Davies R

References (7)

Title : Pharmacogenetic meta-analysis of baseline risk factors, pharmacodynamic, efficacy and tolerability endpoints from two large global cardiovascular outcomes trials for darapladib - Yeo_2017_PLoS.One_12_e0182115
Author(s) : Yeo A , Li L , Warren L , Aponte J , Fraser D , King K , Johansson K , Barnes A , Macphee C , Davies R , Chissoe S , Tarka E , O'Donoghue ML , White HD , Wallentin L , Waterworth D
Ref : PLoS ONE , 12 :e0182115 , 2017
Abstract : Darapladib, a lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor, failed to demonstrate efficacy for the primary endpoints in two large phase III cardiovascular outcomes trials, one in stable coronary heart disease patients (STABILITY) and one in acute coronary syndrome (SOLID-TIMI 52). No major safety signals were observed but tolerability issues of diarrhea and odor were common (up to 13%). We hypothesized that genetic variants associated with Lp-PLA2 activity may influence efficacy and tolerability and therefore performed a comprehensive pharmacogenetic analysis of both trials. We genotyped patients within the STABILITY and SOLID-TIMI 52 trials who provided a DNA sample and consent (n = 13,577 and 10,404 respectively, representing 86% and 82% of the trial participants) using genome-wide arrays with exome content and performed imputation using a 1000 Genomes reference panel. We investigated baseline and change from baseline in Lp-PLA2 activity, two efficacy endpoints (major coronary events and myocardial infarction) as well as tolerability parameters at genome-wide and candidate gene level using a meta-analytic approach. We replicated associations of published loci on baseline Lp-PLA2 activity (APOE, CELSR2, LPA, PLA2G7, LDLR and SCARB1) and identified three novel loci (TOMM5, FRMD5 and LPL) using the GWAS-significance threshold P<=5E-08. Review of the PLA2G7 gene (encoding Lp-PLA2) within these datasets identified V279F null allele carriers as well as three other rare exonic null alleles within various ethnic groups, however none of these variants nor any other loci associated with Lp-PLA2 activity at baseline were associated with any of the drug response endpoints. The analysis of darapladib efficacy endpoints, despite low power, identified six low frequency loci with main genotype effect (though with borderline imputation scores) and one common locus (minor allele frequency 0.24) with genotype by treatment interaction effect passing the GWAS-significance threshold. This locus conferred risk in placebo subjects, hazard ratio (HR) 1.22 with 95% confidence interval (CI) 1.11-1.33, but was protective in darapladib subjects, HR 0.79 (95% CI 0.71-0.88). No major loci for tolerability were found. Thus, genetic analysis confirmed and extended the influence of lipoprotein loci on Lp-PLA2 levels, identified some novel null alleles in the PLA2G7 gene, and only identified one potentially efficacious subgroup within these two large clinical trials.
ESTHER : Yeo_2017_PLoS.One_12_e0182115
PubMedSearch : Yeo_2017_PLoS.One_12_e0182115
PubMedID: 28753643
Gene_locus related to this paper: human-PLA2G7

Title : The genome of the protist parasite Entamoeba histolytica - Loftus_2005_Nature_433_865
Author(s) : Loftus B , Anderson I , Davies R , Alsmark UC , Samuelson J , Amedeo P , Roncaglia P , Berriman M , Hirt RP , Mann BJ , Nozaki T , Suh B , Pop M , Duchene M , Ackers J , Tannich E , Leippe M , Hofer M , Bruchhaus I , Willhoeft U , Bhattacharya A , Chillingworth T , Churcher C , Hance Z , Harris B , Harris D , Jagels K , Moule S , Mungall K , Ormond D , Squares R , Whitehead S , Quail MA , Rabbinowitsch E , Norbertczak H , Price C , Wang Z , Guillen N , Gilchrist C , Stroup SE , Bhattacharya S , Lohia A , Foster PG , Sicheritz-Ponten T , Weber C , Singh U , Mukherjee C , El-Sayed NM , Petri WA, Jr. , Clark CG , Embley TM , Barrell B , Fraser CM , Hall N
Ref : Nature , 433 :865 , 2005
Abstract : Entamoeba histolytica is an intestinal parasite and the causative agent of amoebiasis, which is a significant source of morbidity and mortality in developing countries. Here we present the genome of E. histolytica, which reveals a variety of metabolic adaptations shared with two other amitochondrial protist pathogens: Giardia lamblia and Trichomonas vaginalis. These adaptations include reduction or elimination of most mitochondrial metabolic pathways and the use of oxidative stress enzymes generally associated with anaerobic prokaryotes. Phylogenomic analysis identifies evidence for lateral gene transfer of bacterial genes into the E. histolytica genome, the effects of which centre on expanding aspects of E. histolytica's metabolic repertoire. The presence of these genes and the potential for novel metabolic pathways in E. histolytica may allow for the development of new chemotherapeutic agents. The genome encodes a large number of novel receptor kinases and contains expansions of a variety of gene families, including those associated with virulence. Additional genome features include an abundance of tandemly repeated transfer-RNA-containing arrays, which may have a structural function in the genome. Analysis of the genome provides new insights into the workings and genome evolution of a major human pathogen.
