| 1. |
|
|
| 2. |
|
|
| 3. |
- Campbell, PJ, et al.
(författare)
-
Pan-cancer analysis of whole genomes
- 2020
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
-
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.
|
|
| 4. |
|
|
| 5. |
- Kinyoki, DK, et al.
(författare)
-
Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017
- 2020
-
Ingår i: Nature medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 26:5, s. 750-759
-
Tidskriftsartikel (refereegranskat)abstract
- A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Gao, J, et al.
(författare)
-
Monkeypox outbreaks in the context of the COVID-19 pandemic: Network and clustering analyses of global risks and modified SEIR prediction of epidemic trends
- 2023
-
Ingår i: Frontiers in public health. - : Frontiers Media SA. - 2296-2565. ; 11, s. 1052946-
-
Tidskriftsartikel (refereegranskat)abstract
- Ninety-eight percent of documented cases of the zoonotic disease human monkeypox (MPX) were reported after 2001, with especially dramatic global spread in 2022. This longitudinal study aimed to assess spatiotemporal risk factors of MPX infection and predict global epidemiological trends.MethodTwenty-one potential risk factors were evaluated by correlation-based network analysis and multivariate regression. Country-level risk was assessed using a modified Susceptible-Exposed-Infectious-Removed (SEIR) model and a risk-factor-driven k-means clustering analysis.ResultsBetween historical cases and the 2022 outbreak, MPX infection risk factors changed from relatively simple [human immunodeficiency virus (HIV) infection and population density] to multiple [human mobility, population of men who have sex with men, coronavirus disease 2019 (COVID-19) infection, and socioeconomic factors], with human mobility in the context of COVID-19 being especially key. The 141 included countries classified into three risk clusters: 24 high-risk countries mainly in West Europe and Northern America, 70 medium-risk countries mainly in Latin America and Asia, and 47 low-risk countries mainly in Africa and South Asia. The modified SEIR model predicted declining transmission rates, with basic reproduction numbers ranging 1.61–7.84 in the early stage and 0.70–4.13 in the current stage. The estimated cumulative cases in Northern and Latin America may overtake the number in Europe in autumn 2022.ConclusionsIn the current outbreak, risk factors for MPX infection have changed and expanded. Forecasts of epidemiological trends from our modified SEIR models suggest that Northern America and Latin America are at greater risk of MPX infection in the future.
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
- Zang, ZL, et al.
(författare)
-
Valproic acid exposure decreases neurogenic potential of outer radial glia in human brain organoids
- 2022
-
Ingår i: Frontiers in molecular neuroscience. - : Frontiers Media SA. - 1662-5099. ; 15, s. 1023765-
-
Tidskriftsartikel (refereegranskat)abstract
- Valproic acid (VPA) exposure during pregnancy leads to a higher risk of autism spectrum disorder (ASD) susceptibility in offspring. Human dorsal forebrain organoids were used to recapitulate course of cortical neurogenesis in the developing human brain. Combining morphological characterization with massive parallel RNA sequencing (RNA-seq) on organoids to analyze the pathogenic effects caused by VPA exposure and critical signaling pathway. We found that VPA exposure in organoids caused a reduction in the size and impairment in the proliferation and expansion of neural progenitor cells (NPCs) in a dose-dependent manner. VPA exposure typically decreased the production of outer radial glia-like cells (oRGs), a subtype of NPCs contributing to mammalian neocortical expansion and delayed their fate toward upper-layer neurons. Transcriptomics analysis revealed that VPA exposure influenced ASD risk gene expression in organoids, which markedly overlapped with irregulated genes in brains or organoids originating from ASD patients. We also identified that VPA-mediated Wnt/β-catenin signaling pathway activation is essential for sustaining cortical neurogenesis and oRGs output. Taken together, our study establishes the use of dorsal forebrain organoids as an effective platform for modeling VPA-induced teratogenic pathways involved in the cortical neurogenesis and oRGs output, which might contribute to ASD pathogenesis in the developing brain.
|
|
