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https://www.readbyqxmd.com/read/30104352/archaeogenomic-evidence-from-the-southwestern-us-points-to-a-pre-hispanic-scarlet-macaw-breeding-colony
#1
Richard J George, Stephen Plog, Adam S Watson, Kari L Schmidt, Brendan J Culleton, Thomas K Harper, Patricia A Gilman, Steven A LeBlanc, George Amato, Peter Whiteley, Logan Kistler, Douglas J Kennett
Hundreds of scarlet macaw ( Ara macao cyanoptera ) skeletons have been recovered from archaeological contexts in the southwestern United States and northwestern Mexico (SW/NW). The location of these skeletons, >1,000 km outside their Neotropical endemic range, has suggested a far-reaching Pre-Hispanic acquisition network. Clear evidence for scarlet macaw breeding within this network is only known from the settlement of Paquimé in NW dating between 1250 and 1450 CE. Although some scholars have speculated on the probable existence of earlier breeding centers in the SW/NW region, there has been no supporting evidence...
August 13, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/30038396/gene-discovery-and-polygenic-prediction-from-a-genome-wide-association-study-of-educational-attainment-in-1-1-million-individuals
#2
James J Lee, Robbee Wedow, Aysu Okbay, Edward Kong, Omeed Maghzian, Meghan Zacher, Tuan Anh Nguyen-Viet, Peter Bowers, Julia Sidorenko, Richard Karlsson Linnér, Mark Alan Fontana, Tushar Kundu, Chanwook Lee, Hui Li, Ruoxi Li, Rebecca Royer, Pascal N Timshel, Raymond K Walters, Emily A Willoughby, Loïc Yengo, Maris Alver, Yanchun Bao, David W Clark, Felix R Day, Nicholas A Furlotte, Peter K Joshi, Kathryn E Kemper, Aaron Kleinman, Claudia Langenberg, Reedik Mägi, Joey W Trampush, Shefali Setia Verma, Yang Wu, Max Lam, Jing Hua Zhao, Zhili Zheng, Jason D Boardman, Harry Campbell, Jeremy Freese, Kathleen Mullan Harris, Caroline Hayward, Pamela Herd, Meena Kumari, Todd Lencz, Jian'an Luan, Anil K Malhotra, Andres Metspalu, Lili Milani, Ken K Ong, John R B Perry, David J Porteous, Marylyn D Ritchie, Melissa C Smart, Blair H Smith, Joyce Y Tung, Nicholas J Wareham, James F Wilson, Jonathan P Beauchamp, Dalton C Conley, Tõnu Esko, Steven F Lehrer, Patrik K E Magnusson, Sven Oskarsson, Tune H Pers, Matthew R Robinson, Kevin Thom, Chelsea Watson, Christopher F Chabris, Michelle N Meyer, David I Laibson, Jian Yang, Magnus Johannesson, Philipp D Koellinger, Patrick Turley, Peter M Visscher, Daniel J Benjamin, David Cesarini
Here we conducted a large-scale genetic association analysis of educational attainment in a sample of approximately 1.1 million individuals and identify 1,271 independent genome-wide-significant SNPs. For the SNPs taken together, we found evidence of heterogeneous effects across environments. The SNPs implicate genes involved in brain-development processes and neuron-to-neuron communication. In a separate analysis of the X chromosome, we identify 10 independent genome-wide-significant SNPs and estimate a SNP heritability of around 0...
August 2018: Nature Genetics
https://www.readbyqxmd.com/read/30010810/genome-wide-sequence-analysis-of-kaposi-s-sarcoma-associated-herpesvirus-shows-diversification-driven-by-recombination
#3
Neneh Sallah, Anne L Palser, Simon J Watson, Nazzarena Labo, Gershim Asiki, Vickie Marshall, Robert Newton, Denise Whitby, Paul Kellam, Inês Barroso
Background: Kaposi's Sarcoma-associated herpesvirus (KSHV) establishes lifelong infection in the human host and has been associated with a variety of malignancies. KSHV displays striking geographic variation in prevalence, which is highest in sub-Saharan Africa. The current KSHV genomes sequences available are all tumour cell line-derived or primary tumour associated viruses, which have provided valuable insights into KSHV genetic diversity. Methods: Here, we sequenced 45 KSHV genomes from a Ugandan population cohort in which KSHV is endemic; these are the only genome sequences obtained from non-diseased individuals and of KSHV DNA isolated from saliva...
