based gene signatures perform as expected when applied to datasets other than those that the signatures were trained upon. Complex signatures, describing multiple independent biological components, are also easily identified. Anders E. Berglund, Eric A. Welsh, and Steven A. Eschrich Copyright © 2017 Anders E. Berglund et al. All rights reserved. Genetic Diversity and Association Analysis for Solvent Retention Capacity in the Accessions Derived from Soft Wheat Ningmai 9 Sun, 05 Feb 2017 06:58:38 +0000 Solvent retention capacity (SRC) test is an effective method for quality evaluation of soft wheat. Ningmai 9 is a founder in soft wheat breeding. The SRC and genotype of Ningmai 9 and its 117 derivatives were tested. Association mapping was employed to identify the quantitative trait loci (QTL) associated with SRCs. Ningmai 9 had the allele frequency of 75.60% and 67.81% to its first- and second-generation derivatives, respectively, indicating higher contribution than theoretical expectation. Neighbor-joining cluster based on the genotyping data showed that Ningmai 9 and most of its first-generation derivatives were clustered together, whereas its second-generation derivatives were found in another group. The variation coefficients of SRCs in the derivatives ranged from 5.35% to 8.63%. A total of 29 markers on 13 chromosomes of the genome were associated with the SRCs. There were 6 markers associated with more than one SRC or detected in two years. The results suggested that QTL controlling SRCs in Ningmai 9 might be different from other varieties. Markers Xgwm44, Xbarc126, Xwmc790, and Xgwm232 associated with SRCs in Ningmai 9 might be used for quality improvement in soft wheat breeding. Peng Jiang, Ping-Ping Zhang, Xu Zhang, and Hong-Xiang Ma Copyright © 2017 Peng Jiang et al. All rights reserved. The Utilization of Formalin Fixed-Paraffin-Embedded Specimens in High Throughput Genomic Studies Thu, 26 Jan 2017 08:13:45 +0000 High throughput genomic assays empower us to study the entire human genome in short time with reasonable cost. Formalin fixed-paraffin-embedded (FFPE) tissue processing remains the most economical approach for longitudinal tissue specimen storage. Therefore, the ability to apply high throughput genomic applications to FFPE specimens can expand clinical assays and discovery. Many studies have measured the accuracy and repeatability of data generated from FFPE specimens using high throughput genomic assays. Together, these studies demonstrate feasibility and provide crucial guidance for future studies using FFPE specimens. Here, we summarize the findings of these studies and discuss the limitations of high throughput data generated from FFPE specimens across several platforms that include microarray, high throughput sequencing, and NanoString. Pan Zhang, Brian D. Lehmann, Yu Shyr, and Yan Guo Copyright © 2017 Pan Zhang et al. All rights reserved. Preparing and Analyzing Expressed Sequence Tags (ESTs) Library for the Mammary Tissue of Local Turkish Kivircik Sheep Mon, 23 Jan 2017 00:00:00 +0000 Kivircik sheep is an important local Turkish sheep according to its meat quality and milk productivity. The aim of this study was to analyze gene expression profiles of both prenatal and postnatal stages for the Kivircik sheep. Therefore, two different cDNA libraries, which were taken from the same Kivircik sheep mammary gland tissue at prenatal and postnatal stages, were constructed. Total 3072 colonies which were randomly selected from the two libraries were sequenced for developing a sheep ESTs collection. We used Phred/Phrap computer programs for analysis of the raw EST and readable EST sequences were assembled with the CAP3 software. Putative functions of all unique sequences and statistical analysis were determined by Geneious software. Total 422 ESTs have over 80% similarity to known sequences of other organisms in NCBI classified by Panther database for the Gene Ontology (GO) category. By comparing gene expression profiles, we observed some putative genes that may be relative to reproductive performance or play important roles in milk synthesis and secretion. A total of 2414 ESTs have been deposited to the NCBI GenBank database (GW996847–GW999260). EST data in this study have provided a new source of information to functional genome studies of sheep. Nehir Ozdemir Ozgenturk, Zehra Omeroglu Ulu, Salih Ulu, Cemal Un, Kemal Ozdem Oztabak, and Kemal Altunatmaz Copyright © 2017 Nehir Ozdemir Ozgenturk et al. All rights reserved. Association of PTPN22 Haplotypes (−1123G>C/+1858C>T) with Rheumatoid Arthritis in Western Mexican Population Sun, 22 Jan 2017 07:31:46 +0000 Rheumatoid arthritis (RA) is an autoimmune disease characterized by the presence of antibodies against cyclic citrullinated peptide (anti-CCP), a consequence of the breakdown of immune tolerance. The lymphoid tyrosine phosphatase (Lyp) protein has significant effects on maintenance of peripheral immune tolerance. Two polymorphic variants (−1123G>C and +1858C>T) at PTPN22 gene that encodes this protein have been associated with autoimmune disorders and found in strong linkage disequilibrium in Caucasian population. We evaluated whether PTPN22 haplotypes (−1123G>C/+1858C>T) are associated with anti-CCP antibodies, as well as susceptibility to RA in a Western Mexican population. A total of 315 RA patients and 315 control subjects (CS) were included. The polymorphisms were genotyped by PCR-RFLP and the anti-CCP antibodies were determined by ELISA. The PTPN22 