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Functional genomics

Héctor Cervera, Silvia Ambrós, Guillermo P Bernet, Guillermo Rodrigo, Santiago F Elena
Determining the fitness of viral genotypes has become a standard practice in virology as it is essential to evaluate their evolutionary potential. Darwinian fitness, defined as the advantage of a given genotype with respect to a reference, is a complex property that captures, in a single figure, differences in performance at every stage of viral infection. To what extent does viral fitness result from specific molecular interactions with host factors and regulatory networks during infection? Can we identify host genes in functional classes whose expression depends on viral fitness? Here, we compared the transcriptomes of tobacco plants infected with seven genotypes of tobacco etch potyvirus (TEV) that differ in fitness...
March 19, 2018: Molecular Biology and Evolution
Sora Yoon, Hai C T Nguyen, Yun J Yoo, Jinhwan Kim, Bukyung Baik, Sounkou Kim, Jin Kim, Sangsoo Kim, Dougu Nam
Pathway-based analysis in genome-wide association study (GWAS) is being widely used to uncover novel multi-genic functional associations. Many of these pathway-based methods have been used to test the enrichment of the associated genes in the pathways, but exhibited low powers and were highly affected by free parameters. We present the novel method and software GSA-SNP2 for pathway enrichment analysis of GWAS P-value data. GSA-SNP2 provides high power, decent type I error control and fast computation by incorporating the random set model and SNP-count adjusted gene score...
March 19, 2018: Nucleic Acids Research
Joel A Boyd, Ben J Woodcroft, Gene W Tyson
Large-scale metagenomic datasets enable the recovery of hundreds of population genomes from environmental samples. However, these genomes do not typically represent the full diversity of complex microbial communities. Gene-centric approaches can be used to gain a comprehensive view of diversity by examining each read independently, but traditional pairwise comparison approaches typically over-classify taxonomy and scale poorly with increasing metagenome and database sizes. Here we introduce GraftM, a tool that uses gene specific packages to rapidly identify gene families in metagenomic data using hidden Markov models (HMMs) or DIAMOND databases, and classifies these sequences using placement into pre-constructed gene trees...
March 19, 2018: Nucleic Acids Research
Graham M Hughes, Emma M Boston, John A Finarelli, William J Murphy, Desmond G Higgins, Emma C Teeling
The olfactory receptor (OR) gene families, which govern mammalian olfaction, have undergone extensive expansion and contraction through duplication and pseudogenization. Previous studies have shown that broadly-defined environmental adaptations (e.g terrestrial vs aquatic) are correlated with the number of functional and non-functional OR genes retained. However, to date, no study has examined species-specific gene duplications in multiple phylogenetically divergent mammals to elucidate OR evolution and adaptation...
March 19, 2018: Molecular Biology and Evolution
R A Leo Elworth, Chabrielle Allen, Travis Benedict, Peter Dulworth, Luay Nakhleh
Summary: The evolutionary histories of individual regions across a genomic alignment - called 'local genealogies' - can differ from each other, due to processes such as recombination. Elucidating and analyzing these local genealogies are important for a large number of inference tasks, including those pertaining to species phylogenies, evolutionary processes, and trait mapping. In this paper, we present a toolkit for automated local phylogenomic analyses, or ALPHA. The purpose of this toolkit is to provide a wide array of functionalities for automated inference of local genealogies as well as analyses based on these local genealogies...
March 19, 2018: Bioinformatics
Paul D Blischak, Julia Chifman, Andrea D Wolfe, Laura S Kubatko
The analysis of hybridization and gene flow among closely related taxa is a common goal for researchers studying speciation and phylogeography. Many methods for hybridization detection use simple site pattern frequencies from observed genomic data and compare them to null models that predict an absence of gene flow. The theory underlying the detection of hybridization using these site pattern probabilities exploits the relationship between the coalescent process for gene trees within population trees and the process of mutation along the branches of the gene trees...
March 19, 2018: Systematic Biology
Patrick J Short, Jeremy F McRae, Giuseppe Gallone, Alejandro Sifrim, Hyejung Won, Daniel H Geschwind, Caroline F Wright, Helen V Firth, David R FitzPatrick, Jeffrey C Barrett, Matthew E Hurles
We previously estimated that 42% of patients with severe developmental disorders carry pathogenic de novo mutations in coding sequences. The role of de novo mutations in regulatory elements affecting genes associated with developmental disorders, or other genes, has been essentially unexplored. We identified de novo mutations in three classes of putative regulatory elements in almost 8,000 patients with developmental disorders. Here we show that de novo mutations in highly evolutionarily conserved fetal brain-active elements are significantly and specifically enriched in neurodevelopmental disorders...
