Complete chloroplast genomes of five Cuscuta species and their evolutionary significance in the Cuscuta genus.

BACKGROUND: Cuscuta, a parasitic plant species in the Convolvulaceae family, grows in many countries and regions. However, the relationship between some species is still unclear. Therefore, more studies are needed to assess the variation of the chloroplast (cp) genome in Cuscuta species and their relationship with subgenera or sections, thus, providing important information on the evolution of Cuscuta species. RESULTS: In the present study, we identified the whole cp genomes of C. epithymum, C. europaea, C. gronovii, C. chinensis and C. japonica, and then constructed a phylogenetic tree of 23 Cuscuta species based on the complete genome sequences and protein-coding genes. The complete cp genome sequences of C. epithymum and C. europaea were 96,292 and 97,661 bp long, respectively, and lacked an inverted repeat region. Most cp genomes of Cuscuta spp. have tetragonal and circular structures except for C. epithymum, C. europaea, C. pedicellata and C. approximata. Based on the number of genes and the structure of cp genome and the patterns of gene reduction, we found that C. epithymum and C. europaea belonged to subgenus Cuscuta. Most of the cp genomes of the 23 Cuscuta species had single nucleotide repeats of A and T. The inverted repeat region boundaries among species were similar in the same subgenera. Several cp genes were lost. In addition, the numbers and types of the lost genes in the same subgenus were similar. Most of the lost genes were related to photosynthesis (ndh, rpo, psa, psb, pet, and rbcL), which could have gradually caused the plants to lose the ability to photosynthesize. CONCLUSION: Our results enrich the data on cp. genomes of genus Cuscuta. This study provides new insights into understanding the phylogenetic relationships and variations in the cp genome of Cuscuta species.

Nur77 Serves as a Potential Prognostic Biomarker That Correlates with Immune Infiltration and May Act as a Good Target for Prostate adenocarcinoma.

Prostate adenocarcinoma (PRAD) is the most frequent malignancy, and is the second leading cause of death due to cancer in men. Thus, new prognostic biomarkers and drug targets for PRAD are urgently needed. As we know, nuclear receptor Nur77 is important in cancer development and changes in the tumor microenvironment; whereas, the function of Nur77 in PRAD remains to be elucidated. The TCGA database was used to explore the Nur77 expression and its role in the prognosis of PRAD. It was shown that Nur77 was down regulated in PRAD, and low Nur77 expression was correlated with advanced clinical pathologic characteristics (high grade, histological type, age) and poor prognosis. Furthermore, key genes screening was examined by univariate Cox analysis and Kaplan-Meier survival. Additionally, Nur77 was closely related to immune infiltration and some anti-tumor immune functions. The differentially expressed genes (DEGs) were presented by protein-protein interaction (PPI) network analysis. Therefore, the expression level of Nur77 might help predict the survival of PRAD cases, which presents a new insight and a new target for the treatment of PRAD. In vitro experiments verified that natural product malayoside targeting Nur77 exhibited significant therapeutic effects on PRAD and largely induced cell apoptosis by up-regulating the expression of Nur77 and its mitochondrial localization. Taken together, Nur77 is a prognostic biomarker for patients with PRAD, which may refresh the profound understanding of PRAD individualized treatment.

Comprehensive analysis of the NAC transcription factor gene family in Kandelia obovata reveals potential members related to chilling tolerance.

