| 1. |
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| 2. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 4. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 5. |
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| 6. |
- 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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| 7. |
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| 8. |
- Munk, P., et al.
(författare)
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Genomic analysis of sewage from 101 countries reveals global landscape of antimicrobial resistance
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial resistance (AMR) is a major threat to global health. Understanding the emergence, evolution, and transmission of individual antibiotic resistance genes (ARGs) is essential to develop sustainable strategies combatting this threat. Here, we use metagenomic sequencing to analyse ARGs in 757 sewage samples from 243 cities in 101 countries, collected from 2016 to 2019. We find regional patterns in resistomes, and these differ between subsets corresponding to drug classes and are partly driven by taxonomic variation. The genetic environments of 49 common ARGs are highly diverse, with most common ARGs carried by multiple distinct genomic contexts globally and sometimes on plasmids. Analysis of flanking sequence revealed ARG-specific patterns of dispersal limitation and global transmission. Our data furthermore suggest certain geographies are more prone to transmission events and should receive additional attention.
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| 9. |
- Bar, N., et al.
(författare)
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A reference map of potential determinants for the human serum metabolome
- 2020
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Ingår i: Nature. - : Nature Research. - 0028-0836 .- 1476-4687. ; 588:7836, s. 135-140
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Tidskriftsartikel (refereegranskat)abstract
- The serum metabolome contains a plethora of biomarkers and causative agents of various diseases, some of which are endogenously produced and some that have been taken up from the environment1. The origins of specific compounds are known, including metabolites that are highly heritable2,3, or those that are influenced by the gut microbiome4, by lifestyle choices such as smoking5, or by diet6. However, the key determinants of most metabolites are still poorly understood. Here we measured the levels of 1,251 metabolites in serum samples from a unique and deeply phenotyped healthy human cohort of 491 individuals. We applied machine-learning algorithms to predict metabolite levels in held-out individuals on the basis of host genetics, gut microbiome, clinical parameters, diet, lifestyle and anthropometric measurements, and obtained statistically significant predictions for more than 76% of the profiled metabolites. Diet and microbiome had the strongest predictive power, and each explained hundreds of metabolites—in some cases, explaining more than 50% of the observed variance. We further validated microbiome-related predictions by showing a high replication rate in two geographically independent cohorts7,8 that were not available to us when we trained the algorithms. We used feature attribution analysis9 to reveal specific dietary and bacterial interactions. We further demonstrate that some of these interactions might be causal, as some metabolites that we predicted to be positively associated with bread were found to increase after a randomized clinical trial of bread intervention. Overall, our results reveal potential determinants of more than 800 metabolites, paving the way towards a mechanistic understanding of alterations in metabolites under different conditions and to designing interventions for manipulating the levels of circulating metabolites.
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| 10. |
- Santangelo, James S., et al.
(författare)
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Global urban environmental change drives adaptation in white clover
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375
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Tidskriftsartikel (refereegranskat)abstract
- Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural dines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale.
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| 11. |
- Solmi, M, et al.
(författare)
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- 2022
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Ingår i: Journal of affective disorders. - : Elsevier BV. - 1573-2517 .- 0165-0327. ; 299, s. 367-376
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Tidskriftsartikel (refereegranskat)
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| 12. |
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| 13. |
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| 14. |
- Yakneen, S, et al.
(författare)
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Butler enables rapid cloud-based analysis of thousands of human genomes
- 2020
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Ingår i: Nature biotechnology. - : Springer Science and Business Media LLC. - 1546-1696 .- 1087-0156. ; 38:3, s. 288-
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Tidskriftsartikel (refereegranskat)abstract
- We present Butler, a computational tool that facilitates large-scale genomic analyses on public and academic clouds. Butler includes innovative anomaly detection and self-healing functions that improve the efficiency of data processing and analysis by 43% compared with current approaches. Butler enabled processing of a 725-terabyte cancer genome dataset from the Pan-Cancer Analysis of Whole Genomes (PCAWG) project in a time-efficient and uniform manner.
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| 15. |
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| 16. |
- Zhang, B., et al.
