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Genes, Volume 10, Issue 1 (January 2019)

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Cover Story (view full-size image) How epigenetic Modifications (Mods) of small RNAs facilitate adaptation and the way back to [...] Read more.
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Open AccessArticle Genome-Wide Identification and Expression Profiling of Sugar Transporter Protein (STP) Family Genes in Cabbage (Brassica oleracea var. capitata L.) Reveals their Involvement in Clubroot Disease Responses
Received: 9 December 2018 / Revised: 12 January 2019 / Accepted: 18 January 2019 / Published: 21 January 2019
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Abstract
Sugar transporter protein (STP) genes are involved in multiple biological processes, such as plant responses to various stresses. However, systematic analysis and functional information of STP family genes in Brassica oleracea are very limited. A comprehensive analysis was carried out to [...] Read more.
Sugar transporter protein (STP) genes are involved in multiple biological processes, such as plant responses to various stresses. However, systematic analysis and functional information of STP family genes in Brassica oleracea are very limited. A comprehensive analysis was carried out to identify BoSTP genes and dissect their phylogenetic relationships and to investigate the expression profiles in different organs and in response to the clubroot disease. A total of 22 BoSTP genes were identified in the B. oleracea genome and they were further classified into four clades based on the phylogenetic analysis. All the BoSTP proteins harbored the conserved sugar transporter (Sugar_tr, PF00083) domain, and the majority of them contained 12 transmembrane helices (TMHs). Rates of synonymous substitution in B. oleracea relative to Arabidopsis thaliana indicated that STP genes of B. oleracea diverged from those of A. thaliana approximately 16.3 million years ago. Expression profiles of the BoSTP genes in different organs derived from RNA-Seq data indicated that a large number of the BoSTP genes were expressed in specific organs. Additionally, the expression of BoSTP4b and BoSTP12 genes were induced in roots of the clubroot-susceptible cabbage (CS-JF1) at 28 days after inoculation with Plasmodiophora brassicae, compared with mock-inoculated plants. We speculated that the two BoSTPs might be involved in monosaccharide unloading and carbon partitioning associated with P. brassicae colonization in CS-JF1. Subcellular localization analysis indicated that the two BoSTP proteins were localized in the cell membrane. This study provides insights into the evolution and potential functions of BoSTPs. Full article
(This article belongs to the Section Plant Genetics and Genomics)
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Open AccessArticle An Exonic Switch Regulates Differential Accession of microRNAs to the Cd34 Transcript in Atherosclerosis Progression
Received: 18 December 2018 / Revised: 7 January 2019 / Accepted: 14 January 2019 / Published: 21 January 2019
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Abstract
Background: CD34+ Endothelial Progenitor Cells (EPCs) play an important role in the recovery of injured endothelium and contribute to atherosclerosis (ATH) pathogenesis. Previously we described a potential atherogenic role for miR-125 that we aimed to confirm in this work. Methods: Microarray hybridization, [...] Read more.
Background: CD34+ Endothelial Progenitor Cells (EPCs) play an important role in the recovery of injured endothelium and contribute to atherosclerosis (ATH) pathogenesis. Previously we described a potential atherogenic role for miR-125 that we aimed to confirm in this work. Methods: Microarray hybridization, TaqMan Low Density Array (TLDA) cards, qPCR, and immunohistochemistry (IHC) were used to analyze expression of the miRNAs, proteins and transcripts here studied. Results: Here we have demonstrated an increase of resident CD34-positive cells in the aortic tissue of human and mice during ATH progression, as well as the presence of clusters of CD34-positive cells in the intima and adventitia of human ATH aortas. We introduce miR-351, which share the seed sequence with miR-125, as a potential effector of CD34. We show a splicing event at an internal/cryptic splice site at exon 8 of the murine Cd34 gene (exonic-switch) that would regulate the differential accession of miRNAs (including miR-125) to the coding region or to the 3’UTR of Cd34. Conclusions: We introduce new potential mediators of ATH progression (CD34 cell-clusters, miR-351), and propose a new mechanism of miRNA action, linked to a cryptic splicing site in the target-host gene, that would regulate the differential accession of miRNAs to their cognate binding sites. Full article
(This article belongs to the Special Issue microRNA in Health and Disease)
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Open AccessArticle De Novo Sequencing and Hybrid Assembly of the Biofuel Crop Jatropha curcas L.: Identification of Quantitative Trait Loci for Geminivirus Resistance
Received: 24 October 2018 / Revised: 3 December 2018 / Accepted: 7 December 2018 / Published: 21 January 2019
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Abstract
Jatropha curcas is an important perennial, drought tolerant plant that has been identified as a potential biodiesel crop. We report here the hybrid de novo genome assembly of J. curcas generated using Illumina and PacBio sequencing technologies, and identification of quantitative loci for [...] Read more.
Jatropha curcas is an important perennial, drought tolerant plant that has been identified as a potential biodiesel crop. We report here the hybrid de novo genome assembly of J. curcas generated using Illumina and PacBio sequencing technologies, and identification of quantitative loci for Jatropha Mosaic Virus (JMV) resistance. In this study, we generated scaffolds of 265.7 Mbp in length, which correspond to 84.8% of the gene space, using Benchmarking Universal Single-Copy Orthologs (BUSCO) analysis. Additionally, 96.4% of predicted protein-coding genes were captured in RNA sequencing data, which reconfirms the accuracy of the assembled genome. The genome was utilized to identify 12,103 dinucleotide simple sequence repeat (SSR) markers, which were exploited in genetic diversity analysis to identify genetically distinct lines. A total of 207 polymorphic SSR markers were employed to construct a genetic linkage map for JMV resistance, using an interspecific F2 mapping population involving susceptible J. curcas and resistant Jatropha integerrima as parents. Quantitative trait locus (QTL) analysis led to the identification of three minor QTLs for JMV resistance, and the same has been validated in an alternate F2 mapping population. These validated QTLs were utilized in marker-assisted breeding for JMV resistance. Comparative genomics of oil-producing genes across selected oil producing species revealed 27 conserved genes and 2986 orthologous protein clusters in Jatropha. This reference genome assembly gives an insight into the understanding of the complex genetic structure of Jatropha, and serves as source for the development of agronomically improved virus-resistant and oil-producing lines. Full article
(This article belongs to the Section Plant Genetics and Genomics)
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Open AccessReview Convergent Evolution of the Seed Shattering Trait
Received: 13 December 2018 / Revised: 15 January 2019 / Accepted: 17 January 2019 / Published: 19 January 2019
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Abstract
Loss of seed shattering is a key trait in crop domestication, particularly for grain crops. For wild plants, seed shattering is a crucial mechanism to achieve greater fitness, although in the agricultural context, this mechanism reduces harvesting efficiency, especially under dry conditions. Loss [...] Read more.