Background: Kandelia obovata is an important mangrove species extensively distributed in Eastern Asia that is susceptible to low-temperature stress. NAC (NAM, ATAF1/2 and CUC2) domain proteins are transcription factors (TFs) that play various roles in plant growth and development and in the plant response to environmental stresses. Nevertheless, genome-wide analyses of K. obovata NAC genes (KoNACs) and their responses to chilling stress have rarely been studied. Methods: The KoNAC gene family was identified and characterized using bioinformatic analysis, the subcellular location of some NAC proteins was confirmed using confocal microscopy analysis, and the KoNACs that responded to chilling stress were screened using RNA-seq and qRT-PCR analysis. Results: A total of 79 KoNACs were identified, and they were unequally distributed across all 18 chromosomes of K. obovata. The KoNAC proteins could be divided into 16 subgroups according to the phylogenetic tree based on NAC family members of Arabidopsis thaliana. The KoNACs exhibited greater synteny with A. thaliana sequences than with Oryza sativa sequences, indicating that KoNACs underwent extensive evolution after the divergence of dicotyledons and monocotyledons. Segmental duplication was the main driving force of the expansions of KoNAC genes. Confocal microscopy analysis verified that the four randomly selected KoNACs localized to the nucleus, indicating the accuracy of the bioinformatic predictions. Tissue expression pattern analysis demonstrated that some KoNAC genes showed tissue-specific expression, suggesting that these KoNACs might be important for plant development and growth. Additionally, the expression levels of 19 KoNACs were significantly (15 positively and 4 negatively) induced by cold treatment, demonstrating that these KoNACs might play important roles during cold stress responses and might be candidate genes for the genetic engineering of K. obovata with enhanced chilling stress tolerance. Coexpression network analysis revealed that 381 coexpressed pairs (between 13 KoNACs and 284 other genes) were significantly correlated. Conclusions: Seventy-nine KoNACs were identified in K. obovata, nineteen of which displayed chilling-induced expression patterns. These genes may serve as candidates for functional analyses of KoNACs engaged in chilling stress. Our results lay the foundation for evolutionary analyses of KoNACs and their molecular mechanisms in response to environmental stress.

Genome-wide identification and analysis of bZIP gene family reveal their roles during development and drought stress in Wheel Wingnut (Cyclocarya paliurus).

BACKGROUND: The bZIP gene family has important roles in various biological processes, including development and stress responses. However, little information about this gene family is available for Wheel Wingnut (Cyclocarya paliurus).  RESULTS: In this study, we identified 58 bZIP genes in the C. paliurus genome and analyzed phylogenetic relationships, chromosomal locations, gene structure, collinearity, and gene expression profiles. The 58 bZIP genes could be divided into 11 groups and were unevenly distributed among 16 C. paliurus chromosomes. An analysis of cis-regulatory elements indicated that bZIP promoters were associated with phytohormones and stress responses. The expression patterns of bZIP genes in leaves differed among developmental stages. In addition, several bZIP members were differentially expressed under drought stress. These expression patterns were verified by RT-qPCR. CONCLUSIONS: Our results provide insights into the evolutionary history of the bZIP gene family in C. paliurus and the function of these genes during leaf development and in the response to drought stress. In addition to basic genomic information, our results provide a theoretical basis for further studies aimed at improving growth and stress resistance in C. paliurus, an important medicinal plant.

Plant Virome Analysis by the Deep Sequencing of Small RNAs of Fritillaria thunbergii var. chekiangensis and the Rapid Identification of Viruses.

Thunberg fritillary (Fritillaria thunbergii), a perennial used in traditional Chinese herbal medicine, is a members of the family Liliaceae. The degeneration of germplasm is a severe problem in the production of Fritillaria thunbergii var. chekiangensis. However, no information about viral infections of F. thunbergii var. chekiangensis has been reported. In this study, we sequenced the small RNAs of F. thunbergii var. chekiangensis from leaves and bulbs, and viruses were identified using a phylogenetic analysis and BLAST search for sequence. In addition, multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) was used to rapidly detect viruses in this variety. Our study first reported that five viruses infected F. thunbergii var. chekiangensis. Among them, fritillary virus Y (FVY), lily mottle virus (LMoV), Thunberg fritillary mosaic virus (TFMV), and hop yellow virus (HYV) had been reported in F. thunbergii, while apple stem grooving virus was first reported in the genus Fritillaria. A multiplex RT-PCR method was developed to rapidly test the four viruses FVY, LMoV, TFMV, and HYV in F. thunbergii var. chekiangensis. Our results provide a better understanding of the infection of F. thunbergii var. chekiangensis by viruses and a basic reference for the better design of suitable control measures.

Predicted mouse interactome and network-based interpretation of differentially expressed genes.

The house mouse or Mus musculus has become a premier mammalian model for genetic research due to its genetic and physiological similarities to humans. It brought mechanistic insights into numerous human diseases and has been routinely used to assess drug efficiency and toxicity, as well as to predict patient responses. To facilitate molecular mechanism studies in mouse, we present the Mouse Interactome Database (MID, Version 1), which includes 155,887 putative functional associations between mouse protein-coding genes inferred from functional association evidence integrated from 9 public databases. These putative functional associations are expected to cover 19.32% of all mouse protein interactions, and 26.02% of these function associations may represent protein interactions. On top of MID, we developed a gene set linkage analysis (GSLA) web tool to annotate potential functional impacts from observed differentially expressed genes. Two case studies show that the MID/GSLA system provided precise and informative annotations that other widely used gene set annotation tools, such as PANTHER and DAVID, did not. Both MID and GSLA are accessible through the website http://mouse.biomedtzc.cn.