July 14, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/30005805/a-closely-related-clade-of-globally-distributed-bloom-forming-cyanobacteria-within-the-nostocales
#4
Connor B Driscoll, Kevin A Meyer, Sigitas Šulčius, Nathan M Brown, Gregory J Dick, Huansheng Cao, Giedrius Gasiūnas, Albertas Timinskas, Yanbin Yin, Zachary C Landry, Timothy G Otten, Timothy W Davis, Susan B Watson, Theo W Dreher
In order to better understand the relationships among current Nostocales cyanobacterial blooms, eight genomes were sequenced from cultured isolates or from environmental metagenomes of recent planktonic Nostocales blooms. Phylogenomic analysis of publicly available sequences placed the new genomes among a group of 15 genomes from four continents in a distinct ADA clade (Anabaena/Dolichospermum/Aphanizomenon) within the Nostocales. This clade contains four species-level groups, two of which include members with both Anabaena-like and Aphanizomenon flos-aquae-like morphology...
July 2018: Harmful Algae
https://www.readbyqxmd.com/read/29988158/genomic-signatures-of-mitonuclear-coevolution-across-populations-of-tigriopus-californicus
#5
Felipe S Barreto, Eric T Watson, Thiago G Lima, Christopher S Willett, Suzanne Edmands, Weizhong Li, Ronald S Burton
The copepod Tigriopus californicus shows extensive population divergence and is becoming a model for understanding allopatric differentiation and the early stages of speciation. Here, we report a high-quality reference genome for one population (~190 megabases across 12 scaffolds, and ~15,500 protein-coding genes). Comparison with other arthropods reveals 2,526 genes presumed to be specific to T. californicus, with an apparent proliferation of genes involved in ion transport and receptor activity. Beyond the reference population, we report re-sequenced genomes of seven additional populations, spanning the continuum of reproductive isolation...
August 2018: Nature Ecology & Evolution
https://www.readbyqxmd.com/read/29979968/enhanced-bacterial-immunity-and-mammalian-genome-editing-via-rna-polymerase-mediated-dislodging-of-cas9-from-double-strand-dna-breaks
#6
Ryan Clarke, Robert Heler, Matthew S MacDougall, Nan Cher Yeo, Alejandro Chavez, Maureen Regan, Leslyn Hanakahi, George M Church, Luciano A Marraffini, Bradley J Merrill
The ability to target the Cas9 nuclease to DNA sequences via Watson-Crick base pairing with a single guide RNA (sgRNA) has provided a dynamic tool for genome editing and an essential component of adaptive immune systems in bacteria. After generating a double-stranded break (DSB), Cas9 remains stably bound to DNA. Here, we show persistent Cas9 binding blocks access to the DSB by repair enzymes, reducing genome editing efficiency. Cas9 can be dislodged by translocating RNA polymerases, but only if the polymerase approaches from one direction toward the Cas9-DSB complex...
July 5, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29979736/gene-expression-assay-and-watson-for-oncology-for-optimization-of-treatment-in-er-positive-her2-negative-breast-cancer
#7
Yun Yeong Kim, Se Jeong Oh, Yong Soon Chun, Woon Kee Lee, Heung Kyu Park
BACKGROUND: Personalized treatment for cancer patients is a hot topic of debate, particularly the decision to initiate chemotherapy in patients with Estrogen receptor (ER)-positive, HER2-negative tumors in the early stages of breast cancer (BC). Owing to significant advancements in information technology (IT) and genomics, clinicians are increasingly attaining therapeutic goals rapidly and safely by effectively differentiating patient subsets that require chemotherapy. IBM Watson for Oncology (WFO) is a cognitive computing system employed by clinicians to provide evidence-based treatment options for cancer...
2018: PloS One
https://www.readbyqxmd.com/read/29934293/mechanism-of-aptx-nicked-dna-sensing-and-pleiotropic-inactivation-in-neurodegenerative-disease
#8
Percy Tumbale, Matthew J Schellenberg, Geoffrey A Mueller, Emma Fairweather, Mandy Watson, Jessica N Little, Juno Krahn, Ian Waddell, Robert E London, R Scott Williams
The failure of DNA ligases to complete their catalytic reactions generates cytotoxic adenylated DNA strand breaks. The APTX RNA-DNA deadenylase protects genome integrity and corrects abortive DNA ligation arising during ribonucleotide excision repair and base excision DNA repair, and APTX human mutations cause the neurodegenerative disorder ataxia with oculomotor ataxia 1 (AOA1). How APTX senses cognate DNA nicks and is inactivated in AOA1 remains incompletely defined. Here, we report X-ray structures of APTX engaging nicked RNA-DNA substrates that provide direct evidence for a wedge-pivot-cut strategy for 5'-AMP resolution shared with the alternate 5'-AMP processing enzymes POLβ and FEN1...
