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Briefings in Functional Genomics

Qi-Feng He, Yong Xu, Jun Li, Zheng-Ming Huang, Xiu-Hui Li, Xiaochen Wang
Immunotherapies have emerged as the most promising area in cancer treatments in recent years. CD8+ T cells, as one of the primary effector cells of anticancer immunity, however, when infiltrating in cancer tissues, are generally in dysfunctional states termed T-cell exhaustion. Exhausted CD8+ T cells are characterized by impaired activity and proliferative ability, increased apoptotic rate and reduced production of effector cytokines. Such dysfunctional CD8+ T cells serve as a barrier in successful cancer elimination...
March 15, 2018: Briefings in Functional Genomics
Peter Vegh, Muzlifah Haniffa
Application of single-cell genomics technologies has revolutionized our approach to study the immune system. Unravelling the functional diversity of immune cells and their coordinated response is key to understanding immunity. Single-cell transcriptomics technologies provide high-dimensional assessment of the transcriptional states of immune cells and have been successfully applied to discover new immune cell types, reveal haematopoietic lineages, identify gene modules dictating immune responses and investigate lymphocyte antigen receptor diversity...
March 14, 2018: Briefings in Functional Genomics
An-Liang Xia, Jin-Cheng Wang, Kun Yang, Dong Ji, Zheng-Ming Huang, Yong Xu
In chronic infection and cancer, T cells gradually become exhausted because of the persistent stimulation by antigens. In this process, the overexpression of multiple inhibitory receptors is induced, the production of effective cytokines decreases and the cytotoxicity and proliferation of T cells impairs, all contributing to the failure of T cells in fighting against cancer. Reversing T-cell exhaustion is a promising immunotherapy for cancer that has yielded encouraging results. In this review, we discuss the genomic and epigenomic landscape of T-cell exhaustion in cancer...
March 6, 2018: Briefings in Functional Genomics
Georgi K Marinov, Anshul Kundaje
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...
February 26, 2018: Briefings in Functional Genomics
Vilas Menon
No abstract text is available yet for this article.
January 16, 2018: Briefings in Functional Genomics
Mark W E J Fiers, Liesbeth Minnoye, Sara Aibar, Carmen Bravo González-Blas, Zeynep Kalender Atak, Stein Aerts
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...
January 12, 2018: Briefings in Functional Genomics
Mario Fernando Ortiz-Matamoros, Marco A Villanueva, Tania Islas-Flores
Transformation techniques are a fundamental tool for functional genomics studies. These techniques are routinely used in many prokaryotic and eukaryotic organisms, but in eukaryotes that are surrounded by a cell wall, these protocols have proven difficult to successfully deliver heterologous or homologous DNA within their cytoplasm and nucleus. Such cell-walled organisms represent a challenge that requires the development of genetic transformation techniques that are able to overcome their natural barrier, to achieve targeted gene expression...
January 1, 2018: Briefings in Functional Genomics
Michal Lazniewski, Wayne K Dawson, Teresa Szczepinska, Dariusz Plewczynski
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...
December 13, 2017: Briefings in Functional Genomics
Xiaoxia Ma, Ziwei Zuo, Weishan Shao, Yongfeng Jin, Yijun Meng
Argonaute (AGO) protein family is highly conserved in eukaryotes and prokaryotes, reflecting its evolutionarily indispensible role in maintaining normal life cycle of the organisms. Small RNA-guided, AGO-dependent RNA interference (RNAi) is a well-studied pathway for gene expression regulation, which can be performed at transcriptional, posttranscriptional or translational level. In addition to RNAi, growing pieces of evidence point to a novel role of AGOs in pre-mRNA (messenger RNA precursor) splicing in animals...
December 11, 2017: Briefings in Functional Genomics
Vilas Menon
Advances in single-cell RNA-sequencing technology have resulted in a wealth of studies aiming to identify transcriptomic cell types in various biological systems. There are multiple experimental approaches to isolate and profile single cells, which provide different levels of cellular and tissue coverage. In addition, multiple computational strategies have been proposed to identify putative cell types from single-cell data. From a data generation perspective, recent single-cell studies can be classified into two groups: those that distribute reads shallowly over large numbers of cells and those that distribute reads more deeply over a smaller cell population...
December 11, 2017: Briefings in Functional Genomics
Shriram N Rajpathak, Deepti D Deobagkar
Maintaining a balance in gene dosage and protein activity is essential to sustain normal cellular functions. Males and females have a wide range of genetic as well as epigenetic differences, where X-linked gene dosage is an essential regulatory factor. Basic understanding of gene dosage maintenance has emerged from the studies carried out using mouse models with FCG (four core genotype) and chromosomal aneuploidy as well as from mono-chromosomal hybrid cells. In mammals, aneuploidy often leads to embryonic lethality particularly in early development with major developmental and structural abnormalities...