March 21, 2018: Nature
Suraiya Haroon, Annie Li, Jaye L Weinert, Clark Fritsch, Nolan G Ericson, Jasmine Alexander-Floyd, Bart P Braeckman, Cole M Haynes, Jason H Bielas, Tali Gidalevitz, Marc Vermulst
Genetic instability of the mitochondrial genome (mtDNA) plays an important role in human aging and disease. Thus far, it has proven difficult to develop successful treatment strategies for diseases that are caused by mtDNA instability. To address this issue, we developed a model of mtDNA disease in the nematode C. elegans, an animal model that can rapidly be screened for genes and biological pathways that reduce mitochondrial pathology. These worms recapitulate all the major hallmarks of mtDNA disease in humans, including increased mtDNA instability, loss of respiration, reduced neuromuscular function, and a shortened lifespan...
March 20, 2018: Cell Reports
Kanchan Thapa, Sulochana Manandhar, Manisha Bista, Jivan Shakya, Govind Sah, Maheshwar Dhakal, Netra Sharma, Bronwyn Llewellyn, Claudia Wultsch, Lisette P Waits, Marcella J Kelly, Jean-Marc Hero, Jane Hughes, Dibesh Karmacharya
With fewer than 200 tigers (Panthera tigris tigris) left in Nepal, that are generally confined to five protected areas across the Terai Arc Landscape, genetic studies are needed to provide crucial information on diversity and connectivity for devising an effective country-wide tiger conservation strategy. As part of the Nepal Tiger Genome Project, we studied landscape change, genetic variation, population structure, and gene flow of tigers across the Terai Arc Landscape by conducting Nepal's first comprehensive and systematic scat-based, non-invasive genetic survey...
2018: PloS One
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
Songzhen He, Xiaoling Tong, Minjin Han, Yanmin Bai, Fangyin Dai
The tyrosine kinases (TKs) are important parts of metazoan signaling pathways and play significant roles in cell growth, development, apoptosis and disease. Genome-wide characterization of TKs has been conducted in many metazoans, however, systematic information about this family in Lepidoptera is still lacking. We retrieved 33 TK-encoding genes in silkworm and classified them into 25 subfamilies by sequence analysis, without members in AXL, FRK, PDGFR, STYK1 and TIE subfamilies. Although domain sequences in each subfamily are conserved, TKs in vertebrates tend to be remarkably conserved and stable...
March 21, 2018: International Journal of Molecular Sciences
Ayako Casanova-Nakayama, Elena Wernicke von Siebenthal, Christian Kropf, Elisabeth Oldenberg, Helmut Segner
Genomic actions of estrogens in vertebrates are exerted via two intracellular estrogen receptor (ER) subtypes, ERα and ERβ, which show cell- and tissue-specific expression profiles. Mammalian immune cells express ERs and are responsive to estrogens. More recently, evidence became available that ERs are also present in the immune organs and cells of teleost fish, suggesting that the immunomodulatory function of estrogens has been conserved throughout vertebrate evolution. For a better understanding of the sensitivity and the responsiveness of the fish immune system to estrogens, more insight is needed on the abundance of ERs in the fish immune system, the cellular ratios of the ER subtypes, and their autoregulation by estrogens...
March 21, 2018: International Journal of Molecular Sciences
Leonardo C de Oliveira, Bruno S A F Brasil, Bethany Unger, Giliane S Trindade, Jonatas S Abrahão, Erna G Kroon, Paula Traktman, Cláudio A Bonjardim
Evolution has equipped poxvirus genomes with the coding capacity for several virus-host interaction products which interfere with host cell gene expression and protein function, creating an adequate intracellular environment for a productive infection. We show here that Vaccinia virus (VACV) induces the expression of the cellular transcription factor EGR-1 (early growth response-1) in Mouse Embryonic Fibroblasts (MEFs) through the MEK (mitogen-activated protein kinase (MAPK)/ERK)/ERK (extracellular signal-regulated kinases) pathway, from 3 to 12 h post infection (h...
