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  • 1.

    【2hr】Applications of the site-specific recombinase Cre to the study of genomic imprinting

    包量

    机译 位点特异性重组酶Cre在基因组印迹研究中的应用
    摘要：The development of gene targeting approaches has had a tremendous impact on the functional analysis of the mouse genome. A specific application of this technique has been the adaptation of the bacteriophage P1 Cre/loxP site-specific recombinase system which allows for the precise recombination between two loxP sites, resulting in deletion or inversion of the intervening sequences. Because of the efficiency of this system, it can be applied to conditional deletions of relatively short coding sequences or regulatory elements but also to more extensive chromosomal rearrangement strategies. Both mechanistic and functional studies of genomic imprinting have benefited from the development of the Cre/loxP technology. Since imprinted genes within large chromosomal regions are regulated by the action of cis-acting sequences known as imprinting centres, chromosomal engineering approaches are particularly well suited to the elucidation of long-range mechanisms controlling the imprinting of autosomal genes. Here we review the applications of the Cre/loxP technology to the study of genomic imprinting, highlight important insights gained from these studies and discuss future directions in the field.
  • 2.

    【2hr】Retrotransposition and genomic imprinting

    包量

    机译 逆转座和基因组印迹
    摘要：Studies of large imprinted clusters, such as the Gnas locus, have revealed much about the significance of DNA methylation, transcription and other factors in the establishment and maintenance of imprinted gene expression. However, the complexity of such loci can make manipulating them and interpreting the results challenging. We review here a distinct class of imprinted genes, which have arisen by retrotransposition, and which have the potential to be used as models for the dissection of the fundamental features and mechanisms required for imprinting. They are also of interest in their own right, generating diversity in the transcriptome and providing raw material upon which selection can act.
  • 3.

    【2hr】The executable pathway to biological networks

    包量

    机译 通往生物网络的可执行途径
    摘要：As time goes by, it becomes more and more apparent that the puzzles of life involve more and more molecular pieces that fit together in increasingly complex ways. Genomics and Proteomics technologies nowadays, produce reliable and quantitative data that could potentially reveal all the molecular pieces of a particular puzzle. However, this is akin to the opening of Pandora’s box; and we are now facing the problem of integrating this vast amount of data with its incredible complexity into some coherent whole. With the aid of engineering methods designed to build and analyze computerized man-made systems, a new emerging field called ‘Executable Biology’ aims to create computer programmes that put together the pieces in ways that allows capturing their dynamicity and ultimately elucidating how molecular function generates cellular function. This review aspires to highlight the main features characterizing these kinds of executable models and what makes them uniquely qualified to reason about and analyze biological networks.
  • 4.

    【2hr】Lineage-specific transcription factors and the evolution of gene regulatory networks

    包量

    机译 谱系特异性转录因子与基因调控网络的进化
    摘要：Nature is replete with examples of diverse cell types, tissues and body plans, forming very different creatures from genomes with similar gene complements. However, while the genes and the structures of proteins they encode can be highly conserved, the production of those proteins in specific cell types and at specific developmental time points might differ considerably between species. A full understanding of the factors that orchestrate gene expression will be essential to fully understand evolutionary variety. Transcription factor (TF) proteins, which form gene regulatory networks (GRNs) to act in cooperative or competitive partnerships to regulate gene expression, are key components of these unique regulatory programs. Although many TFs are conserved in structure and function, certain classes of TFs display extensive levels of species diversity. In this review, we highlight families of TFs that have expanded through gene duplication events to create species-unique repertoires in different evolutionary lineages. We discuss how the hierarchical structures of GRNs allow for flexible small to large-scale phenotypic changes. We survey evidence that explains how newly evolved TFs may be integrated into an existing GRN and how molecular changes in TFs might impact the GRNs. Finally, we review examples of traits that evolved due to lineage-specific TFs and species differences in GRNs.
  • 5.

    【2hr】Understanding protein phosphorylation on a systems level

    包量

    机译 在系统水平上了解蛋白质磷酸化
    摘要：Protein kinase phosphorylation is central to the regulation and control of protein and cellular function. Over the past decade, the development of many high-throughput approaches has revolutionized the understanding of protein phosphorylation and allowed rapid and unbiased surveys of phosphoproteins and phosphorylation events. In addition to this technological advancement, there have also been computational improvements; recent studies on network models of protein phosphorylation have provided many insights into the cellular processes and pathways regulated by phosphorylation. This article gives an overview of experimental and computational techniques for identifying and analyzing protein phosphorylation on a systems level.
  • 6.