ESTHER : Loftus_2005_Nature_433_865
PubMedSearch : Loftus_2005_Nature_433_865
PubMedID: 15729342
Gene_locus related to this paper: entds-b0efg6 , entds-b0egj2 , enthi-b1n4x1 , enthi-b1n449 , enthi-b1n456 , enthi-c4lsp4 , enthi-c4lte6 , enthi-c4lu03 , enthi-c4lu54 , enthi-c4lve4 , enthi-c4lwe1 , enthi-c4m0c3 , enthi-c4m0e4 , enthi-c4m1e7 , enthi-c4m2a9 , enthi-c4m2i4 , enthi-c4m3r1 , enthi-c4m4l3 , enthi-c4m6g0 , enthi-c4m6k3 , enthi-c4m7k7 , enthi-c4m7n4 , enthi-c4m7v0 , enthi-c4m8y5 , enthi-c4m793 , enthi-c4mb48 , enthi-DPP , enthi-q50rh1 , enthi-q50ya6 , enthi-q51a37 , enthi-q51aw6 , enthi-q51ch3 , enthi-q51cz6 , enthi-q51ds3 , enthi-q513q8 , enthi-q513w3 , enthi-q519v1

Title : The genome of the social amoeba Dictyostelium discoideum - Eichinger_2005_Nature_435_43
Author(s) : Eichinger L , Pachebat JA , Glockner G , Rajandream MA , Sucgang R , Berriman M , Song J , Olsen R , Szafranski K , Xu Q , Tunggal B , Kummerfeld S , Madera M , Konfortov BA , Rivero F , Bankier AT , Lehmann R , Hamlin N , Davies R , Gaudet P , Fey P , Pilcher K , Chen G , Saunders D , Sodergren E , Davis P , Kerhornou A , Nie X , Hall N , Anjard C , Hemphill L , Bason N , Farbrother P , Desany B , Just E , Morio T , Rost R , Churcher C , Cooper J , Haydock S , van Driessche N , Cronin A , Goodhead I , Muzny D , Mourier T , Pain A , Lu M , Harper D , Lindsay R , Hauser H , James K , Quiles M , Madan Babu M , Saito T , Buchrieser C , Wardroper A , Felder M , Thangavelu M , Johnson D , Knights A , Loulseged H , Mungall K , Oliver K , Price C , Quail MA , Urushihara H , Hernandez J , Rabbinowitsch E , Steffen D , Sanders M , Ma J , Kohara Y , Sharp S , Simmonds M , Spiegler S , Tivey A , Sugano S , White B , Walker D , Woodward J , Winckler T , Tanaka Y , Shaulsky G , Schleicher M , Weinstock G , Rosenthal A , Cox EC , Chisholm RL , Gibbs R , Loomis WF , Platzer M , Kay RR , Williams J , Dear PH , Noegel AA , Barrell B , Kuspa A
Ref : Nature , 435 :43 , 2005
Abstract : The social amoebae are exceptional in their ability to alternate between unicellular and multicellular forms. Here we describe the genome of the best-studied member of this group, Dictyostelium discoideum. The gene-dense chromosomes of this organism encode approximately 12,500 predicted proteins, a high proportion of which have long, repetitive amino acid tracts. There are many genes for polyketide synthases and ABC transporters, suggesting an extensive secondary metabolism for producing and exporting small molecules. The genome is rich in complex repeats, one class of which is clustered and may serve as centromeres. Partial copies of the extrachromosomal ribosomal DNA (rDNA) element are found at the ends of each chromosome, suggesting a novel telomere structure and the use of a common mechanism to maintain both the rDNA and chromosomal termini. A proteome-based phylogeny shows that the amoebozoa diverged from the animal-fungal lineage after the plant-animal split, but Dictyostelium seems to have retained more of the diversity of the ancestral genome than have plants, animals or fungi.
