BackgroundThere is a rapidly increasing amount of de novo genome assembly using next-generation sequencing (NGS) short reads; however, several big challenges remain to be overcome in order for this to be efficient and accurate. SOAPdenovo has been successfully applied to assemble many published genomes, but it still needs improvement in continuity, accuracy and coverage, especially in repeat regions.FindingsTo overcome these challenges, we have developed its successor, SOAPdenovo2, which has the advantage of a new algorithm design that reduces memory consumption in graph construction, resolves more repeat regions in contig assembly, increases coverage and length in scaffold construction, improves gap closing, and optimizes for large genome.ConclusionsBenchmark using the Assemblathon1 and GAGE datasets showed that SOAPdenovo2 greatly surpasses its predecessor SOAPdenovo and is competitive to other assemblers on both assembly length and accuracy. We also provide an updated assembly version of the 2008 Asian (YH) genome using SOAPdenovo2. Here, the contig and scaffold N50 of the YH genome were ~20.9 kbp and ~22 Mbp, respectively, which is 3-fold and 50-fold longer than the first published version. The genome coverage increased from 81.16% to 93.91%, and memory consumption was ~2/3 lower during the point of largest memory consumption.
The conventional view of gene regulation in biology has centered around protein-coding genes via the central dogma of DNA-mRNA-protein. The discovery of thousands of long non-coding RNAs (lncRNAs) has certainly changed our view of the complexity of mammalian genomes and transcriptomes, as well as many other aspects of biology including transcriptional and posttranscriptional regulation of gene expression. Accumulating reports of misregulated lncRNA expression across numerous cancer types suggest that aberrant lncRNA expression may be a major contributor to tumorigenesis. Here, we summarize recent data about the biological characteristics of lncRNAs in cancer pathways. These include examples with a wide range of molecular mechanisms involved in gene regulation. We also consider the medical implications, and discuss how lncRNAs can be used for cancer diagnosis and prognosis, and serve as potential therapeutic targets. As more examples of regulation by lncRNA are uncovered, one might predict that the large transcripts will eventually rival small RNAs and proteins in their versatility as regulators of genetic information.
Long non-coding RNAs (lncRNAs) comprise a diverse class of RNA transcripts >200 nucleotides in length with limited protein-coding potential. In addition to their possible role in cancer biology, circulating lncRNAs have emerged as a new class of promising cancer biomarkers, with independent studies demonstrating the feasibility of their use as tools in the diagnosis and prognosis of different types of malignancies and for predicting and possibly monitoring treatment response. However, critical issues are represented by nonuniform sample choice, handling and processing, blood cell contamination during sample preparation and the lack of consensus regarding data normalization. In this review, we discuss the value of circulating lncRNAs in the clinical setting, particularly with respect to their possible implementation as diagnostic and prognostic markers in cancer. Although the great potential of circulating lncRNAs as cancer biomarkers would be an important development in disease management, both intrinsic and extrinsic factors that may affect their measurement have not been fully characterized. Moreover, the clinical significance of circulating lncRNA may not be proven without a global consensus regarding procedures and standardized protocols for their detection.
Cancer immunotherapy and tumor microenvironment have been at the forefront of research over the past decades. Targeting immune checkpoints especially programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) has made a breakthrough in treating advanced malignancies. However, the low response rate brings a daunting challenge, changing the focus to dig deeply into the tumor microenvironment for alternative therapeutic targets. Strikingly, the inhibitory immune checkpoint lymphocyte activation gene-3 (LAG-3) holds considerable potential. LAG-3 suppresses T cells activation and cytokines secretion, thereby ensuring immune homeostasis. It exerts differential inhibitory impacts on various types of lymphocytes and shows a remarkable synergy with PD-1 to inhibit immune responses. Targeting LAG-3 immunotherapy is moving forward in active clinical trials, and combination immunotherapy of anti-LAG-3 and anti-PD-1 has shown exciting efficacy in fighting PD-1 resistance. Herein, we shed light on the significance of LAG-3 in the tumor microenvironment, highlight its role to regulate different lymphocytes, interplay with other immune checkpoints especially PD-1, and emphasize new advances in LAG-3-targeted immunotherapy.
The long, noncoding RNA (lncRNA) is an important epigenetic regulator with a critical role in human tumors. Here, we aimed to investigate the clinical application and the potential molecular mechanisms of in gastric cancer tumorigenesis and progression. The expression level of was determined by RT-qPCR analysis in 190 pairs of gastric cancer tissues and adjacent normal gastric mucosa tissues (ANT). The biologic functions of were assessed by and functional experiments. RNA protein pull-down assays and LS/MS mass spectrometry analysis were performed to detect and identify the interacting protein FOXM1. Protein-RNA immunoprecipitation assays were conducted to examine the interaction of FOXM1 and Chromatin immunoprecipitation (ChIP) and luciferase analyses were utilized to identify the binding site of FOXM1 on the promoter. The lncRNA was significantly upregulated in gastric cancer tissues compared with ANTs. High expression of predicted poor prognosis in patients with gastric cancer. enhanced gastric cancer cell proliferation and invasion and directly bound FOXM1 protein and increased FOXM1 posttranslationally. Moreover, is also a FOXM1-responsive lncRNA, and FOXM1 directly binds to the promoter to activate its transcription. Finally, fulfilled its oncogenic functions in a FOXM1-mediated manner. Our study suggests that promotes tumor progression by interacting with FOXM1. may be a valuable prognostic predictor for gastric cancer, and the positive feedback loop of -FOXM1 could be a therapeutic target in pharmacologic strategies..
