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Briefings in Functional Genomics

Reham Ajina, Danielle Zamalin, Louis M Weiner
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...
May 11, 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...
May 5, 2018: Briefings in Functional Genomics
Dariusz Izak, Joanna Klim, Szymon Kaczanowski
Malaria remains one of the highest mortality infectious diseases. Malaria is caused by parasites from the genus Plasmodium. Most deaths are caused by infections involving Plasmodium falciparum, which has a complex life cycle. Malaria parasites are extremely well adapted for interactions with their host and their host's immune system and are able to suppress the human immune system, erase immunological memory and rapidly alter exposed antigens. Owing to this rapid evolution, parasites develop drug resistance and express novel forms of antigenic proteins that are not recognized by the host immune system...
April 25, 2018: Briefings in Functional Genomics
Peterson W Wambugu, Marie-Noelle Ndjiondjop, Robert J Henry
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...
April 23, 2018: Briefings in Functional Genomics
Mazahar Moin, Achala Bakshi, M S Madhav, P B Kirti
One of the important and direct ways of investigating the function of a gene is to characterize the phenotypic consequences associated with loss or gain-of-function of the corresponding gene. These mutagenesis strategies have been successfully deployed in Arabidopsis, and subsequently extended to crop species including rice. Researchers have made vast advancements in the area of rice genomics and functional genomics, as it is a diploid plant with a relatively smaller genome size unlike other cereals. The advent of rice genome research and the annotation of high-quality genome sequencing along with the developments in databases and computer searches have enabled the functional characterization of unknown genes in rice...
March 22, 2018: Briefings in Functional Genomics
Hong-Yan Wu, Chun-Yu Cao
Clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (CRISPR-Cas9) system was originally discovered in prokaryotes functioned as a part of the adaptive immune system. Because of its high efficiency and easy operability, CRISPR-Cas9 system has been developed to be a powerful and versatile gene editing tool shortly after its discovery. Given that multiple genetic alterations are the main factors that drive genesis and development of tumor, CRISPR-Cas9 system has been applied to correct cancer-causing gene mutations and deletions and to engineer immune cells, such as chimeric antigen receptor T (CAR T) cells, for cancer immunotherapeutic applications...
March 22, 2018: Briefings in Functional Genomics
Christoph Ziegenhain, Beate Vieth, Swati Parekh, Ines Hellmann, Wolfgang Enard
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...
March 22, 2018: Briefings in Functional Genomics
Yuuta Moriyama, Kazuko Koshiba-Takeuchi
Acquisition of evolutionary novelties is a fundamental process for adapting to the external environment and invading new niches and results in the diversification of life, which we can see in the world today. How such novel phenotypic traits are acquired in the course of evolution and are built up in developing embryos has been a central question in biology. Whole-genome duplication (WGD) is a process of genome doubling that supplies raw genetic materials and increases genome complexity. Recently, it has been gradually revealed that WGD and subsequent fate changes of duplicated genes can facilitate phenotypic evolution...
March 22, 2018: Briefings in Functional Genomics
Shan Jiang, Ali Mortazavi
Transcription is regulated by transcription factor (TF) binding at promoters and distal regulatory elements and histone modifications that control the accessibility of these elements. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) has become the standard assay for identifying genome-wide protein-DNA interactions in vitro and in vivo. As large-scale ChIP-seq data sets have been collected for different TFs and histone modifications, their potential to predict gene expression can be used to test hypotheses about the mechanisms of gene regulation...
March 20, 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...
March 16, 2018: 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
Georgi K Marinov
No abstract text is available yet for this article.
March 1, 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
Guillermo A Silva-Martínez, Silvio Zaina, Gertrud Lund
The HumanMethylation450 BeadChip array (450K; Infinium) is a widely used tool in epigenomics. A recognized concern in the 450K platform is the potential effect of the number of probes/gene (PG) on ranking differentially methylated (DM) CpGs (DM-CpGs) before testing for enrichment of gene ontology categories. We previously showed in a fatty acid (FA)-induced DNA methylation profiling study that when DM-CpGs are ranked by the number of called DM-CpGs-to-PG ratio, the 150 top-ranking gene list is enriched in pathways that overlap with the corresponding Affymetrix array-based expression data...
January 1, 2018: Briefings in Functional Genomics
Luciane T Kagohara, Genevieve L Stein-O'Brien, Dylan Kelley, Emily Flam, Heather C Wick, Ludmila V Danilova, Hariharan Easwaran, Alexander V Favorov, Jiang Qian, Daria A Gaykalova, Elana J Fertig
Cancer is a complex disease, driven by aberrant activity in numerous signaling pathways in even individual malignant cells. Epigenetic changes are critical mediators of these functional changes that drive and maintain the malignant phenotype. Changes in DNA methylation, histone acetylation and methylation, noncoding RNAs, posttranslational modifications are all epigenetic drivers in cancer, independent of changes in the DNA sequence. These epigenetic alterations were once thought to be crucial only for the malignant phenotype maintenance...
January 1, 2018: Briefings in Functional Genomics
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