ESTHER : Eichinger_2005_Nature_435_43
PubMedSearch : Eichinger_2005_Nature_435_43
PubMedID: 15875012
Gene_locus related to this paper: dicdi-abhd , dicdi-ACHE , dicdi-apra , dicdi-cinbp , dicdi-CMBL , dicdi-crysp , dicdi-DPOA , dicdi-P90528 , dicdi-ppme1 , dicdi-Q8MYE7 , dicdi-q54cf7 , dicdi-q54cl7 , dicdi-q54cm0 , dicdi-q54ct5 , dicdi-q54cu1 , dicdi-q54d54 , dicdi-q54d66 , dicdi-q54dj5 , dicdi-q54dy7 , dicdi-q54ek1 , dicdi-q54eq6 , dicdi-q54et1 , dicdi-q54et7 , dicdi-q54f01 , dicdi-q54g24 , dicdi-q54g47 , dicdi-q54gi7 , dicdi-q54gw5 , dicdi-q54gx3 , dicdi-q54h23 , dicdi-q54h73 , dicdi-q54i38 , dicdi-q54ie5 , dicdi-q54in4 , dicdi-q54kz1 , dicdi-q54l36 , dicdi-q54li1 , dicdi-q54m29 , dicdi-q54n21 , dicdi-q54n35 , dicdi-q54n85 , dicdi-q54qe7 , dicdi-q54qi3 , dicdi-q54qk2 , dicdi-q54rl3 , dicdi-q54rl8 , dicdi-q54sy6 , dicdi-q54sz3 , dicdi-q54t49 , dicdi-q54t91 , dicdi-q54th2 , dicdi-q54u01 , dicdi-q54vc2 , dicdi-q54vw1 , dicdi-q54xe3 , dicdi-q54xl3 , dicdi-q54xu1 , dicdi-q54xu2 , dicdi-q54y48 , dicdi-q54yd0 , dicdi-q54ye0 , dicdi-q54yl1 , dicdi-q54yr8 , dicdi-q54z90 , dicdi-q55bx3 , dicdi-q55d01 , dicdi-q55d81 , dicdi-q55du6 , dicdi-q55eu1 , dicdi-q55eu8 , dicdi-q55fk4 , dicdi-q55gk7 , dicdi-Q54ZA6 , dicdi-q86h82 , dicdi-Q86HC9 , dicdi-Q86HM5 , dicdi-Q86HM6 , dicdi-q86iz7 , dicdi-q86jb6 , dicdi-Q86KU7 , dicdi-q550s3 , dicdi-q552c0 , dicdi-q553t5 , dicdi-q555e5 , dicdi-q555h0 , dicdi-q555h1 , dicdi-q557k5 , dicdi-q558u2 , dicdi-Q869Q8 , dicdi-u554 , dicdi-y9086 , dicdi-q54r44 , dicdi-f172a

Title : Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus - Nierman_2005_Nature_438_1151
Author(s) : Nierman WC , Pain A , Anderson MJ , Wortman JR , Kim HS , Arroyo J , Berriman M , Abe K , Archer DB , Bermejo C , Bennett J , Bowyer P , Chen D , Collins M , Coulsen R , Davies R , Dyer PS , Farman M , Fedorova N , Feldblyum TV , Fischer R , Fosker N , Fraser A , Garcia JL , Garcia MJ , Goble A , Goldman GH , Gomi K , Griffith-Jones S , Gwilliam R , Haas B , Haas H , Harris D , Horiuchi H , Huang J , Humphray S , Jimenez J , Keller N , Khouri H , Kitamoto K , Kobayashi T , Konzack S , Kulkarni R , Kumagai T , Lafon A , Latge JP , Li W , Lord A , Lu C , Majoros WH , May GS , Miller BL , Mohamoud Y , Molina M , Monod M , Mouyna I , Mulligan S , Murphy L , O'Neil S , Paulsen I , Penalva MA , Pertea M , Price C , Pritchard BL , Quail MA , Rabbinowitsch E , Rawlins N , Rajandream MA , Reichard U , Renauld H , Robson GD , Rodriguez de Cordoba S , Rodriguez-Pena JM , Ronning CM , Rutter S , Salzberg SL , Sanchez M , Sanchez-Ferrero JC , Saunders D , Seeger K , Squares R , Squares S , Takeuchi M , Tekaia F , Turner G , Vazquez de Aldana CR , Weidman J , White O , Woodward J , Yu JH , Fraser C , Galagan JE , Asai K , Machida M , Hall N , Barrell B , Denning DW
Ref : Nature , 438 :1151 , 2005