Loss of seed shattering is a key trait in crop domestication, particularly for grain crops. For wild plants, seed shattering is a crucial mechanism to achieve greater fitness, although in the agricultural context, this mechanism reduces harvesting efficiency, especially under dry conditions. Loss of seed shattering was acquired independently in different monocotyledon and dicotyledon crop species by ‘convergent phenotypic evolution’, leading to similar low dehiscent and indehiscent phenotypes. Here, the main aim is to review the current knowledge about seed shattering in crops, in order to highlight the tissue modifications that underlie the convergent phenotypic evolution of reduced shattering in different types of fruit, from the silique of Brassicaceae species, to the pods of legumes and spikes of cereals. Emphasis is given to legumes, with consideration of recent data obtained for the common bean. The current review also discusses to what extent convergent phenotypes arose from parallel changes at the histological and/or molecular levels. For this reason, an overview is included of the main findings relating to the genetic control of seed shattering in the model species Arabidopsis thaliana and in other important crops. Full article
(This article belongs to the Special Issue Genomics of Plant Domestication and Crop Evolution)
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Open AccessReview Writing Histone Monoubiquitination in Human Malignancy—The Role of RING Finger E3 Ubiquitin Ligases
Received: 24 December 2018 / Revised: 15 January 2019 / Accepted: 15 January 2019 / Published: 18 January 2019
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Abstract
There is growing evidence highlighting the importance of monoubiquitination as part of the histone code. Monoubiquitination, the covalent attachment of a single ubiquitin molecule at specific lysines of histone tails, has been associated with transcriptional elongation and the DNA damage response. Sites function [...] Read more.
There is growing evidence highlighting the importance of monoubiquitination as part of the histone code. Monoubiquitination, the covalent attachment of a single ubiquitin molecule at specific lysines of histone tails, has been associated with transcriptional elongation and the DNA damage response. Sites function as scaffolds or docking platforms for proteins involved in transcription or DNA repair; however, not all sites are equal, with some sites resulting in actively transcribed chromatin and others associated with gene silencing. All events are written by E3 ubiquitin ligases, predominantly of the RING (really interesting new gene) finger type. One of the most well-studied events is monoubiquitination of histone H2B at lysine 120 (H2Bub1), written predominantly by the RING finger complex RNF20-RNF40 and generally associated with active transcription. Monoubiquitination of histone H2A at lysine 119 (H2AK119ub1) is also well-studied, its E3 ubiquitin ligase constituting part of the Polycomb Repressor Complex 1 (PRC1), RING1B-BMI1, associated with transcriptional silencing. Both modifications are activated as part of the DNA damage response. Histone monoubiquitination is a key epigenomic event shaping the chromatin landscape of malignancy and influencing how cells respond to DNA damage. This review discusses a number of these sites and the E3 RING finger ubiquitin ligases that write them. Full article
(This article belongs to the Special Issue Histone Modification Enzymes and Long Noncoding RNAs in Cancer)
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Open AccessArticle A Random Walk Based Cluster Ensemble Approach for Data Integration and Cancer Subtyping
Received: 27 November 2018 / Revised: 11 January 2019 / Accepted: 14 January 2019 / Published: 18 January 2019
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Abstract
Availability of diverse types of high-throughput data increases the opportunities for researchers to develop computational methods to provide a more comprehensive view for the mechanism and therapy of cancer. One fundamental goal for oncology is to divide patients into subtypes with clinical and [...] Read more.
Availability of diverse types of high-throughput data increases the opportunities for researchers to develop computational methods to provide a more comprehensive view for the mechanism and therapy of cancer. One fundamental goal for oncology is to divide patients into subtypes with clinical and biological significance. Cluster ensemble fits this task exactly. It can improve the performance and robustness of clustering results by combining multiple basic clustering results. However, many existing cluster ensemble methods use a co-association matrix to summarize the co-occurrence statistics of the instance-cluster, where the relationship in the integration is only encapsulated at a rough level. Moreover, the relationship among clusters is completely ignored. Finding these missing associations could greatly expand the ability of cluster ensemble methods for cancer subtyping. In this paper, we propose the RWCE (Random Walk based Cluster Ensemble) to consider similarity among clusters. We first obtained a refined similarity between clusters by using random walk and a scaled exponential similarity kernel. Then, after being modeled as a bipartite graph, a more informative instance-cluster association matrix filled with the aforementioned cluster similarity was fed into a spectral clustering algorithm to get the final clustering result. We applied our method on six cancer types from The Cancer Genome Atlas (TCGA) and breast cancer from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC). Experimental results show that our method is competitive against existing methods. Further case study demonstrates that our method has the potential to find subtypes with clinical and biological significance. Full article
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Open AccessReview Coordinated Dialogue between UHRF1 and DNMT1 to Ensure Faithful Inheritance of Methylated DNA Patterns
Received: 26 November 2018 / Revised: 22 December 2018 / Accepted: 11 January 2019 / Published: 18 January 2019
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Abstract
DNA methylation, catalyzed by DNA methyltransferases (DNMTs), is an epigenetic mark that needs to be faithfully replicated during mitosis in order to maintain cell phenotype during successive cell divisions. This epigenetic mark is located on the 5′-carbon of the cytosine mainly within cytosine–phosphate–guanine [...] Read more.