polymorphisms were in strong linkage disequilibrium (D′ = 1.00 in CS). The susceptibility haplotype CT was significantly more frequent in RA patients than in CS (OR 2.18, 95% CI 1.15–4.16, ). No association between haplotypes and anti-CCP antibodies levels was observed. In conclusion, this study confirmed that −1123G>C and +1858C>T PTPN22 polymorphisms are in strong linkage disequilibrium and the CT haplotype is a susceptibility marker to RA in Western Mexico. However, the PTPN22 haplotypes are not associated with anti-CCP antibodies. Yeniley Ruiz-Noa, Jorge Ramón Padilla-Gutiérrez, Jorge Hernández-Bello, Claudia Azucena Palafox-Sánchez, Yeminia Valle, Edith Oregón-Romero, Ana Laura Pereira-Suárez, Ana Guilaisne Bernard-Medina, and José Francisco Muñoz-Valle Copyright © 2017 Yeniley Ruiz-Noa et al. All rights reserved. Module Anchored Network Inference: A Sequential Module-Based Approach to Novel Gene Network Construction from Genomic Expression Data on Human Disease Mechanism Wed, 18 Jan 2017 00:00:00 +0000 Different computational approaches have been examined and compared for inferring network relationships from time-series genomic data on human disease mechanisms under the recent Dialogue on Reverse Engineering Assessment and Methods (DREAM) challenge. Many of these approaches infer all possible relationships among all candidate genes, often resulting in extremely crowded candidate network relationships with many more False Positives than True Positives. To overcome this limitation, we introduce a novel approach, Module Anchored Network Inference (MANI), that constructs networks by analyzing sequentially small adjacent building blocks (modules). Using MANI, we inferred a 7-gene adipogenesis network based on time-series gene expression data during adipocyte differentiation. MANI was also applied to infer two 10-gene networks based on time-course perturbation datasets from DREAM3 and DREAM4 challenges. MANI well inferred and distinguished serial, parallel, and time-dependent gene interactions and network cascades in these applications showing a superior performance to other in silico network inference techniques for discovering and reconstructing gene network relationships. Annamalai Muthiah, Susanna R. Keller, and Jae K. Lee Copyright © 2017 Annamalai Muthiah et al. All rights reserved. Comparative RNA-Sequence Transcriptome Analysis of Phenolic Acid Metabolism in Salvia miltiorrhiza, a Traditional Chinese Medicine Model Plant Tue, 17 Jan 2017 00:00:00 +0000 Salvia miltiorrhiza Bunge is an important traditional Chinese medicine (TCM). In this study, two S. miltiorrhiza genotypes (BH18 and ZH23) with different phenolic acid concentrations were used for de novo RNA sequencing (RNA-seq). A total of 170,787 transcripts and 56,216 unigenes were obtained. There were 670 differentially expressed genes (DEGs) identified between BH18 and ZH23, 250 of which were upregulated in ZH23, with genes involved in the phenylpropanoid biosynthesis pathway being the most upregulated genes. Nine genes involved in the lignin biosynthesis pathway were upregulated in BH18 and thus result in higher lignin content in BH18. However, expression profiles of most genes involved in the core common upstream phenylpropanoid biosynthesis pathway were higher in ZH23 than that in BH18. These results indicated that genes involved in the core common upstream phenylpropanoid biosynthesis pathway might play an important role in downstream secondary metabolism and demonstrated that lignin biosynthesis was a putative partially competing pathway with phenolic acid biosynthesis. The results of this study expanded our understanding of the regulation of phenolic acid biosynthesis in S. miltiorrhiza. Zhenqiao Song, Linlin Guo, Tian Liu, Caicai Lin, Jianhua Wang, and Xingfeng Li Copyright © 2017 Zhenqiao Song et al. All rights reserved. Development of a New Marker System for Identification of Spirodela polyrhiza and Landoltia punctata Thu, 12 Jan 2017 00:00:00 +0000 Lemnaceae (commonly called duckweed) is an aquatic plant ideal for quantitative analysis in plant sciences. Several species of this family represent the smallest and fastest growing flowering plants. Different ecotypes of the same species vary in their biochemical and physiological properties. Thus, selecting of desirable ecotypes of a species is very important. Here, we developed a simple and rapid molecular identification system for Spirodela polyrhiza and Landoltia punctata based on the sequence polymorphism. First, several pairs of primers were designed and three markers were selected as good for identification. After PCR amplification, DNA fragments (the combination of three PCR products) in different duckweeds were detected using capillary electrophoresis. The high-resolution capillary electrophoresis displayed high identity to the sequencing results. The combination of the PCR products containing several DNA fragments highly improved the identification frequency. These results indicate that this method is not only good for interspecies identification but also ideal for intraspecies distinguishing. Meanwhile, 11 haplotypes were found in both the S. polyrhiza and L. punctata ecotypes. The results suggest that this marker system is useful for large-scale identification of duckweed and for the screening of desirable ecotypes to improve the diverse usage in duckweed utilization. Bo Feng, Yang Fang, Zhibin Xu, Chao Xiang, Chunhong Zhou, Fei Jiang, Tao Wang, and Hai Zhao Copyright © 2017 Bo Feng et al. All rights reserved.