Abstract : Aspergillus fumigatus is exceptional among microorganisms in being both a primary and opportunistic pathogen as well as a major allergen. Its conidia production is prolific, and so human respiratory tract exposure is almost constant. A. fumigatus is isolated from human habitats and vegetable compost heaps. In immunocompromised individuals, the incidence of invasive infection can be as high as 50% and the mortality rate is often about 50% (ref. 2). The interaction of A. fumigatus and other airborne fungi with the immune system is increasingly linked to severe asthma and sinusitis. Although the burden of invasive disease caused by A. fumigatus is substantial, the basic biology of the organism is mostly obscure. Here we show the complete 29.4-megabase genome sequence of the clinical isolate Af293, which consists of eight chromosomes containing 9,926 predicted genes. Microarray analysis revealed temperature-dependent expression of distinct sets of genes, as well as 700 A. fumigatus genes not present or significantly diverged in the closely related sexual species Neosartorya fischeri, many of which may have roles in the pathogenicity phenotype. The Af293 genome sequence provides an unparalleled resource for the future understanding of this remarkable fungus.
ESTHER : Nierman_2005_Nature_438_1151
PubMedSearch : Nierman_2005_Nature_438_1151
PubMedID: 16372009
Gene_locus related to this paper: aspfc-b0xp50 , aspfc-b0xu40 , aspfc-b0xzj6 , aspfc-dpp5 , aspfu-apth1 , aspfu-axe1 , aspfu-CBPYA , aspfu-faec , aspfu-kex1 , aspfu-ppme1 , aspfu-q4wa39 , aspfu-q4wa78 , aspfu-q4wf56 , aspfu-q4wg73 , aspfu-q4wk44 , aspfu-q4wkh6 , aspfu-q4wnx3 , aspfu-q4wpb9 , aspfu-q4wqv2 , aspfu-q4wub2 , aspfu-q4wxr1 , aspfu-q4x0n6 , aspfu-q4x1n0 , aspfu-q5vjg7 , neofi-a1cwa6 , neofi-a1dfr9 , aspfm-a0a084bf80 , aspfu-fmac

Title : The DNA sequence of chromosome I of an African trypanosome: gene content, chromosome organisation, recombination and polymorphism - Hall_2003_Nucleic.Acids.Res_31_4864
Author(s) : Hall N , Berriman M , Lennard NJ , Harris BR , Hertz-Fowler C , Bart-Delabesse EN , Gerrard CS , Atkin RJ , Barron AJ , Bowman S , Bray-Allen SP , Bringaud F , Clark LN , Corton CH , Cronin A , Davies R , Doggett J , Fraser A , Gruter E , Hall S , Harper AD , Kay MP , Leech V , Mayes R , Price C , Quail MA , Rabbinowitsch E , Reitter C , Rutherford K , Sasse J , Sharp S , Shownkeen R , MacLeod A , Taylor S , Tweedie A , Turner CM , Tait A , Gull K , Barrell B , Melville SE
Ref : Nucleic Acids Research , 31 :4864 , 2003
Abstract : The African trypanosome, Trypanosoma brucei, causes sleeping sickness in humans in sub-Saharan Africa. Here we report the sequence and analysis of the 1.1 Mb chromosome I, which encodes approximately 400 predicted genes organised into directional clusters, of which more than 100 are located in the largest cluster of 250 kb. A 160-kb region consists primarily of three gene families of unknown function, one of which contains a hotspot for retroelement insertion. We also identify five novel gene families. Indeed, almost 20% of predicted genes