DNA methylation, catalyzed by DNA methyltransferases (DNMTs), is an epigenetic mark that needs to be faithfully replicated during mitosis in order to maintain cell phenotype during successive cell divisions. This epigenetic mark is located on the 5′-carbon of the cytosine mainly within cytosine–phosphate–guanine (CpG) dinucleotides. DNA methylation is asymmetrically positioned on both DNA strands, temporarily generating a hemi-methylated state after DNA replication. Hemi-methylation is a particular status of DNA that is recognized by ubiquitin-like containing plant homeodomain (PHD) and really interesting new gene (RING) finger domains 1 (UHRF1) through its SET- (Su(var)3-9, Enhancer-of-zeste and Trithorax) and RING-associated (SRA) domain. This interaction is considered to be involved in the recruitment of DNMT1 to chromatin in order to methylate the adequate cytosine on the newly synthetized DNA strand. The UHRF1/DNMT1 tandem plays a pivotal role in the inheritance of DNA methylation patterns, but the fine-tuning mechanism remains a mystery. Indeed, because DNMT1 experiences difficulties in finding the cytosine to be methylated, it requires the help of a guide, i.e., of UHRF1, which exhibits higher affinity for hemi-methylated DNA vs. non-methylated DNA. Two models of the UHRF1/DNMT1 dialogue were suggested to explain how DNMT1 is recruited to chromatin: (i) an indirect communication via histone H3 ubiquitination, and (ii) a direct interaction of UHRF1 with DNMT1. In the present review, these two models are discussed, and we try to show that they are compatible with each other. Full article
(This article belongs to the Special Issue Role of DNA Methyltransferases in the Epigenome)
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Open AccessArticle EPA and DHA Inhibit Myogenesis and Downregulate the Expression of Muscle-related Genes in C2C12 Myoblasts
Received: 2 January 2019 / Accepted: 11 January 2019 / Published: 18 January 2019
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Abstract
This study was conducted to elucidate the biological effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on cell proliferation, differentiation and gene expression in C2C12 myoblasts. C2C12 were treated with various concentrations of EPA or DHA under proliferation and differentiation conditions. Cell [...] Read more.
This study was conducted to elucidate the biological effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on cell proliferation, differentiation and gene expression in C2C12 myoblasts. C2C12 were treated with various concentrations of EPA or DHA under proliferation and differentiation conditions. Cell viability was analyzed using cell counting kit-8 assays (CCK-8). The Edu assays were performed to analyze cell proliferation. To analyze cell differentiation, the expressions of myogenic marker genes were determined at the transcriptional and translational levels by qRT-PCR, immunoblotting and immunofluorescence. Global gene expression patterns were characterized using RNA-sequencing. Phosphorylation levels of ERK and Akt were examined by immunoblotting. Cell viability and proliferation was significantly inhibited after incubation with EPA (50 and 100 μM) or DHA (100 μM). Both EPA and DHA suppressed C2C12 myoblasts differentiation. RNA-sequencing analysis revealed that some muscle-related genes were significantly downregulated following EPA or DHA (50 μM) treatment, including insulin-like growth factor 2 (IGF-2), troponin T3 (Tnnt3), myoglobin (Mb), myosin light chain phosphorylatable fast skeletal muscle (Mylpf) and myosin heavy polypeptide 3 (Myh3). IGF-2 was crucial for the growth and differentiation of skeletal muscle and could activate the PI3K/Akt and the MAPK/ERK cascade. We found that EPA and DHA (50 μM) decreased the phosphorylation levels of ERK1/2 and Akt in C2C12 myoblasts. Thus, this study suggested that EPA and DHA exerted an inhibitory effect on myoblast proliferation and differentiation and downregulated muscle-related genes expression. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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Open AccessArticle Genomic and Transcriptomic Changes That Mediate Increased Platinum Resistance in Cupriavidus metallidurans
Received: 7 December 2018 / Revised: 11 January 2019 / Accepted: 15 January 2019 / Published: 18 January 2019
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Abstract
The extensive anthropogenic use of platinum, a rare element found in low natural abundance in the Earth’s continental crust and one of the critical raw materials in the EU innovation partnership framework, has resulted in increased concentrations in surface environments. To minimize its [...] Read more.
The extensive anthropogenic use of platinum, a rare element found in low natural abundance in the Earth’s continental crust and one of the critical raw materials in the EU innovation partnership framework, has resulted in increased concentrations in surface environments. To minimize its spread and increase its recovery from the environment, biological recovery via different microbial systems is explored. In contrast, studies focusing on the effects of prolonged exposure to Pt are limited. In this study, we used the metal-resistant Cupriavidus metallidurans NA4 strain to explore the adaptation of environmental bacteria to platinum exposure. We used a combined Nanopore–Illumina sequencing approach to fully resolve all six replicons of the C. metallidurans NA4 genome, and compared them with the C. metallidurans CH34 genome, revealing an important role in metal resistance for its chromid rather than its megaplasmids. In addition, we identified the genomic and transcriptomic changes in a laboratory-evolved strain, displaying resistance to 160 µM Pt4+. The latter carried 20 mutations, including a large 69.9 kb deletion in its plasmid pNA4_D (89.6 kb in size), and 226 differentially-expressed genes compared to its parental strain. Many membrane-related processes were affected, including up-regulation of cytochrome c and a lytic transglycosylase, down-regulation of flagellar and pili-related genes, and loss of the pNA4_D conjugative machinery, pointing towards a significant role in the adaptation to platinum. Full article
(This article belongs to the Special Issue Genomics of Bacterial Metal Resistance)
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Open AccessArticle A High-Quality De novo Genome Assembly from a Single Mosquito Using PacBio Sequencing
Received: 18 December 2018 / Revised: 14 January 2019 / Accepted: 15 January 2019 / Published: 18 January 2019
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Abstract
A high-quality reference genome is a fundamental resource for functional genetics, comparative genomics, and population genomics, and is increasingly important for conservation biology. PacBio Single Molecule, Real-Time (SMRT) sequencing generates long reads with uniform coverage and high consensus accuracy, making it a powerful [...] Read more.