(författare)
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A novel nano delivery system targeting different stages of osteoclasts
- 2022
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Ingår i: Biomaterials Science. - : Royal Society of Chemistry (RSC). - 2047-4830 .- 2047-4849. ; 10:7, s. 1821-1830
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Tidskriftsartikel (refereegranskat)abstract
- Osteoclast (OC) abnormalities represent osteoporosis's critical mechanism (OP). OCs undergo multiple processes that range from monocytic to functional. Different drugs target OCs at different developmental stages; however, almost no Suitable drug-targeted delivery systems exist. Therefore, we designed two dual-targeting nanoparticles to target OCs at different functional stages. Using the calcitonin gene-related peptide receptor (CGRPR), which OC precursors highly express, and specific TRAPpeptides screened in the bone resorption lacuna, where mature OCs function, respectively, two types of dual-targeted nanoparticles were constructed. Afterwards, nanoparticles were grafted with hyaluronic acid (HA), which specifically binds to CD44 on the surface of the OCs. In vivo and in vitro experiments show that both nanoparticles have noticeable targeting effects on OCs. This suggests that dual-targeting nanoparticles designed for different functional periods of OC can be well targeted to the corresponding OC, and further promote the more precise delivery of drugs used to treat OP.
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| 17. |
- Gao, J, et al.
(författare)
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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
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Ingår i: Frontiers in public health. - : Frontiers Media SA. - 2296-2565. ; 11, s. 1052946-
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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.
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| 18. |
- Li, Constance H., et al.
(författare)
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Sex differences in oncogenic mutational processes
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.
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| 19. |
- Aglago, Elom K., et al.
(författare)
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Soluble Receptor for Advanced Glycation End-products (sRAGE) and Colorectal Cancer Risk : A Case-Control Study Nested within a European Prospective Cohort
- 2021
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 30:1, s. 182-192
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Overexpression of the receptor for advanced glycation end-product (RAGE) has been associated with chronic inflammation, which in turn has been associated with increased colorectal cancer risk. Soluble RAGE (sRAGE) competes with RAGE to bind its ligands, thus potentially preventing RAGE-induced inflammation.METHODS: To investigate whether sRAGE and related genetic variants are associated with colorectal cancer risk, we conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC). Plasma sRAGE concentrations were measured by ELISA in 1,361 colorectal cancer matched case-control sets. Twenty-four SNPs encoded in the genes associated with sRAGE concentrations were available for 1,985 colorectal cancer cases and 2,220 controls. Multivariable adjusted ORs and 95% confidence intervals (CIs) were computed using conditional and unconditional logistic regression for colorectal cancer risk and circulating sRAGE and SNPs, respectively.RESULTS: Higher sRAGE concentrations were inversely associated with colorectal cancer (ORQ5vs.Q1, 0.77; 95% CI, 0.59-1.00). Sex-specific analyses revealed that the observed inverse risk association was restricted to men (ORQ5vs.Q1, 0.63; 95% CI, 0.42-0.94), whereas no association was observed in women (ORQ5vs.Q1, 1.00; 95% CI, 0.68-1.48; Pheterogeneity for sex = 0.006). Participants carrying minor allele of rs653765 (promoter region of ADAM10) had lower colorectal cancer risk (C vs. T, OR, 0.90; 95% CI, 0.82-0.99).CONCLUSIONS: Prediagnostic sRAGE concentrations were inversely associated with colorectal cancer risk in men, but not in women. An SNP located within ADAM10 gene, pertaining to RAGE shedding, was associated with colorectal cancer risk.IMPACT: Further studies are needed to confirm our observed sex difference in the association and better explore the potential involvement of genetic variants of sRAGE in colorectal cancer development.
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| 20. |
- He, Haoran, et al.
(författare)
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Deciphering microbiomes dozens of meters under our feet and their edaphoclimatic and spatial drivers
- 2024
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Ingår i: Global Change Biology. - 1354-1013. ; 30:1
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Tidskriftsartikel (refereegranskat)abstract
- Microbes inhabiting deep soil layers are known to be different from their counterpart in topsoil yet remain under investigation in terms of their structure, function, and how their diversity is shaped. The microbiome of deep soils (>1 m) is expected to be relatively stable and highly independent from climatic conditions. Much less is known, however, on how these microbial communities vary along climate gradients. Here, we used amplicon sequencing to investigate bacteria, archaea, and fungi along fifteen 18-m depth profiles at 20–50-cm intervals across contrasting aridity conditions in semi-arid forest ecosystems of China's Loess Plateau. Our results showed that bacterial and fungal α diversity and bacterial and archaeal community similarity declined dramatically in topsoil and remained relatively stable in deep soil. Nevertheless, deep soil microbiome still showed the functional potential of N cycling, plant-derived organic matter degradation, resource exchange, and water coordination. The deep soil microbiome had closer taxa–taxa and bacteria–fungi associations and more influence of dispersal limitation than topsoil microbiome. Geographic distance was more influential in deep soil bacteria and archaea than in topsoil. We further showed that aridity was negatively correlated with deep-soil archaeal and fungal richness, archaeal community similarity, relative abundance of plant saprotroph, and bacteria–fungi associations, but increased the relative abundance of aerobic ammonia oxidation, manganese oxidation, and arbuscular mycorrhizal in the deep soils. Root depth, complexity, soil volumetric moisture, and clay play bridging roles in the indirect effects of aridity on microbes in deep soils. Our work indicates that, even microbial communities and nutrient cycling in deep soil are susceptible to changes in water availability, with consequences for understanding the sustainability of dryland ecosystems and the whole-soil in response to aridification. Moreover, we propose that neglecting soil depth may underestimate the role of soil moisture in dryland ecosystems under future climate scenarios.