A computer based facial flaps simulator using projective dynamics.

BACKGROUND AND OBJECTIVES: Interactive surgical simulation using the finite element method to model human skin mechanics has been an elusive goal. Mass-spring networks, while fast, do not provide the required accuracy. METHODS: This paper presents an interactive, cognitive, facial flaps simulator based on a projective dynamics computational framework. Projective dynamics is able to generate rapid, stable results following changes to the facial soft tissues created by the surgeon, even in the face of sudden increases in skin resistance as its stretch limit is reached or collision between tissues occurs. Our prior work with the finite element method had been hampered by these considerations. Surgical tools are provided for; skin incision, undermining, deep tissue cutting, and excision. A spring-like "skin hook" is used for retraction. Spring-based sutures can be placed individually or automatically placed as a row between cardinal sutures. RESULTS: Examples of an Abbe/Estlander lip reconstruction, a paramedian forehead flap to the nose, a retroauricular flap reconstruction of the external ear, and a cervico-facial flap reconstruction of a cheek defect are presented. CONCLUSIONS: Projective dynamics has significant advantages over mass-spring and finite element methods as the physics backbone for interactive soft tissue surgical simulation.

Long-Term Results of the Murawski Unilateral Cleft Lip Repair.

BACKGROUND: In 1968, Ralph Millard published his "Millard II" method for repair of wide, complete unilateral cleft lip and nose deformity. In 1979, Murawski published a major modification of the Millard II procedure in Polish. This motif was taken up 8 years later by Mohler and 22 years later by Cutting. The Murawski variation on the Millard II procedure has become a dominant motif in unilateral cleft lip repair worldwide. This brief report intends to introduce the method to the English language literature and present long-term results. METHODS: The Murawski method alters the Millard II procedure by changing the upper medial curve into a point in the columellar base. This creates a broad C flap used to fill the entire defect produced by downward rotation of the medial lip. Millard's lateral advancement flap becomes unnecessary. A lateral approach to primary nasal reconstruction allows the lateral C flap to be used to construct the nasal floor and sill. The method is described using a physics-based surgical simulator. RESULTS: Long-term results of the method are demonstrated with four patients with 15 to 25-year follow-up. None of these patients had any revisions to the lip or nose. CONCLUSIONS: The Murawski repair was the first to modify the Millard II repair by sharpening the medial columellar incision, eliminating the need for a lateral advancement flap. This motif was put forth in the years to follow by Mohler and Cutting. Long-term results of the method are presented.

Variation and Evolution of the Whole Chloroplast Genomes of Fragaria spp. (Rosaceae).

Species identification is vital for protecting species diversity and selecting high-quality germplasm resources. Wild Fragaria spp. comprise rich and excellent germplasm resources; however, the variation and evolution of the whole chloroplast (cp) genomes in the genus Fragaria have been ignored. In the present study, 27 complete chloroplast genomes of 11 wild Fragaria species were sequenced using the Illumina platform. Then, the variation among complete cp genomes of Fragaria was analyzed, and phylogenetic relationships were reconstructed from those genome sequences. There was an overall high similarity of sequences, with some divergence. According to analysis with mVISTA, non-coding regions were more variable than coding regions. Inverted repeats (IRs) were observed to contract or expand to different degrees, which resulted in different sizes of cp genomes. Additionally, five variable loci, trnS-trnG, trnR-atpA, trnC-petN, rbcL-accD, and psbE-petL, were identified that could be used to develop DNA barcoding for identification of Fragaria species. Phylogenetic analyses based on the whole cp genomes supported clustering all species into two groups (A and B). Group A species were mainly distributed in western China, while group B contained several species from Europe and Americas. These results support allopolyploid origins of the octoploid species F. chiloensis and F. virginiana and the tetraploid species F. moupinensis and F. tibetica. The complete cp genomes of these Fragaria spp. provide valuable information for selecting high-quality Fragaria germplasm resources in the future.

HIR V2: a human interactome resource for the biological interpretation of differentially expressed genes via gene set linkage analysis.