A high-quality reference genome is a fundamental resource for functional genetics, comparative genomics, and population genomics, and is increasingly important for conservation biology. PacBio Single Molecule, Real-Time (SMRT) sequencing generates long reads with uniform coverage and high consensus accuracy, making it a powerful technology for de novo genome assembly. Improvements in throughput and concomitant reductions in cost have made PacBio an attractive core technology for many large genome initiatives, however, relatively high DNA input requirements (~5 µg for standard library protocol) have placed PacBio out of reach for many projects on small organisms that have lower DNA content, or on projects with limited input DNA for other reasons. Here we present a high-quality de novo genome assembly from a single Anopheles coluzzii mosquito. A modified SMRTbell library construction protocol without DNA shearing and size selection was used to generate a SMRTbell library from just 100 ng of starting genomic DNA. The sample was run on the Sequel System with chemistry 3.0 and software v6.0, generating, on average, 25 Gb of sequence per SMRT Cell with 20 h movies, followed by diploid de novo genome assembly with FALCON-Unzip. The resulting curated assembly had high contiguity (contig N50 3.5 Mb) and completeness (more than 98% of conserved genes were present and full-length). In addition, this single-insect assembly now places 667 (>90%) of formerly unplaced genes into their appropriate chromosomal contexts in the AgamP4 PEST reference. We were also able to resolve maternal and paternal haplotypes for over 1/3 of the genome. By sequencing and assembling material from a single diploid individual, only two haplotypes were present, simplifying the assembly process compared to samples from multiple pooled individuals. The method presented here can be applied to samples with starting DNA amounts as low as 100 ng per 1 Gb genome size. This new low-input approach puts PacBio-based assemblies in reach for small highly heterozygous organisms that comprise much of the diversity of life. Full article
(This article belongs to the Special Issue Advances in Single Molecule, Real-Time (SMRT) Sequencing)
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Open AccessArticle Genetics and Genomic Regions Affecting Response to Newcastle Disease Virus Infection under Heat Stress in Layer Chickens
Received: 8 December 2018 / Revised: 8 January 2019 / Accepted: 14 January 2019 / Published: 18 January 2019
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Abstract
Newcastle disease virus (NDV) is a highly contagious avian pathogen that poses a tremendous threat to poultry producers in endemic zones due to its epidemic potential. To investigate host genetic resistance to NDV while under the effects of heat stress, a genome-wide association [...] Read more.
Newcastle disease virus (NDV) is a highly contagious avian pathogen that poses a tremendous threat to poultry producers in endemic zones due to its epidemic potential. To investigate host genetic resistance to NDV while under the effects of heat stress, a genome-wide association study (GWAS) was performed on Hy-Line Brown layer chickens that were challenged with NDV while under high ambient temperature to identify regions associated with host viral titer, circulating anti-NDV antibody titer, and body weight change. A single nucleotide polymorphism (SNP) on chromosome 1 was associated with viral titer at two days post-infection (dpi), while 30 SNPs spanning a quantitative trait loci (QTL) on chromosome 24 were associated with viral titer at 6 dpi. Immune related genes, such as CAMK1d and CCDC3 on chromosome 1, associated with viral titer at 2 dpi, and TIRAP, ETS1, and KIRREL3, associated with viral titer at 6 dpi, were located in two QTL regions for viral titer that were identified in this study. This study identified genomic regions and candidate genes that are associated with response to NDV during heat stress in Hy-Line Brown layer chickens. Regions identified for viral titer on chromosome 1 and 24, at 2 and 6 dpi, respectively, included several genes that have key roles in regulating the immune response. Full article
(This article belongs to the Special Issue Genomics of Avian Viral Infections)
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Open AccessArticle Functional Comparison of XPF Missense Mutations Associated to Multiple DNA Repair Disorders
Received: 21 December 2018 / Revised: 11 January 2019 / Accepted: 11 January 2019 / Published: 17 January 2019
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Abstract
XPF endonuclease is one of the most important DNA repair proteins. Encoded by XPF/ERCC4, XPF provides the enzymatic activity of XPF-ERCC1 heterodimer, an endonuclease that incises at the 5’ side of various DNA lesions. XPF is essential for nucleotide excision [...] Read more.
XPF endonuclease is one of the most important DNA repair proteins. Encoded by XPF/ERCC4, XPF provides the enzymatic activity of XPF-ERCC1 heterodimer, an endonuclease that incises at the 5’ side of various DNA lesions. XPF is essential for nucleotide excision repair (NER) and interstrand crosslink repair (ICLR). XPF/ERCC4 mutations are associated with several human diseases: Xeroderma Pigmentosum (XP), Segmental Progeria (XFE), Fanconi Anemia (FA), Cockayne Syndrome (CS), and XP/CS combined disease (XPCSCD). Most affected individuals are compound heterozygotes for XPF/ERCC4 mutations complicating the identification of genotype/phenotype correlations. We report a detailed overview of NER and ICLR functional studies in human XPF-KO (knock-out) isogenic cells expressing six disease-specific pathogenic XPF amino acid substitution mutations. Ultraviolet (UV) sensitivity and unscheduled DNA synthesis (UDS) assays provide the most reliable information to discern mutations associated with ICLR impairment from mutations related to NER deficiency, whereas recovery of RNA synthesis (RRS) assays results hint to a possible role of XPF in resolving R-loops. Our functional studies demonstrate that a defined cellular phenotype cannot be easily correlated to each XPF mutation. Substituted positions along XPF sequences are not predictive of cellular phenotype nor reflect a particular disease. Therefore, in addition to mutation type, allelic interactions, protein stability and intracellular distribution of mutant proteins may also contribute to alter DNA repair pathways balance leading to clinically distinct disorders. Full article
(This article belongs to the Special Issue Chromosome Replication and Genome Integrity)
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Open AccessArticle Cysteine-Rich Receptor-Like Kinase Gene Family Identification in the Phaseolus Genome and Comparative Analysis of Their Expression Profiles Specific to Mycorrhizal and Rhizobial Symbiosis
Received: 20 December 2018 / Revised: 6 January 2019 / Accepted: 9 January 2019 / Published: 17 January 2019
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Abstract
Receptor-like kinases (RLKs) are conserved upstream signaling molecules that regulate several biological processes, including plant development and stress adaptation. Cysteine (C)-rich receptor-like kinases (CRKs) are an important class of RLK that play vital roles in disease resistance and cell death in plants. Genome-wide [...] Read more.