July 13, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29928300/genotyping-by-sequencing-of-genome-wide-microsatellite-loci-reveals-fine-scale-harvest-composition-in-a-coastal-atlantic-salmon-fishery
#9
Ian R Bradbury, Brendan F Wringe, Beth Watson, Ian Paterson, John Horne, Robert Beiko, Sarah J Lehnert, Marie Clément, Eric C Anderson, Nicholas W Jeffery, Steven Duffy, Emma Sylvester, Martha Robertson, Paul Bentzen
Individual assignment and genetic mixture analysis are commonly utilized in contemporary wildlife and fisheries management. Although microsatellite loci provide unparalleled numbers of alleles per locus, their use in assignment applications is increasingly limited. However, next-generation sequencing, in conjunction with novel bioinformatic tools, allows large numbers of microsatellite loci to be simultaneously genotyped, presenting new opportunities for individual assignment and genetic mixture analysis. Here, we scanned the published Atlantic salmon genome to identify 706 microsatellite loci, from which we developed a final panel of 101 microsatellites distributed across the genome (average 3...
July 2018: Evolutionary Applications
https://www.readbyqxmd.com/read/29899538/assigning-biological-function-using-hidden-signatures-in-cystine-stabilized-peptide-sequences
#10
S M Ashiqul Islam, Christopher Michel Kearney, Erich J Baker
Cystine-stabilized peptides have great utility as they naturally block ion channels, inhibit acetylcholine receptors, or inactivate microbes. However, only a tiny fraction of these peptides has been characterized. Exploration for novel peptides most efficiently starts with the identification of candidates from genome sequence data. Unfortunately, though cystine-stabilized peptides have shared structures, they have low DNA sequence similarity, restricting the utility of BLAST and even more powerful sequence alignment-based annotation algorithms, such as PSI-BLAST and HMMER...
June 13, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29880023/hundreds-of-novel-composite-genes-and-chimeric-genes-with-bacterial-origins-contributed-to-haloarchaeal-evolution
#11
Raphaël Méheust, Andrew K Watson, François-Joseph Lapointe, R Thane Papke, Philippe Lopez, Eric Bapteste
BACKGROUND: Haloarchaea, a major group of archaea, are able to metabolize sugars and to live in oxygenated salty environments. Their physiology and lifestyle strongly contrast with that of their archaeal ancestors. Amino acid optimizations, which lowered the isoelectric point of haloarchaeal proteins, and abundant lateral gene transfers from bacteria have been invoked to explain this deep evolutionary transition. We use network analyses to show that the evolution of novel genes exclusive to Haloarchaea also contributed to the evolution of this group...
June 7, 2018: Genome Biology
https://www.readbyqxmd.com/read/29878652/genotypes-phenotypes-and-whole-genome-sequence-approaches-from-the-my-life-our-future-haemophilia-project
#12
REVIEW
B A Konkle, J M Johnsen, M Wheeler, C Watson, M Skinner, G F Pierce
INTRODUCTION: Information from the genes encoding factor VIII (F8) and IX (F9) is used in reproductive planning and to inform inhibitor formation, bleeding severity and response to therapies. Advances in technology and our understanding of the human genome now allows more comprehensive methods to study genomic variation and its impact on haemophilia. AIMS: The My Life Our Future (MLOF) programme was begun in 2012 to provide genetic analysis and to expand research in haemophilia through a research repository...
May 2018: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/29875251/divergent-human-origin-influenza-viruses-detected-in-australian-swine-populations
#13
Frank Y K Wong, Celeste Donato, Yi-Mo Deng, Don Teng, Naomi Komadina, Chantal Baas, Joyanta Modak, Mark O'Dea, David W Smith, Paul V Effler, Julie Cooke, Kelly R Davies, Aeron Hurt, Nina Kung, Avram Levy, Richmond Loh, Songhua Shan, Mustaghfira W Shinwari, Vittoria Stevens, Joanne Taylor, David T Williams, James Watson, Debbie Eagles, Sam McCullough, Ian G Barr, Vijaykrishna Dhanasekaran
Global swine populations infected with influenza A viruses pose a persistent pandemic risk. With the exception of a few countries, our understanding of the genetic diversity of swine influenza viruses is limited, hampering control measures and pandemic risk assessment. Here we report the genomic characteristics and evolutionary history of influenza A viruses isolated in Australia during 2012-2016 from two geographically isolated swine populations in the states of Queensland and Western Australia. Phylogenetic analysis with an expansive human and swine influenza virus dataset comprising >40,000 sequences sampled globally, revealed evidence of the pervasive introduction and long-term establishment of gene segments derived from several human influenza viruses of past seasons, including H1N1/1977, H1N1/1995, H3N2/1968, H3N2/2003, and H1N1pdm09, and a genotype that contained gene segments derived from the past three pandemics (1968, re-emerged 1977 and 2009)...