    【2hr】A combined immunoprecipitation mass spectrometric and nucleic acid sequencing approach to determine microRNA-mediated post-transcriptional gene regulatory networks

    包量

    机译 结合免疫沉淀质谱和核酸测序方法确定microRNA介导的转录后基因调控网络
    摘要：While initiation of transcription has attracted the most attention in the field of gene regulation, it has become clear that additional stages in the gene expression cascade including post-transcriptional events are under equally exquisite control. The seminal discovery that short RNAs (microRNA, small interfering RNA, Piwi-interacting RNA), play important roles in repressing gene expression has spurred a rush of new interest in post-transcriptional gene silencing mechanisms. The development of affinity tags and high-resolution tandem mass spectrometry (MS/MS) has greatly simplified the analysis of proteins that regulate gene expression. Further, the use of DNA microarrays and ‘second generation’ nucleic acid sequencing (‘deep sequencing’) technologies has facilitated the identification of their regulatory targets. These technological advancements mark a significant step towards a comprehensive understanding of gene regulatory networks. The purpose of this review is to highlight several recent reports that illustrate the value of affinity-purification (immunoprecipitation) followed by mass spectrometric protein analysis and nucleic acid analysis by deep sequencing (AP-MS/Seq) to examine mRNA after it has been transcribed. The ability to identify the direct nucleic acid targets of post-transcriptional gene regulatory machines is a critical first step towards understanding the contribution of post-transcriptional pathways on gene expression.
  • 7.

    【2hr】Insights to transcriptional networks by using high throughput RNAi strategies

    包量

    机译 使用高通量RNAi策略洞悉转录网络
    摘要：RNA interference (RNAi) is a powerful method to unravel the role of a given gene in eukaryotic cells. The development of high throughput assay platforms such as fluorescence plate readers and high throughput microscopy has allowed the design of genome wide RNAi screens to systemically discern members of regulatory networks around various cellular processes. Here we summarize the different strategies employed in RNAi screens to reveal regulators of transcriptional networks. We focus our discussion in experimental approaches designed to uncover regulatory interactions modulating transcription factor activity.
  • 8.

    【2hr】Interplay between miRNAs and host genes and their role in cancer

    包量

    机译 miRNA与宿主基因之间的相互作用及其在癌症中的作用
    摘要：MicroRNAs (miRNAs) are small endogenous non-coding functional RNAs that post-transcriptionally regulate gene expression. They play essential roles in nearly all biological processes including cell development and differentiation, DNA damage repair, cell death as well as intercellular communication. They are highly involved in cancer, acting as tumor suppressors and/or promoters to modulate cell proliferation, epithelial-mesenchymal transition and tumor invasion and metastasis. Recent studies have shown that more than half of miRNAs are located within protein-coding or non-coding genes. Intragenic miRNAs and their host genes either share the promoter or have independent transcription. Meanwhile, miRNAs work as partners or antagonists of their host genes by fine-tuning their target genes functionally associated with host genes. This review outlined the complicated relationship between intragenic miRNAs and host genes. Focusing on miRNAs known as oncogenes or tumor suppressors in specific cancer types, it studied co-expression relationships between these miRNAs and host genes in the cancer types using TCGA data sets, which validated previous findings and revealed common, tumor-specific and even subtype-specific patterns. These observations will help understand the function of intragenic miRNAs and further develop miRNA therapeutics in cancer.
  • 9.

    【2hr】Next-generation sequencing technologies accelerate advances in T-cell therapy for cancer

    包量

    机译 下一代测序技术加速了T细胞治疗癌症的进展
    摘要：Next-generation sequencing has produced a large quantity of DNA or RNA sequences related to the processes occurring within tumors and their microenvironment in a reasonable time and cost. These data have been used to guide the identification of neoantigens and to determine their specific T-cell receptors. Furthermore, adoptive T-cell therapy targeting neoantigens is under development for cancer treatment. In this review, we first provide an overview of sequencing technologies and the updated findings concerning neoantigens related to adoptive T-cell therapy and then summarize the methods and principles underlying the development of next-generation sequencing-based neoantigen-reactive T-cell therapy for cancer.
  • 10.

    【2hr】Functional genomics: paving the way for more successful cancer immunotherapy

    包量

    机译 功能基因组学：为更成功的癌症免疫疗法铺平道路
    摘要：Immunotherapies have revolutionized cancer treatment. Immunotherapy is effective for the treatment of a wide range of cancer types and can mediate complete and durable tumor regression. Nonetheless, the field still faces many significant challenges, such as the need for personalized therapeutic strategies and better biomarkers, the difficulty of selecting the right combination therapy, and resistance to currently available immunotherapies. Both cancer and host immunity comprise significantly diverse and complex ecosystems, making immunogenomics an ideal field for functional genomics analysis. In this review, we describe the cancer–immunity cycle, how cancer cells manage to evade immune attack and the current hurdles in the path of cancer immunotherapy. Then, we discuss how functional genomics approaches can pave the way for more successful cancer immunotherapies.
  • 11.