December 8, 2017: Briefings in Functional Genomics
Bryan J Venters
One of the central goals in molecular biology is to understand how cell-type-specific expression patterns arise through selective recruitment of RNA polymerase II (Pol II) to a subset of gene promoters. Pol II needs to be recruited to a precise genomic position at the proper time to produce messenger RNA from a DNA template. Ostensibly, transcription is a relatively simple cellular process; yet, experimentally measuring and then understanding the combinatorial possibilities of transcriptional regulators remain a daunting task...
December 2, 2017: Briefings in Functional Genomics
Sumanta Ray, Ujjwal Maulik, Anirban Mukhopadhyay
Chronic infection of hepatitis C virus (HCV) leads to severe life-threatening liver diseases such as cirrhosis of liver, fibrosis and hepatocellular carcinoma (HCC). Severity of the disease infects >180 million people worldwide. In recent years, many computational approaches have been proposed to study and analyze the progression of liver fibrosis, HCC and other liver diseases developed from chronic HCV infection. In this article, we review the literature published in this area of study. Here we categorize all the approaches into two basic groups: analyzing gene expression and studying protein-protein interaction network among HCV-infected human proteins...
November 29, 2017: Briefings in Functional Genomics
Omar Ibrahim, Heidi G Sutherland, Larisa M Haupt, Lyn R Griffiths
Executive function (EF) includes a range of decision-making and higher-order thinking processes. Although the genetic basis of EF has been studied and reviewed, epigenetic factors that influence EF are an emerging field of interest; here, we summarize the current research. Work relating to different word combinations of 'Executive Function' and 'Epigenetic' was identified through three academic search directories. Inclusion criteria were human populations, EF testing, epigenetic testing or genotyping related to epigenetic regulation...
November 20, 2017: Briefings in Functional Genomics
Anupam Banerjee, Abantika Pal, Debnath Pal, Pralay Mitra
Zaire ebolavirus, one of the most pathogenic species of Ebolavirus, is a significant threat to the human community being both highly infectious and lethal. The viral proteins (VPs), specifically VP24 and VP35, antagonize the interferon (IFN) proteins accountable for human immune response. Several efforts have been made to design vaccines and therapeutics drugs. However, the success is not encouraging because of limited knowledge about the binding site information of the VPs. Such limitations stem largely from the highly infectious nature of the virus that requires specialized personnel and biosafety laboratories...
November 13, 2017: Briefings in Functional Genomics
Tomasz Wolkowicz
Modern diagnostics is in general based on molecular biology methods. Nowadays sequencing-based methods, especially whole genome sequencing, are becoming increasingly important. Implementation of such methods into routine diagnostic of highly dangerous pathogens, like Bacillus anthracis, Francisella tularensis, Yersinia pestis, Ebola virus, MERS, Lassa virus etc. would be very helpful. The best diagnostic strategy would be the metagenomic sequencing directly from the clinical sample. Implementation of majority of currently available WGS platforms inside the BSL-3 or 4 laboratory is impractical because of the size of the equipment and time consuming wet lab part (e...
November 10, 2017: Briefings in Functional Genomics
Jeanette Baran-Gale, Tamir Chandra, Kristina Kirschner
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...
November 8, 2017: Briefings in Functional Genomics
Martin Machyna, Matthew D Simon
The growing appreciation of the importance of long noncoding RNAs (lncRNAs), together with the awareness that some of these RNAs are associated with chromatin, has inspired the development of methods to detect their sites of interaction on a genome-wide scale at high resolution. Hybridization capture methods combine antisense oligonucleotide hybridization with enrichment of RNA from cross-linked chromatin extracts. These techniques have provided insight into lncRNA localization and the interactions of lncRNAs with protein to better understand biological roles of lncRNAs...
November 8, 2017: Briefings in Functional Genomics
Mattias Rantalainen
Precision medicine is emerging as a cornerstone of future cancer care with the objective of providing targeted therapies based on the molecular phenotype of each individual patient. Traditional bulk-level molecular phenotyping of tumours leads to significant information loss, as the molecular profile represents an average phenotype over large numbers of cells, while cancer is a disease with inherent intra-tumour heterogeneity at the cellular level caused by several factors, including clonal evolution, tissue hierarchies, rare cells and dynamic cell states...
November 2, 2017: Briefings in Functional Genomics
Greg Elgar
No abstract text is available yet for this article.
November 1, 2017: Briefings in Functional Genomics
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