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Briefings in Functional Genomics

Qingfang Zhao, Liang Cao, Lulu Guan, Liangyu Bie, Saiqi Wang, Bojian Xie, Xiaobing Chen, Xiaokun Shen, Feiling Cao
Gastric cancer remains the second most common cause of cancer-related death worldwide. Because of the poor prognosis of late-stage gastric cancer patients, it is imperative to develop new strategies to improve the survival rate of this disease. Currently, immunotherapy is considered as an innovative approach for cancers such as lung cancer, gastric cancer and breast cancer. In fact, previous works have revealed promising results in this field. With further understanding of immunogenomics of gastric cancer, new immune checkpoint regulators could become more important...
November 2, 2018: Briefings in Functional Genomics
Kamalakshi Devi, Kuntal Kumar Dey, Sanjay Singh, Surajit Kumar Mishra, Mahendra Kumar Modi, Priyabrata Sen
miRNAs are class of endogenously initiated noncoding RNAs, which are most critical in gene expression and regulation at posttranscriptional level. They do so either by cleavage of the target mRNA or by translational repression. miRNAs are being given enough attention in recent years because of its role in myriad developmental processes including tumorogenesis and host-pathogen interaction. Advent of Next Generation Sequencing (NGS) technology and computational approach made it possible to pinpoint the precise role of miRNA and their target...
October 18, 2018: Briefings in Functional Genomics
Yan Guo, Hui Yu, David C Samuels, Wei Yue, Scott Ness, Ying-Yong Zhao
Through analysis of paired high-throughput DNA-Seq and RNA-Seq data, researchers quickly recognized that RNA-Seq can be used for more than just gene expression quantification. The alternative applications of RNA-Seq data are abundant, and we are particularly interested in its usefulness for detecting single-nucleotide variants, which arise from RNA editing, genomic variants and other RNA modifications. A stunning discovery made from RNA-Seq analyses is the unexpectedly high prevalence of RNA-editing events, many of which cannot be explained by known RNA-editing mechanisms...
October 12, 2018: Briefings in Functional Genomics
Dareen Alyousfi, Diana Baralle, Andrew Collins
The evolution of next-generation sequencing technologies has facilitated the detection of causal genetic variants in diseases previously undiagnosed at a molecular level. However, in genome sequencing studies, the identification of disease genes among a candidate gene list is often difficult because of the large number of apparently damaging (but usually neutral) variants. A number of variant prioritization tools have been developed to help detect disease-causal sites. However, the results may be misleading as many variants scored as damaging by these tools are often tolerated, and there are inconsistencies in prediction results among the different variant-level prediction tools...
October 12, 2018: Briefings in Functional Genomics
Zhiqiang Zhang, Yi Zhao, Xiangke Liao, Wenqiang Shi, Kenli Li, Quan Zou, Shaoliang Peng
Omics, such as genomics, transcriptome and proteomics, has been affected by the era of big data. A huge amount of high dimensional and complex structured data has made it no longer applicable for conventional machine learning algorithms. Fortunately, deep learning technology can contribute toward resolving these challenges. There is evidence that deep learning can handle omics data well and resolve omics problems. This survey aims to provide an entry-level guideline for researchers, to understand and use deep learning in order to solve omics problems...
September 26, 2018: Briefings in Functional Genomics
Koichi Nishigaki
The short lifetime structures of nucleic acids are not well studied because of the poor recognition of their importance and the methodological difficulty. In case of proteins, which are a type of single-stranded biopolymers, the essential roles of their transient structures are well established. Therefore, the role of transient structures of nucleic acids is, naturally, of great interest. There have been multiple reports on the function-related unstable (transient) structures of single-stranded nucleotides, though not as many as at present...
September 24, 2018: Briefings in Functional Genomics
Xing Chen, Ya-Zhou Sun, Na-Na Guan, Jia Qu, Zhi-An Huang, Ze-Xuan Zhu, Jian-Qiang Li
From transcriptional noise to dark matter of biology, the rapidly changing view of long non-coding RNA (lncRNA) leads to deep understanding of human complex diseases induced by abnormal expression of lncRNAs. There is urgent need to discern potential functional roles of lncRNAs for further study of pathology, diagnosis, therapy, prognosis, prevention of human complex disease and disease biomarker detection at lncRNA level. Computational models are anticipated to be an effective way to combine current related databases for predicting most potential lncRNA functions and calculating lncRNA functional similarity on the large scale...
September 21, 2018: Briefings in Functional Genomics
Ya-Fei Yan, Yong-Fa Zheng, Ping-Po Ming, Xiao-Xi Deng, Wei Ge, Yao-Gui Wu
Since 2015, immunotherapies, especially immune checkpoint inhibitors (ICIs), have made great breakthroughs in non-small-cell lung cancer (NSCLC). Among them, nivolumab, pembrolizumab and atezolizumab have been granted US Food and Drug Administration approval for NSCLC. It is imperative to combine ICIs with chemotherapy, radiotherapy, antivascular therapy and targeted therapy. But in the bright future, there are two problems. One is how to use biomarkers to select the beneficiaries. The other is how to achieve a balance between drug effectiveness and safety...
