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Integrative genomics

Amanda C Carroll, Alex Wong
Plasmids are extrachromosomal DNA elements that can be found throughout bacteria, as well as in other domains of life. Nonetheless, the evolutionary processes underlying the persistence of plasmids are incompletely understood. Bacterial plasmids may encode genes for traits which are sometimes beneficial to their hosts, such as antimicrobial resistance, virulence, heavy metal tolerance, and the catabolism of unique nutrient sources. In the absence of selection for these traits, however, plasmids generally impose a fitness cost on their hosts...
March 21, 2018: Canadian Journal of Microbiology
Yanting Luo, Jianlin He, Xiguang Xu, Ming-An Sun, Xiaowei Wu, Xuemei Lu, Hehuang Xie
Embryonic stem cells (ESCs) consist of a population of self-renewing cells displaying extensive phenotypic and functional heterogeneity. Research towards the understanding of the epigenetic mechanisms underlying the heterogeneity among ESCs is still in its initial stage. Key issues, such as how to identify cell-subset specifically methylated loci and how to interpret the biological meanings of methylation variations remain largely unexplored. To fill in the research gap, we implemented a computational pipeline to analyze single-cell methylome and to perform an integrative analysis with single-cell transcriptome data...
March 2018: PLoS Computational Biology
Inuk Jung, Hyejin Kang, Jang Uk Kim, Hyeonsook Chang, Sun Kim, Woosuk Jung
BACKGROUND: Ginseng is a popular traditional herbal medicine in north-eastern Asia. It has been used for human health for over thousands of years. With the rise in global temperature, the production of Korean ginseng (Panax ginseng C.A.Meyer) in Korea have migrated from mid to northern parts of the Korean peninsula to escape from the various higher temperature related stresses. Under the high ambient temperature, vegetative growth was accelerated, which resulted in early flowering. This precocious phase change led to yield loss...
March 19, 2018: BMC Systems Biology
Sara Pagotto, Angelo Veronese, Alessandra Soranno, Paola Lanuti, Mirco Di Marco, Marco Vincenzo Russo, Alice Ramassone, Marco Marchisio, Pasquale Simeone, Paolo E Guanciali Franchi, Giandomenico Palka, Renato Mariani Costantini, Carlo M Croce, Rosa Visone
Hsa-miR-155-5p (miR-155) is overexpressed in most solid and hematological malignancies. It promotes loss of genomic integrity in cancer cells by targeting genes involved in microsatellite instability and DNA repair; however, the link between miR-155 and aneuploidy has been scarcely investigated. Here we describe a novel mechanism by which miR-155 causes chromosomal instability. Using osteosarcoma cells (U2OS) and normal human dermal fibroblast (HDF), two well-established models for the study of chromosome congression, we demonstrate that miR-155 targets the spindle checkpoint proteins BUB1, CENP-F, and ZW10, thus compromising chromosome alignment at the metaphase plate...
February 27, 2018: Oncotarget
Balázs Győrffy, Lőrinc Pongor, Giulia Bottai, Xiaotong Li, Jan Budczies, András Szabó, Christos Hatzis, Lajos Pusztai, Libero Santarpia
BACKGROUND: Sequence variations in coding and non-coding regions of the genome can affect gene expression and signalling pathways, which in turn may influence disease outcome. METHODS: In this study, we integrated somatic mutations, gene expression and clinical data from 930 breast cancer patients included in the TCGA database. Genes associated with single mutations in molecular breast cancer subtypes were identified by the Mann-Whitney U-test and their prognostic value was evaluated by Kaplan-Meier and Cox regression analyses...
March 21, 2018: British Journal of Cancer
Elizabeth S Silagi, Philip Batista, Irving M Shapiro, Makarand V Risbud
The integrity of the avascular nucleus pulposus (NP) phenotype plays a crucial role in the maintenance of intervertebral disc health. While advances have been made to define the molecular phenotype of healthy NP cells, the functional relevance of several of these markers remains unknown. In this study, we test the hypothesis that expression of Carbonic Anhydrase III (CAIII), a marker of the notochordal NP, is hypoxia-responsive and functions as a potent antioxidant without a significant contribution to pH homeostasis...