Receptor-like kinases (RLKs) are conserved upstream signaling molecules that regulate several biological processes, including plant development and stress adaptation. Cysteine (C)-rich receptor-like kinases (CRKs) are an important class of RLK that play vital roles in disease resistance and cell death in plants. Genome-wide analyses of CRK genes have been carried out in Arabidopsis and rice, while functional characterization of some CRKs has been carried out in wheat and tomato in addition to Arabidopsis. A comprehensive analysis of the CRK gene family in leguminous crops has not yet been conducted, and our understanding of their roles in symbiosis is rather limited. Here, we report the comprehensive analysis of the Phaseolus CRK gene family, including identification, sequence similarity, phylogeny, chromosomal localization, gene structures, transcript expression profiles, and in silico promoter analysis. Forty-six CRK homologs were identified and phylogenetically clustered into five groups. Expression analysis suggests that PvCRK genes are differentially expressed in both vegetative and reproductive tissues. Further, transcriptomic analysis revealed that shared and unique CRK genes were upregulated during arbuscular mycorrhizal and rhizobial symbiosis. Overall, the systematic analysis of the PvCRK gene family provides valuable information for further studies on the biological roles of CRKs in various Phaseolus tissues during diverse biological processes, including Phaseolus-mycorrhiza/rhizobia symbiosis. Full article
(This article belongs to the Section Plant Genetics and Genomics)
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Open AccessArticle The Gene Structure and Expression Level Changes of the GH3 Gene Family in Brassica napus Relative to Its Diploid Ancestors
Received: 3 December 2018 / Revised: 10 January 2019 / Accepted: 15 January 2019 / Published: 17 January 2019
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Abstract
The GH3 gene family plays a vital role in the phytohormone-related growth and developmental processes. The effects of allopolyploidization on GH3 gene structures and expression levels have not been reported. In this study, a total of 38, 25, and 66 GH3 genes were [...] Read more.
The GH3 gene family plays a vital role in the phytohormone-related growth and developmental processes. The effects of allopolyploidization on GH3 gene structures and expression levels have not been reported. In this study, a total of 38, 25, and 66 GH3 genes were identified in Brassica rapa (ArAr), Brassica oleracea (CoCo), and Brassica napus (AnACnCn), respectively. BnaGH3 genes were unevenly distributed on chromosomes with 39 on An and 27 on Cn, in which six BnaGH3 genes may appear as new genes. The whole genome triplication allowed the GH3 gene family to expand in diploid ancestors, and allopolyploidization made the GH3 gene family re-expand in B. napus. For most BnaGH3 genes, the exon-intron compositions were similar to diploid ancestors, while the cis-element distributions were obviously different from its ancestors. After allopolyploidization, the expression patterns of GH3 genes from ancestor species changed greatly in B. napus, and the orthologous gene pairs between An/Ar and Cn/Co had diverged expression patterns across four tissues. Our study provides a comprehensive analysis of the GH3 gene family in B. napus, and these results could contribute to identifying genes with vital roles in phytohormone-related growth and developmental processes. Full article
(This article belongs to the Section Plant Genetics and Genomics)
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Open AccessArticle A Multi-Label Supervised Topic Model Conditioned on Arbitrary Features for Gene Function Prediction
Received: 30 November 2018 / Revised: 1 January 2019 / Accepted: 10 January 2019 / Published: 17 January 2019
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Abstract
With the continuous accumulation of biological data, more and more machine learning algorithms have been introduced into the field of gene function prediction, which has great significance in decoding the secret of life. Recently, a multi-label supervised topic model named labeled latent Dirichlet [...] Read more.
With the continuous accumulation of biological data, more and more machine learning algorithms have been introduced into the field of gene function prediction, which has great significance in decoding the secret of life. Recently, a multi-label supervised topic model named labeled latent Dirichlet allocation (LLDA) has been applied to gene function prediction, and obtained more accurate and explainable predictions than conventional methods. Nonetheless, the LLDA model is only able to construct a bag of amino acid words as a classification feature, and does not support any other features, such as hydrophobicity, which has a profound impact on gene function. To achieve more accurate probabilistic modeling of gene function, we propose a multi-label supervised topic model conditioned on arbitrary features, named Dirichlet multinomial regression LLDA (DMR-LLDA), for introducing multiple types of features into the process of topic modeling. Based on DMR framework, DMR-LLDA applies an exponential a priori construction, previously with weighted features, on the hyper-parameters of gene-topic distribution, so as to reflect the effects of extra features on function probability distribution. In the five-fold cross validation experiment of a yeast datasets, DMR-LLDA outperforms the compared model significantly. All of these experiments demonstrate the effectiveness and potential value of DMR-LLDA for predicting gene function. Full article
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Open AccessArticle Overexpression of Rice Rab7 Gene Improves Drought and Heat Tolerance and Increases Grain Yield in Rice (Oryza sativa L.)
Received: 7 December 2018 / Revised: 21 December 2018 / Accepted: 28 December 2018 / Published: 17 January 2019
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Abstract
Rab family proteins play a crucial role in plant developmental processes and tolerance to environmental stresses. The current study investigated whether rice Rab7 (OsRab7) overexpression could improve rice tolerance to drought and heat stress conditions. The OsRab7 gene was cloned and [...] Read more.
Rab family proteins play a crucial role in plant developmental processes and tolerance to environmental stresses. The current study investigated whether rice Rab7 (OsRab7) overexpression could improve rice tolerance to drought and heat stress conditions. The OsRab7 gene was cloned and transformed into rice plants. The survival rate, relative water content, chlorophyll content, gas-exchange characteristics, soluble protein content, soluble sugar content, proline content, and activities of antioxidant enzymes (CAT, SOD, APX, POD) of the transgenic rice lines were significantly higher than that of the wild-type. In contrast, the levels of hydrogen peroxide, electrolyte leakage, and malondialdehyde of the transgenic lines were significantly reduced when compared to wild-type. Furthermore, the expression of four genes encoding reactive oxygen species (ROS)-scavenging enzymes (OsCATA, OsCATB, OsAPX2, OsSOD-Cu/Zn) and eight genes conferring abiotic stress tolerance (OsLEA3, OsRD29A, OsSNAC1, OsSNAC2, OsDREB2A, OsDREB2B, OsRAB16A, OsRAB16C) was significantly up-regulated in the transformed rice lines as compared to their expression in wild-type. OsRab7 overexpression also increased grain yield in rice. Taken together, the current study indicates that the OsRab7 gene improves grain yield and enhances drought and heat tolerance in transgenic rice by modulating osmolytes, antioxidants and abiotic stress-responsive genes expression. Therefore, OsRab7 gene could be exploited as a promising candidate for improving rice grain yield and stress tolerance. Full article
(This article belongs to the Section Plant Genetics and Genomics)
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Open AccessEditorial Special Issue: Computational Analysis of RNA Structure and Function
Received: 4 January 2019 / Accepted: 8 January 2019 / Published: 16 January 2019
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Abstract
RNA structure often plays a key role in determining the function of non-coding and coding transcripts [...] Full article
(This article belongs to the Special Issue Computational Analysis of RNA Structure and Function)
Open AccessArticle Genomes of Three Closely Related Caribbean Amazons Provide Insight for Species History and Conservation
Received: 15 October 2018 / Revised: 13 December 2018 / Accepted: 8 January 2019 / Published: 16 January 2019
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Abstract
Islands have been used as model systems for studies of speciation and extinction since Darwin published his observations about finches found on the Galapagos. Amazon parrots inhabiting the Greater Antillean Islands represent a fascinating model of species diversification. Unfortunately, many of these birds [...] Read more.