September 20, 2018: Briefings in Functional Genomics
Babar Hussain, Stuart James Lucas, Hikmet Budak
The clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system uses single-guide RNAs for genome editing, making it a simple, robust, powerful tool for targeted gene mutagenesis, knockout and knock-in/replacement, as well as transcriptional regulation. Here, we review the working principles, components and potential modifications of CRISPR/Cas9 for efficient single and multiplex gene editing in plants. We also describe recent work that has used CRISPR/Cas9 to improve economically important traits in crop plants...
September 27, 2018: Briefings in Functional Genomics
Julie A Osgood, Julian C Knight
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...
September 27, 2018: Briefings in Functional Genomics
Koh Onimaru, Shigehiro Kuraku
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...
September 27, 2018: Briefings in Functional Genomics
Katherine M Buckley, Ping Dong, R Andrew Cameron, Jonathan P Rast
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...
September 27, 2018: Briefings in Functional Genomics
Ryan Park, Mary Winnicki, Evan Liu, Wen-Ming Chu
Immune checkpoints have been the subject of a wave of new studies. Among these checkpoints are tytotoxic T-lymphocyte-associated antigen 4, checkpoints programmed death-1 and programmed death-ligand 1; their blockades have been approved by the Food and Drug Administration for therapy of melanoma and other types of cancers. Immunogenomics, which combines the latest nucleic acid sequencing strategy with immunotherapy, provides precise information about genomic alterations (e.g. mutations) and enables a paradigm shift of immune checkpoint therapy from tumor types to molecular signatures...
August 17, 2018: Briefings in Functional Genomics
Debostuti Ghoshdastidar, Manju Bansal
DNA is a complex molecule with phenomenal inherent plasticity and the ability to form different hydrogen bonding patterns of varying stabilities. These properties enable DNA to attain a variety of structural and conformational polymorphic forms. Structurally, DNA can exist in single-stranded form or as higher-order structures, which include the canonical double helix as well as the noncanonical duplex, triplex and quadruplex species. Each of these structural forms in turn encompasses an ensemble of dynamically heterogeneous conformers depending on the sequence composition and environmental context...
August 8, 2018: Briefings in Functional Genomics
Kenji Kojima, Misato Baba, Motoki Tsukiashi, Takuto Nishimura, Kiyoshi Yasukawa
Ribonuclease H (RNase H) [EC] is an enzyme that specifically degrades RNA from RNA/DNA hybrids. Since its discovery in 1969, the enzyme has been extensively studied for its catalytic mechanism and physiological role. RNase H has been classified into two major families, Type 1 and Type 2. Type 1 enzymes are designated RNase HI in prokaryotes and RNase H1 in eukaryotes, while Type 2 enzymes are designated RNase HII in prokaryotes and RNase H2 in eukaryotes. Type 2 enzymes are able to cleave the 5'-phosphodiester bond of one ribonucleotide embedded in a DNA double strand...
July 12, 2018: Briefings in Functional Genomics
Sagnik Sen, Ujjwal Maulik
In the current era of epigenetics research, we have observed many examples of epigenetic modifications, like histone modification and DNA methylation, in various fatal diseases. These include solid tumors, hematological malignancies and viral infections with DNA or RNA viruses. The purpose of this review is to summarize the role of epigenetic modifications during the abovementioned viral infections, viral-associated and independent malignancies. In this article, the essential biological aspects of DNA methylation are discussed...
July 9, 2018: Briefings in Functional Genomics
Xiaobo Wang, Shaoyi Fan, Hehai Pan, Wenli Chen, Hua Wang
Cancer is a complex and refractory disease, which can disseminate from primary site to a different site even at an early stage. Cancer immunotherapy harnesses host immune system to battle against cancer, but only a minority of patients benefit from it. Genetic-based technologies have significantly promoted the development of cancer immunotherapy. Here we describe genetic-based cancer immunotherapies in three aspects: recombinant cancer vaccine, immune checkpoint blockade therapy and adoptive cell transfer. In the future, multi-disciplinary collaboration will greatly increase the scope and effectiveness of cancer immunotherpy...
July 9, 2018: Briefings in Functional Genomics
Kashyap Kumar Dubey, Garry A Luke, Caroline Knox, Punit Kumar, Brett I Pletschke, Puneet Kumar Singh, Pratyoosh Shukla
Plants as bioreactors have been widely used to express efficient vaccine antigens against viral, bacterial and protozoan infections. To date, many different plant-based expression systems have been analyzed, with a growing preference for transient expression systems. Antibody expression in diverse plant species for therapeutic applications is well known, and this review provides an overview of various aspects of plant-based biopharmaceutical production. Here, we highlight conventional and gene expression technologies in plants along with some illustrative examples...
July 5, 2018: Briefings in Functional Genomics
Vladimir N Uversky
Although for more than a century a protein function was intimately associated with the presence of unique structure in a protein molecule, recent years witnessed a skyrocket rise of the appreciation of protein intrinsic disorder concept that emphasizes the importance of the biologically active proteins without ordered structures. In different proteins, the depth and breadth of disorder penetrance are different, generating an amusing spatiotemporal heterogeneity of intrinsically disordered proteins (IDPs) and intrinsically disordered protein region regions (IDPRs), which are typically described as highly dynamic ensembles of rapidly interconverting conformations (or a multitude of short lifetime structures)...
July 3, 2018: Briefings in Functional Genomics
Qinan Yin, Jiaxing Tang, Xuekai Zhu
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...
July 2, 2018: Briefings in Functional Genomics
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