Super-enhancers are important for controlling and defining the expression of cell-specific genes. With research on human disease and biological processes, human H3K27ac ChIP-seq datasets are accumulating rapidly, creating the urgent need to collect and process these data comprehensively and efficiently. More importantly, many studies showed that super-enhancer-associated single nucleotide polymorphisms (SNPs) and transcription factors (TFs) strongly influence human disease and biological processes. Here, we developed a comprehensive human super-enhancer database (SEdb, http://www.licpathway.net/sedb) that aimed to provide a large number of available resources on human super-enhancers. The database was annotated with potential functions of super-enhancers in the gene regulation. The current version of SEdb documented a total of 331 601 super-enhancers from 542 samples. Especially, unlike existing super-enhancer databases, we manually curated and classified 410 available H3K27ac samples from >2000 ChIP-seq samples from NCBI GEO/SRA. Furthermore, SEdb provides detailed genetic and epigenetic annotation information on super-enhancers. Information includes common SNPs, motif changes, expression quantitative trait locus (eQTL), risk SNPs, transcription factor binding sites (TFBSs), CRISPR/Cas9 target sites and Dnase I hypersensitivity sites (DHSs) for in-depth analyses of super-enhancers. SEdb will help elucidate super-enhancer-related functions and find potential biological effects.
Colobines are a unique group of Old World monkeys that principally eat leaves and seeds rather than fruits and insects. We report the sequencing at 146× coverage, de novo assembly and analyses of the genome of a male golden snub-nosed monkey (Rhinopithecus roxellana) and resequencing at 30× coverage of three related species (Rhinopithecus bieti, Rhinopithecus brelichi and Rhinopithecus strykeri). Comparative analyses showed that Asian colobines have an enhanced ability to derive energy from fatty acids and to degrade xenobiotics. We found evidence for functional evolution in the colobine RNASE1 gene, encoding a key secretory RNase that digests the high concentrations of bacterial RNA derived from symbiotic microflora. Demographic reconstructions indicated that the profile of ancient effective population sizes for R. roxellana more closely resembles that of giant panda rather than its congeners. These findings offer new insights into the dietary adaptations and evolutionary history of colobine primates.Knowledge of the patterns and processes underlying the evolution of alternative dietary strategies in nonhuman primates is critical to understanding hominin evolution, nutritional ecology and applications in biomedicine 1 . Colobines, a group of Old World monkeys, serve as an important model organism for studying the evolution of the primate diet because of their adaptation to folivory: they primarily eat leaves and seeds rather than fruits and insects as their major food source. In their specialized and compartmentalized stomachs, colobines allow symbiotic bacteria in the foregut to ferment structural carbohydrates and then recover nutrients by digesting the bacteria 2 . This strategy is similar to that used by other foregut fermenters found in an evolutionarily distantly related group of mammals (for example, artiodactyls). Although a number of primate genomes have been sequenced thus far, high-quality genome sequence information is absent for Asian and African colobines, a key group for elucidating the evolution and adaptation of primates as a whole. Snub-nosed monkeys (Rhinopithecus species) are a group of endangered colobines, which were once widely distributed in Asia but are now limited to mountain forests in China and Vietnam 3 (Supplementary Fig. 1).The golden snub-nosed monkey (GSM, R. roxellana) is recognized as an iconic endangered species in China for its golden coat, blue facial coloration, snub nose and specialized life history. Among its congeners, the black-white snub-nosed monkey (R. bieti), endemic to the Tibetan plateau, has the highest altitudinal distribution (>4,000 m above sea level) of any nonhuman primate. Given the above features and the fact that Rhinopithecus species consume difficult-to-digest foods that contain tannins (for example, leaves and pine seeds), we expected to identify genetic adaptations that enhance the breakdown of toxins, improve the regulation of energy metabolism and facilitate the digestion of symbiotic microbacteria. RESULTS Genomic sequences and the accumulation of...
Uncovering genetic variation through resequencing is limited by the fact that only sequences with similarity to the reference genome are examined. Reference genomes are often incomplete and cannot represent the full range of genetic diversity as a result of geographical divergence and independent demographic events. To more comprehensively characterize genetic variation of pigs (Sus scrofa), we generated de novo assemblies of nine geographically and phenotypically representative pigs from Eurasia. By comparing them to the reference pig assembly, we uncovered a substantial number of novel SNPs and structural variants, as well as 137.02-Mb sequences harboring 1737 protein-coding genes that were absent in the reference assembly, revealing variants left by selection. Our results illustrate the power of whole-genome de novo sequencing relative to resequencing and provide valuable genetic resources that enable effective use of pigs in both agricultural production and biomedical research.
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