March 20, 2018: Scientific Reports
C De La Fuente Canto, D I Kalogiros, M Ptashnyk, T S George, R Waugh, A G Bengough, J Russell, L X Dupuy
Discoveries on the genetics of resource acquisition efficiency are limited by the ability to measure plant roots in sufficient number and adequate genotypic variability. This paper presents a root phenotyping study that explores ways to combine live imaging and computer algorithms for model-based extraction of root growth parameters. The study is based on a subset of barley Recombinant Chromosome Substitution Lines (RCSLs) and a combinatorial approach was designed for fast identification of the regions of the genome that contribute the most to variations in root system architecture (RSA)...
March 17, 2018: Journal of Theoretical Biology
Dwight D Bowman
Parasitology is a relevant and integral part of veterinary medicine, and the WAAVP membership has skills ranging from morphological diagnostics and routine parasite control recommendations through the cutting edges of many disciplines, e.g., pharmacology, immunology, molecular biology and genomics. We regularly face a majority of students who want only the practical information useful the moment they enter the clinics. However, we are preparing them for careers lasting 30-50 years. Thus, we also must help them prepare for their futures...
March 15, 2018: Veterinary Parasitology
Guo-Hua Liu, Long-Xian Zhang, Feng-Cai Zou, Zi-Guo Yuan, Guang-Hui Zhao, Min Hu, Xun Suo, Xing-Quan Zhu
China has made significant achievements in social-economic development in the last three decades, and the numbers of livestock and companion animals are rapidly increasing. Some advances have been made in the control and prevention of animal parasitic diseases, but there are still some significant challenges, particularly in relation to foodborne parasitic zoonoses and vector-borne diseases. In addition, new molecular (e.g., genomic and transcriptomic) technologies have been developed and are gradually being introduced into the veterinary parasitology field...
March 15, 2018: Veterinary Parasitology
Huan Liu, Gang Wang, Wei Li, Xingzhong Liu, Erwei Li, Wen-Bing Yin
Trichoderma hypoxylon is a fungicolous species which produces rich secondary metabolites. However, no genetic transformation method is available for further studies. Here, we developed a marker-less transformation system based on the complementation of an uridine/uracil biosynthetic gene by protoplast transformation. An uridine/uracil auxotrophic mutant of Δthpyr4 was obtained by using a positive screening protocol with 5'-fluoroorotic acid as a selective reagent. To improve the homologous integration rates, the orthologues of ku70 and lig4 which play critical roles in non-homologous end-joining recombination were disrupted...
March 19, 2018: Microbiology
Muriel W Lambert
Nonerythroid αII-spectrin is a structural protein whose roles in the nucleus have just begun to be explored. αII-spectrin is an important component of the nucleoskelelton and has both structural and non-structural functions. Its best known role is in repair of DNA ICLs both in genomic and telomeric DNA. αII-spectrin aids in the recruitment of repair proteins to sites of damage and a proposed mechanism of action is presented. It interacts with a number of different groups of proteins in the nucleus, indicating it has roles in additional cellular functions...
March 2018: Experimental Biology and Medicine
Peter J Turnbaugh
Although the importance of human genetic polymorphisms in therapeutic outcomes is well established, the role of specific genotypic or copy number variants in our "second genome" (the microbiome) has been largely overlooked. In this Perspective, I will discuss three major barriers to integrating metagenomics into pharmacology, highlighting ongoing research by us and others that has begun to shed light on the mechanisms that link the human microbiome to the efficacy and toxicity of small-molecule and biological therapies...
March 2018: MSystems
Linda Wegley Kelly, Andreas F Haas, Craig E Nelson
Over the past 2 decades, molecular techniques have established the critical role of both free-living and host-associated microbial partnerships in the environment. Advancing research to link microbial community dynamics simultaneously to host physiology and ecosystem biogeochemistry is required to broaden our understanding of the ecological roles of environmental microbes. Studies on coral reefs are actively integrating these data streams at multiple levels, from the symbiotic habitat of the coral holobiont to microbially mediated interactions between corals and algae to the effects of these interactions on the microbial community structure, metabolism, and organic geochemistry of the reef ecosystem...
