An interactive protein secondary structure prediction Internet server is presented. The server allows a single sequence or multiple alignment to be submitted, and returns predictions from six ...secondary structure prediction algorithms that exploit evolutionary information from multiple sequences. A consensus prediction is also returned which improves the average Q3 accuracy of prediction by 1% to 72.9%. The server simplifies the use of current prediction algorithms and allows conservation patterns important to structure and function to be identified.
http://barton.ebi.ac.uk/servers/jpred.h tml
geoff@ebi.ac.uk
Rucaparib, a poly(ADP-ribose) polymerase inhibitor, has anticancer activity in recurrent ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity. In this ...trial we assessed rucaparib versus placebo after response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian carcinoma.
In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients from 87 hospitals and cancer centres across 11 countries. Eligible patients were aged 18 years or older, had a platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma, had received at least two previous platinum-based chemotherapy regimens, had achieved complete or partial response to their last platinum-based regimen, had a cancer antigen 125 concentration of less than the upper limit of normal, had a performance status of 0–1, and had adequate organ function. Patients were ineligible if they had symptomatic or untreated central nervous system metastases, had received anticancer therapy 14 days or fewer before starting the study, or had received previous treatment with a poly(ADP-ribose) polymerase inhibitor. We randomly allocated patients 2:1 to receive oral rucaparib 600 mg twice daily or placebo in 28 day cycles using a computer-generated sequence (block size of six, stratified by homologous recombination repair gene mutation status, progression-free interval after the penultimate platinum-based regimen, and best response to the most recent platinum-based regimen). Patients, investigators, site staff, assessors, and the funder were masked to assignments. The primary outcome was investigator-assessed progression-free survival evaluated with use of an ordered step-down procedure for three nested cohorts: patients with BRCA mutations (carcinoma associated with deleterious germline or somatic BRCA mutations), patients with homologous recombination deficiencies (BRCA mutant or BRCA wild-type and high loss of heterozygosity), and the intention-to-treat population, assessed at screening and every 12 weeks thereafter. This trial is registered with ClinicalTrials.gov, number NCT01968213; enrolment is complete.
Between April 7, 2014, and July 19, 2016, we randomly allocated 564 patients: 375 (66%) to rucaparib and 189 (34%) to placebo. Median progression-free survival in patients with a BRCA-mutant carcinoma was 16·6 months (95% CI 13·4–22·9; 130 35% patients) in the rucaparib group versus 5·4 months (3·4–6·7; 66 35% patients) in the placebo group (hazard ratio 0·23 95% CI 0·16–0·34; p<0·0001). In patients with a homologous recombination deficient carcinoma (236 63% vs 118 62%), it was 13·6 months (10·9–16·2) versus 5·4 months (5·1–5·6; 0·32 0·24–0·42; p<0·0001). In the intention-to-treat population, it was 10·8 months (8·3–11·4) versus 5·4 months (5·3–5·5; 0·36 0·30–0·45; p<0·0001). Treatment-emergent adverse events of grade 3 or higher in the safety population (372 99% patients in the rucaparib group vs 189 100% in the placebo group) were reported in 209 (56%) patients in the rucaparib group versus 28 (15%) in the placebo group, the most common of which were anaemia or decreased haemoglobin concentration (70 19% vs one 1%) and increased alanine or aspartate aminotransferase concentration (39 10% vs none).
Across all primary analysis groups, rucaparib significantly improved progression-free survival in patients with platinum-sensitive ovarian cancer who had achieved a response to platinum-based chemotherapy. ARIEL3 provides further evidence that use of a poly(ADP-ribose) polymerase inhibitor in the maintenance treatment setting versus placebo could be considered a new standard of care for women with platinum-sensitive ovarian cancer following a complete or partial response to second-line or later platinum-based chemotherapy.
Clovis Oncology.
Chromosome 6 is a metacentric chromosome that constitutes about 6% of the human genome. The finished sequence comprises 166,880,988 base pairs, representing the largest chromosome sequenced so far. ...The entire sequence has been subjected to high-quality manual annotation, resulting in the evidence-supported identification of 1,557 genes and 633 pseudogenes. Here we report that at least 96% of the protein-coding genes have been identified, as assessed by multi-species comparative sequence analysis, and provide evidence for the presence of further, otherwise unsupported exons/genes. Among these are genes directly implicated in cancer, schizophrenia, autoimmunity and many other diseases. Chromosome 6 harbours the largest transfer RNA gene cluster in the genome; we show that this cluster co-localizes with a region of high transcriptional activity. Within the essential immune loci of the major histocompatibility complex, we find HLA-B to be the most polymorphic gene on chromosome 6 and in the human genome.