To facilitate biomedical studies of disease mechanisms, a high-quality interactome that connects functionally related genes is needed to help investigators formulate pathway hypotheses and to interpret the biological logic of a phenotype at the biological process level. Interactions in the updated version of the human interactome resource (HIR V2) were inferred from 36 mathematical characterizations of six types of data that suggest functional associations between genes. This update of the HIR consists of 88 069 pairs of genes (23.2% functional interactions of HIR V2 are in common with the previous version of HIR), representing functional associations that are of strengths similar to those between well-studied protein interactions. Among these functional interactions, 57% may represent protein interactions, which are expected to cover 32% of the true human protein interactome. The gene set linkage analysis (GSLA) tool is developed based on the high-quality HIR V2 to identify the potential functional impacts of the observed transcriptomic changes, helping to elucidate their biological significance and complementing the currently widely used enrichment-based gene set interpretation tools. A case study shows that the annotations reported by the HIR V2/GSLA system are more comprehensive and concise compared to those obtained by the widely used gene set annotation tools such as PANTHER and DAVID. The HIR V2 and GSLA are available at http://human.biomedtzc.cn.

Predicted rat interactome database and gene set linkage analysis.

Rattus norvegicus, or the rat, has been widely used as animal models for a diversity of human diseases in the last 150 years. The rat, as a disease model, has the advantage of relatively large body size and highly similar physiology to humans. In drug discovery, rat models are routinely used in drug efficacy and toxicity assessments. To facilitate molecular pharmacology studies in rats, we present the predicted rat interactome database (PRID), which is a database of high-quality predicted functional gene interactions with balanced sensitivity and specificity. PRID integrates functional gene association data from 10 public databases and infers 305 939 putative functional associations, which are expected to include 13.02% of all rat protein interactions, and 52.59% of these function associations may represent protein interactions. This set of functional interactions may not only facilitate hypothesis formulation in molecular mechanism studies, but also serve as a reference interactome for users to perform gene set linkage analysis (GSLA), which is a web-based tool to infer the potential functional impacts of a set of changed genes observed in transcriptomics analyses. In a case study, we show that GSLA based on PRID may provide more precise and informative annotations for investigators to understand the physiological mechanisms underlying a phenotype and lead investigators to testable hypotheses for further studies. Widely used functional annotation tools such as Gene Ontology (GO) analysis, and Database for Annotation, Visualization and Integrated Discovery (DAVID) did not provide similar insights. Database URL: http://rat.biomedtzc.cn.

Predicted functional interactome of Caenorhabditis elegans and a web tool for the functional interpretation of differentially expressed genes.

BACKGROUND: The nematode worm, Caenorhabditis elegans, is a saprophytic species that has been emerging as a standard model organism since the early 1960s. This species is useful in numerous fields, including developmental biology, neurobiology, and ageing. A high-quality comprehensive molecular interaction network is needed to facilitate molecular mechanism studies in C. elegans. RESULTS: We present the predicted functional interactome of Caenorhabditis elegans (FIC), which integrates functional association data from 10 public databases to infer functional gene interactions on diverse functional perspectives. In this work, FIC includes 108,550 putative functional associations with balanced sensitivity and specificity, which are expected to cover 21.42% of all C. elegans protein interactions, and 29.25% of these associations may represent protein interactions. Based on FIC, we developed a gene set linkage analysis (GSLA) web tool to interpret potential functional impacts from a set of differentially expressed genes observed in transcriptome analyses. CONCLUSION: We present the predicted C. elegans interactome database FIC, which is a high-quality database of predicted functional interactions among genes. The functional interactions in FIC serve as a good reference interactome for GSLA to annotate differentially expressed genes for their potential functional impacts. In a case study, the FIC/GSLA system shows more comprehensive and concise annotations compared to other widely used gene set annotation tools, including PANTHER and DAVID. FIC and its associated GSLA are available at the website http://worm.biomedtzc.cn .

MosaicBase: A Knowledgebase of Postzygotic Mosaic Variants in Noncancer Disease-related and Healthy Human Individuals.