    【2hr】Translating GWAS in rheumatic disease: approaches to establishing mechanism and function for genetic associations with ankylosing spondylitis

    包量

    机译 在风湿性疾病中翻译GWAS：建立与强直性脊柱炎遗传关联的机制和功能的方法
    摘要：Ankylosing spondylitis (AS) is a highly heritable chronic inflammatory arthritis characterized by osteoproliferation, fusion of affected joints and systemic manifestations. Many disease associations for AS have been reported through genome-wide association studies; however, identifying modulated genes and functional mechanism remains challenging. This review summarizes current genetic associations involving AS and describes strategic approaches for functional follow-up of disease-associated variants. Fine mapping using methods leveraging Bayesian approaches are outlined. Evidence highlighting the importance of context specificity for regulatory variants is reviewed, noting current evidence in AS for the relevant cell and tissue type to conduct such analyses. Technological advances for understanding the regulatory landscape within which functional variants may act are discussed using exemplars. Approaches include defining regulatory elements based on chromatin accessibility, effects of variants on genes at a distance through evidence of physical interactions (chromatin conformation capture), expression quantitative trait loci mapping and single-cell methodologies. Opportunities for mechanistic studies to investigate the function of specific variants, regulatory elements and genes enabled by genome editing using clustered regularly interspaced short palindromic repeats/Cas9 are also described. Further progress in our understanding of the genetics of AS through functional genomic and epigenomic approaches offers new opportunities to understand mechanism and develop innovative treatments.
  • 12.

    【2hr】Role of genomics in promoting the utilization of plant genetic resources in genebanks

    包量

    机译 基因组学在促进基因库植物遗传资源利用中的作用
    摘要：Global efforts have seen the world’s plant genetic resources (PGRs) conserved in about 1625 germ plasm repositories. Utility of these resources is important in increasing the resilience and productivity of agricultural production systems. However, despite their importance, utility of these resources has been poor. This article reviews the real and potential application of the current advances in genomic technologies in improving the utilization of these resources. The actual and potential application of these genomic approaches in plant identification, phylogenetic analysis, analysing the genetic value of germ plasm, facilitating germ plasm selection in genebanks as well as instilling confidence in international germ plasm exchange system is discussed. We note that if genebanks are to benefit from this genomic revolution, there is need for fundamental changes in the way genebanks are managed, perceived, organized and funded. Increased collaboration between genebank managers and the user community is also recommended
  • 13.

    【2hr】Quantitative single-cell transcriptomics

    包量

    机译 定量单细胞转录组学
    摘要：Single-cell RNA sequencing (scRNA-seq) is currently transforming our understanding of biology, as it is a powerful tool to resolve cellular heterogeneity and molecular networks. Over 50 protocols have been developed in recent years and also data processing and analyzes tools are evolving fast. Here, we review the basic principles underlying the different experimental protocols and how to benchmark them. We also review and compare the essential methods to process scRNA-seq data from mapping, filtering, normalization and batch corrections to basic differential expression analysis. We hope that this helps to choose appropriate experimental and computational methods for the research question at hand.
  • 14.

    【2hr】Inference of the ancestral vertebrate phenotype through vestiges of the whole-genome duplications

    包量

    机译 通过全基因组重复的痕迹推断祖先脊椎动物的表型
    摘要：Inferring the phenotype of the last common ancestor of living vertebrates is a challenging problem because of several unresolvable factors. They include the lack of reliable out-groups of living vertebrates, poor information about less fossilizable organs and specialized traits of phylogenetically important species, such as lampreys and hagfishes (e.g. secondary loss of vertebrae in adult hagfishes). These factors undermine the reliability of ancestral reconstruction by traditional character mapping approaches based on maximum parsimony. In this article, we formulate an approach to hypothesizing ancestral vertebrate phenotypes using information from the phylogenetic and functional properties of genes duplicated by genome expansions in early vertebrate evolution. We named the conjecture as ‘chronological reconstruction of ohnolog functions (CHROF)’. This CHROF conjecture raises the possibility that the last common ancestor of living vertebrates may have had more complex traits than currently thought.
  • 15.

