SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Sunyaev Shamil) "

Sökning: WFRF:(Sunyaev Shamil)

  • Resultat 1-6 av 6
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Brownstein, Catherine A., et al. (författare)
  • An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge
  • 2014
  • Ingår i: ; 15:3, s. R53-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups.
  •  
2.
  • Lenz, Tobias L., et al. (författare)
  • Widespread non-additive and interaction effects within HLA loci modulate the risk of autoimmune diseases
  • 2015
  • Ingår i: Nature Genetics. - : Macmillan Publishers Ltd.. - 1061-4036 .- 1546-1718. ; 47:9, s. 1085-1090
  • Tidskriftsartikel (refereegranskat)abstract
    • Human leukocyte antigen (HLA) genes confer substantial risk for autoimmune diseases on a log-additive scale. Here we speculated that differences in autoantigen-binding repertoires between a heterozygote's two expressed HLA variants might result in additional non-additive risk effects. We tested the non-additive disease contributions of classical HLA alleles in patients and matched controls for five common autoimmune diseases: rheumatoid arthritis (n(cases) = 5,337), type 1 diabetes (T1D; n(cases) = 5,567), psoriasis vulgaris (n(cases) = 3,089), idiopathic achalasia (n(cases) = 727) and celiac disease (ncases = 11,115). In four of the five diseases, we observed highly significant, non-additive dominance effects (rheumatoid arthritis, P = 2.5 x 10(-12); T1D, P = 2.4 x 10(-10); psoriasis, P = 5.9 x 10(-6); celiac disease, P = 1.2 x 10(-87)). In three of these diseases, the non-additive dominance effects were explained by interactions between specific classical HLA alleles (rheumatoid arthritis, P = 1.8 x 10(-3); T1D, P = 8.6 x 10(-27); celiac disease, P = 6.0 x 10(-100)). These interactions generally increased disease risk and explained moderate but significant fractions of phenotypic variance (rheumatoid arthritis, 1.4%; T1D, 4.0%; celiac disease, 4.1%) beyond a simple additive model.
  •  
3.
  • Seplyarskiy, Vladimir B., et al. (författare)
  • Error-prone bypass of DNA lesions during lagging-strand replication is a common source of germline and cancer mutations
  • 2019
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:1, s. 36-
  • Tidskriftsartikel (refereegranskat)abstract
    • Studies in experimental systems have identified a multitude of mutational mechanisms including DNA replication infidelity and DNA damage followed by inefficient repair or replicative bypass. However, the relative contributions of these mechanisms to human germline mutation remain unknown. Here, we show that error-prone damage bypass on the lagging strand plays a major role in human mutagenesis. Transcription-coupled DNA repair removes lesions on the transcribed strand; lesions on the non-transcribed strand are preferentially converted into mutations. In human polymorphism we detect a striking similarity between mutation types predominant on the non-transcribed strand and on the strand lagging during replication. Moreover, damage-induced mutations in cancers accumulate asymmetrically with respect to the direction of replication, suggesting that DNA lesions are resolved asymmetrically. We experimentally demonstrate that replication delay greatly attenuates the mutagenic effect of ultraviolet irradiation, confirming that replication converts DNA damage into mutations. We estimate that at least 10% of human mutations arise due to DNA damage.
  •  
4.
  • Birney, Ewan, et al. (författare)
  • Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
  • 2007
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
  •  
5.
  • Li, Jin Billy, et al. (författare)
  • Multiplex padlock targeted sequencing reveals human hypermutable CpG variations
  • 2009
  • Ingår i: Genome Research. - 1088-9051 .- 1549-5469. ; 19:9, s. 1606-1615
  • Tidskriftsartikel (refereegranskat)abstract