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| 21. |
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| 22. |
- Liu, Y., et al.
(författare)
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Inorganic carbon and alkalinity biogeochemistry and fluxes in an intertidal beach aquifer: Implications for ocean acidification
- 2021
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Ingår i: Journal of Hydrology. - : Elsevier BV. - 0022-1694. ; 595
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Tidskriftsartikel (refereegranskat)abstract
- While submarine groundwater discharge (SGD) is well known to release large amounts of dissolved nutrients and organic carbon into the ocean, the contribution of SGD to the marine inorganic carbon cycle is poorly understood. Here, the biogeochemistry of inorganic carbon in an intertidal aquifer and related SGD-derived fluxes into Tolo Harbor, Hong Kong was investigated over tidal and seasonal time scales. The results revealed the production of total alkalinity (TAlk) and dissolved inorganic carbon (DIC) in the intertidal aquifer over the entire salinity range. The locally produced TAlk and DIC in the intertidal aquifer contributed to >50% of the TAlk and DIC discharged with SGD to the ocean. The distributions of TAlk and DIC in the transition (mangrove) and high salinity (bare beach) zones were different due to the distinct hydrogeological and geochemical conditions. In the organic-rich mangrove zone, TAlk and DIC productions were driven by biotic processes such as aerobic respiration, denitrification, and sulfate reduction. In the organic-poor bare beach zone, TAlk and DIC productions were likely driven by abiotic processes such as precipitation/dissolution of carbonate minerals. Temperature, pH, physical mixing, and iron cycling in the intertidal aquifer also considerably influenced the carbonate biogeochemistry. TAlk inventory in the intertidal aquifer was seasonally stable but TAlk discharged with SGD was similar to 60% greater in the wet season than in the dry season (73.3 vs. 45.6 mol d(-1) per m coastline). The DIC inventory in the intertidal aquifer and DIC discharged with SGD were similar to 24% and 95% higher, respectively, in the wet season than dry season. Overall, through analyzing TAlk:DIC ratios and related fluxes, SGD was thought to reduce the CO2 buffering capacity of the receiving ocean, and act as a local driver of ocean acidification.
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| 23. |
- Mahdi, A., et al.
(författare)
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The red blood cell as a mediator of endothelial dysfunction in patients with familial hypercholesterolemia and dyslipidemia
- 2023
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 293:2, s. 228-245
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Tidskriftsartikel (refereegranskat)abstract
- Background Patients with familial hypercholesterolemia (FH) display high levels of low-density lipoprotein cholesterol (LDL-c), endothelial dysfunction, and increased risk of premature atherosclerosis. We have previously shown that red blood cells (RBCs) from patients with type 2 diabetes induce endothelial dysfunction through increased arginase 1 and reactive oxygen species (ROS). Objective To test the hypothesis that RBCs from patients with FH (FH-RBCs) and elevated LDL-c induce endothelial dysfunction. Methods and results FH-RBCs and LDL-c >5.0 mM induced endothelial dysfunction following 18-h incubation with isolated aortic rings from healthy rats compared to FH-RBCs and LDL-c <2.5 mM or RBCs from healthy subjects (H-RBCs). Inhibition of vascular but not RBC arginase attenuated the degree of endothelial dysfunction induced by FH-RBCs and LDL-c >5.0 mM. Furthermore, arginase 1 but not arginase 2 was elevated in the vasculature of aortic segments after incubation with FH-RBCs and LDL-c >5.0 mM. A superoxide scavenger, present throughout the 18-h incubation, attenuated the degree of endothelial dysfunction induced by FH-RBCs and LDL-c >5.0 mM. ROS production was elevated in these RBCs in comparison with H-RBCs. Scavenging of vascular ROS through various antioxidants also attenuated the degree of endothelial dysfunction induced by FH-RBCs and LDL-c >5.0 mM. This was corroborated by an increase in the lipid peroxidation product 4-hydroxynonenal. Lipidomic analysis of RBC lysates did not reveal any significant changes across the groups. Conclusion FH-RBCs induce endothelial dysfunction dependent on LDL-c levels via arginase 1 and ROS-dependent mechanisms.