    【2hr】ChIP-ping the branches of the tree: functional genomics and the evolution of eukaryotic gene regulation

    包量

    机译 修剪树枝：功能基因组学和真核基因调控的进化
    摘要：Advances in the methods for detecting protein–DNA interactions have played a key role in determining the directions of research into the mechanisms of transcriptional regulation. The most recent major technological transformation happened a decade ago, with the move from using tiling arrays [chromatin immunoprecipitation (ChIP)-on-Chip] to high-throughput sequencing (ChIP-seq) as a readout for ChIP assays. In addition to the numerous other ways in which it is superior to arrays, by eliminating the need to design and manufacture them, sequencing also opened the door to carrying out comparative analyses of genome-wide transcription factor occupancy across species and studying chromatin biology in previously less accessible model and nonmodel organisms, thus allowing us to understand the evolution and diversity of regulatory mechanisms in unprecedented detail. Here, we review the biological insights obtained from such studies in recent years and discuss anticipated future developments in the field.
  • 16.

    【2hr】Mapping gene regulatory networks from single-cell omics data

    包量

    机译 从单细胞组学数据映射基因调控网络
    摘要：Single-cell techniques are advancing rapidly and are yielding unprecedented insight into cellular heterogeneity. Mapping the gene regulatory networks (GRNs) underlying cell states provides attractive opportunities to mechanistically understand this heterogeneity. In this review, we discuss recently emerging methods to map GRNs from single-cell transcriptomics data, tackling the challenge of increased noise levels and data sparsity compared with bulk data, alongside increasing data volumes. Next, we discuss how new techniques for single-cell epigenomics, such as single-cell ATAC-seq and single-cell DNA methylation profiling, can be used to decipher gene regulatory programmes. We finally look forward to the application of single-cell multi-omics and perturbation techniques that will likely play important roles for GRN inference in the future.
  • 17.

    【2hr】The structural variability of the influenza A hemagglutinin receptor-binding site

    包量

    机译 甲型流感血凝素受体结合位点的结构变异性
    摘要：Hemagglutinin (HA) is a transmembrane protein of the influenza A virus and a key component in its life cycle. The protein allows the virus to enter a host cell by recognizing specific glycans attached to transmembrane proteins of the host, which leads to viral endocytosis. In recent years, significant progress has been made in understanding the structural relationship between changes in the HA receptor-binding site (RBS) and the sialylated glycans that bind them. Several mutations were identified in the HA RBS that allows the virus to change host tropism. Their impact on binding the analogs of human and avian receptors was determined with X-ray crystallography. In this article, we provide a short overview of the HA protein structure and briefly discuss the adaptive mutations introduced to different HA subtypes.
  • 18.

    【2hr】Experimental design for single-cell RNA sequencing

    包量

    机译 单细胞RNA测序的实验设计
    摘要：Single-cell RNA sequencing (scRNA-seq) has opened new avenues for the characterization of heterogeneity in a large variety of cellular systems. As this is a relatively new technique, the field is fast evolving. Here, we discuss general considerations in experimental design and the two most popular approaches, plate-based Smart-Seq2 and microdroplet-based scRNA-seq at the example of 10x Chromium. We discuss advantages and disadvantages of both methods and point out major factors to consider in designing successful experiments.
  • 19.

    【2hr】The Human Cell Atlas: Technical approaches and challenges

    包量

    机译 人类细胞图集：技术方法和挑战
    摘要：The Human Cell Atlas is a large, international consortium that aims to identify and describe every cell type in the human body. The comprehensive cellular maps that arise from this ambitious effort have the potential to transform many aspects of fundamental biology and clinical practice. Here, we discuss the technical approaches that could be used today to generate such a resource and also the technical challenges that will be encountered.
  • 20.

    【2hr】Bacterial artificial chromosomes as recombinant reporter constructs to investigate gene expression and regulation in echinoderms

    包量

    机译 细菌人工染色体作为重组报告基因构建体研究棘皮动物中的基因表达和调控
    摘要：Genome sequences contain all the necessary information—both coding and regulatory sequences—to construct an organism. The developmental process translates this genomic information into a three-dimensional form. One interpretation of this translation process can be described using gene regulatory network (GRN) models, which are maps of interactions among regulatory gene products in time and space. As high throughput investigations reveal increasing complexity within these GRNs, it becomes apparent that efficient methods are required to test the necessity and sufficiency of regulatory interactions. One of the most complete GRNs for early development has been described in the purple sea urchin, Strongylocentrotus purpuratus. This work has been facilitated by two resources: a well-annotated genome sequence and transgenes generated in bacterial artificial chromosome (BAC) constructs. BAC libraries played a central role in assembling the S. purpuratus genome sequence and continue to serve as platforms for generating reporter constructs for use in expression and regulatory analyses. Optically transparent echinoderm larvae are highly amenable to transgenic approaches and are therefore particularly well suited for experiments that rely on BAC-based reporter transgenes. Here, we discuss the experimental utility of BAC constructs in the context of understanding developmental processes in echinoderm embryos and larvae.
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