Islands have been used as model systems for studies of speciation and extinction since Darwin published his observations about finches found on the Galapagos. Amazon parrots inhabiting the Greater Antillean Islands represent a fascinating model of species diversification. Unfortunately, many of these birds are threatened as a result of human activity and some, like the Puerto Rican parrot, are now critically endangered. In this study we used a combination of de novo and reference-assisted assembly methods, integrating it with information obtained from related genomes to perform genome reconstruction of three amazon species. First, we used whole genome sequencing data to generate a new de novo genome assembly for the Puerto Rican parrot (Amazona vittata). We then improved the obtained assembly using transcriptome data from Amazona ventralis and used the resulting sequences as a reference to assemble the genomes Hispaniolan (A. ventralis) and Cuban (Amazona leucocephala) parrots. Finally, we, annotated genes and repetitive elements, estimated genome sizes and current levels of heterozygosity, built models of demographic history and provided interpretation of our findings in the context of parrot evolution in the Caribbean. Full article
(This article belongs to the Special Issue Conservation Genetics and Genomics)
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Open AccessReview Tuberculosis Genetic Epidemiology: A Latin American Perspective
Received: 6 December 2018 / Revised: 9 January 2019 / Accepted: 11 January 2019 / Published: 16 January 2019
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Abstract
There are an estimated 10 million new cases of tuberculosis worldwide annually, with 282,000 new or relapsed cases each year reported from the Americas. With improvements in genome sequencing technology, it is now possible to study the genetic diversity of tuberculosis with much [...] Read more.
There are an estimated 10 million new cases of tuberculosis worldwide annually, with 282,000 new or relapsed cases each year reported from the Americas. With improvements in genome sequencing technology, it is now possible to study the genetic diversity of tuberculosis with much greater resolution. Although tuberculosis bacteria do not engage in horizontal gene transfer, the genome is far more variable than previously thought. The study of genome-wide variation in tuberculosis has improved our understanding of the evolutionary origins of tuberculosis, the arrival of tuberculosis in Latin America, the genetic determinants of drug resistance, and lineage-specific associations with important clinical phenotypes. This article reviews what is known about the arrival of tuberculosis in Latin America, the genetic diversity of tuberculosis in Latin America, and the genotypic determinants of clinical phenotypes. Full article
(This article belongs to the Special Issue Genetic Epidemiology of Complex Diseases in Latin America)
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Open AccessReview Epitranscriptomic Signatures in lncRNAs and Their Possible Roles in Cancer
Received: 11 December 2018 / Revised: 9 January 2019 / Accepted: 9 January 2019 / Published: 16 January 2019
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Abstract
In contrast to the amazing exponential growth in knowledge related to long non-coding RNAs (lncRNAs) involved in cell homeostasis or dysregulated pathological states, little is known so far about the links between the chemical modifications occurring in lncRNAs and their function. Generally, ncRNAs [...] Read more.
In contrast to the amazing exponential growth in knowledge related to long non-coding RNAs (lncRNAs) involved in cell homeostasis or dysregulated pathological states, little is known so far about the links between the chemical modifications occurring in lncRNAs and their function. Generally, ncRNAs are post-transcriptional regulators of gene expression, but RNA modifications occurring in lncRNAs generate an additional layer of gene expression control. Chemical modifications that have been reported in correlation with lncRNAs include m6A, m5C and pseudouridylation. Up to date, several chemically modified long non-coding transcripts have been identified and associated with different pathologies, including cancers. This review presents the current level of knowledge on the most studied cancer-related lncRNAs, such as the metastasis associated lung adenocarcinoma transcript 1 (MALAT1), the Hox transcript antisense intergenic RNA (HOTAIR), or the X-inactive specific transcript (XIST), as well as more recently discovered forms, and their potential roles in different types of cancer. Understanding how these RNA modifications occur, and the correlation between lncRNA changes in structure and function, may open up new therapeutic possibilities in cancer. Full article
(This article belongs to the Special Issue The Epitranscriptome in Human Disease)
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Open AccessArticle A Direct Comparison of the Relationship of Epigenetic Aging and Epigenetic Substance Consumption Markers to Mortality in the Framingham Heart Study
Received: 10 December 2018 / Revised: 8 January 2019 / Accepted: 10 January 2019 / Published: 15 January 2019
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Abstract
A number of studies have examined the relationship of indices of epigenetic aging (EA) to key health outcomes. Unfortunately, our understanding of the relationship of EA to mortality and substance use-related health variables is unclear. In order to clarify these interpretations, we analyzed [...] Read more.
A number of studies have examined the relationship of indices of epigenetic aging (EA) to key health outcomes. Unfortunately, our understanding of the relationship of EA to mortality and substance use-related health variables is unclear. In order to clarify these interpretations, we analyzed the relationship of the Levine EA index (LEA), as well as established epigenetic indices of cigarette (cg05575921) and alcohol consumption (cg04987734), to all-cause mortality in the Framingham Heart Study Offspring Cohort (n = 2256) Cox proportional hazards regression. We found that cg05575921 and cg04987734 had an independent effect relative to LEA and vice versa, with the model including all the predictors having better performance than models with either LEA or cg05575921 and cg04987734 alone. After correction for multiple comparisons, 195 and 327, respectively, of the 513 markers in the LEA index, as well as the overall index itself, were significantly associated with cg05575921 and cg04987734 methylation status. We conclude that the epigenetic indices of substance use have an independent effect over and above LEA, and are slightly stronger predictors of mortality in head-to-head comparisons. We also conclude that the majority of the strength of association conveyed by the LEA is secondary to smoking and drinking behaviors, and that efforts to promote healthy aging should continue to focus on addressing substance use. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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Open AccessArticle Comparative Analysis of Developmental Transcriptome Maps of Arabidopsis thaliana and Solanum lycopersicum
Received: 3 December 2018 / Revised: 31 December 2018 / Accepted: 4 January 2019 / Published: 15 January 2019
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Abstract
The knowledge of gene functions in model organisms is the starting point for the analysis of gene function in non-model species, including economically important ones. Usually, the assignment of gene functions is based on sequence similarity. In plants, due to a highly intricate [...] Read more.