June 6, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29875240/-in-vivo-knock-down-of-the-hsv-1-latency-associated-transcript-reduces-reactivation-from-latency
#14
Zachary L Watson, Shannan D Washington, Dane M Phelan, Alfred S Lewin, Sonal S Tuli, Gregory S Schultz, Donna M Neumann, David C Bloom
During Herpes Simplex Virus (HSV) latency, most viral genes are silenced with the exception of one region of the genome encoding the latency-associated transcript (LAT). This long non-coding RNA was originally described as having a role in enhancing HSV-1 reactivation. However, subsequent evidence showing that the LAT blocked apoptosis and promoted efficient establishment of latency suggested that its effects on reactivation were secondary to establishment. Here, we utilize an Adeno-associated Virus (AAV) vector to deliver a LAT-targeting hammerhead ribozyme to HSV-1-infected neurons of rabbits after the establishment of HSV-1 latency...
June 6, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29869540/gene-therapy-for-osteoarthritis-pharmacokinetics-of-intra-articular-self-complementary-adeno-associated-virus-interleukin-1-receptor-antagonist-delivery-in-an-equine-model
#15
Rachael S Watson Levings, Ted A Broome, Andrew D Smith, Brett L Rice, Eric P Gibbs, David A Myara, E Viktoria Hyddmark, Elham Nasri, Ali Zarezadeh, Padraic P Levings, Yuan Lu, Margaret E White, E Anthony Dacanay, Gregory B Foremny, Christopher H Evans, Alison J Morton, Mathew Winter, Michael J Dark, David M Nickerson, Patrick T Colahan, Steven C Ghivizzani
Toward the treatment of osteoarthritis (OA), the authors have been investigating self-complementary adeno-associated virus (scAAV) for intra-articular delivery of therapeutic gene products. As OA frequently affects weight-bearing joints, pharmacokinetic studies of scAAV gene delivery were performed in the joints of the equine forelimb to identify parameters relevant to clinical translation in humans. Using interleukin-1 receptor antagonist (IL-1Ra) as a secreted therapeutic reporter, scAAV vector plasmids containing codon-optimized cDNA for equine IL-1Ra (eqIL-1Ra) were generated, which produced eqIL-1Ra at levels 30- to 50-fold higher than the native sequence...
June 2018: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/29869535/self-complementary-adeno-associated-virus-mediated-interleukin-1-receptor-antagonist-gene-delivery-for-the-treatment-of-osteoarthritis-test-of-efficacy-in-an-equine-model
#16
Rachael S Watson Levings, Andrew D Smith, Ted A Broome, Brett L Rice, Eric P Gibbs, David A Myara, E Viktoria Hyddmark, Elham Nasri, Ali Zarezadeh, Padraic P Levings, Yuan Lu, Margaret E White, E Anthony Dacanay, Gregory B Foremny, Christopher H Evans, Alison J Morton, Mathew Winter, Michael J Dark, David M Nickerson, Patrick T Colahan, Steven C Ghivizzani
The authors are investigating self-complementary adeno-associated virus (scAAV) as a vector for intra-articular gene-delivery of interleukin-1 receptor antagonist (IL-1Ra), and its therapeutic capacity in the treatment of osteoarthritis (OA). To model gene transfer on a scale proportional to the human knee, a frequent site of OA incidence, studies were focused on the joints of the equine forelimb. Using AAV2.5 capsid and equine IL-1Ra as a homologous transgene, a functional ceiling dose of ∼5 × 1012 viral genomes was previously identified, which elevated the steady state levels of eqIL-1Ra in synovial fluids by >40-fold over endogenous production for at least 6 months...