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| 24. |
- Mao, Ziling, et al.
(författare)
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Dietary intake of advanced glycation end products (Ages) and mortality among individuals with colorectal cancer
- 2021
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Ingår i: Nutrients. - : MDPI. - 2072-6643. ; 13:12
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Tidskriftsartikel (refereegranskat)abstract
- Advanced glycation end-products (AGEs) may promote oxidative stress and inflammation and have been linked to multiple chronic diseases, including cancer. However, the association of AGEs with mortality after colorectal cancer (CRC) diagnosis has not been previously investigated. Multivariable Cox proportional hazards models were used to calculate hazard ratios and corresponding 95% confidence intervals for associations between dietary intake of AGEs with CRC-specific and all-cause mortality among 5801 participant cases diagnosed with CRC in the European Prospective Investigation into Cancer and Nutrition study between 1993 and 2013. Dietary intakes of AGEs were estimated using country-specific dietary questionnaires, linked to an AGE database, that accounted for food preparation and processing. During a median of 58 months of follow-up, 2421 cases died (1841 from CRC). Individually or combined, dietary intakes of AGEs were not associated with all-cause and CRC-specific mortality among cases. However, there was a suggestion for a positive association between AGEs and all-cause or CRC-specific mortality among CRC cases without type II diabetes (all-cause, Pinteraction = 0.05) and CRC cases with the longest follow-up between recruitment and cancer diagnosis (CRC-specific, Pinteraction = 0.003; all-cause, Pinteraction = 0.01). Our study suggests that pre-diagnostic dietary intakes of AGEs were not associated with CRC-specific or all-cause mortality among CRC patients. Further investigations using biomarkers of AGEs and stratifying by sex, diabetes status, and timing of exposure to AGEs are warranted.
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| 25. |
- O’Connor, Antoinette, et al.
(författare)
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Tau accumulation in autosomal dominant Alzheimer’s disease: a longitudinal [18F]flortaucipir study
- 2023
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Ingår i: Alzheimer's Research and Therapy. - 1758-9193. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Cortical tau accumulation is a key pathological event that partly defines Alzheimer’s disease (AD) onset and is associated with cognitive decline and future disease progression. However, an improved understanding of the timing and pattern of early tau deposition in AD and how this may be tracked in vivo is needed. Data from 59 participants involved in two longitudinal cohort studies of autosomal dominant AD (ADAD) were used to investigate whether tau PET can detect and track presymptomatic change; seven participants were symptomatic, and 52 were asymptomatic but at a 50% risk of carrying a pathogenic mutation. All had baseline flortaucipir (FTP) PET, MRI and clinical assessments; 26 individuals had more than one FTP PET scan. Standardised uptake value ratios (SUVRs) in prespecified regions of interest (ROIs) were obtained using inferior cerebellar grey matter as the reference region. We compared the changes in FTP SUVRs between presymptomatic carriers, symptomatic carriers and non-carriers, adjusting for age, sex and study site. We also investigated the relationship between regional FTP SUVRs and estimated years to/from symptom onset (EYO). Compared to both non-carriers and presymptomatic carriers, FTP SUVRs were significantly higher in symptomatic carriers in all ROIs tested (p < 0.001). There were no significant regional differences between presymptomatic carriers and non-carriers in FTP SUVRs, or their rates of change (p > 0.05), although increased FTP signal uptake was seen posteriorly in some individuals around the time of expected symptom onset. When we examined the relationship of FTP SUVR with respect to EYO, the earliest significant regional difference between mutation carriers and non-carriers was detected within the precuneus prior to estimated symptom onset in some cases. This study supports preliminary studies suggesting that presymptomatic tau tracer uptake is rare in ADAD. In cases where early uptake was seen, there was often a predilection for posterior regions (the precuneus and post-cingulate) as opposed to the medial temporal lobe, highlighting the importance of examining in vivo tau uptake beyond the confines of traditional Braak staging.
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