The knowledge of gene functions in model organisms is the starting point for the analysis of gene function in non-model species, including economically important ones. Usually, the assignment of gene functions is based on sequence similarity. In plants, due to a highly intricate gene landscape, this approach has some limitations. It is often impossible to directly match gene sets from one plant species to another species based only on their sequences. Thus, it is necessary to use additional information to identify functionally similar genes. Expression patterns have great potential to serve as a source of such information. An important prerequisite for the comparative analysis of transcriptomes is the existence of high-resolution expression maps consisting of comparable samples. Here, we present a transcriptome atlas of tomato (Solanum lycopersicum) consisting of 30 samples of different organs and developmental stages. The samples were selected in a way that allowed for side-by-side comparison with the Arabidopsis thaliana transcriptome map. Newly obtained data are integrated in the TraVA database and are available online, together with tools for their analysis. In this paper, we demonstrate the potential of comparing transcriptome maps for inferring shifts in the expression of paralogous genes. Full article
(This article belongs to the Special Issue Evolutionary Genetics of Gene Expression)
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Open AccessReview m6A mRNA Destiny: Chained to the rhYTHm by the YTH-Containing Proteins
Received: 10 December 2018 / Revised: 8 January 2019 / Accepted: 10 January 2019 / Published: 15 January 2019
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Abstract
The control of gene expression is a multi-layered process occurring at the level of DNA, RNA, and proteins. With the emergence of highly sensitive techniques, new aspects of RNA regulation have been uncovered leading to the emerging field of epitranscriptomics dealing with RNA [...] Read more.
The control of gene expression is a multi-layered process occurring at the level of DNA, RNA, and proteins. With the emergence of highly sensitive techniques, new aspects of RNA regulation have been uncovered leading to the emerging field of epitranscriptomics dealing with RNA modifications. Among those post-transcriptional modifications, N6-methyladenosine (m6A) is the most prevalent in messenger RNAs (mRNAs). This mark can either prevent or stimulate the formation of RNA-protein complexes, thereby influencing mRNA-related mechanisms and cellular processes. This review focuses on proteins containing a YTH domain (for YT521-B Homology), a small building block, that selectively detects the m6A nucleotide embedded within a consensus motif. Thereby, it contributes to the recruitment of various effectors involved in the control of mRNA fates through adjacent regions present in the different YTH-containing proteins. Full article
(This article belongs to the Special Issue RNA Modifications)
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Open AccessEditorial Acknowledgement to Reviewers of Genes in 2018
Received: 15 January 2019 / Accepted: 15 January 2019 / Published: 15 January 2019
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Abstract
Rigorous peer-review is the corner-stone of high-quality academic publishing [...] Full article
Open AccessReview Animal Models and Their Contribution to Our Understanding of the Relationship Between Environments, Epigenetic Modifications, and Behavior
Received: 22 November 2018 / Revised: 29 December 2018 / Accepted: 10 January 2019 / Published: 15 January 2019
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Abstract
The use of non-human animals in research is a longstanding practice to help us understand and improve human biology and health. Animal models allow researchers, for example, to carefully manipulate environmental factors in order to understand how they contribute to development, behavior, and [...] Read more.
The use of non-human animals in research is a longstanding practice to help us understand and improve human biology and health. Animal models allow researchers, for example, to carefully manipulate environmental factors in order to understand how they contribute to development, behavior, and health. In the field of behavioral epigenetics such approaches have contributed novel findings of how the environment physically interacts with our genes, leading to changes in behavior and health. This review highlights some of this research, focused on prenatal immune challenges, environmental toxicants, diet, and early-life stress. In conjunction, we also discuss why animal models were integral to these discoveries and the translational relevance of these discoveries. Full article
(This article belongs to the Special Issue Epigenetics, Environment, and Brain Disorders)
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Open AccessArticle Genome-Wide Identification and Transcriptional Expression of the PAL Gene Family in Common Walnut (Juglans Regia L.)
Received: 2 November 2018 / Revised: 10 January 2019 / Accepted: 10 January 2019 / Published: 15 January 2019
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Abstract
Juglans regia L. is an economically important crop cultivated worldwide for its high quality and quantity of wood and nuts. Phenylalanine ammonia-lyase (PAL) is the first enzyme in the phenylpropanoid pathway that plays a critical role in plant growth, development, and adaptation, but [...] Read more.
Juglans regia L. is an economically important crop cultivated worldwide for its high quality and quantity of wood and nuts. Phenylalanine ammonia-lyase (PAL) is the first enzyme in the phenylpropanoid pathway that plays a critical role in plant growth, development, and adaptation, but there have been few reports of the PAL gene family in common walnut. Here, we report a genome-wide study of J. regia PAL genes and analyze their phylogeny, duplication, microRNA, and transcriptional expression. A total of 12 PAL genes were identified in the common walnut and clustered into two subfamilies based on phylogenetic analysis. These common walnut PALs are distributed on eight different pseudo-chromosomes. Seven of the 12 PALs (JrPAL2-3, JrPAL4-2, JrPAL2-1, JrPAL4-1, JrPAL8, JrPAL9, and JrPAL6) were specific found in J. regia, and JrPAL3, JrPAL5, JrPAL1-2, JrPAL7, and JrPAL2-2 were found to be closely associated with the woody plant Populus trichocarpa. Additionally, the expression patterns of JrPAL3, JrPAL7, JrPAL9, and JrPAL2-1 showed that they had high expression in female and male flowers. The miRNA ath-miR830-5p regulates two genes, JrPAL5 and JrPAL1, such that they have low expression in the male and female flowers of the common walnut. Our research provides useful information for further research into the function of PAL genes in common walnut and Juglans. Full article
(This article belongs to the Section Plant Genetics and Genomics)
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Open AccessArticle Network Analyses of Integrated Differentially Expressed Genes in Papillary Thyroid Carcinoma to Identify Characteristic Genes
Received: 8 November 2018 / Revised: 26 December 2018 / Accepted: 9 January 2019 / Published: 14 January 2019
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Abstract
Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Identifying characteristic genes of PTC are of great importance to reveal its potential genetic mechanisms. In this paper, we proposed a framework, as well as a measure named Normalized Centrality Measure [...] Read more.
Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Identifying characteristic genes of PTC are of great importance to reveal its potential genetic mechanisms. In this paper, we proposed a framework, as well as a measure named Normalized Centrality Measure (NCM), to identify characteristic genes of PTC. The framework consisted of four steps. First, both up-regulated genes and down-regulated genes, collectively called differentially expressed genes (DEGs), were screened and integrated together from four datasets, that is, GSE3467, GSE3678, GSE33630, and GSE58545; second, an interaction network of DEGs was constructed, where each node represented a gene and each edge represented an interaction between linking nodes; third, both traditional measures and the NCM measure were used to analyze the topological properties of each node in the network. Compared with traditional measures, more genes related to PTC were identified by the NCM measure; fourth, by mining the high-density subgraphs of this network and performing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, several meaningful results were captured, most of which were demonstrated to be associated with PTC. The experimental results proved that this network framework and the NCM measure are useful for identifying more characteristic genes of PTC. Full article
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Open AccessArticle A Sequence-Based Novel Approach for Quality Evaluation of Third-Generation Sequencing Reads
Received: 29 November 2018 / Revised: 7 January 2019 / Accepted: 8 January 2019 / Published: 14 January 2019
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Abstract
The advent of third-generation sequencing (TGS) technologies, such as the Pacific Biosciences (PacBio) and Oxford Nanopore machines, provides new possibilities for contig assembly, scaffolding, and high-performance computing in bioinformatics due to its long reads. However, the high error rate and poor quality of [...] Read more.
The advent of third-generation sequencing (TGS) technologies, such as the Pacific Biosciences (PacBio) and Oxford Nanopore machines, provides new possibilities for contig assembly, scaffolding, and high-performance computing in bioinformatics due to its long reads. However, the high error rate and poor quality of TGS reads provide new challenges for accurate genome assembly and long-read alignment. Efficient processing methods are in need to prioritize high-quality reads for improving the results of error correction and assembly. In this study, we proposed a novel Read Quality Evaluation and Selection Tool (REQUEST) for evaluating the quality of third-generation long reads. REQUEST generates training data of high-quality and low-quality reads which are characterized by their nucleotide combinations. A linear regression model was built to score the quality of reads. The method was tested on three datasets of different species. The results showed that the top-scored reads prioritized by REQUEST achieved higher alignment accuracies. The contig assembly results based on the top-scored reads also outperformed conventional approaches that use all reads. REQUEST is able to distinguish high-quality reads from low-quality ones without using reference genomes, making it a promising alternative sequence-quality evaluation method to alignment-based algorithms. Full article
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Open AccessReview Genomic Enhancers in Brain Health and Disease
Received: 27 November 2018 / Revised: 8 January 2019 / Accepted: 9 January 2019 / Published: 14 January 2019
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Abstract
Enhancers are non-coding DNA elements that function in cis to regulate transcription from nearby genes. Through direct interactions with gene promoters, enhancers give rise to spatially and temporally precise gene expression profiles in distinct cell or tissue types. In the brain, the accurate [...] Read more.
Enhancers are non-coding DNA elements that function in cis to regulate transcription from nearby genes. Through direct interactions with gene promoters, enhancers give rise to spatially and temporally precise gene expression profiles in distinct cell or tissue types. In the brain, the accurate regulation of these intricate expression programs across different neuronal classes gives rise to an incredible cellular and functional diversity. Newly developed technologies have recently allowed more accurate enhancer mapping and more sophisticated enhancer manipulation, producing rapid progress in our understanding of enhancer biology. Furthermore, identification of disease-linked genetic variation in enhancer regions has highlighted the potential influence of enhancers in brain health and disease. This review outlines the key role of enhancers as transcriptional regulators, reviews the current understanding of enhancer regulation in neuronal development, function and dysfunction and provides our thoughts on how enhancers can be targeted for technological and therapeutic goals. Full article
(This article belongs to the Special Issue Epigenetics, Environment, and Brain Disorders)
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Open AccessArticle Stress-Tolerant Yeasts: Opportunistic Pathogenicity Versus Biocontrol Potential
Received: 3 December 2018 / Revised: 3 January 2019 / Accepted: 9 January 2019 / Published: 14 January 2019
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Abstract
Stress-tolerant fungi that can thrive under various environmental extremes are highly desirable for their application to biological control, as an alternative to chemicals for pest management. However, in fungi, the mechanisms of stress tolerance might also have roles in mammal opportunism. We tested [...] Read more.
Stress-tolerant fungi that can thrive under various environmental extremes are highly desirable for their application to biological control, as an alternative to chemicals for pest management. However, in fungi, the mechanisms of stress tolerance might also have roles in mammal opportunism. We tested five species with high biocontrol potential in agriculture (Aureobasidium pullulans, Debayomyces hansenii, Meyerozyma guilliermondii, Metschnikowia fructicola, Rhodotorula mucilaginosa) and two species recognized as emerging opportunistic human pathogens (Exophiala dermatitidis, Aureobasidium melanogenum) for growth under oligotrophic conditions and at 37 °C, and for tolerance to oxidative stress, formation of biofilms, production of hydrolytic enzymes and siderophores, and use of hydrocarbons as sole carbon source. The results show large overlap between traits desirable for biocontrol and traits linked to opportunism (growth under oligotrophic conditions, production of siderophores, high oxidative stress tolerance, and specific enzyme activities). Based on existing knowledge and these data, we suggest that oligotrophism and thermotolerance together with siderophore production at 37 °C, urease activity, melanization, and biofilm production are the main traits that increase the potential for fungi to cause opportunistic infections in mammals. These traits should be carefully considered when assessing safety of potential biocontrol agents. Full article
(This article belongs to the Section Microbial Genetics and Genomics)
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