June 2018: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/29802345/identification-of-rare-de-novo-epigenetic-variations-in-congenital-disorders
#17
Mafalda Barbosa, Ricky S Joshi, Paras Garg, Alejandro Martin-Trujillo, Nihir Patel, Bharati Jadhav, Corey T Watson, William Gibson, Kelsey Chetnik, Chloe Tessereau, Hui Mei, Silvia De Rubeis, Jennifer Reichert, Fatima Lopes, Lisenka E L M Vissers, Tjitske Kleefstra, Dorothy E Grice, Lisa Edelmann, Gabriela Soares, Patricia Maciel, Han G Brunner, Joseph D Buxbaum, Bruce D Gelb, Andrew J Sharp
Certain human traits such as neurodevelopmental disorders (NDs) and congenital anomalies (CAs) are believed to be primarily genetic in origin. However, even after whole-genome sequencing (WGS), a substantial fraction of such disorders remain unexplained. We hypothesize that some cases of ND-CA are caused by aberrant DNA methylation leading to dysregulated genome function. Comparing DNA methylation profiles from 489 individuals with ND-CAs against 1534 controls, we identify epivariations as a frequent occurrence in the human genome...
May 25, 2018: Nature Communications
https://www.readbyqxmd.com/read/29788473/enhancing-psychosis-spectrum-nosology-through-an-international-data-sharing-initiative
#18
Anna R Docherty, Eduardo Fonseca-Pedrero, Martin Debbané, Raymond C K Chan, Richard J Linscott, Katherine G Jonas, David C Cicero, Melissa J Green, Leonard J Simms, Oliver Mason, David Watson, Ulrich Ettinger, Monika Waszczuk, Alexander Rapp, Phillip Grant, Roman Kotov, Colin G DeYoung, Camilo J Ruggero, Nicolas R Eaton, Robert F Krueger, Christopher Patrick, Christopher Hopwood, F Anthony O'Neill, David H Zald, Christopher C Conway, Daniel E Adkins, Irwin D Waldman, Jim van Os, Patrick F Sullivan, John S Anderson, Andrey A Shabalin, Scott R Sponheim, Stephan F Taylor, Rachel G Grazioplene, Silviu A Bacanu, Tim B Bigdeli, Corinna Haenschel, Dolores Malaspina, Diane C Gooding, Kristin Nicodemus, Frauke Schultze-Lutter, Neus Barrantes-Vidal, Christine Mohr, William T Carpenter, Alex S Cohen
The latent structure of schizotypy and psychosis-spectrum symptoms remains poorly understood. Furthermore, molecular genetic substrates are poorly defined, largely due to the substantial resources required to collect rich phenotypic data across diverse populations. Sample sizes of phenotypic studies are often insufficient for advanced structural equation modeling approaches. In the last 50 years, efforts in both psychiatry and psychological science have moved toward (1) a dimensional model of psychopathology (eg, the current Hierarchical Taxonomy of Psychopathology [HiTOP] initiative), (2) an integration of methods and measures across traits and units of analysis (eg, the RDoC initiative), and (3) powerful, impactful study designs maximizing sample size to detect subtle genomic variation relating to complex traits (the Psychiatric Genomics Consortium [PGC])...
May 16, 2018: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/29784784/uncovering-universal-rules-governing-the-selectivity-of-the-archetypal-dna-glycosylase-tdg
#19
Thomas Dodd, Chunli Yan, Bradley R Kossmann, Kurt Martin, Ivaylo Ivanov
Thymine DNA glycosylase (TDG) is a pivotal enzyme with dual roles in both genome maintenance and epigenetic regulation. TDG is involved in cytosine demethylation at CpG sites in DNA. Here we have used molecular modeling to delineate the lesion search and DNA base interrogation mechanisms of TDG. First, we examined the capacity of TDG to interrogate not only DNA substrates with 5-carboxyl cytosine modifications but also G:T mismatches and nonmismatched (A:T) base pairs using classical and accelerated molecular dynamics...
June 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29718337/quadruplexes-in-dicty-crystal-structure-of-a-four-quartet-g-quadruplex-formed-by-g-rich-motif-found-in-the-dictyostelium-discoideum-genome
#20
Aurore Guédin, Linda Yingqi Lin, Samir Armane, Laurent Lacroix, Jean-Louis Mergny, Stéphane Thore, Liliya A Yatsunyk
Guanine-rich DNA has the potential to fold into non-canonical G-quadruplex (G4) structures. Analysis of the genome of the social amoeba Dictyostelium discoideum indicates a low number of sequences with G4-forming potential (249-1055). Therefore, D. discoideum is a perfect model organism to investigate the relationship between the presence of G4s and their biological functions. As a first step in this investigation, we crystallized the dGGGGGAGGGGTACAGGGGTACAGGGG sequence from the putative promoter region of two divergent genes in D...
June 1, 2018: Nucleic Acids Research
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