Mosaic variants resulting from postzygotic mutations are prevalent in the human genome and play important roles in human diseases. However, except for cancer-related variants, there is no collection of postzygotic mosaic variants in noncancer disease-related and healthy individuals. Here, we present MosaicBase, a comprehensive database that includes 6698 mosaic variants related to 266 noncancer diseases and 27,991 mosaic variants identified in 422 healthy individuals. Genomic and phenotypic information of each variant was manually extracted and curated from 383 publications. MosaicBase supports the query of variants with Online Mendelian Inheritance in Man (OMIM) entries, genomic coordinates, gene symbols, or Entrez IDs. We also provide an integrated genome browser for users to easily access mosaic variants and their related annotations for any genomic region. By analyzing the variants collected in MosaicBase, we find that mosaic variants that directly contribute to disease phenotype show features distinct from those of variants in individuals with mild or no phenotypes, in terms of their genomic distribution, mutation signatures, and fraction of mutant cells. MosaicBase will not only assist clinicians in genetic counseling and diagnosis but also provide a useful resource to understand the genomic baseline of postzygotic mutations in the general human population. MosaicBase is publicly available at http://mosaicbase.com/ or http://49.4.21.8:8000.

Predicted yeast interactome and network-based interpretation of transcriptionally changed genes.

Saccharomyces cerevisiae, budding yeast, is a widely used model organism and research tool in genetics studies. Many efforts have been directed at constructing a high-quality comprehensive molecular interaction network to elucidate the design logic of the gene circuitries in this classic model organism. In this work, we present the yeast interactome resource (YIR), which includes 22,238 putative functional gene interactions inferred from functional gene association data integrated from 10 databases focusing on diverse functional perspectives. These putative functional gene interactions are expected to cover 18.84% of yeast protein interactions, and 38.49% may represent protein interactions. Based on the YIR, a gene set linkage analysis (GSLA) web tool was developed to annotate the potential functional impacts of a set of transcriptionally changed genes. In a case study, we show that the YIR/GSLA system produced more extensive and concise annotations compared with widely used gene set annotation tools, including PANTHER and DAVID. Both YIR and GSLA are accessible through the website http://yeast.biomedtzc.cn.

Predicted Drosophila Interactome Resource and web tool for functional interpretation of differentially expressed genes.

Drosophila melanogaster is a well-established model organism that is widely used in genetic studies. This species enjoys the availability of a wide range of research tools, well-annotated reference databases and highly similar gene circuitry to other insects. To facilitate molecular mechanism studies in Drosophila, we present the Predicted Drosophila Interactome Resource (PDIR), a database of high-quality predicted functional gene interactions. These interactions were inferred from evidence in 10 public databases providing information for functional gene interactions from diverse perspectives. The current version of PDIR includes 102 835 putative functional associations with balanced sensitivity and specificity, which are expected to cover 22.56% of all Drosophila protein interactions. This set of functional interactions is a good reference for hypothesis formulation in molecular mechanism studies. At the same time, these interactions also serve as a high-quality reference interactome for gene set linkage analysis (GSLA), which is a web tool for the interpretation of the potential functional impacts of a set of changed genes observed in transcriptomics analyses. In a case study, we show that the PDIR/GSLA system was able to produce a more comprehensive and concise interpretation of the collective functional impact of multiple simultaneously changed genes compared with the widely used gene set annotation tools, including PANTHER and David. PDIR and its associated GSLA service can be accessed at http://drosophila.biomedtzc.cn.

Intraspecific Diversity of Fission Yeast Mitochondrial Genomes.

The fission yeast Schizosaccharomyces pombe is an important model organism, but its natural diversity and evolutionary history remain under-studied. In particular, the population genomics of the S. pombe mitochondrial genome (mitogenome) has not been thoroughly investigated. Here, we assembled the complete circular-mapping mitogenomes of 192 S. pombe isolates de novo, and found that these mitogenomes belong to 69 nonidentical sequence types ranging from 17,618 to 26,910 bp in length. Using the assembled mitogenomes, we identified 20 errors in the reference mitogenome and discovered two previously unknown mitochondrial introns. Analyzing sequence diversity of these 69 types of mitogenomes revealed two highly distinct clades, with only three mitogenomes exhibiting signs of inter-clade recombination. This diversity pattern suggests that currently available S. pombe isolates descend from two long-separated ancestral lineages. This conclusion is corroborated by the diversity pattern of the recombination-repressed K-region located between donor mating-type loci mat2 and mat3 in the nuclear genome. We estimated that the two ancestral S. pombe lineages diverged about 31 million generations ago. These findings shed new light on the evolution of S. pombe and the data sets generated in this study will facilitate future research on genome evolution.