| 1. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 2. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Ferrari, Raffaele, et al.
(författare)
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Frontotemporal dementia and its subtypes: a genome-wide association study.
- 2014
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Ingår i: Lancet Neurology. - 1474-4465. ; 13:7, s. 686-699
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72-have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder.
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| 4. |
- Sodergren, Erica, et al.
(författare)
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The genome of the sea urchin Strongylocentrotus purpuratus.
- 2006
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 314:5801, s. 941-52
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Tidskriftsartikel (refereegranskat)abstract
- We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus, a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes.
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| 5. |
- Young, E. D., et al.
(författare)
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The relative abundances of resolved (CH2D2)-C-12 and (CH3D)-C-13 and mechanisms controlling isotopic bond ordering in abiotic and biotic methane gases
- 2017
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Ingår i: Geochimica et Cosmochimica Acta. - : Elsevier BV. - 0016-7037 .- 1872-9533. ; 203, s. 235-264
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Tidskriftsartikel (refereegranskat)abstract
- We report measurements of resolved (CH2D2)-C-12 and (CH3D)-C-13 at natural abundances in a variety of methane gases produced naturally and in the laboratory. The ability to resolve (CH2D2)-C-12 from (CH3D)-C-13 provides unprecedented insights into the origin and evolution of CH4. The results identify conditions under which either isotopic bond order disequilibrium or equilibrium are expected. Where equilibrium obtains, concordant Delta (CH2D2)-C-12 and Delta (CH3D)-C-13 temperatures can be used reliably for thermometry. We find that concordant temperatures do not always match previous hypotheses based on indirect estimates of temperature of formation nor temperatures derived from CH4/H-2 D/H exchange, underscoring the importance of reliable thermometry based on the CH4 molecules themselves. Where Delta (CH2D2)-C-12 and Delta (CH3D)-C-13 values are inconsistent with thermodynamic equilibrium, temperatures of formation derived from these species are spurious. In such situations, while formation temperatures are unavailable, disequilibrium isotopologue ratios nonetheless provide novel information about the formation mechanism of the gas and the presence or absence of multiple sources or sinks. In particular, disequilibrium isotopologue ratios may provide the means for differentiating between methane produced by abiotic synthesis vs. biological processes. Deficits in (CH2D2)-C-12 compared with equilibrium values in CH4 gas made by surface-catalyzed abiotic reactions are so large as to point towards a quantum tunneling origin. Tunneling also accounts for the more moderate depletions in (CH3D)-C-13 that accompany the low (CH2D2)-C-12 abundances produced by abiotic reactions. The tunneling signature may prove to be an important tracer of abiotic methane formation, especially where it is preserved by dissolution of gas in cool hydrothermal systems (e.g., Mars). Isotopologue signatures of abiotic methane production can be erased by infiltration of microbial communities, and Delta (CH2D2)-C-12 values are a key tracer of microbial recycling.
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| 6. |
- Levis, Brooke, et al.
(författare)
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Comparison of major depression diagnostic classification probability using the SCID, CIDI, and MINI diagnostic interviews among women in pregnancy or postpartum : An individual participant data meta-analysis
- 2019
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Ingår i: International Journal of Methods in Psychiatric Research. - : WILEY. - 1049-8931 .- 1557-0657. ; 28:4
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: A previous individual participant data meta-analysis (IPDMA) identified differences in major depression classification rates between different diagnostic interviews, controlling for depressive symptoms on the basis of the Patient Health Questionnaire-9. We aimed to determine whether similar results would be seen in a different population, using studies that administered the Edinburgh Postnatal Depression Scale (EPDS) in pregnancy or postpartum.Methods: Data accrued for an EPDS diagnostic accuracy IPDMA were analysed. Binomial generalised linear mixed models were fit to compare depression classification odds for the Mini International Neuropsychiatric Interview (MINI), Composite International Diagnostic Interview (CIDI), and Structured Clinical Interview for DSM (SCID), controlling for EPDS scores and participant characteristics.Results Among fully structured interviews, the MINI (15 studies, 2,532 participants, 342 major depression cases) classified depression more often than the CIDI (3 studies, 2,948 participants, 194 major depression cases; adjusted odds ratio [aOR] = 3.72, 95% confidence interval [CI] [1.21, 11.43]). Compared with the semistructured SCID (28 studies, 7,403 participants, 1,027 major depression cases), odds with the CIDI (interaction aOR = 0.88, 95% CI [0.85, 0.92]) and MINI (interaction aOR = 0.95, 95% CI [0.92, 0.99]) increased less as EPDS scores increased.Conclusion Different interviews may not classify major depression equivalently.
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| 7. |
- Loeffen, Erik A. H., et al.
(författare)
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Reducing pain in children with cancer : Methodology for the development of a clinical practice guideline
- 2019
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 66:6
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Tidskriftsartikel (refereegranskat)abstract
- Although pain is one of the most prevalent and bothersome symptoms children with cancer experience, evidence-based guidance regarding assessment and management is lacking. With 44 international, multidisciplinary healthcare professionals and nine patient representatives, we aimed to develop a clinical practice guideline (following GRADE methodology), addressing assessment and pharmacological, psychological, and physical management of tumor-, treatment-, and procedure-related pain in children with cancer. In this paper, we present our thorough methodology for this development, including the challenges we faced and how we approached these. This lays the foundation for our clinical practice guideline, for which there is a high clinical demand.
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| 8. |
- van Rheenen, Wouter, et al.
(författare)
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Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis
- 2016
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:9, s. 1043-1048
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Tidskriftsartikel (refereegranskat)abstract
- To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577 cases and 23,475 controls, combined with 2,579 cases and 2,767 controls in an independent replication cohort, we fine-mapped a new risk locus on chromosome 21 and identified C21orf2 as a gene associated with ALS risk. In addition, we identified MOBP and SCFD1 as new associated risk loci. We established evidence of ALS being a complex genetic trait with a polygenic architecture. Furthermore, we estimated the SNP-based heritability at 8.5%, with a distinct and important role for low-frequency variants (frequency 1-10%). This study motivates the interrogation of larger samples with full genome coverage to identify rare causal variants that underpin ALS risk.
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| 10. |
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