are members of families. In some cases, tandemly arrayed genes are 99-100% identical, suggesting an active process of amplification and gene conversion. One end of the chromosome consists of a putative bloodstream-form variant surface glycoprotein (VSG) gene expression site that appears truncated and degenerate. The other chromosome end carries VSG and expression site-associated genes and pseudogenes over 50 kb of subtelomeric sequence where, unusually, the telomere-proximal VSG gene is oriented away from the telomere. Our analysis includes the cataloguing of minor genetic variations between the chromosome I homologues and an estimate of crossing-over frequency during genetic exchange. Genetic polymorphisms are exceptionally rare in sequences located within and around the strand-switches between several gene clusters.
ESTHER : Hall_2003_Nucleic.Acids.Res_31_4864
PubMedSearch : Hall_2003_Nucleic.Acids.Res_31_4864
PubMedID: 12907729
Gene_locus related to this paper: trybr-CHR1.244 , trybr-CHR1.412 , trybr-Q4GYA0

Title : Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13 - Hall_2002_Nature_419_527
Author(s) : Hall N , Pain A , Berriman M , Churcher C , Harris B , Harris D , Mungall K , Bowman S , Atkin R , Baker S , Barron A , Brooks K , Buckee CO , Burrows C , Cherevach I , Chillingworth C , Chillingworth T , Christodoulou Z , Clark L , Clark R , Corton C , Cronin A , Davies R , Davis P , Dear P , Dearden F , Doggett J , Feltwell T , Goble A , Goodhead I , Gwilliam R , Hamlin N , Hance Z , Harper D , Hauser H , Hornsby T , Holroyd S , Horrocks P , Humphray S , Jagels K , James KD , Johnson D , Kerhornou A , Knights A , Konfortov B , Kyes S , Larke N , Lawson D , Lennard N , Line A , Maddison M , McLean J , Mooney P , Moule S , Murphy L , Oliver K , Ormond D , Price C , Quail MA , Rabbinowitsch E , Rajandream MA , Rutter S , Rutherford KM , Sanders M , Simmonds M , Seeger K , Sharp S , Smith R , Squares R , Squares S , Stevens K , Taylor K , Tivey A , Unwin L , Whitehead S , Woodward J , Sulston JE , Craig A , Newbold C , Barrell BG
Ref : Nature , 419 :527 , 2002
Abstract : Since the sequencing of the first two chromosomes of the malaria parasite, Plasmodium falciparum, there has been a concerted effort to sequence and assemble the entire genome of this organism. Here we report the sequence of chromosomes 1, 3-9 and 13 of P. falciparum clone 3D7--these chromosomes account for approximately 55% of the total genome. We describe the methods used to map, sequence and annotate these chromosomes. By comparing our assemblies with the optical map, we indicate the completeness of the resulting sequence. During annotation, we assign Gene Ontology terms to the predicted gene products, and observe clustering of some malaria-specific terms to specific chromosomes. We identify a highly conserved sequence element found in the intergenic region of internal var genes that is not associated with their telomeric counterparts.
ESTHER : Hall_2002_Nature_419_527
PubMedSearch : Hall_2002_Nature_419_527
PubMedID: 12368867
Gene_locus related to this paper: plaf7-c0h4q4 , plafa-MAL6P1.135 , plafa-PFD0185C , plafa-PFI1775W , plafa-PFI1800W

Title : Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence - Cole_1998_Nature_393_537
Author(s) : Cole ST , Brosch R , Parkhill J , Garnier T , Churcher C , Harris D , Gordon SV , Eiglmeier K , Gas S , Barry CE, 3rd , Tekaia F , Badcock K , Basham D , Brown D , Chillingworth T , Connor R , Davies R , Devlin K , Feltwell T , Gentles S , Hamlin N , Holroyd S , Hornsby T , Jagels K , Krogh A , McLean J , Moule S , Murphy L , Oliver K , Osborne J , Quail MA , Rajandream MA , Rogers J , Rutter S , Seeger K , Skelton J , Squares R , Squares S , Sulston JE , Taylor K , Whitehead S , Barrell BG
Ref : Nature , 393 :537 , 1998
Abstract : Countless millions of people have died from tuberculosis, a chronic infectious disease caused by the tubercle bacillus. The complete genome sequence of the best-characterized strain of Mycobacterium tuberculosis, H37Rv, has been determined and analysed in order to improve our understanding of the biology of this slow-growing pathogen and to help the conception of new prophylactic and therapeutic interventions. The genome comprises 4,411,529 base pairs, contains around 4,000 genes, and has a very high guanine + cytosine content that is reflected in the biased amino-acid content of the proteins. M. tuberculosis differs radically from other bacteria in that a very large portion of its coding capacity is devoted to the production of enzymes involved in lipogenesis and lipolysis, and to two new families of glycine-rich proteins with a repetitive structure that may represent a source of antigenic variation.
ESTHER : Cole_1998_Nature_393_537
PubMedSearch : Cole_1998_Nature_393_537
PubMedID: 9634230
Gene_locus related to this paper: myctu-a85a , myctu-a85b , myctu-a85c , myctu-bpoC , myctu-cut3 , myctu-cutas1 , myctu-cutas2 , myctu-d5yk66 , myctu-ephA , myctu-ephB , myctu-ephc , myctu-ephd , myctu-ephE , myctu-ephF , myctu-hpx , myctu-linb , myctu-lipG , myctu-lipJ , myctu-LIPS , myctu-lipv , myctu-LPQC , myctu-LPQP , myctu-MBTB , myctu-metx , myctu-mpt51 , myctu-MT1628 , myctu-MT3441 , myctu-p71654 , myctu-p95011 , myctu-PKS6 , myctu-PKS13 , myctu-ppe42 , myctu-ppe63 , myctu-Rv1430 , myctu-RV0045C , myctu-Rv0077c , myctu-Rv0151c , myctu-Rv0152c , myctu-Rv0159c , myctu-Rv0160c , myctu-rv0183 , myctu-Rv0217c , myctu-Rv0220 , myctu-Rv0272c , myctu-RV0293C , myctu-RV0421C , myctu-RV0457C , myctu-RV0519C , myctu-RV0774C , myctu-RV0782 , myctu-RV0840C , myctu-Rv1069c , myctu-Rv1076 , myctu-RV1123C , myctu-Rv1184c , myctu-Rv1190 , myctu-Rv1191 , myctu-RV1192 , myctu-RV1215C , myctu-Rv1399c , myctu-Rv1400c , myctu-Rv1426c , myctu-RV1639C , myctu-RV1683 , myctu-RV1758 , myctu-Rv1800 , myctu-Rv1833c , myctu-RV2054 , myctu-RV2296 , myctu-Rv2385 , myctu-Rv2485c , myctu-RV2627C , myctu-RV2672 , myctu-RV2695 , myctu-RV2765 , myctu-RV2800 , myctu-RV2854 , myctu-Rv2970c , myctu-Rv3084 , myctu-Rv3097c , myctu-rv3177 , myctu-Rv3312c , myctu-RV3452 , myctu-RV3473C , myctu-Rv3487c , myctu-Rv3569c , myctu-Rv3591c , myctu-RV3724 , myctu-Rv3802c , myctu-Rv3822 , myctu-y0571 , myctu-y963 , myctu-Y1834 , myctu-y1835 , myctu-y2079 , myctu-Y2307 , myctu-yc88 , myctu-ym23 , myctu-ym24 , myctu-YR15 , myctu-yt28