Chromosome 13 is the largest acrocentric human chromosome. It carries genes involved in cancer including the breast cancer type 2 (BRCA2) and retinoblastoma (RB1) genes, is frequently rearranged in ...B-cell chronic lymphocytic leukaemia, and contains the DAOA locus associated with bipolar disorder and schizophrenia. We describe completion and analysis of 95.5 megabases (Mb) of sequence from chromosome 13, which contains 633 genes and 296 pseudogenes. We estimate that more than 95.4% of the protein-coding genes of this chromosome have been identified, on the basis of comparison with other vertebrate genome sequences. Additionally, 105 putative non-coding RNA genes were found. Chromosome 13 has one of the lowest gene densities (6.5 genes per Mb) among human chromosomes, and contains a central region of 38 Mb where the gene density drops to only 3.1 genes per Mb.
Mining the draft human genome Birney, Ewan; Bateman, Alex; Clamp, Michele E ...
Nature,
02/2001, Letnik:
409, Številka:
6822
Journal Article
Recenzirano
Odprti dostop
Now that the draft human genome sequence is available, everyone wants to be able to use it. However, we have perhaps become complacent about our ability to turn new genomes into lists of genes. The ...higher volume of data associated with a larger genome is accompanied by a much greater increase in complexity. We need to appreciate both the scale of the challenge of vertebrate genome analysis and the limitations of current gene prediction methods and understanding.
The well-established inaccuracy of purely computational methods for annotating genome sequences necessitates an interactive tool to allow biological experts to refine these approximations by viewing ...and independently evaluating the data supporting each annotation. Apollo was developed to meet this need, enabling curators to inspect genome annotations closely and edit them. FlyBase biologists successfully used Apollo to annotate the Drosophila melanogaster genome and it is increasingly being used as a starting point for the development of customized annotation editing tools for other genome projects.
Motivation: An automatic sequence searching method (ProtEST) is described which constructs multiple protein sequence alignments from protein sequences and translated expressed sequence tags (ESTs). ...ProtEST is more effective than a simple TBLASTN search of the query against the EST database, as the sequences are automatically clustered, assembled, made non-redundant, checked for sequence errors, translated into protein and then aligned and displayed. Results: A ProtEST search found a non-redundant, translated, error- and length-corrected EST sequence for &58% of sequences when single sequences from 1407 Pfam-A seed alignments were used as the probe. The average family size of the resulting alignments of translated EST sequences contained &10 sequences. In a cross-validated test of protein secondary structure prediction, alignments from the new procedure led to an improvement of 3.4% average Q3 prediction accuracy over single sequences. Availability: The ProtEST method is available as an Internet World Wide Web service at http://barton.ebi.ac.uk/servers/protest.htmlThe Wise2 package for protein and genomic comparisons and the ProtESTWise script can be found at: http://www.sanger.ac.uk/Software/Wise2 Contact: geoff@ebi.ac.uk
•Highest Pb concentrations in gavaged hens emerged in bone, blood, liver, and egg.•Similar to previous research, no clinical signs were noted in Pb-gavaged chickens.•Prolonged contact of poultry to ...Pb should be considered a food protection concern.•Backyard chicken owners should be cautious when consuming products from their birds.
Previous research has demonstrated that lead (Pb2+, for the remainder of the paper referred to as Pb) and other heavy metals are present in table eggs from backyard birds. While the source of Pb exposure is unknown, exposure to the environment via the foraging behavior of backyard poultry is likely a significant factor. A longitudinal cohort study was conducted to better understand how oral Pb consumption correlates with Pb concentration in table eggs and other physiological compartments (i.e. bone, blood, and liver). In order of absolute mean concentration, Pb was most present in bone (226.24 ppb experimental vs. 31.00 ppb control), blood (14.47 ppb experimental vs 0.27 ppb control), liver (11.24 ppb experimental vs 0.75 ppb control), and egg (1.17 ppb experimental vs 0.06 ppb control). The low concentration of Pb in table eggs implies that Pb preferentially accumulates in other tissues aside from the egg. While this study showed that eggs have the lowest overall tropism for Pb, the presence of Pb in other tissues demonstrates a public health risk when chickens are orally exposed to Pb via oral consumption.
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