March 2018: MSystems
Levi Waldron
The Waldron lab for computational biostatistics bridges the areas of cancer genomics and microbiome studies for public health, developing methods to exploit publicly available data resources and to integrate -omics studies.
March 2018: MSystems
Nicola Segata
Metagenomics has transformed microbiology, but its potential has not been fully expressed yet. From computational methods for digging deeper into metagenomes to study designs for addressing specific hypotheses, the Segata Lab is pursuing an integrative metagenomic approach to describe and model human-associated microbial communities as collections of strains. Linking strain variants to host phenotypes and performing cultivation-free population genomics require large cohorts and meta-analysis strategies to synthesize available cohorts but can revolutionize our understanding of the personalized host-microbiome interface which is at the base of human health...
March 2018: MSystems
Xiangchun Li, Weiqi Xu, Wei Kang, Sunny H Wong, Mengyao Wang, Yong Zhou, Xiaodong Fang, Xiuqing Zhang, Huanming Yang, Chi H Wong, Ka F To, Stephen L Chan, Matthew T V Chan, Joseph J Y Sung, William K K Wu, Jun Yu
Objective: Hepatocellular carcinoma (HCC) is a highly heterogeneous disease with a dismal prognosis. However, driver genes and prognostic markers in HCC remain to be identified. It is hoped that in-depth analysis of HCC genomes in relation to available clinicopathological information will give rise to novel molecular prognostic markers. Methods: We collected genomic data of 1,061 HCC patients from previous studies, and performed integrative analysis to identify significantly mutated genes and molecular prognosticators...
2018: Theranostics
V S Sundar, Chun-Chieh Fan, Dominic Holland, Anders M Dale
With the availability of high-throughput sequencing data, identification of genetic causal variants accurately requires the efficient incorporation of function annotation data into the optimization routine. This motivates the need for development of novel methods for genome wide association studies with special focus on fine-mapping capabilities. A penalty function method that is simple to implement and capable of integrating functional annotation information into the estimation procedure, is proposed in this work...
2018: Frontiers in Genetics
Carmela R Guadagno, Brent E Ewers, Cynthia Weinig
A growing body of evidence demonstrates a significant relationship between cellular redox state and circadian rhythms. Each day these two vital components of plant biology influence one another, dictating the pace for metabolism and physiology. Diverse environmental stressors can disrupt this condition and, although plant scientists have made significant progress in re-constructing functional networks of plant stress responses, stress impacts on the clock-redox crosstalk is poorly understood. Inter-connected phenomena such as redox state and metabolism, internal and external environments, cellular homeostasis and rhythms can impede predictive understanding of coordinated regulation of plant stress response...
2018: Frontiers in Plant Science
Achal Rastogi, Uma Maheswari, Richard G Dorrell, Fabio Rocha Jimenez Vieira, Florian Maumus, Adam Kustka, James McCarthy, Andy E Allen, Paul Kersey, Chris Bowler, Leila Tirichine
Diatoms are one of the most successful and ecologically important groups of eukaryotic phytoplankton in the modern ocean. Deciphering their genomes is a key step towards better understanding of their biological innovations, evolutionary origins, and ecological underpinnings. Here, we have used 90 RNA-Seq datasets from different growth conditions combined with published expressed sequence tags and protein sequences from multiple taxa to explore the genome of the model diatom Phaeodactylum tricornutum, and introduce 1,489 novel genes...
March 19, 2018: Scientific Reports
M Charpentier, A H Y Khedher, S Menoret, A Brion, K Lamribet, E Dardillac, C Boix, L Perrouault, L Tesson, S Geny, A De Cian, J M Itier, I Anegon, B Lopez, C Giovannangeli, J P Concordet
In genome editing with CRISPR-Cas9, transgene integration often remains challenging. Here, we present an approach for increasing the efficiency of transgene integration by homology-dependent repair (HDR). CtIP, a key protein in early steps of homologous recombination, is fused to Cas9 and stimulates transgene integration by HDR at the human AAVS1 safe harbor locus. A minimal N-terminal fragment of CtIP, designated HE for HDR enhancer, is sufficient to stimulate HDR and this depends on CDK phosphorylation sites and the multimerization domain essential for CtIP activity in homologous recombination...
March 19, 2018: Nature Communications
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