March 21, 2018: Viruses
Kathy H Y Shair, Akhil Reddy, Vaughn S Cooper
Latent membrane protein 1 (LMP1) is an Epstein-Barr virus (EBV) oncogenic protein that has no intrinsic enzymatic activity or sequence homology to cellular or viral proteins. The oncogenic potential of LMP1 has been ascribed to pleiotropic signaling properties initiated through protein-protein interactions in cytosolic membrane compartments, but the effects of LMP1 extend to nuclear and extracellular processes. Although LMP1 is one of the latent genes required for EBV-immortalization of B cells, the biology of LMP1 in the pathogenesis of the epithelial cancer nasopharyngeal carcinoma (NPC) is more complex...
March 21, 2018: Cancers
Christiana Leimena, Hongyu Qiu
Hypertension is a complex, multifactorial disease that involves the coexistence of multiple risk factors, environmental factors and physiological systems. The complexities extend to the treatment and management of hypertension, which are still the pursuit of many researchers. In the last two decades, various genes have emerged as possible biomarkers and have become the target for investigations of specialized drug design based on its risk factors and the primary cause. Owing to the growing technology of microarrays and next-generation sequencing, the non-protein-coding RNAs (ncRNAs) have increasingly gained attention, and their status of redundancy has flipped to importance in normal cellular processes, as well as in disease progression...
March 21, 2018: International Journal of Molecular Sciences
Francois Dussart, Ryan Douglas, Elisabet Sjökvist, Peter N Hoebe, Steven H Spoel, Graham R D McGrann
Ramularia collo-cygni (Rcc) causes Ramularia leaf spot (RLS) disease of barley. The fungus develops asymptomatically within its host until late in the growing season when necrotic lesions become visible on upper leaves. Fungal secondary metabolites (SMs) have been proposed as important factors in RLS lesion formation, but the biosynthetic pathways involved remain largely unknown. Mining the Rcc genome revealed the presence of ten polyketide synthases (PKSs), ten non-ribosomal peptide synthetases (NRPSs) and three hybrid PKS-NRPS (HPSs) identified within clusters of genes with predicted functions associated with secondary metabolism...
March 21, 2018: Molecular Plant-microbe Interactions: MPMI
Lei Lei, Kesava Phaneendra Cherukuri, Uria Alcolombri, Diana Meltzer, Dan S Tawfik
Marine organisms release dimethylsulfide (DMS) via cleavage of dimethylsulfoniopropionate (DMSP). Different genes encoding proteins with DMSP lyase activity are known, yet these exhibit highly variable levels of activity. Most assigned bacterial DMSP lyases, including DddK, DddL, DddQ, DddW and DddY, appear to belong to one, cupin-like superfamily. Here, we attempted to define and map this superfamily dubbed Cupin-DLL: DMSP lyases and lyase-like. To this end, we have pursued the characterization of various recombinant DMSP lyases belonging to this superfamily of metallo-enzymes, and especially of DddY and DddL that seem to be the most active DMSP lyases in this superfamily...
March 21, 2018: Biochemistry
Sheila Sharp, Scott J Mitchell, Monique Vallée, Elena Kuzmanova, Michelle Cooper, Delia Belelli, Jeremy J Lambert, Jeffrey T-J Huang
Neurosteroids are brain-derived steroids, capable of rapidly modulating neuronal excitability in a non-genomic manner. Dysregulation of their synthesis, or metabolism has been implicated in many pathological conditions. Here, we describe an isotope dilution based targeted and non-targeted (ID-TNT) profiling of carbonyl neurosteroids/steroids. The method combines stable isotope dilution, hydroxylamine derivatization, high-resolution MS scanning and data dependent MS/MS analysis, allowing absolute quantification of pregnenolone, progesterone, 5α-dihydroprogesterone, 3α,5α-tetrahydroprogesterone and 3β,5α-tetrahydroprogesterone, and relative quantification of other carbonyl containing steroids...
March 21, 2018: Analytical Chemistry
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
Andrea Cipriano, Monica Ballarino
The completion of the human genome sequence together with advances in sequencing technologies have shifted the paradigm of the genome, as composed of discrete and hereditable coding entities, and have shown the abundance of functional noncoding DNA. This part of the genome, previously dismissed as "junk" DNA, increases proportionally with organismal complexity and contributes to gene regulation beyond the boundaries of known protein-coding genes. Different classes of functionally relevant nonprotein-coding RNAs are transcribed from noncoding DNA sequences...
2018: Frontiers in Molecular Biosciences
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