    • Utilizing the full power of next-generation sequencing often requires the ability to perform large-scale multiplex enrichment of many specific genomic loci in multiple samples. Several technologies have been recently developed but await substantial improvements. We report the 10,000-fold improvement of a previously developed padlock-based approach, and apply the assay to identifying genetic variations in hypermutable CpG regions across human chromosome 21. From approximately 3 million reads derived from a single Illumina Genome Analyzer lane, approximately 94% (approximately 50,500) target sites can be observed with at least one read. The uniformity of coverage was also greatly improved; up to 93% and 57% of all targets fell within a 100- and 10-fold coverage range, respectively. Alleles at >400,000 target base positions were determined across six subjects and examined for single nucleotide polymorphisms (SNPs), and the concordance with independently obtained genotypes was 98.4%-100%. We detected >500 SNPs not currently in dbSNP, 362 of which were in targeted CpG locations. Transitions in CpG sites were at least 13.7 times more abundant than non-CpG transitions. Fractions of polymorphic CpG sites are lower in CpG-rich regions and show higher correlation with human-chimpanzee divergence within CpG versus non-CpG sites. This is consistent with the hypothesis that methylation rate heterogeneity along chromosomes contributes to mutation rate variation in humans. Our success suggests that targeted CpG resequencing is an efficient way to identify common and rare genetic variations. In addition, the significantly improved padlock capture technology can be readily applied to other projects that require multiplex sample preparation.
  •  
6.
  • Liberles, David A., et al. (författare)
  • The interface of protein structure, protein biophysics, and molecular evolution
  • 2012
  • Ingår i: Protein Science. - 0961-8368 .- 1469-896X. ; 21:6, s. 769-785
  • Forskningsöversikt (refereegranskat)abstract
    • The interface of protein structural biology, protein biophysics, molecular evolution, and molecular population genetics forms the foundations for a mechanistic understanding of many aspects of protein biochemistry. Current efforts in interdisciplinary protein modeling are in their infancy and the state-of-the art of such models is described. Beyond the relationship between amino acid substitution and static protein structure, protein function, and corresponding organismal fitness, other considerations are also discussed. More complex mutational processes such as insertion and deletion and domain rearrangements and even circular permutations should be evaluated. The role of intrinsically disordered proteins is still controversial, but may be increasingly important to consider. Protein geometry and protein dynamics as a deviation from static considerations of protein structure are also important. Protein expression level is known to be a major determinant of evolutionary rate and several considerations including selection at the mRNA level and the role of interaction specificity are discussed. Lastly, the relationship between modeling and needed high-throughput experimental data as well as experimental examination of protein evolution using ancestral sequence resurrection and in vitro biochemistry are presented, towards an aim of ultimately generating better models for biological inference and prediction.
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 1-6 av 6
Typ av publikation
tidskriftsartikel (5)
forskningsöversikt (1)
Typ av innehåll
refereegranskat (6)
Författare/redaktör
de Bakker, Paul I W (3)
Raychaudhuri, S (2)
Antonarakis, Stylian ... (2)
Dermitzakis, Emmanou ... (2)
Zhang, Nancy R. (2)
de Jong, Pieter J. (2)
visa fler...
Lander, Eric S. (2)
Whelan, Simon (2)
Stadler, Peter F (2)
Jaffe, David B (2)
Mardis, Elaine R (2)
Wilson, Richard K (2)
Raychaudhuri, Soumya (2)
Myers, Richard M. (2)
Muzny, Donna M (2)
Gibbs, Richard A (2)
Lowe, Todd M (2)
Zody, Michael C (2)
Collins, Francis S. (2)
Stamatoyannopoulos, ... (2)
Gingeras, Thomas R. (2)
Margulies, Elliott H ... (2)
Thurman, Robert E. (2)
Kuehn, Michael S. (2)
Taylor, Christopher ... (2)
Koch, Christoph M. (2)
Greenbaum, Jason A. (2)
Andrews, Robert M. (2)
Boyle, Patrick J. (2)
Carter, Nigel P. (2)
Clelland, Gayle K. (2)
Dillon, Shane C. (2)
Dorschner, Michael O ... (2)
Giresi, Paul G. (2)
James, Keith D. (2)
Johnson, Brett E. (2)
Johnson, Ericka M. (2)
Frum, Tristan T. (2)
Rosenzweig, Elizabet ... (2)
Lefebvre, Gregory C. (2)
Navas, Patrick A. (2)
Sabo, Peter J. (2)
Lieb, Jason D. (2)
Tullius, Thomas D. (2)
Crawford, Gregory E. (2)
Sunyaev, Shamil (2)
Noble, William S. (2)
Hofacker, Ivo L. (2)
Hirsch, Heather A. (2)
Sekinger, Edward A. (2)
visa färre...
Lärosäte
Kungliga Tekniska Högskolan (3)
Uppsala universitet (2)
Stockholms universitet (2)
Karolinska Institutet (2)
Umeå universitet (1)
Språk
Engelska (6)
Forskningsämne (UKÄ/SCB)
Naturvetenskap (4)
Medicin och hälsovetenskap (2)

År

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy